Patent Docs

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc) -- Opinions by Judge Moore, Judge Newman, and Judges Linn and O'Malley

By Michael Borella --

A previous post presented the background of this case, as well as Judge Lourie's plurality concurrence, and a second post addressed Chief Judge Rader's concurrence-in-part and dissent-in-part.  As noted in those posts, Alice's claimed inventions involved the reduction of settlement risk using a third-party intermediary.  This post continues the story of Alice by discussing the dissenting-in-part opinion by Circuit Judge Moore, the concurring-in-part and dissenting-in-part opinion by Circuit Judge Newman, and the dissenting opinion by Circuit Judges Linn and O'Malley.

Judge Moore's dissent-in-part

Judge Moore begins her opinion, which was joined by Judges Rader, Linn, and O'Malley, with a warning:  "if all of these claims, including the system claims, are not patent-eligible, this case is the death of  hundreds of thousands of patents, including all business method, financial system, and software patents as well as many computer implemented and telecommunications patents."  She noted that 320,799 patents were granted over a 13 year period in the USPTO's "Electrical Computers, Digital Processing Systems, Information Security, Error/Fault Handling" technology area, and that all of these patents were potentially at risk under Judge Lourie's opinion.

Like Judge Rader, Judge Moore stated that claims must be considered as a whole, and under that standard, Alice's system claims would be patent-eligible.  She noted that Prometheus explicitly indicated that interpreting the judicial exceptions to subject matter patentability too broadly would "eviscerate patent law" because at some level all inventions are based on abstract ideas, laws of nature, and/or natural phenomena.

Judge Moore also argued against the conflation of § 101, § 102, and § 103.  She noted that Judge Lourie's "inventive concept" analysis introduced a time-dependency into the § 101 inquiry that was more appropriate for the inquiries of the other sections.  To illustrate this point, she provided examples:

Even though the concept of addition is an abstract idea, the first calculator that could perform addition was a patent-eligible machine under § 101.  If someone subsequently discovered that, by rewiring the calculator, it could perform addition and subtraction (both abstract mathematical concepts), the improved calculator would similarly be patent-eligible.  The act of modifying the circuitry of a known device such that it is configured to apply an abstract idea does not transform it into an abstract idea.

Accordingly, largely based on the same general reasoning as Judge Rader, Judge Moore would have found Alice's system claims patent-eligible.

Judge Newman's concurrence-in-part and dissent-in-part

Judge Newman begins by noting that this case has provided three incompatible standards for § 101 analysis, opening the door for "opportunistic litigation, whose result will depend on the random selection of the panel."  She plainly stated that the Federal Circuit has failed to clarify the interpretation of § 101.

Judge Newman's position, like that of four of her colleagues, is that the § 101, § 102, and § 103 inquiries are separate.  She writes "it is not necessary, or appropriate, to decide whether subject matter is patentable in order to decide whether it is eligible to be considered for patentability."  She propounded a simplification of the § 101 inquiry by suggesting that "when the subject matter is within the statutory classes in section 101, eligibility is established."  Invoking the oft-quoted phrase that patent law embraces "anything under the sun that is made by man," she would push off all considerations of claim breadth to the other sections of the statute.

Ultimately, Judge Newman positioned her separate opinion as call for the Federal Circuit to affirm three basic principles of patentable subject matter.

1)  "The court should hold that section 101 is an inclusive statement of patent-eligible subject matter."  Judge Newman advocated eliminating claims that are abstract or that pre-empt abstract ideas or the other judicial exceptions using "laws of novelty, utility, prior art, obviousness, description, enablement, and specificity."

2)  "The court should hold that the form of the claim does not determine section 101 eligibility."  Whether the invention is claimed as a method, CRM, or system, and whether it is implemented with hardware or software, would not be relevant to the § 101 inquiry for Judge Newman.  Like Judge Lourie, she would attempt to decrease the impact of the so-called "clever draftsman."

3)  "The court should confirm that experimental use of patented information is not barred."  Perhaps most important of the three, Judge Newman believes that the popular media has misconstrued the debate on patentable subject matter to mean that a patented invention cannot further be studied.  In particular, she would have the Court hold that experiments that improve or build upon patented subject matter, compare it with alternatives, seek to understand its mechanisms, and to find new applications should be considered non-infringing activities.

Judge Linn's and Judge O'Malley's dissent

In stark contrast to their colleagues, Judges Linn and O'Malley would reverse the District Court ruling and find all claims patent-eligible for procedural reasons.

Since the summary judgment motions were filed prior to claim construction, the District Court gave the claims, for purposes of considering these motions, an interpretation defined by Alice.  Thus, Judges Linn and O'Malley afforded that the District Court was "required to read into the claims whatever limitations Alice asserted a skilled artisan would assume they possessed."  And, as noted above, the parties stipulated at trial that all claims required a computer and a memory to be performed.

Consequently, Judges Linn and O'Malley faulted Judges Rader and Moore of improperly construing the method claims more broadly than the system claims, and also reproached Judge Lourie for importing the breadth of the method claims into the system and CRM claims.  Judges Linn and O'Malley would have all claims rise or fall together.

With respect to the patent-eligibility of the system claims, the judges reiterated the position of Judge Rader.  However, they would also apply the same analysis to the method and CRM claims, and find those claims meeting the § 101 requirements as well.

Judges Linn and O'Malley concluded with a discussion of software patents at large.  Rather than use § 101 to mitigate a supposed "proliferation and aggressive enforcement of low quality software patents" concerning the various amici curiae, they would push this issue back to Congress for legislative action.  They suggested that Congress could limit the term of software patents, or limit their scope by requiring functional claiming.

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc)
Opinion for the court per curiam; concurring opinion by Circuit Judge Lourie, joined by Circuit Judges Dyk, Prost, Reyna, and Wallach; concurring-in-part and dissenting-in-part opinion by Chief Judge Rader, joined by Circuit Judge Moore, and by Circuit Judges Linn and O'Malley as to all but part VI of that opinion; dissenting-in-part opinion by Circuit Judge Moore, joined by Chief Judge Rader and Circuit Judges Linn and O'Malley; concurring-in-part and dissenting-in-part opinion by Circuit Judge Newman; dissenting opinion by Circuit Judges Linn and O'Malley; additional reflections by Chief Judge Rader.

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc) -- Chief Judge Rader's Concurrence-in-part and Dissent-in-part

By Michael Borella --

A previous post presented the background of this case, as well as Judge Lourie's plurality concurrence.  As noted in that post, Alice's claimed inventions involved the reduction of settlement risk using a third-party intermediary.  Despite the claims being of various statutory classes, including process, article of manufacture, and machine, Judge Lourie found that they were all directed to patent-ineligible abstract ideas, and thus they failed to meet the requirements of 35 U.S.C. § 101.

This post continues the story of Alice by discussing Chief Judge Rader's concurrence-in-part and dissent-in-part.

Chief Judge Rader, joined by Judges Linn, Moore, and O'Malley, presented the lengthiest opinion in opposition to Judge Lourie.  Chief Judge Rader and Judge Moore would have affirmed the patent-ineligibility of Alice's method and computer-readable medium (CRM) claims, but came to this conclusion based on different reasoning than Judge Lourie.  On the other hand, Chief Judge Rader and Judge Moore believed that the system claims passed the § 101 bar.  Judges Linn and O'Malley would have held that all claims were patent-eligible.  Based on the style with which this opinion was drafted, it may have been in competition with Judge Lourie's concurrence for a majority of the en banc panel.

Throughout, Chief Judge Rader expounded the broad language of § 101, as well as for the separation of the §§ 101, 102, and 103 patentability analyses, which he accused Judge Lourie of conflating.  In doing so, he provided an overview of the legislative history, from the 1952 Patent Act, of the modern interpretation of § 101.  He further pointed to both statements of the authors of the 1952 Act, as well as subsequent case law and commentaries, that indicate that the § 101 analysis is not an "inventiveness" analysis, and that such an analysis instead falls within the ambit of § 103.  In a rebuttal of Judge Lourie's "discovery vs. invention" dichotomy, Chief Judge Rader pointed to the language of 35 U.S.C. § 100(a), which states that "[t]he term 'invention' means invention or discovery."

Regarding laws of nature, natural phenomena, and abstract ideas, he advocated restraint when applying these judicial exceptions so that they do not swallow the statutory language of § 101.  He also emphasized that claims pass the § 101 bar if they recite the application of such an exception, such as a practical use of an abstract idea.  As opposed to Judge Lourie's piecemeal approach, Chief Judge Rader advocated that determining whether this is the case for a given claim requires consideration of the claim as a whole.

Citing support in Diehr and Prometheus, he wrote:

Any claim can be stripped down, simplified, generalized, or paraphrased to remove all of its concrete limitations, until at its core, something that could be characterized as an abstract idea is revealed . . . .  A court cannot go hunting for abstractions by ignoring the concrete, palpable, tangible limitations of the invention the patentee actually claims.

Indeed, he strongly implied that Judge Lourie's approach could be used to render virtually any claim abstract.

He then stated that "[t]he relevant inquiry must be whether a claim includes meaningful limitations restricting it to an application, rather than merely an abstract idea," and proposed six factors to consider when undertaking this analysis:

•  First, "a claim is not meaningfully limited if it merely describes an abstract idea or simply adds 'apply it.' "

•  Second, "if a claim covers all practical applications of an abstract idea, it is not meaningfully limited."

•  Third, "if a claim does not wholly pre-empt an abstract idea, it still will not be limited meaningfully if it contains only insignificant or token pre- or post-solution activity -- such as identifying a relevant audience, a category of use, field of use, or technological environment."

•  Fourth, "a claim is not meaningfully limited if its purported limitations provide no real direction, cover all possible ways to achieve the provided result, or are overly-generalized."

•  Fifth, "a claim is meaningfully limited if it requires a particular machine implementing a process or a particular transformation of matter."

•  Sixth, "[a] claim also will be limited meaningfully when, in addition to the abstract idea, the claim recites added limitations" that are "central to the solution itself."

Remarkably, these factors overlap to a large degree with the four factors of Judge Lourie's "inventive analysis."  The main difference between the two is that Judge Lourie suggested considering whether the human contribution to the claim amounts "to more than well-understood, routine, conventional activity previously engaged in by researchers in the field."  Chief Judge Rader would eschew separate consideration of such a human contribution, and instead consider each claim as a whole.  However, the inclusion of the Chief Judge's sixth factor may make this consideration more difficult to achieve in practice.

His factors also reject the notion that there is an inventiveness or ingenuity requirement component in the § 101 analysis.  Instead, he stated that "[t]he eligibility inquiry is not an inquiry into obviousness, novelty, enablement, or any other patent law concept . . . [e]ach section plays a different role and no one section is more important than any other."  Unlike Judge Lourie, Chief Judge Rader would read the "inventive concept" language of Prometheus as:

[S]horthand for its inquiry into whether implementing the abstract idea in the context of the claimed invention inherently requires the recited steps.  Thus, in Prometheus, the Supreme Court recognized that the additional steps were those that anyone wanting to use the natural law would necessarily use.  If, to implement the abstract concept, one must perform the additional step, then the step merely separately restates an element of the abstract idea, and thus does not further limit the abstract concept to a practical application.  (Internal citation omitted.)

He went on to discuss how computer-specific limitations should be considered in light of these factors.  Invoking shades of the Bilski machine or transformation test, he wrote:

The key to this inquiry is whether the claims tie the otherwise abstract idea to a specific way of doing something with a computer, or a specific computer for doing something; if so, they likely will be patent eligible, unlike claims directed to nothing more than the idea of doing that thing on a computer.  While no particular type of limitation is necessary, meaningful limitations may include the computer being part of the solution, being integral to the performance of the method, or containing an improvement in computer technology.  (Emphasis in original.)

While Judge Lourie seemed to believe that adding general purpose computer components (e.g., a processor, data storage, a transceiver, etc.) to a claim failed to provide meaningful limitations, Chief Judge Rader disagreed.  In fact, he quoted the language of In re Alappat, stating that "a general purpose computer in effect becomes a special purpose computer once it is programmed to perform particular functions pursuant to instructions from program software."

Applying his reasoning to the system claims, the Chief Judge found all of them patent-eligible under § 101.  Acknowledging that issue before the Federal Circuit was whether to grant CLS's motion for summary judgment, he found that there was a lack of clear and convincing evidence that the claims were directed to an abstract idea.  Instead, relying on the reasoning of Bilski, he posited that "[i]f tying a method to a machine can be an important indication of patent-eligibility, it would seem that a claim embodying the machine itself, with all its structural and functional limitations, would rarely, if ever, be an abstract idea."  He also noted claiming an invention to include "circuitry, transistors, capacitors, and other tangible electronic components," or "electronically programmable machines that can fit in the palm of your hand," makes no difference on the abstractness of the claim.

Specifically, the representative system claim included "at least four separate structural components:  a computer, a first party device, a data storage unit, and a communications controller coupled via machine components to the computer and the first party device."  Chief Judge Rader found that, given this recited structure as well as further structural limitations of the invention's configuration, labeling the claim as abstract would defy the meaning of that term.  Particularly, he noted that "someone can use an escrow arrangement in many other applications, without computer systems, and even with computers but in other ways without infringing the claims," and that the recited structure was not inherent in the steps of performing a third-party escrow transaction.

With respect to the method and CRM claims, he considered these together because Alice had conceded that the CRM claims rise or fall with the method claims, despite the CRM claims having a different statutory category.  He framed the issue for the Court as "whether the recited steps are inherent in an escrow and claimed at a high level of generality, such that in fact the claim is not to a practical application of the concept of an escrow, but in effect claims the abstract concept of an escrow."

Nonetheless, in applying his analysis, he broke (or, at least, severely bent) his own rules on not conflating the analyses of § 101 and § 103, and considering the claim as a whole.  Particularly, in determining that the concept of an escrow is abstract, he cited to a prior art accounting reference.  He also performed a step-by-step analysis of the claim and found that each step "recites merely a general step inherent within the concept of an escrow, using a third party intermediary in this fashion."

Finally, Chief Judge Rader indicated that that method claims recited no computer structure.  He found that the stipulation of the method merely being performed by computer was insufficient to meet § 101 requirements due to its lack of specificity about how the computer implementation is arranged.  Chief Judge Rader's reasoning echoes that of the panel in Dealertrack v. Huber, which found a computer-aided method unpatentable because "[t]he claims are silent as to how a  computer aids the method, to what extent a computer aids the method, and the significance of a computer performance of the method.

Additional discussion of the open questions coming out of this decision will be the subject of future posts.

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc)
Opinion for the court per curiam; concurring opinion by Circuit Judge Lourie, joined by Circuit Judges Dyk, Prost, Reyna, and Wallach; concurring-in-part and dissenting-in-part opinion by Chief Judge Rader, joined by Circuit Judge Moore, and by Circuit Judges Linn and O'Malley as to all but part VI of that opinion; dissenting-in-part opinion by Circuit Judge Moore, joined by Chief Judge Rader and Circuit Judges Linn and O'Malley; concurring-in-part and dissenting-in-part opinion by Circuit Judge Newman; dissenting opinion by Circuit Judges Linn and O'Malley; additional reflections by Chief Judge Rader.

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc) -- Judge Lourie's Concurrence

By Michael Borella --

On May 10, the Federal Circuit handed down a much anticipated en banc ruling regarding the patent eligibility of computer-implemented inventions under 35 U.S.C. § 101.  In a per curiam opinion that is perhaps the most important § 101 jurisprudence since the Supreme Court's Bilski v. Kappos and Mayo v. Prometheus decisions, a plurality of judges set forth procedures for determining whether claims that recite an abstract idea or a law of nature meet the requirements of this section.  While the overall effect of this case remains to be seen and is likely to be a subject of heated debate, this decision has the potential to impact both patent litigation and prosecution.

In 2007, CLS Bank filed a declaratory judgment action against Alice Corp., contending that, among other things, Alice's U.S. Patents Nos. 5,970,479, 6,912,510, and 7,149,720 were invalid under § 101.  Alice filed counterclaims alleging infringement of these three patents.  Later, Alice's U.S. Patent No. 7,725,375 was added to the mix, and the parties respectively asserted invalidity and infringement contentions for this patent as well.

All four patents are from the same family and "share substantially the same specification."  The plurality described the claimed subject matter as:

[A] computerized trading platform used for conducting financial transactions in which a third party settles obligations between a first and a second party so as to eliminate "counterparty" or "settlement" risk . . . .  Settlement risk refers to the risk to each party in an exchange that only one of the two parties will actually pay its obligation, leaving the paying party without its principal or the benefit of the counterparty's performance.  Alice's patents address that risk by relying on a trusted third party to ensure the exchange of either both parties' obligations or neither obligation.

Between the four patents, method, computer-readable medium (CRM), and system claims were asserted.  The parties stipulated that all claims, including the method claims, require "a computer including at least a processor and memory" and electronic implementation, even though the representative method claim analyzed by the Federal Circuit did not literally recite such a requirement.

The District Court held that all asserted claims failed to meet the requirements of § 101, and thus were invalid.  Particularly, the District Court concluded that the method claims were directed to an unpatentable abstract idea, and that the CRM and system claims would similarly preempt all practical applications of this idea, despite those claims falling under a different statutory category.

On appeal, a Federal Circuit panel reversed the District Court on all counts, holding that all claims, including the method claims, were patent eligible under § 101.  CLS petitioned the full Federal Circuit for review, which was granted.  Sitting en banc, seven of the ten judges overruled the panel and affirmed the District Court's ruling regarding the method and CRM claims.  However, this majority did not agree on the rationale for their conclusion.  Further, five of the judges found that the system claims were unpatentable, while the other five concluded that these claims passed muster under § 101.  Additionally, eight of the judges indicated that the method, CRM, and system claims must rise or fall together.  Consequently, the precedential value of his decision, especially with respect to the system claims, may be limited.

Below, Judge Lourie's plurality concurrence is discussed.  Joining him were Judges Dyk, Prost, Reyna, and Wallach.  The other concurrences and dissents will be examined in subsequent posts.

Judge Lourie admitted the difficulty of analyzing patentability under § 101, and acknowledged the need for a more practical approach to this analysis:

While simple enough to state, the patent-eligibility test has proven quite difficult to apply.  The difficulty lies in consistently and predictably differentiating between, on the one hand, claims that would tie up laws of nature, natural phenomena, or abstract ideas, and, on the other, claims that merely embody, use, reflect, rest upon, or apply those fundamental tools.  For example, deciding whether or not a particular claim is abstract can feel subjective and unsystematic, and the debate often trends toward the metaphysical, littered with unhelpful analogies and generalizations.  What is needed is a consistent, cohesive, and accessible approach to the § 101 analysis -- a framework that will provide guidance and predictability for patent applicants and examiners, litigants, and the courts.  (Citation omitted.)

Judge Lourie then turned to the inevitable overview of Supreme Court decisions impacting § 101 as guideposts for this analysis.  In an example of judicial foreshadowing, he viewed Benson, Flook, Deihr, and Bilski through the lens of Prometheus.  In particular, he focused on the judicial exception to patentable subject matter when the claims at issue incorporate abstract ideas or laws of nature.  Then, he applied Prometheus's approach for analyzing such claims, with special concern for whether a claimed invention would effectively preempt other uses of any potentially abstract idea recited therein.

Particularly, Judge Lourie set forth a four-step analysis for patent eligibility under § 101 based heavily on Prometheus.  These steps are as follows:

1)  Determine "whether the claimed invention fits within one of the four statutory classes set out in § 101."  In other words, is the invention directed to a process, machine, manufacture, or composition of matter?

2)  Determine whether "the claim pose[s] any risk of preempting an abstract idea."  Or, does the claim incorporate an abstract idea?

3)  If an abstract idea is implicated by the claim, then "identify and define whatever fundamental concept appears wrapped up in the claim so that the subsequent analytical steps can proceed on a consistent footing."  Judge Lourie indicates that carrying out claim construction activities prior to this step may be helpful, but is not required.

4)  Finally, "[w]ith the pertinent abstract idea identified, the balance of the claim can be evaluated to determine whether it contains additional substantive limitations that narrow, confine, or otherwise tie down the claim so that, in practical terms, it does not cover the full abstract idea itself."

Judge Lourie refers to this final step as "inventive concept" analysis.  He explicitly states that this "balance of the claim" -- the human contribution -- need not require inventiveness in the same sense that claims must be novel and non-obvious under sections 102 and 103, respectively.  However, he does not clearly differentiate how this inventive concept analysis would differ in practice from, say, an obviousness analysis.  Instead he asserts that:

An "inventive concept" in the § 101 context refers to a genuine human contribution to the claimed subject matter . . . .  [A] person cannot truly "invent" an abstract idea or scientific truth.  He or she can discover it, but not invent it.  Accordingly, an "inventive concept" under § 101 -- in contrast to whatever fundamental concept is also represented in the claim -- must be a product of human ingenuity.

Compared to novelty and non-obviousness analyses "which consider whether particular steps or physical components together constitute a new or nonobvious invention," Judge Lourie states that the inventive concept analysis "considers whether steps combined with a natural law or abstract idea are so insignificant, conventional, or routine as to yield a claim that effectively covers the natural law or abstract idea itself."  But, in practice, this distinction may easily become blurred, and seems to advocate that claims be considered piecemeal under § 101 rather than as a whole.

Furthermore, at first blush, Judge Lourie's differentiation between discovery and invention seems like an aesthetically pleasing dichotomy -- after all, one could say that Pythagoras didn't invent the Pythagorean Theorem, but he did discover it.  However, Judge Lourie went on to point to four potentially subjective factors that would weigh against whether the human contribution to the claimed invention rises to such a level that the claim as a whole meets § 101 requirements:

1)  Is the human contribution necessary to every practical use of the abstract idea and therefore is not truly limiting.

2)  Does the human contribution "amount to more than well-understood, routine, conventional activity previously engaged in by researchers in the field?"

3)  Does the human contribution consist of token or trivial limitations, such as insignificant post-solution activity?

4)  Is the human contribution a "field-of-use limitation . . . where the claim as written still effectively preempts all uses of a fundamental concept within the stated field?"

Applying this approach to the patents in suit, Judge Lourie found that all claims failed under § 101.  The representative method claim was found to be directed to the reduction of settlement risk using a third-party intermediary.  As such, Judge Lourie concluded that this claim recited an abstract idea -- a "disembodied concept, a basic building block of human ingenuity, untethered from any real-world application."  Therefore, he turned to whether the remaining aspects of the claim added anything of substance.  He concluded that they did not.

Notably, this method claim did not recite any required physical structure.  It did not include a memory, a processor, transmitters or receivers, or any other computer component or peripheral.  Despite the parties' stipulation that the claim was computer implemented, Judge Lourie indicated that such a limitation was "insignificant post-solution activity" and that "simply appending generic computer functionality to lend speed or efficiency to the performance of an otherwise abstract concept does not meaningfully limit claim scope for purposes of patent eligibility."  Thus, he concluded that "[a]s in Bilski, upholding Alice's claims to methods of financial intermediation would pre-empt use of this approach in all fields, and would effectively grant a monopoly over an abstract idea."

Judge Lourie similarly found the representative CRM claim unpatentable as well, despite its recitation of a tangible article of manufacture, which would ostensibly be a physical device.  This claim essentially recited the invention of the method claim, but in CRM form.  Judge Lourie asserted that "under § 101 we must look past drafting formalities and let the true substance of the claim guide our analysis."  Applying this analysis he concluded that the CRM claim was actually drawn to "the underlying method of reducing settlement risk using a third-party intermediary," and that it was merely a method claim in the guise of a device claim.  He further warned that one should not allow a competent draftsman to "endow abstract claims with patent-eligible status."

The representative system claim also fell under Judge Lourie's analysis.  This claim recites ample structure -- including a data storage unit and a computer that receives data, performs operations on the data, and generates an instruction to an "exchange institution."  Nonetheless, Judge Lourie found that the similarity between the method and system claims required application of the same abstract idea analysis for both.  In this case, the question was whether "the limitations of the claim, including any computer-based limitations, add enough beyond the abstract idea itself to limit the claim to a narrower, patent-eligible application of that idea."  Viewing the "generic" computer structure recited by the claim sufficient to "encompass any device capable of performing the same ubiquitous calculation, storage, and connectivity functions required by the method claims," Judge Lourie found that they did not because this structure did not provide a significant "inventive concept."  Summing up, he wrote that:

We are not here faced with a computer per se.  Such are surely patent-eligible machines.  We are faced with abstract methods coupled with computers adapted to perform those methods . . . .  Abstract methods do not become patent-eligible machines by being clothed in computer language.

In order to properly seek protection of their inventions, Applicants need to understand the requirements of § 101.  Despite the plurality's cry for "a consistent, cohesive, and accessible approach to the § 101 analysis," at best, a handful of dirt has been tossed into already muddied waters.  Judge Lourie's procedures for § 101 analysis allow significant opportunities for subjectivity on the part of the fact finder.  As a result, an Applicant's best practice for obtaining suitable protection of its computer-implemented technologies remains unclear.  A more detailed discussion of the open questions coming out of this decision will be the subject of future posts.

CLS Bank Int'l v. Alice Corp. (Fed. Cir. 2013) (en banc)
Opinion for the court per curiam; concurring opinion by Circuit Judge Lourie, joined by Circuit Judges Dyk, Prost, Reyna, and Wallach; concurring-in-part and dissenting-in-part opinion by Chief Judge Rader, joined by Circuit Judge Moore, and by Circuit Judges Linn and O'Malley as to all but part VI of that opinion; dissenting-in-part opinion by Circuit Judge Moore, joined by Chief Judge Rader and Circuit Judges Linn and O'Malley; concurring-in-part and dissenting-in-part opinion by Circuit Judge Newman; dissenting opinion by Circuit Judges Linn and O'Malley; additional reflections by Chief Judge Rader.

The Myriad Case and "Gene" Patents: Much Ado about Nothing?

By Kevin E. Noonan --

The biggest concern of the biotechnology industry caused by the impending Supreme Court decision in the AMP v. Myriad Genetics case is the threat to existing patents having claims to isolated human DNA (and the DNA from other species) that a negative decision from the Court could raise.  Patent protection has been an important component of the success of companies from Genentech to Myriad and many others, and the prospect of a categorical ban (ironic, in view of the Court's anathema for "bright line" rules promulgated by the Federal Circuit) threatens the success paradigm developed over the past 30 years.  While the extent of whatever deleterious effects on the progress of the biotechnology arts that the Court may impose by its Myriad decision is still to come, an article in the May edition of Nature Biotechnology suggests that those effects may be ameliorated by the anachronistic aspects of the Myriad case:  in many ways this argument is coming 30 years to late, and the future of biotechnology is less dependent on so-called "gene patents" than at any other time in the history of the biotechnology industry.

The article, "Not quite a myriad of gene patents," by Gregory Graff, Devon Phillips, Zhen Lei, Sooyoung Oh, Carol Nottenburg, and Philip Pardey, provides a survey of existing patents claiming isolated human DNA.  After providing a brief history of the Myriad case, the paper provides data on the number of U.S. patents containing different types and extents of isolated human DNA:

• Patents that identify DNA or RNA "anywhere" in the patent document
• Patents that identify DNA or RNA in the claims (providing upper and lower estimates)
• Patents with at least one composition of matter claim directed to isolated DNA or RNA (numbering 15,359 patents according to these authors)

Previously published estimates of the number of such patents claiming human DNA vary widely, with a high of 40,000 from a National Research Council report to a emerging consensus of ~4,000 – 5,000 patents that claims isolated human DNA.  The paper also addresses the philosophical and practical consequences that could arise if the Court narrowly answered the Question Presented in a decision limited to human DNA, in contrast to DNA from other species.

The quantitative aspects of the paper involve an analysis of claim language in claims reciting isolated human DNA, thereby identifying 72,052 U.S. patents that "in some way identify or make reference to nucleotide sequences."  Of these, the authors report that from 30-39% of these patents (21,870 – 28,410 patents) were "likely to contain or refer to nucleotide sequences in at least one of the claims of the patent."  Finally, the paper identifies from this population patents that contain at least one composition of matter claim to an isolated human nucleic acid, which are reported to be 15,359 patents.  (As an interesting aside, there were 82,952 method claims in the 72,052 patents that recited human DNA or RNA.)  Of these 15,359 patents, 5,936 (39%) "primarily involve" isolated human DNA, with the remainder being directed to isolated DNA molecules from other animals (1,056; 7%); plants (1,847; 12%);  microbes (3,228; 21); and synthetic or artificial sequences (3,292; 21%).  (Methodologically, the authors considered claims to artificial or synthetic sequences to be "markedly different" from naturally occurring DNA and omitted these patents from further analysis.)

Looking at the timing of patents granted on isolated DNA, the authors report that the number of patents containing such claims peaked in 1999 and has been declining since 2005 (no doubt due to a combination of the more stringent utility requirements imposed by the U.S. PTO in 2001 and the change from isolating DNA encoding a particular protein and isolating human DNA containing an open reading frame as identified by genome sequencing efforts, predominantly related to the Human Genome Project).  The proportion of patents claiming isolated human DNA peaked in 2000, where 58% of "gene" patents recited human DNA, and by 2010 this percentage had fallen to 19%.

Of the patents containing claims to isolated DNA that could encompass "naturally occurring" molecules, the authors identified 8,703 that remain in force, with 3,535 (41%) of these patents claiming isolated human DNA and less than half of these patents being related to human medicine (an area about which at least Justice Breyer has evinced a particular concern on the possibility of negative effects of patenting on patient care).  The assignee data the authors report are a little surprising, with 65% of the 15,359 patents containing composition of matter claims reciting isolated DNA molecules being owned by private-sector commercial assignees, and only 24% being owned by public-sector (identified as "government, university, nonprofit") assignees (the remainder being owned by some combination of public- and private-sector assignees).  The "Top Twenty-five" assignees (and the number of patents assigned to them) are reported to be:

The authors speculate on the reason for the decline in patents claiming isolated nucleic acids, providing some clear correlations (the crash of the tech bubble at the turn of the century, the availability on public databases of human genomic DNA sequences and the prior art effect, and the more stringent utility requirements).  The authors also recognized that the 1999-2000 timeframe also marked a change from claims to isolated human DNA molecules per se to claims reciting "complex genetic constructs" (presumably including expression constructs).  The authors also note the trend over the past decade towards claims to molecules comprising artificial or synthetic sequences (from 14% to 40%) rather than "naturally occurring" DNA molecules (from 58% to 19%).  Nevertheless, the 3,535 patents claiming isolated human DNA remain at risk for invalidation to some extent by the Supreme Court's Myriad decision (and, the authors note, the remaining 4,538 patents claiming isolated DNA from other species might also be at risk if the Court rules more broadly).  Consequently:

[A]n overturn by the Supreme Court will affect claims of patents not only on human genetic diagnostics and therapeutics but also on a wide range of other genetic technologies in other industries, particularly in agriculture, based upon our analysis of top assignee portfolios.

The authors attempt to find a silver lining in their analyses, particularly with regard to sequence variants and genetically engineered constructs, which may have a greater likelihood to evince "the hand of man" and to be "markedly different" from naturally occurring DNA.  They perceive a trend towards this type of innovation that a "product of nature" exception from the Court would "accelerate," and more recent events (the PTO's decision to examine one sequence per invention and the Federal Circuit's expansion of obviousness towards isolated DNA in In re Kubin) are not accounted for in the data.  Thus:

The outcome of the Myriad case, regardless, is thus likely to be less profound than either abolitionists or advocates seem to expect.  In the end, any policy effects resulting from the Myriad case may prove to have been largely preempted by a combination of less dramatic changes in examination practices and patent law.

While outside the scope of the data presented in their paper, the authors also neglect to consider the effects of a broad "product of nature" ban by the Court on biotechnology more generally (a concern voiced by Judge Moore in oral argument and her concurring opinions in the Federal Circuit's review of the Myriad decision).  It is possible, as the authors posit, that the negative effects of whatever decision is handed down by the Court will be ameliorated by advances in DNA technology (and the capacity of competent patent draftsmen to adapt claiming strategies to accommodate their clients' needs in view of the Court's proscriptions).  But it is equally likely that the Court will seriously harm the economic incentives for commercializing genetic technology and inhibit disclosure of new correlations between disease and genetic variation, all to the detriment of progress in this industry.  And it is a near certainty that the purported purpose behind the controversy, better access to genetic testing for patients, will not be one of the outcomes of any decision that impairs the ability to commercializing genetic testing.  In the end, the question is not how many patents are at risk from the Court's consideration of the question before it, but rather why do the Justices not realize that now is not the time to wade unnecessarily into these particular philosophical waters.  It is ultimately a political, not a legal, question, and one better suited for consideration by the (expressly) political branches of the government.

What We May Learn from the Myriad Oral Argument

By Kevin E. Noonan --

The U.S. Supreme Court heard oral argument in Association for Molecular Pathology v. Myriad Genetics, Inc. on Monday, and many have commented on the Court's interrogation of the parties' representatives (and the government) and how those representatives responded to the Justices' questioning.  On balance, it seems fruitless to bemoan the apparent difficulties the Court has with these issues; to paraphrase the sponsor of the aspartame patent term extension (private) bill, "you go to patent law with the Supreme Court you have."  Equally unavailing are discussions of the ACLU's perfidity (in advancing arguments having little resemblance to the law or the facts), the government's duplicity (asserting that genomic DNA should not be patent-eligible after more than thirty years of granting, and continuing to grant, such patents), any perceived incompetence by Myriad's representatives (for being unable to do the near impossible in answering the Court's sometimes incoherent questions) or Myriad's irresponsibility (for continuing a suit on patents that do not protect its core business and putting at risk patents to others necessary for commercialization).

While assessing (or worse, trying to predict) the Court's take on the issue, there are a few aspects that are evident:

Bad analogies make bad law:  Isolated human DNA is not a tree (Justice Kagan); sap from a tree (Justice Breyer); a chocolate chip cookie (Justice Sotomayor); a baseball bat (Greg Castanias); or a liver or kidney (Chris Hanson).  Instead of dancing around the issues by waxing poetic with analogies, the Court might have (and at least Myriad should have given them an opportunity to) considered more realistic comparisons.  For example, it should not too much to ask the Court if any of the following are or should be patent-eligible:

• Isolated chemical compound from crude oil useful as a lubricant
• Isolated chemical compound from a plant useful as a drug
• Isolated antibiotic produced by bacteria
• Isolated protein from an animal useful to cure/ameliorate human disease
• Isolated cucumber gene that extends freshness
• Isolated human gene (erythropoietin)

The Goldilocks view of patent law:  Justice Breyer still believes it is the Court's role to make sure the amount of patenting is just right regarding the balance between too much (retarding innovation) and too little (providing insufficient incentives for commercialization).  And while colorful, colloquies such as the following:

It's important to keep products of nature free of the restrictions that patents there are, so when Captain Ferno goes to the Amazon and discovers 50 new types of plants, saps and medicines, discovers them, although that expedition was expensive, although nobody had found it before, he can't get a patent on the thing itself.  He gets a patent on the process, on the use of the thing, but not the thing itself.

Not only do not answer the question but obscure it.  It is also disquieting to hear that the Justice thinks that the "product of nature" prohibition is "horn-book law"; were that the case, the Court would not need to consider the question before it.

The Court remains cautious regarding its capacity to harm incentives for commercialization:  This concern was expressed by many members of the Court, not limited to those Justices (such as Justices Scalia or Alito) who might be expected to voice these sentiments.  Indeed, Justice Kennedy's questions regarding the effects of a negative decision might indicate that there are sufficient members of the Court who might be persuaded that the more prudent course would be to affirm.

The government's position has the best chance of prevailing:  Not surprisingly, the "compromise" position espoused by the government (that cDNA is patent-eligible, but genomic DNA is not) seemed to have significant traction with the Court, if only because (as it did at the Federal Circuit) the presence of the "hand of man" is most evident for these embodiments of isolated DNA claims.  (The question of whether cDNA is obvious, as discussed by some members of the Court, falls into the category of battles to be fought another day.)  The Court did not fail to appreciate the change in the government's position, with Justice Kagan dismissing the PTO's history of granting patents encompassing genomic DNA because the Office was "patent-happy" (this disparagement, while unfair is not surprising in view of the general drumbeat of a "broken patent system" over the past decade from various interest groups).

Patent-eligibility will depend on how subject matter is claimed:  This isn't new, but may take on renewed significance.  Many members of the Court seemed to think that "method" claims (of using or producing) isolated DNA would be sufficient, ignoring the experience of foreign patent systems that eschewed composition protection for pharmaceuticals, for example in favor of such method claims; these generally did not result in robust commercialization of such pharmaceutical products.  Paradoxically, of course, for isolated DNA, "use" claims may be the most important in the future, as the composition of matter claims to DNA per se will not survive into the next decade by the action of patent term limits to 20 years from filing and the publication of the fruits of the Human Genome Project between 1998-2001.  What may not be as clear (or, more troubling, may become crystal clear) is the fate of claims such as Claim 2 in this sequence:

1.  Penicillin.
2.  An isolated preparation of penicillin having a specific activity of x Units/mg.
3.  A pharmaceutical composition comprising a therapeutically effective amount of penicillin and an acceptable diluent, excipient or carrier.

Claim 1 is not patent-eligible today, as it reads on the molecule as it exists in nature, and Claim 3 should remain eligible regardless of the Court's decision in Myriad.  Whether Claim 2 remains patent-eligible will depend on how narrowly the Court bases its decision (in the event that It reverses any portion of the Federal Circuit's decision below) and the amount of dicta that accompanies such a decision.

Ironically, the ACLU may have provided the best rationale for the Court to render a decision that does not do violence to traditional concepts of patenting molecules found in nature, in the following response to Justice Alito's question:

JUSTICE ALITO: Suppose there is a substance, a -- a chemical, a molecule in the -- the leaf -- the leaves of a plant that grows in the Amazon, and it's discovered that this has tremendous medicinal purposes. Let's say it -- it treats breast cancer.

A new discovery, a new way -- a way is found, previously unknown, to extract that. You make a drug out of that. Your answer is that cannot be patent -- patented; it's not eligible for patenting,

MR. HANSEN: If there is no alteration, if we simply pick the leaf off of the tree and swallow it and it has some additional value, then I think it is not patentable. You might be able to get a method patent on it, you might be able to get a use patent on it, but you can't get a composition patent.

JUSTICE ALITO: But you're making -- you the hypotheticals easier than they're
 intended to be. It's not just the case of taking the leaf off the tree and chewing it.  Let's say if you do that, you'd have to eat the whole forest to get the [] value of this. But it's extracted and -- and reduced to a concentrated form. That's not patent -- that's not eligible?

MR. HANSEN: No, that may well be eligible, because you have now taken what was in nature and you've transformed it in two ways. First of all, you've made it substantially more concentrated than it was in nature; and second, you've given it a function. If it doesn't work in the diluted form but does work in a concentrated form, you've given it a new function. And the -- by both changing its nature and by giving it a new function, you may well have patent -­

JUSTICE ALITO: Well, when you concede that, then I'm not sure how you distinguish the isolated DNA here, because it has a different function.

Finally, the fate of claims to oligonucleotide claims is uncertain, although these claims raise other issues of patentability (not patent-eligibility) that may render them invalid if ever asserted against an accuse infringer.

The Court's decision is expected by the end of this term, some time in June.

PBS NewsHour Examines Oral Argument in AMP v. Myriad -- Patent Docs Author Kevin Noonan Appears on Program

On Monday, the Supreme Court heard oral argument in Association for Molecular Pathology v. Myriad Genetics, Inc. (a transcript of the oral argument can be found here).  The PBS NewsHour examined yesterday's argument in a segment on Monday's program.  PBS senior correspondent Jeffrey Brown discussed the case with Marcia Coyle, chief Washington correspondent for The National Law Journal, as well as Ellen Matloff, Director, Cancer Genetic Counseling for the Yale Cancer Center, a plaintiff in the case; and Patent Docs author Dr. Kevin Noonan.  The NewsHour segment can be viewed below:

Watch Supreme Court Tackles Case of Patent Law, Human Genetics on PBS. See more from PBS NewsHour.

A Response to Dr. Mason's "Rebuttal" to Criticisms of His Genomics Medicine Article

By Kevin E. Noonan --

Much of the gene patenting debate has appeared, to experienced patent practitioners, to be akin to a conversation with Kevin Kline's character in A Fish Called Wanda, or perhaps a passage from P.G. Wodehouse's The Luck of the Bodkins.  In short, it has been the tale of doctors, scientists, and legal academics interpreting claims to isolated DNA in ways both bizarre and unlikely to anyone with any experience in actually claiming DNA.  However, as Dr. Mason's response illustrates those of us on the patent side of the debate have contributed to the confusion.

Reviewing Dr. Mason's assessment of the patents and applications he identified as encompassing almost the entirety of the human genome reveals two sources of misunderstanding.  The first is between the disclosure of patent specifications and the claims:  while sometimes in their zeal to provide the broadest disclosure possible, patent practitioners have been overly expansive in defining the scope of the isolated nucleic acids that are the subject of their clients' inventions, the claims have typically been more circumspect.  Most claims to isolated DNA have the canonical structure:

An isolated nucleic acid/human DNA molecule, encoding an amino acid sequence identified by SEQ ID NO. X.

Occasionally the word "comprising" is used in such claims:

An isolated nucleic acid/human DNA molecule, comprising a nucleotide sequence encoding an amino acid sequence identified by SEQ ID NO. X.

And there are claims to oligonucleotides, usually dependent on the claimed sequence:

An oligonucleotide comprising about 15 nucleotides of SEQ ID NO: X.

Considered in a vacuum, in the context of definitions as illustrated in Dr. Mason's response, it could be thought that such claims encompass a greater scope than they actually do.  What is missing is context, both historical and legal, that provides the insights needed to properly understand the scope of these claims.

The base canonical form above was developed about thirty years ago, during the age when "cloning" a DNA molecule that encoded a protein of interest (erythropoietin, tissue plasminogen activator, blood clotting Factor VIII, interferon, etc.) was a Herculean feat, and such claims were expressly directed towards full-length versions of these genes.  In the days before the Human Genome Project and the vast amount of genetic information it produced, such cloned genes had but one utility:  to permit the production of recombinant cells that expressed the gene product, typically to be used as one of the first "biologic" drugs.  In order for the claimed DNA molecule to have that utility, however, what was required almost always was that the full-length gene be isolated, because truncated proteins could not be expected to have the desired biological properties (and could have deleterious ones, such as increased immunogenicity or reduced half-life).  Accordingly, such claims do not have the scope Dr. Mason ascribes to them, because any such claim would be invalidated for failing to have the necessary utility.

Moreover, the scope of such claims are extremely narrow, being limited to isolated DNA molecules that encode the specifically recited amino acid sequence identified as SEQ ID NO: X.  An isolated human DNA comprising any change in this encoded amino acid sequence is not exclusive to the patentee and can be performed freely without literal infringement liability by anyone.  (The availability of the doctrine of equivalents for isolated human DNA claims is severely limited by U.S. Patent and Trademark Office practice in interpreting the application of 35 U.S.C. § 112(a) to such claims, and by ensuing prosecution history estoppel.)

The significance of this limitation in scope of isolated DNA claims can be understood by the following example.  If the single change in the amino acid sequence expressly recited in the claim is from a valine (Val) residue to an isoleucine (Ile) residue, the number of atoms in the protein would be increased by a mere 3 atoms (the difference in structure between these two amino acids is a methylene group,-CH₂-) out a total of 50-100,000 atoms in the protein.  Yet, even such a molecule changed to such a small degree would not literally infringe the generic claim.  Similarly, insertions or deletions of the sequence, mutations and sequence variants (naturally occurring or man-made) do not fall within the scope of claims to a specific, particular isolated human DNA, due to this restricted scope.  Such claims reciting such full-length "genes" are simply not preclusive of any other gene in the genome.

Turning to the oligonucleotide claims, there are two issues.  First, the work of Bob Cook-Deegan and his collaborators have shown (Kepler et al., "Metastasizing patent claims on BRCA1") that oligonucleotides on the order of 15-16 nucleotide residues in length are much more ubiquitous in the genome than was once thought.  This stems from the simplistic and incorrect assumption that any sequence of n nucleotides will occur once per 4ⁿ times in the genome.  Thus, the random 15-mer was expected to arise once every 1,073,741,824 basepairs, and the random 16-mer once every 4,294,967,296 basepairs.  The (false) conclusion was that in a haploid genome comprising 3 x 10⁹ basepairs, the 15-mer and 16-mer (and larger species) would be unique.  The source of the error is that human DNA is a historical molecule, and that many sequence motifs would be expected to arise many more times than random statistics would predict; the Human Genome Project (and basic biology) illustrates the fact that the human genome evolved by gene duplication and recombination, so that certain motifs (the ATP-binding cassette sequences, for example) sharing certain amino acid sequence and thus the nucleotide sequences encoding them, are much more common that was predicted.  The consequence of this biological fact is not that claims to such oligonucleotide encompass the entirety of the genome.  Rather, it is that claims of this scope are invalid, since the prior art is much more replete with these sequences than was expected.

The other distinction that should be appreciated is that what is disclosed (and even claimed) in patent applications does not raise infringement issues.  Indeed, filing overbroad claims in International Applications can be a strategic decision, to produce prior art against competitors (this stratagem became available in the U.S. with publication of U.S. applications under the American Inventor Protection Act of 1999).  Mere inspection of the published patent application database can find patents to a variety of "inventions" unlikely to ever grant with patentable claims, and their existence is thus not relevant to a serious debate over the scope of patents claiming isolated human DNA.

It is difficult to avoid the conclusion that a failure to appreciate these distinctions informs much of the angst enunciated by Dr. Mason and other physicians and researchers confronted by the prospect of infringement liability (or at least the fear that threats from patent holders will inhibit progress in genetics research).  But the patent community is not entirely blameless either, as illustrated by Dr. Mason in his Rebuttal.  There exists a certain amount of loose language in patent specifications that creates understandable confusion as to the claim scope the patentee believes she is entitled to, and thus uncertainty as to whether claims will be asserted as broadly as these specifications can be interpreted to support.  (Of course, some have interpreted these claims to encompass isolated DNA itself, an interpretation that would render the claims unpatentable since the time of Friedrich Miescher's work in the 19th Century.)  Some comfort should be taken by the fact that no gene patent holder has ever asserted claims to this extent, and that any attempt to do so would likely result in invalidation of the claims.  And the patent case law has provided more and more illustrations of claims (including Myriad's method claims) being interpreted in view of these overbroad specifications and invalidated based on broad claim construction.  In short, while there may be specifications suffering from symptoms of overbroad disclosure, the disease is self-correcting (even more so with the post-grant review and inter partes review provisions of the Leahy-Smith America Invents Act).

What is clearly needed is more dialog (and perhaps fewer assumptions) from both physicians and the patent community.  This debate comes thirty years too late to be particularly meaningful to claims to isolated nucleic acids.  But as the complexities of "modern" gene-based inventions increase (and their capacity to be ever more resistant to reverse engineering), the potential to eschew patent protection will increase, with the concomitant reduction in disclosure of biologically relevant inventions.  Such a trend, and Supreme Court decisions that promote that trend, particularly if based on unrealistic apprehensions over the (vanishingly small) possibility that claims to isolated human DNA will negatively impact developing genetic technologies, could paradoxically promote the outcome that opponents of gene patenting purportedly are committed to prevent.

A Primer on Claim Construction -- Comments on Dr. Mason's Response

By Donald Zuhn --

Yesterday, we posted a response from Dr. Chris Mason of Cornell University to a recent Patent Docs post and an article posted by Dr. Chris Holman on Holman's Biotech IP Blog.  Dr. Mason co-authored an article in the current issue of Genome Medicine, which contends that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences.  In his response, Dr. Mason comments on several aspects of the Holman and Patent Docs posts, which he says suggest that the analysis from his paper "was mistaken or did not embody an accurate characterization of the claims' construction."

In response to Dr. Holman's assertion that Dr. Mason and his co-author Jeffrey Rosenfeld "seem to assume that every patent with a claim mentioning a gene sequence also claims every 15mer present in the sequence," Dr. Mason states that the authors did not make such an assumption, and that their paper instead describes the results of two distinct analyses.  In the first analysis, the authors "examined the uniqueness of 15mers in general, which was shown to be exceedingly non-unique genome-wide."  However, as we noted in our first post on Dr. Mason's paper, the conclusion regarding the broad scope of claims to 15mers -- and in particular claims 5 and 6 of Myriad's U.S. Patent No. 5,747,282 -- is not particularly ground-breaking given that Kepler et al. similarly concluded in a 2010 Genomics paper that claim 5 of the '282 patent was "exceptionally broad" (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  Kepler et al. also suggested that "if human genes were random strings of nucleotides, one would expect a human gene to contain an average of 15 15-mers claimed under the ['282] patent," and in fact found that 80% of 713 human mRNAs deposited in 1994 (the earliest effective filing date of the '282 patent is August 12, 1994) contained at least one of the claimed 15mers.

With respect to their second analysis, Dr. Mason states that the authors "used patents that claimed 15mer sequences in their construction, and we indicated the matches we could find given their sequence composition."  Unfortunately, given Dr. Mason's views regarding the subject matter encompassed by the claims of U.S. Patent No. 7,795,422 -- one of "58 patents [according to Dr. Mason] whose claims covered at least 10% of the bases of all human genes," and a patent Dr. Mason labeled as their "top patent . . . whose claims' sequences matched 91.5% of human genes" -- it is not entirely clear what Dr. Mason means when he says that the authors "used patents that claimed 15mer sequences in their construction" (emphasis added).  An analysis of the claims in the '422 patent, as well as those in U.S. Patent No. 7,468,248 (a second patent discussed in the Genome Medicine article), clearly indicates that Dr. Mason's top two candidates do not contain "explicit claims for 15mers that matched 84% of human genes," as asserted in his paper (assuming that by "explicit claims," Dr. Mason means that the claims cover or encompass 15mers).  It is also abundantly clear from both the Genome Medicine paper and his subsequent response that Dr. Mason does not understand the process of claim construction (which is not surprising given that Dr. Mason is not a patent practitioner).

So, what follows is a short primer on claim construction.  Claim construction is the process of giving proper meaning to the language of the claims.  Abtox Inc. v. Exitron Corp., 122 F.3d 1019, 1023 (Fed. Cir. 1997).  The language of the claim frames and ultimately resolves all issues of claim interpretation, since it is the language of the claim that defines the scope of the protected invention.  Id.  However, in determining the scope and meaning of a claim term, three additional sources may be considered:  the descriptions in the rest of the patent specification, the prosecution history, and relevant extrinsic evidence.  Phillips v. AWH Corp., 415 F.3d 1303, 1315, 1317 (Fed. Cir. 2005).

With regard to the use of the specification and prosecution history to construe claim terms, the Federal Circuit has stated that:

Claims must be read in view of the specification, of which they are a part.  The specification contains a written description of the invention that must enable one of ordinary skill in the art to make and use the invention.  For claim construction purposes, the description may act as a sort of dictionary, which explains the invention and may define terms used in the claims.  . . .  The written description part of the specification itself does not delimit the right to exclude.  That is the function and purpose of the claims.

To construe claim language, the court should also consider the patent’s prosecution history[.]  . . .  Although the prosecution history can and should be used to understand the language used in the claims, it too cannot "enlarge, diminish, or vary" the limitations in the claims.

Markman v. Westview Instruments, Inc., 52 F.3d 967, 979-80 (Fed. Cir. 1995) (in banc), aff’d, 517 U.S. 370 (1996) (citations omitted).

In Phillips, the Federal Circuit noted that where the intrinsic evidence (i.e., claim language, specification, and file history) does not resolve ambiguity in the meaning of a claim term, a court may also consider extrinsic evidence, such as expert testimony, dictionaries, and treatises.  Phillips, 415 F.3d at 1317-19.  Such "extrinsic evidence can help educate the court regarding the field of the invention and can help the court determine what a person of ordinary skill in the art would understand claim terms to mean."  Id. at 1319.

With the above legal principles in mind, we turn back to the claims of the '422 and '248 patents.  The '422 patent contains five claims, only one of which is an independent claim (i.e., does not depend from, and include the limitations of, another claim):

1.  A chemically modified short interfering nucleic acid (siNA) molecule, wherein:
    (a) the siNA molecule comprises a sense strand and an antisense strand, each strand having one or more pyrimidine nucleotides and one or more purine nucleotides;
    (b) each strand is independently 18 to 27 nucleotides in length, and together comprise a duplex having between 17 and 23 base pairs;
    (c) the antisense strand is complementary to a human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567;
    (d) a plurality of pyrimidine nucleotides present in the sense strand are 2'-deoxy-2-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the sense strand are 2'-deoxy purine nucleotides; and
    (e) a plurality of pyrimidine nucleotides present in the antisense strand are 2'-deoxy-2'-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the antisense strand are 2'-O-methyl-purine nucleotides.

A cursory analysis of claim 1 (a more thorough analysis being unnecessary) indicates that the claim is directed to a "chemically modified short interfering nucleic acid (siNA) molecule."  Therefore, claim 1 does not cover or encompass molecules other than chemically modified short interfering nucleic acids (siNAs).  More importantly, the siNA molecules that are covered or encompassed by claim 1 must possess a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  2'-deoxy-2'-fluoro pyrimidine nucleotides are not naturally-occurring nucleotides.

In response to Dr. Holman's statement that "DNA does not contain 2'-deoxy-2-fluoro pyrimidine nucleotides and 2'-deoxy purine nucleotides," Dr. Mason notes that "'2'-deoxy purine nucleotides' are simply the 'A' and 'G' nucleotides in normal DNA."  He does not, however, contend that 2'-deoxy-2'-fluoro pyrimidine nucleotides are found in "normal DNA."  Dr. Mason also takes Patent Docs to task for stating that "the lone independent claim of the '422 patent is directed to a 'chemically modified' double-stranded nucleic acid molecule," and "[i]t is therefore difficult to see how the claimed sequences of the '422 patent could 'match[] 91.5% of human genes.'"  Dr. Mason counters that "[i]t is notable that one of the claimed chemical modifications allowed from [the '422 patent] claims is '2'-deoxyribonucleotides,' which is the same thing as dexoyribonucleotides, or DNA."  However, as noted above, the siNA molecules of claim 1 of the '422 patent must possess a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  And 2'-deoxy-2'-fluoro pyrimidine nucleotides are not naturally-occurring nucleotides found in "normal DNA."  Dr. Mason also lists "six other potential embodiments (of many) from [the '422] patent that could easily cover unmodified bases or fragments thereof," adding that "[t]he claims must be interpreted in plain language first, of course, but also in light of their specifications of the patent."  Notwithstanding the importance of the specification in claim construction, absent a clear and specific statement giving a claim term a special definition, that term should be construed as having the plain and ordinary meaning given by persons experienced in the field of the invention.  Renishaw plc v. Marposs Societa' per Azioni, 158 F.3d 1243, 1249 (Fed. Cir. 1998).  Therefore, the disclosure in the '422 patent specification of unclaimed embodiments such as unmodified siNA molecules does not trump the express recitation in claim 1 of "[a] chemically modified short interfering nucleic acid (siNA) molecule" possessing a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  Thus, contrary to Dr. Mason's assertion, the claims of the '422 patent do not "claim[] 15mer sequences."

The same is true for the claims of the '248 patent.  As we noted in our last post, the claims of the '248 patent are directed to methods of inferring a trait of a bovine subject, determining a nucleotide occurrence of a polymorphism in a bovine sample, and identifying a bovine single nucleotide polymorphism (SNP) associated with a trait, and not 15mer nucleic acid molecules.  In response to Dr. Holman's observation that the independent claims of the '248 patent are method claims, Dr. Mason agrees, but suggests that "their specifications allow for a broad interpretation."  However, the disclosure of "an isolated polynucleotide that includes at least 20 contiguous nucleotides of any one of SEQ ID NOS:24493 to 64886" in the specification simply does not convert a claim directed to a method into a claim directed to a oligonucleotide.  As with the '422 patent, therefore, the claims of the '248 patent simply do not "claim[] 15mer sequences."

To put the above in layman's terms, Dr. Mason could make or use a 15mer derived from the human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567 or the nucleotide sequence of SEQ ID NO:21645 and not be found liable for infringing either the '422 or '248 patents -- provided, of course, that he was not using either sequence to generate the claimed siNA of the '422 patent or practice the claimed methods of the '248 patent.

In his response, Dr. Mason argues that even if one disagrees with his analysis of the '422 patent, related U.S. Patent No. 8,273,866 supports his assertions.  Claim 1 of the '866 patent recites:

1.  A short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference, wherein:
    (a) each strand is between 18 and 24 nucleotides in length;
    (b) the sense strand comprises 10 or more 2'-deoxy, 2'-O-methyl, 2'-deoxy-2'-fluoro, or universal base modified nucleotides, and a terminal cap molecule at the 3'-end, the 5'-end, or both 3' and 5'-ends of the sense strand;
    (c) the antisense strand comprises 10 or more 2'-deoxy, 2'-O-methyl, 2'-deoxy-2'-fluoro, or universal base modified nucleotides; and
    (d) 10 or more pyrimidine nucleotides of the sense and antisense strand are 2'-deoxy, 2'-O-methyl or 2'-deoxy-2'-fluoro nucleotides.

Dr. Mason argues that "any sequence that is 18-24 bases can be constructed from these claims, [and] this may mean that every single 18-24mer is potentially claimed by this patent."  Not quite.  Claim 1 is directed to "[a] short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference."  A "single 18-24mer" is not "[a] short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference."

Turning back to Dr. Mason's response, he counters Dr. Holman's assertion that the 15mer claims of Myriad's '282 patent are "extremely rare" by pointing out that "[a]fter searching for a short time on Google Patents, I was able to find two potential examples of recently published patent applications that directly claim a large subset of genes."  As noted in an editorial comment to Dr. Mason's response, the response was revised per Dr. Mason's request to indicate that the documents Dr. Mason identified were published patent applications rather than patents as he stated in the original version of his response.  However, it is unclear whether Dr. Mason understands that identifying two "published patent applications" as "issued patents" was not merely an unfortunate typographical error.  Instead, Dr. Mason's citation of two published patent applications provides no support for his argument that 15mer claims can be readily found in recently issued patents because infringement liability arises only when an individual "without authority makes, uses, offers to sell, or sells any patented invention" (35 U.S.C. § 271(a)), and the published patent applications he cites are not patents.

Finally, when defending the assertion in paragraph 10 of his Declaration that "Claim #1 and #2 of '282 are so broad that they can include up to 100% of the genes in the human genome," Dr. Mason counters with more of the same flawed argument.  He first notes that "55% homology is a very low threshold," and then points to claim 6, which is directed to "[a]n isolated DNA having at least 15 nucleotides of the DNA of claim 2."  But claims 1 and 2 do not recite 15mer fragments of DNA encoding the amino acid sequence of SEQ ID NO:2 or the nucleotide sequence of SEQ ID NO:1 that share 55% identity with those sequences.  Instead, claims 1 and 2 are directed to a nucleic acid encoding a protein of 1863 amino acids and a nucleic acid of 5914 nucleotides.

Dr. Chris Mason Responds to Blog Posts on Genome Medicine Article -- Updated

[Ed. Patent Docs recently reported on an article in the current issue of Genome Medicine which contends that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences (see "Genome Medicine Article Calls for Limits on Patenting of Existing Nucleotide Sequences" and "Revisiting Genome Medicine Article on 'Pervasive Sequence Patents' That 'Cover the Entire Human Genome'".  The article was authored by Jeffrey Rosenfeld of the University of Medicine & Dentistry of New Jersey and Christopher Mason of Cornell University.  Dr. Mason (below) has provided Patent Docs with a response to our posts -- as well as a response to an article posted by Prof. Chris Holman on Holman's Biotech IP Blog (see "A Critique of a Recent Article Which Found That Sequence Patents Cover the Entire Human Genome").  To promote further discussion of the issue of "gene" patenting, we are posting Dr. Mason's response today.  As always, we invite Patent Docs readers to join in the discussion by submitting comments to any of the above posts.  Our reply to Dr. Mason's post will follow tomorrow.]

Several recent posts and commentaries have suggested that the analysis from our recent paper, "Pervasive Sequence Patents Cover the Entire Human Genome," was mistaken or did not embody an accurate characterization of the claims' construction.  I would like to comment on several aspects of the posts from both Holman's Biotech IP Blog and the Patent Docs blog, but foremost I would like to thank both sites for their dialogue and debate on this important issue.

Part One: The Holman Critique:  "A Critique of a Recent Article Which Found That Sequence Patents Cover the Entire Human Genome"

1)  In his post, Prof. Holman states "the authors seem to assume that every patent with a claim mentioning a gene sequence also claims every 15mer present in the sequence, i.e., every contiguous 15 nucleotide sequence appearing in the gene."

We do not.  We performed two distinct analyses that were described in the main text.  First, we examined the uniqueness of 15mers in general, which was shown to be exceedingly non-unique genome-wide (no gene is unique at the 15mer level).  Secondly, we used patents that claimed 15mer sequences in their construction, and we indicated the matches we could find given their sequence composition.  From these, we found many exact matches, ranging from 4% (for BRCA1) to potentially as high 91%.

2)  Prof. Holman continues, "In my experience, claims of this type are extremely rare.  I looked at [a] hundred patents identified as gene patents in the Jensen Murray study and found that most only claim the full-length gene sequence.  . . .  I looked through hundreds of gene patents trying to find another 15mer claim analogous to those in the Myriad patents and could not find one.  The patent claims at issue in the Myriad case will be expiring within the next few years.  . . .  I doubt that this sort of broad 15mer claim has been issued by the patent office in recent years, or if it has it seems to be extremely rare."

After searching for a short time on Google Patents, I was able to find two potential examples of recently published patent applications that directly claim a large subset of genes.

US 20130030040 A1

Methods and compositions for increasing sialic acid production and treating sialic related disease conditions

14. An isolated nucleic acid molecule the sequence set forth in SEQ ID NO:1 or SEQ ID NO:2.

"In some embodiments, the therapeutic product is a polynucleotide, while in other embodiments, the therapeutic product is a polypeptide.  In some embodiments, the polynucleotide is a DNA molecule, which can comprise the full-length coding region for a protein, the coding region for a domain of a protein, or a coding region for a protein fragment, which is shorter than a recognized and identified domain of a protein.  Thus, the polynucleotides disclosed herein can range from oligomers of at least 15 base pairs in length to DNA molecule comprising the full-length coding region for a protein."

This patent application refers to the gene "GNE," which allows it to also claim 15mers.  Given the thousands of nucleotides in this patent application, it turns out that this patent application can cover 1,306 other genes, using the same 15-mer matching algorithm.

US 20130041209 A1

Methods and compositions for improved fertilization and embryonic survival

"An isolated nucleic acid molecule comprising a nucleotide corresponding to a nucleotide at a first polymorphic position selected from the group consisting of positions 85146, 85161, 85216, 85292, and 85300 of the nucleic acid sequence shown in FIG. 1 (SEQ ID NO: 1), and at least 10 contiguous nucleotides of SEQ ID NO: 1 adjacent to the first polymorphic position, wherein position 85146 is guanine, position 85161 is guanine, position 85216 is adenosine, position 85292 is cytosine, or position 85300 is guanine; or an isolated nucleic acid molecule comprising a nucleotide corresponding to a nucleotide at a second polymorphic position selected from the group consisting of positions 35728, 36016, and 38867 of the nucleic acid sequence shown in FIG. 2 (SEQ ID NO: 2), and at least 10 contiguous nucleotides of SEQ ID NO: 2 adjacent to the second polymorphic position, wherein position 35728 is guanine, position 36016 is guanine, or position 38867 is guanine.

2. A nucleic acid molecule according to claim 1, which comprises at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 contiguous bases of SEQ ID NO: 1 adjacent to the first polymorphic position, or of SEQ ID NO: 2 adjacent to second polymorphic position.

7. A nucleic acid molecule according to claim 1, wherein the first or second polymorphic site is within 4 nucleotides of the center of the nucleic acid molecule.

8. A nucleic acid molecule according to claim 7, wherein the first or second polymorphic site is at the center of the nucleic acid molecule."

Notably, these are highly polymorphic sites in the human genome, so if you look at any piece of DNA anywhere near this gene, you will easily match the specified variants from this gene, and then be entitled to any genes that are on the same fragment.  From simple pipetting, this can be anywhere from 10,000-100,000 bases.

3)  Prof. Holman then says, "DNA does not contain 2'-deoxy-2-fluoro pyrimidine nucleotides and 2'-deoxy purine nucleotides, these are synthetic analogues to the nucleotides that appear in DNA."

This is completely false.  "2'-deoxy purine nucleotides" are simply the "A" and "G" nucleotides in normal DNA, and they indeed appear in normal DNA.  Modifications of these bases are allowed in this patent for "chemical variations" of RNA, even though (in this case) they just turn RNA bases into DNA bases.

4)  Prof. Holman continues, "the authors reported that US7468248 contains 'explicit claims for 15mers that matched 84% of human genes.'  In fact, the '248 patent has only two independent claims, both of them method claims."

We agree that these are method claims, but their specifications allow for a broad interpretation.  In particular, from the patent:

"In one embodiment, the present invention provides an isolated polynucleotide that includes at least 20 contiguous nucleotides of any one of SEQ ID NOS:24493 to 64886, a polynucleotide at least 90% identical to the 20 contiguous nucleotide fragment, or a complement thereof, wherein the isolated polynucleotide includes a nucleotide occurrence of a single nucleotide polymorphism (SNP) associated with a trait, wherein the SNP corresponds to position 300 of SEQ ID NOS:19473 to 21982."

5)  Prof. Holman then says, "the publication of the article highlights the limitations of peer review (assuming Genome Medicine engages in peer review)."

The publication of contentious research or discordant viewpoints does not demonstrate a failure of the entire peer-review system.  Rather, discussion and debate are key drivers of scientific progress through these peer-reviewed publications.  Five scientific reviewers and two patent attorneys reviewed and approved our article before its publication, and the site of the Journal clearly indicates that it conducts a thorough peer review.  We also note that the journal is open-access, allowing for easier dissemination of data and results, and that the Journal hosts a large set of leading researchers on its Editorial Board.

Part Two: The Patent Docs blog post:  "Revisiting Genome Medicine Article on 'Pervasive Sequence Patents' That 'Cover the Entire Human Genome'"

1)  Patent Docs states that "the lone independent claim of the '422 patent is directed to a "chemically modified" double-stranded nucleic acid molecule.  It is therefore difficult to see how the claimed sequences of the '422 patent could "match[] 91.5% of human genes."

It is notable that one of the claimed chemical modifications allowed from their claims is "2′-deoxyribonucleotides," which is the same thing as dexoyribonucleotides, or DNA ("Ribonucleotides versus Deoxyribonucleotides").

Also, here is a listing of six other potential embodiments (of many) from this patent that could easily cover unmodified bases or fragments thereof.  The claims must be interpreted in plain language first, of course, but also in light of their specifications of the patent, which include:

1.1)  In one embodiment, the invention features one or more chemically modified siNA constructs having specificity for HIF1 expressing nucleic acid molecules, such as RNA encoding a HIF1 protein.  In one embodiment, the invention features a RNA based siNA molecule (e.g., an siNA comprising 2′-OH nucleotides) having specificity for HIF1 expressing nucleic acid molecules that includes one or more chemical modifications described herein.

1.2)  Non-limiting examples of such chemical modifications include without limitation phosphorothioate internucleotide linkages, 2′-deoxyribonucleotides, 2′-O-methyl ribonucleotides, 2′-deoxy-2′-fluoro ribonucleotides, "universal base" nucleotides, "acyclic" nucleotides, 5-C-methyl nucleotides, and terminal glyceryl and/or inverted deoxy abasic residue incorporation.

1.3)  In another embodiment, the invention features a double-stranded short interfering nucleic acid (siNA) molecule that down-regulates expression of a HIF1 gene comprising an antisense region, wherein the antisense region comprises a nucleotide sequence that is complementary to a nucleotide sequence of the HIF1 gene or a portion thereof, and a sense region, wherein the sense region comprises a nucleotide sequence substantially similar to the nucleotide sequence of the HIF1 gene or a portion thereof.  In one embodiment, the antisense region and the sense region independently comprise about 15 to about 30 (e.g. about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides, wherein the antisense region comprises about 15 to about 30 (e.g. about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30) nucleotides that are complementary to nucleotides of the sense region.

1.4)  In one embodiment, an siNA molecule of the invention comprises no ribonucleotides.  In another embodiment, an siNA molecule of the invention comprises ribonucleotides.

1.5)  In one embodiment, the invention features a chemically synthesized double-stranded RNA molecule that directs cleavage of a HIF1 RNA via RNA interference, wherein each strand of said RNA molecule is about 15 to about 30 nucleotides in length; one strand of the RNA molecule comprises nucleotide sequence having sufficient complementarity to the HIF1 RNA for the RNA molecule to direct cleavage of the HIF1 RNA via RNA interference; and wherein at least one strand of the RNA molecule optionally comprises one or more chemically modified nucleotides described herein, such as without limitation deoxynucleotides, 2′-O-methyl nucleotides, 2′-deoxy-2′-fluoro nucleotides, 2′-O-methoxyethyl nucleotides etc.

1.6)  In any of the above-described embodiments of a double-stranded short interfering nucleic acid (siNA) molecule that inhibits expression of a HIF1 gene, wherein a majority of the pyrimidine nucleotides present in the double-stranded siNA molecule comprises a sugar modification, each of the two strands of the siNA molecule can comprise about 15 to about 30 or more (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 or more) nucleotides.

2)  Even if you disagree with our analysis of the '422 patent, you can look at patent 8,273,866, which is in the same family as 7,795,422.

Notably, Claim 1 says:

"1.  A short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference, wherein:
    (a) each strand is between 18 and 24 nucleotides in length;
    (b) the sense strand comprises 10 or more 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, or universal base modified nucleotides, and a terminal cap molecule at the 3′-end, the 5′-end, or both 3′ and 5′-ends of the sense strand;
    (c) the antisense strand comprises 10 or more 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, or universal base modified nucleotides; and
    (d) 10 or more pyrimidine nucleotides of the sense and antisense strand are 2′-deoxy, 2′-O-methyl or 2′-deoxy-2′-fluoro nucleotides."

The patent also specifies considerable flexibility for the terminal cap molecule, stating "[t]he cap moiety can be an inverted deoxy abasic moiety, an inverted deoxy thymidine moiety, or a thymidine moiety."

Again, given that "2'deoxy nucleotides" and "a thymidine moiety" are simply normal DNA bases, and that any sequence that is 18-24 bases can be constructed from these claims, this may mean that every single 18-24mer is potentially claimed by this patent.

3)  Patent Docs then says, "while the '248 patent recites oligonucleotides -- which the specification states "[i]n certain aspects" can be "at least 15 nucleotides in length" -- it is difficult to see how the authors can conclude that the '248 patent has "explicit claims for 15mers that matched 84% of human genes."

See above for our further analysis on this point.  Our main point is that 15mers from these patents match both human and bovine genomes, and that claim construction becomes non-specific (even across species) at these low k-mer sizes.

4)  "In paragraph 10 of his Declaration, Dr. Mason surprisingly states that "Claim #I and #2 of '282 are so broad that they can include up to 100% of the genes in the human genome."

I made this point for two reasons:

4.1)  The 55% homology is a very low threshold, and it allows matches to many other genes, because "homology" and "identity" are not the same thing in biology; homology allows for far more flexibility in the mismatches.

4.2)  The Myriad patents claim any "isolated DNA having at least 15 nucleotides of the DNA of claim 2," which was my focus.  Notably, this is not the same as claiming 15 contiguous nucleotides.  Most other gene patents I have found will describe contiguous nucleotides, which obviously limits their scope.  But, if we allow any 15 nucleotides, in any order, it is easy to match these sequences to the entire genome and indeed every gene.

5)  "As with the '422 and '248 patents, Dr. Mason appears to be having some difficulty ascertaining the subject matter that is actually encompassed by claims 1 and 2 of the '282 patent."

I would agree, insofar as I am worried about the likely overly broad scope of these claims.  Since I risk liability whenever I perform genetic testing on my own DNA, or the DNA from any of my patients, I welcome the Supreme Court or the legal scholars to clarify the issue.  In the absence of a statutory research exemption for infringement liability or some other guarantee, I am restricted from researching thousands of genes for many years to come.

But, if any lawyer is confident enough about the irrelevance of these patents that he or she would be willing to state, in writing, the willingness to defend me in Court and pay all legal fees or damages if I get sued, then I will happily join you and start working again to develop new tests, tools, and algorithms to ameliorate and eliminate human diseases.

Thank you,

Christopher Mason, Ph.D.

[Ed. At Dr. Mason's request, his response has been revised to indicate that US 20130030040 A1 and US 20130041209 A1 are published patent applications rather than patents as Dr. Mason stated in the original version of his response.]

Revisiting Genome Medicine Article on "Pervasive Sequence Patents" That "Cover the Entire Human Genome"

By Donald Zuhn --

Last week, we reported on an article in the current issue of Genome Medicine which contends that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences (see "Genome Medicine Article Calls for Limits on Patenting of Existing Nucleotide Sequences").  The authors of the paper, Jeffrey Rosenfeld and Christopher Mason, worried that "the non-specificity of 15mer sequences creates unclear infringement liability," examined the incidence with which 15mers from a given gene matched 15mers in other genes using the Consensus Coding Sequences (CCDS) database of 18,382 high-confidence genes.  According to the authors, their analysis showed that "every gene in the CCDS database had a 15mer that matched the sequence of at least one other gene," with the "[t]he number of matching genes ranged from as few as 5 (for MTRNR2L7) or 689 (for BRCA1) to as high as 7,688 (for TTN)."  The authors also noted that 99.999% of 15mers in the human genome are repeated at least twice.

While the authors' analysis may be relevant to claims directed to 15mers, such as claims 5 and 6 of Myriad's U.S. Patent No. 5,747,282, the authors also listed claims 1 and 2 of the '282 patent when stating that in the Association for Molecular Pathology v. Myriad Genetics, Inc. case, "the broadest intellectual property rights on BRCA sequences come from several related claims in patent 5,747,282."  Claims 1, 2, 5, and 6 of the '282 patent recite:

1.  An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

2.  The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1.

5.  An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

6.  An isolated DNA having at least 15 nucleotides of the DNA of claim 2.

In support of their conclusion that "short patent sequences are extremely non-specific and that a 15mer patent claim from one gene will always 'cross-match' and patent a portion of another gene as well," the authors state that:

When we examined the amount of total sequence space in human genes that is covered by 15mers in claims from current patents (Additional file 2), we found 58 patents whose claims covered at least 10% of the bases of all human genes.  The top patent was US7795422, whose claims' sequences matched 91.5% of human genes.  Interestingly, we also observed a patent for improving bovine traits (US7468248) with explicit claims for 15mers that matched 84% of human genes.  This patent was not even aimed at any human sequence, yet covered a majority of human genes once we examined the claim's matches at the 15mer scale.

A Patent Docs reader has suggested that the claimed sequences of U.S. Patent No. 7,795,422 do not appear to "match[] 91.5% of human genes," and that U.S. Patent No. 7,468,248 does not appear to contain "explicit claims for 15mers that matched 84% of human genes," as asserted by the authors of the Genome Medicine paper.  The '422 patent, which is directed to compounds, compositions, and methods useful for modulating the expression and activity of genes involved in pathways of hypoxia inducible factor 1 (HIF1) gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules, has five claims:

1.  A chemically modified short interfering nucleic acid (siNA) molecule, wherein: (a) the siNA molecule comprises a sense strand and an antisense strand, each strand having one or more pyrimidine nucleotides and one or more purine nucleotides; (b) each strand is independently 18 to 27 nucleotides in length, and together comprise a duplex having between 17 and 23 base pairs; (c) the antisense strand is complementary to a human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567; (d) a plurality of pyrimidine nucleotides present in the sense strand are 2'-deoxy-2-fluoro pyrimidine nucleotides and a plurality of purine nucleotide present in the sense strand are 2'-deoxy purine nucleotides; and (e) a plurality of pyrimidine nucleotides present in the antisense strand are 2'-deoxy-2'-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the antisense strand are 2'-O-methyl-puine nucleotides.

2.  The siNA molecule of claim 1, wherein the sense strand has a cap at both 5'- and 3'- ends of the sense strand.

3.  The siNA molecule of claim 1, comprising a 3'-overhang on one or both strands.

4.  A composition comprising the siNA molecule of claim 1, and a pharmaceutically acceptable carrier or diluent.

5.  The siNA of claim 1, wherein the antisense strand has a phosphorothioate internucleotide linkage at the 3'end.

Unlike claims 5 and 6 of the '282 patent, which are directed to 15mers of the BRCA1 sequence, the lone independent claim of the '422 patent is directed to a "chemically modified" double-stranded nucleic acid molecule.  It is therefore difficult to see how the claimed sequences of the '422 patent could "match[] 91.5% of human genes."  Of course, because the authors state that the "claims' sequences matched 91.5% of human genes," it is possible that they are referring to the human Hypoxia Inducible Factor 1 (HIF1) RNA sequence of SEQ ID NO:567 recited in claim 1 (the Sequence Listing for the '422 patent indicates that the RNA sequence set forth as SEQ ID NO: 567 is 3933 nucleotides in length).  However, claim 1 of the '422 patent does not claim a 17mer or 27mer of the HIF sequence, but rather claims a chemically modified siNA duplex molecule.

The '248 patent, which is also cited by the authors, and which is directed to methods, compositions, and systems for managing bovine subjects in order to maximize their individual potential performance and edible meat value, has 33 method claims, of which claims 1, 22, and 28 are the only independent claims.  These claims recite:

1.  A method for inferring a trait of a bovine subject from a nucleic acid sample of the bovine subject, comprising identifying in the nucleic acid sample, a nucleotide occurrence of a single nucleotide polymorphism (SNP) at position 300 of SEQ ID NO:21645, thereby inferring the trait, wherein the trait is marbling, tenderness, fat thickness, red meat yield, or average daily weight gain.

22.  A method for determining a nucleotide occurrence of a polymorphism in a bovine sample, comprising: a) contacting a bovine polynucleotide in the sample with an oligonucleotide that binds to a target region, wherein the target region comprises a position at position 300 of SEQ ID NO:21645 or wherein the target region is within 3000 nucleotides of a nucleotide at position 300 of SEQ ID NO:21645, and b) determining the nucleotide occurrence of a single nucleotide polymorphism (SNP) at position 300 of SEQ ID NO:21645, wherein the determination comprises analyzing binding of the oligonucleotide or detecting an amplification product generated using the oligonucleotide, thereby determining the nucleotide occurrence of the polymorphism.

28.  A method for identifying a bovine single nucleotide polymorphism (SNP) associated with a trait, comprising identifying a test SNP that is in disequilibrium with a SNP position at position 300 of SEQ ID NO:21645.

Thus, while the '248 patent recites oligonucleotides -- which the specification states "[i]n certain aspects" can be "at least 15 nucleotides in length" -- it is difficult to see how the authors can conclude that the '248 patent has "explicit claims for 15mers that matched 84% of human genes."  Again, the authors may be referring to the sequence set forth in SEQ ID NO: 21645, but the claims of the '248 patent are directed to methods of inferring a trait of a bovine subject, determining a nucleotide occurrence of a polymorphism in a bovine sample, and identifying a bovine single nucleotide polymorphism (SNP) associated with a trait, and not 15mers derived from the sequence of SEQ ID NO: 21645.

Returning to the authors' assertion that claims 1 and 2 of Myriad's '282 patent, along with claims 5 and 6 of the patent, provide "the broadest intellectual property rights on BRCA sequences," a clue as to why the authors refer to claims 1 and 2 in their Genome Medicine paper can be found in the Supplemental Declaration that Dr. Mason submitted in response to Myriad's brief and Statement of Material Facts when the Myriad case was before the District Court.  In paragraph 10 of his Declaration, Dr. Mason surprisingly states that "Claim #I and #2 of '282 are so broad that they can include up to 100% of the genes in the human genome."  As indicated above, claim 1 of the '282 patent is directed to an isolated nucleic acid encoding the amino acid sequence of SEQ ID NO: 2 (which is 1863 amino acids in length), and claim 1 is directed to an isolated nucleic acid having the nucleotide sequence of SEQ ID NO: 1 (which is 5914 nucleotides in length).  In explaining how a nucleic acid encoding a protein of 1863 amino acids or a nucleic acid of 5914 nucleotides could "include up to 100% of the genes in the human genome," Dr. Mason states in his Declaration that "[b]ecause fragments of the BRCA 1 gene can also be informative about susceptibility to disease, [Myriad] also sought claims on DNA molecules or fragments of DNA molecules with 'substantial homology.'"  Dr. Mason notes that the '282 patent discloses that "substantial homology or (similarity) exists when a nucleic acid or fragment thereof will hybridize to another nucleic acid (or a complementary strand thereof) under selective hybridization conditions," and further, that "selective hybridization will occur when there is at least about 55% homology over a stretch of at least about 14 nucleotides" (emphasis in Dr. Mason's Declaration).

Dr. Mason then declares in paragraph 12 that:

Because of this low threshold of homology, any 55% homology of 14 nucleotides is now any 8 nucleotides from BRCA1 cDNA.  Also, homology could include any 9-13 nucleotide sequence with insertions and deletions.  Utilizing the same algorithm from above, the conclusion is that 100% of the genes in the human genome have at least one 8mer from the BRCA1 cDNA.

As with the '422 and '248 patents, Dr. Mason appears to be having some difficulty ascertaining the subject matter that is actually encompassed by claims 1 and 2 of the '282 patent.  As discussed above, claims 1 and 2 of the '282 patent are directed to a nucleic acid encoding a protein of 1863 amino acids or a nucleic acid of 5914 nucleotides, and are not "so broad" that they encompass 9mers, 13mers, or 14mers derived from those nucleic acids that exhibit 55% homology and which can include insertions and deletions.  Given the authors' analysis of the '422 and '248 patents, and their "construction" of the claims in those patents, a closer examination of the "58 patents whose claims covered at least 10% of the bases of all human gene" appears to be warranted.

Professor Chris Holman's critique of the Genome Medicine paper can be found on his blog (Holman's Biotech IP Blog) (A Critique of a Recent Article Which Found That Sequence Patents Cover the Entire Human Genome").

Genome Medicine Article Calls for Limits on Patenting of Existing Nucleotide Sequences

By Donald Zuhn --

In an article published in the current issue of Genome Medicine, Jeffrey Rosenfeld of the University of Medicine & Dentistry of New Jersey and Christopher Mason of Cornell University contend that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences ("Pervasive sequence patents cover the entire human genome," Genome Medicine 5:27 (2013)).  According to the two researchers, the Association for Molecular Pathology v. Myriad Genetics, Inc. case affords the Supreme Court with an opportunity to resolve the "sharp conflict between the public goods of medical knowledge and improved health and the private goods of rewarding innovation and entrepreneurial risk-taking" that is presented by gene patents.

The authors begin by stating that "the broadest intellectual property rights on BRCA sequences" come from four claims in Myriad's U.S. Patent No. 5,747,282:

1.  An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

2.  The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1.

5.  An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

6.  An isolated DNA having at least 15 nucleotides of the DNA of claim 2.

The article takes the Federal Circuit to task for (twice) "declar[ing] that even a short, isolated DNA molecule such as 'ACGT' is different from the 'NNNNN-ACGT-NNNNN' present within a chromosome (AMP v. Myriad, Federal Circuit 2012), because it will not be connected to sugar via a phosphodiester bond and will have a hydroxyl group instead of a bond to a phosphate."  According to the authors, the Federal Circuit's ruling means that "even a 15 nucleotide fragment of DNA in Claim #6 from Patent '282 is claimed to be 'markedly different'."

The authors, however, find the Federal Circuit's ruling to be overly broad for three reasons:

First, it relies on the sequences having chemical features and side-chains that are not actually present in the patents . . . : the claims are for a linear series of nucleotides, not a specific chemical structure.  Second, if allowed to be so broad, these claims could also create a monopoly on all epigenetic and chemical variations of these sequences. Third, and perhaps most importantly, the non-specificity of 15mer sequences creates unclear infringement liability that has been even noted by the Court.

To investigate this last point, the authors examined the incidence with which 15mers from a given gene matched 15mers in other genes using the Consensus Coding Sequences (CCDS) database of 18,382 high-confidence genes.  This analysis showed that "every gene in the CCDS database had a 15mer that matched the sequence of at least one other gene," with the "[t]he number of matching genes ranged from as few as 5 (for MTRNR2L7) or 689 (for BRCA1) to as high as 7,688 (for TTN), corresponding to 0.01%, 4%, and 42% of all genes in the human genome."  The authors note that 99.999% of 15mers in the human genome are repeated at least twice.

According to the authors, this analysis "demonstrate[s] that short patent sequences are extremely non-specific and that a 15mer patent claim from one gene will always 'cross-match' and patent a portion of another gene as well."  In support of this point, the authors identified 58 patents whose claims covered at least 10% of the bases of all human genes, with the claimed sequences of U.S. Patent No. 7,795,422 matching 91.5% of human genes, and the claimed bovine sequences of U.S. Patent No. 7,468,248 matching 84% of human genes.  Arguing that "[t]he demonstrated non-specificity of sequence uniqueness across the genome suggests that the Supreme Court should use [the Myriad] case to clarify the law on gene patents," the authors contend that "[i]f patent claims that use these 15mer or other short k-mer sizes are enforced, it could potentially create a situation where a piece of every gene in the human genome is patented by a phalanx of competing patents, with potentially harmful consequences for genetic testing laboratories and research groups performing targeted sequencing on any gene, in virtually all species."

The authors' conclusion regarding the broad scope of Myriad's 15mer claims, however, is not particularly ground-breaking given that Kepler et al. similarly concluded in a 2010 Genomics paper that claim 5 of the '282 patent was "exceptionally broad" (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  Kepler et al. suggested that "if human genes were random strings of nucleotides, one would expect a human gene to contain an average of 15 15-mers claimed under the ['282] patent," and in fact found that 80% of 713 human mRNAs deposited in 1994 (the earliest effective filing date of the '282 patent is August 12, 1994) contained at least one of the claimed 15mers.  Thus, Kepler et al. indicates that claims 5 and 6 are sufficiently overbroad as to be easily invalidated.  Because the analysis of Kepler et al. and Rosenfeld and Mason suggest that claims 5 and 6 of the '282 patent (and perhaps 15mer claims in other patents) would likely not withstand an invalidity challenge, it is unlikely that these claims will have the adverse impact on the "medical good" suggested by the authors of the Genome Medicine article.

One interesting result presented in the Genome Medicine article is that even longer nucleotide fragments from known genes matched the sequence of sequences in other genes.  In particular, the paper points out that "even 1,000 nucleotide fragments from known genes could still match 117 other genes."  However, the paper does not present any additional information regarding the 1,000 nucleotide fragment (or fragments) that yielded such matches.

Finally, it should be noted that Dr. Mason submitted two declarations when the Myriad case was before the District Court.  In a Supplemental Declaration submitted in response to Myriad's brief and Statement of Material Facts, Dr. Mason stated that claim 6 of the '282 patent was "so broad that it includes at least 4% and as much as 100% of the genes in the human genome."

Is Lack of Preemption the Key for the Supreme Court to Decide in Myriad's Favor?

By Kevin E. Noonan --

The U.S. Supreme Court will hear arguments in Association for Molecular Pathology v. Myriad Genetics, Inc. on April 15th, and the parties and their different cadres of amici have submitted briefs of varying degrees of helpfulness and coherence to the Court.  In reviewing these briefs, and the Mayo Collaborative Services v. Prometheus Laboratories, Inc. decision that forms the basis for re-review by the Federal Circuit (albeit with little having been changed from that reconsideration), the question arises whether what is at issue in this case is the extent to which Myriad's claims unduly preempt what should be "free to all men and reserved exclusively to none."  Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127,130 (1948).

The context for the Court's decision is its own recognition that patent eligibility should be given an expansive scope, as mandated by Congress under 35 U.S.C. § 101.  The Court recognized Congress's intent expressly in Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980), quoting the famous aphorism from the legislative history that statutory subject matter should "include anything under the sun that is made by man," a sentiment sounding in Thomas Jefferson's vision that "ingenuity should receive a liberal encouragement."  5 Writings of Thomas Jefferson 75-76 (Washington ed. 1871).  The Court has been parsimonious in setting forth what is not patent-eligible:  "laws of nature, physical phenomena, and abstract ideas" have fallen outside the statutory scope, and the Court has provided explicit examples of what should reside inside those excluded categories ("a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter" and "[l]ikewise, Einstein could not patent his celebrated law that E=mc²; nor could Newton have patented the law of gravity."  Chakrabarty, 447 U.S. at 309).

These concerns were of primary importance in the Court's Mayo v Prometheus decision, in which the claims (according to the Court) were directed to a natural law relating to the proper therapeutic dosage of a drug for treating Crohn's disease.  In finding the claim ineligible for patenting, the Court said that:

The claims purport to apply natural laws describing the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that the drug dosage will be ineffective or induce harmful side-effects.  We must determine whether the claimed processes have transformed these unpatentable natural laws into patent­ eligible applications of those laws.  We conclude that they have not done so and that therefore the processes are not patentable.

The deficiency in the claim was thus that it did no more than "inform a relevant audience about certain laws of nature," and "any additional steps [recited in the claim] consist of well ­understood, routine, conventional activity already engaged in by the scientific community."  Accordingly, "those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately" and thus the claimed method was unpatentable.

These concerns frequently arise when the claims produce nothing more than information ("inform a relevant audience about certain laws of nature"); this deficiency can be seen to be in common with Mayo and earlier cases involving the limits of statutory subject matter.  These include O'Reilly v. Morse, claiming a method of transmitting information using electromagnetism (56 U.S. 62 (1853)); Benson v. Gottschalk, claiming methods for converting binary-coded decimal (BCD) numerals into pure binary numerals on a general purpose digital computer using a particular algorithm (409 U.S. 63 (1972)); Parker v. Flook, claiming methods for determining an alarm limit (437 U.S. 584 (1978)); and Bilski v. Kappos, claiming methods for hedging commodity trading outcomes (130 S. Ct. 3218 (2010)).  These decisions of the Court stand in contrast with its decision in Diamond v. Diehr, where a method for curing rubber using an application of the Arrhenius equation was deemed patent-eligible (450 U.S. 175 (1981)).  The production of a tangible outcome, cured rubber, distinguishes the patent-eligible claims in Diehr from the information produced in those methods deemed patent-ineligible by the Court in Mayo, Morse, Benson, Flook, and Bilski.

The distinction can also be drawn that in Diehr the claimed methods were particularly drawn to a specific, tangible result (the cured rubber) and that the claim did not preempt all uses of the Arrhenius equation.  The Supreme Court has been wary of claims that preempt all uses of a law of nature, as it deemed them to be in Mayo, Benson, Flook, and Bilski; in Mayo, the Court warned that "upholding the patents would risk disproportionately tying up the use of the underlying natural laws, inhibiting their use in the making of further discoveries" and would "threaten to inhibit the development of more refined treatment recommendations (like that embodied in Mayo's test), that combine Prometheus' correlations with later discovered features of metabolites, human physiology or individual patient characteristics." These statements illustrate this Court's continuing concern voiced in Funk Brothers that laws of nature should not be burdened with patent exclusivity.

Unlike the method claims in Mayo, Benson, Flook, and Bilski, Myriad's composition of matter claims at issue in the Myriad case are not broadly preemptive in the same way.  They are both specific and particular and as such do not implicate the policy concerns enunciated by the Court in those earlier cases where preemption rendered claims patient-ineligible.  Myriad's claims, when considered as a whole are narrowly focused on isolated human DNA molecules that encode a protein having a particular amino acid sequence.  The consequences of this specificity narrow the scope of these claims substantially.  Taking claim 1 of Myriad's U.S. Patent No. 5,837,492 as an example:

An isolated DNA molecule coding for a BRCA2 polypeptide, said DNA molecule comprising a nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO:2.

The scope of this claim should be understood by these affirmatively recited limitations:

• an isolated DNA molecule that
• encodes a specifically-recited amino acid sequence.

Much of the discussion surrounding these claims in the Federal Circuit's opinion and in Plaintiffs' and their amici's briefs to the Court focus on the requirement that the DNA molecule is isolated.  Neglected in this discussion, and particularly relevant to the question of preemption and the scope of Myriad's composition of matter claims, is the narrowness of the scope of this claim and the consequences of this narrow scope on the preemption issue.  First, the only isolated (human) DNA molecules falling within the scope of this claim are those that encode this (and only this) particular amino acid sequence encoding BRCA2, which in this case encompasses 3,418 amino acids arrayed in a particular and specific order.  An isolated human DNA comprising any change in this encoded amino acid sequence is not exclusive to the patentee and can be performed freely without literal infringement liability by anyone.  (The availability of the doctrine of equivalents for isolated human DNA claims is severely limited by U.S. Patent and Trademark Office practice in interpreting the application of 35 U.S.C. § 112(a) to such claims, and by ensuing prosecution history estoppel.)

The significance of this limitation in scope of Myriad's claims can be understood by the following example. If the single change in the amino acid sequence of the BRCA2 protein encoded by the claimed isolated human DNA is from a valine (Val) residue to an isoleucine (Ile) residue, the number of atoms in the protein would be increased by a mere 3 atoms (the difference in structure between these two amino acids is a methylene group,-CH₂-) out a total of more than 60,000 atoms in the protein.  Yet, even such a molecule changed to such a small degree would not literally infringe claim 1 of Myriad's '492 patent.  Similarly, insertions or deletions of the sequence, mutations and sequence variants (naturally occurring or man-made) do not fall within the scope of Myriad's claims to a specific, particular isolated human DNA, due to this restricted scope.  Properly construed, claims to isolated human DNA are the antithesis of the type of broadly preemptive claims that have concerned the Supreme Court in its earlier precedent, because by their nature such claims do not "impede the flow of information that might permit, indeed spur, invention" and thus do not call within the Court's proscriptions based on these concerns.

Moreover, such changes, insertions or deletions in the sequence, mutations and sequence variants (naturally occurring or man-made) are independently patentable to future researchers who describe such variants and satisfy the statutory requirements embodied in 35 U.S.C § 112.  (The Federal Circuit has interpreted the disclosure requirements of 35 US.C. § 112 to require that claims to isolated human DNA must disclose the specific sequence claimed (or provide a biological deposit thereof).  Regents of the University of California v. Eli Lilly & Co.; Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. (en banc).  The U.S. Patent and Trademark Office has implemented this interpretation of the statutory requirements (see USPTO Written Description Examination Guidelines, 66 Fed. Reg. 1092 (2001)).  In fact, disclosure of the predicted amino acid sequence encoded by the human BRCA2 gene in Myriad's '492 patent, required as it is by 35 U.S.C. § 112(a) to provide "a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and [] the best mode contemplated by the inventor or joint inventor of carrying out the invention" provides the best starting point for work by future inventors to identify or produce such changes, insertions or deletions of the sequence, mutations and sequence variants (naturally occurring or man-made) and patent them, independent of any restrictions that can be imposed by Myriad (or any other patentee).  Disclosure as required by the Patent Act is "the quid pro quo of the right to exclude."  Kewanee Oil Co. v. Bicron Corp., 416 U.S. 470, 484 (1974), and Myriad's disclosure of the BRCA1 and BRCA2 gene sequence provides future researchers with the ability to continue to research and make improvements, as envisioned in Article I of the U.S. Constitution.

In view of these distinctions, it should be evident that Myriad's claims to isolated human DNA are different in both kind and effect than the claims the Court has proscribed due to their capacity to unduly preempt future invention.  Viewed in this light, and stripped of the emotional and political implications generated by presenting the question of whether human genes should be patent-eligible (a legal question) (as opposed to whether isolated human DNA should be patented, a policy decision best left to Congress), the real question before the Court is whether there are grounds consistent with the issues and concerns motivating prior decisions that support those who would have the Court apply a categorical rule that isolated human DNA should be proscribed.  The Court can certainly decide that such policymaking falls within its purview, but only by expanding the grounds is has previously applied for finding otherwise statutory subject matter not to be eligible for patenting.

IPO Files Amicus Brief in Support of Respondents in AMP v. Myriad Genetics

By Donald Zuhn --

In an amicus brief filed last week in support of respondents Myriad Genetics, Inc. et al., the Intellectual Property Owners Association (IPO) asked the Supreme Court to affirm the Federal Circuit's decision in Association for Molecular Pathology v. Myriad Genetics, Inc. that claims to isolated human DNA are patent-eligible.  The IPO brief opens by noting that "[w]hile Petitioners and their amici provocatively refer to the subject matter at issue in this case as 'human gene patenting,' this term inaccurately characterizes the claims in Myriad's patent," and that "what is claimed is a specific sequence of isolated human DNA."

The IPO argues first that isolated human DNA constitutes patent-eligible subject matter.  Citing Diamond v. Chakrabarty, the brief reminds the Court that it "fashioned a straightforward test of whether a manufacture or composition of matter was patent-eligible: it must demonstrate the 'hand of man,' something that is 'a product of human ingenuity 'having a distinctive name, character [and] use.''"  The IPO argues that "[t]he Court's Chakrabarty test is the proper standard for patent-eligibility, not the imposition of bright line, categorical rules applying broad, categorical prohibitions such as that advanced by Plaintiffs and their amici," and thus, "[a]nything that evinces the 'hand of man' is patent-eligible" (emphasis in brief).

According to the IPO, isolated human DNA satisfies the requirement in Chakrabarty that claimed subject matter show "the hand of man," and therefore is patent-eligible.  With respect to the characteristic of being "isolated," the brief notes that "the entire genetic complement (or genome) in the cell comprises about six billion nucleotides of DNA," and that "[a]n individual gene typically comprises about 1,000 of these nucleotides."  The brief points out that "to isolate a gene requires these specific 1,000 nucleotides to be separated from the remaining (approximately) 5,999,999,000 nucleotides in the cellular genome."

The IPO next addresses the impact of other Supreme Court decisions on the Myriad case, arguing that no other precedent controverts Chakrabarty.  Noting that the Court recently addressed the issue of patent eligibility in Mayo Collaborative Services v. Prometheus Labs., Inc., the brief states that the Court's concerns about the scope of patent eligibility "arise when the claims produce no more than information (inform a relevant audience about certain laws of nature)."  Citing the Court's decisions in O'Reilly v. Morse, Gottschalk v. Benson, Parker v. Flook, and Bilski v. Kappos, the brief contends that "[i]n each of these decisions, the Court found a lack of patentable subject matter because the claimed method provided little (or nothing) more than abstract information as opposed to concrete inventions that 'promote the Progress of . . . the useful Arts.'"  Contrasting these cases with Myriad, the brief states that:

Unlike the method claims in Mayo, Benson, Flook and Bilski, Myriad's composition of matter claims at issue here are not broadly preemptive. They are both specific and concrete and as such do not implicate the policy concerns enunciated by this Court in those cases where preemption rendered claims patient-ineligible.  Rather than being directed to mere information, the claims at issue are drawn to a useful and concrete composition of matter that falls within the statutory classes of patentable subject matter defined by Congress in Section 101 of the patent statute.  Since Myriad's claimed inventions "evince the hand of man," they are directed to patentable subject matter per Chakrabarty.

Turning to Petitioners' argument that isolated human DNA is patent ineligible because it constitutes a product of nature, the IPO counters that "[t]his contention is incorrect as a matter of law and as a matter of fact."  The brief explains that:

The claimed isolated human BCRA1 and BCRA2 DNA are not "products of nature" because, as claimed, they are not found in nature.  These isolated human DNAs are never found "isolated" in nature.  First, they are not merely associated with contaminants (like the "intracellular material" contaminating cellulose in the Wood Paper Patent Cases); they are intrinsically (and covalently) attached to and are a part of the physical and chemical structure of the chromosomal DNA, and their isolation requires them to be separated from this DNA, i.e., to be present in an entirely new chemical structure.  . . .  [I]n other (cDNA) embodiments the claimed isolated human DNA is also not merely "isolated" but chemically changed in the process, first by the cell in making mRNA, and again by the inventor in converting the mRNA into cDNA.  Thus, the claimed subject matter is different, physically and chemically, from the DNA present in nature.

The brief continues by arguing that:

[Another] line of reasoning, enunciated by the Court in Funk Brothers and recited with approval in Chakrabarty and more recently in Mayo, is that claims cannot encompass a "natural law" or "phenomenon of nature."  Myriad's claims to isolated human DNA do neither.  These claims recite man-made manufactures or compositions of matter, not phenomena.  They are tangible, physical compounds, having particular and specific structures capable of being elucidated and described.  They do not foreclose anything other than making, using, selling, offering to sell, or importing these specific and particular chemical compounds.

The IPO also takes the Petitioners to task for "wrongly equat[ing]" the patenting of isolated human DNA with the patenting genetic information.  While acknowledging that "[t]here is no dispute that genetic information, standing alone, is not patentable subject matter and does not belong to one of the statutory categories required for patent-eligibility," the IPO argues that "[p]atent claims to isolated DNA only cover the isolated DNA itself, and not the genetic information per se."  The brief also argues that:

The dichotomy between patent-eligible isolated human DNA and patent-ineligible genetic information is consistent with precedent.  For example, in O'Reilly v. Morse, 56 U.S. 62, 63 (1853), the ability to use electricity for communication was found to be patent-ineligible, but the specific telegraph invented by Morse was determined to be patent-eligible.  Algorithms per se have also been held to be patent-ineligible, Parker v. Flook, 437 U.S. 584, 585 (1978); Gottschalk v. Benson, 409 U.S. 63, 64 (1972), while the use of an algorithm (an equation) in a patented process has been found to be patent-eligible, Diamond v. Diehr, 450 U.S. 175, 177 (1981).

The brief next discusses the adverse impact that a ban on isolated human DNA patenting would have on the development of biologic drugs and personalized medicine.  The brief also suggests that "[a]bsent patent protection, and under the circumstances of multigenic causation (or at least association) of common diseases, the impetus will be to develop and protect this nascent technology using, inter alia, trade secret protection."  The brief predicts that "[u]nder these circumstances, innovation in genetic-based diagnostics would be severely limited, since there would be no incentive (indeed, there would be strong disincentives) to disclose the genetic basis of the diagnostic assay," and that as a result, genetic information "as a trade secret, could be kept out of the public domain indefinitely."

The brief concludes by arguing that isolated human DNA patenting does not impede research.  In support of this conclusion, the brief cites a study performed by the American Association for the Advancement of Science on the effects of isolated human DNA patenting on basic research in the U.S., Germany, the U.K, and Japan, the study finding that "intellectual property rights had little negative impact on the practice of science."  Suggesting that "[p]erhaps the best measure of [research] activity is the number of research reports in public databases that reflect ongoing basic scientific research in peer-reviewed scientific journals," the brief notes that "[w]hile reported estimates differ depending on the search term used, a simple search of 'brca1 or brca2' resulted in 10,652 publications [in the scientific literature]."  The brief then adds that:

If [Myriad's] patents had a chilling effect on basic research, the expectation would be that the number of scientific research reports would have declined in the face of these patents.  On the contrary, the number of such publications has steadily increased each year, which is precisely what would be expected if these patents had no significant effect on basic scientific research.

What these patents do, of course, is prevent commercial activity -- using the patented isolated human DNA or performing the patented methods for profit.  This is a legitimate exercise of the patent grant.

Note: the IPO brief was co-authored by Patent Docs author Dr. Kevin Noonan.

AIPLA Submits Amicus Brief to Supreme Court in AMP v. Myriad Genetics

By Kevin E. Noonan --

There is a great cultural divide that has been illuminated by the Myriad case (AMP v. Myriad Genetics), between producers of technology and its consumers, governments and non-government organizations such as patient groups who are goal-driven to reduce present costs (especially in healthcare) regardless of future disadvantages, and the more general schism between those who understand science and technology and those who don't.  There is also the problem of bright, educated, ambitious, and motivated graduates of America's best colleges and universities who have the natural propensity of their class and age to think they have better answers than their elders who have actually tackled the problems of investment and commercialization.  This becomes a problem, of course, when many of these folks go into government, resulting in the Justice Department's "magic microscope" as but one example.

Another consequence is that briefs for both sides of the "gene patenting" question repeat the same arguments based on the same policy rationales to come to the same conclusions.  The AIPLA's amicus brief in the Myriad case illustrates the issue.  The brief sets forth the following propositions:

I. MYRIAD'S CLAIMED DNA MOLECULES ARE NOT PRODUCTS OF NATURE
    A. Human DNA Is Complex in Both Structure and Function
    B. Myriad Claims Isolated DNA Molecules, Not Found in Humans, That Can Perform New Functions
II. THE FEDERAL CIRCUIT APPLIED THE CORRECT TEST
    A. Patent Eligibility of Isolated DNA Molecules, Which Are Compositions of Matter, Must Be Analyzed Under the Applicable Precedents
    B. Prometheus Applies to Method Claims, Not to the Isolated DNA Molecule Claims at Issue Here
    C. Myriad's Claims May Not Be Patentable, But That Does Not Make Them Patent-Ineligible Under Section 101
III. PATENT PREEMPTION DOES NOT PRECLUDE THE PATENTABILITY OF THE CLAIMED SUBJECT MATTER
    A. The Importance of Broad Patent Eligibility
    B. The Experimental Use Exception Allows For Some Uses of the Claimed DNA Molecules
IV. CONGRESS HAS RECOGNIZED THE PATENT ELIGIBILITY OF ISOLATED DNA MOLECULES
    A. Moral and Ethical Considerations Are for Congress, Not the Courts

There is not an incorrect statement of the law in any of this, nor the science.  (There are a few aspects that bear closer scrutiny, as set forth below.)  But it is true that the science of DNA does not resemble either the pointedly incorrect analogies set forth by the petitioners (DNA as a kidney, or a leaf, or a mineral) or the equally inapt analogies by courts (such as the distinctions between a tree and a baseball bat or a statue and a piece of marble).  Ignoring the facts makes it easy to misapply the law; indeed, the old aphorism may need to be updated to read "Bad analogies make bad law."  The distinctions set forth in Section I of the AIPLA's brief are not news to anyone who understands the scientific basis of isolated DNA.  But generalist lawyers and judges can be understood (if not forgiven) to have believed that the ways scientists have tried to explain DNA (as a library or a book or a code or software) are in fact what DNA actually is.  "A gene is but a chemical compound, albeit a complex one" is the proper measure of what is encompassed in claims to isolated DNA, and the conflation of the patent-eligible molecule for the patent-ineligible sequence has made it easier for petitioners to convince some judges and the public that patents for human genes are a bad idea.

Nor is the brief incorrect on the law, setting forth the "applicable precedents" of Chakrabarty, Funk Bros., and J.E.M. Ag Supply to support the proposition that isolated human DNA satisfies the requirements for the "hand of man" and new utilities of isolated natural products.  Unfortunately, the matter is before the Court because the patent eligibility of isolated human DNA has not been decided before, despite the 30 years and thousands of patents in this area.  And the brief is also correct that the principles enunciated in Benson, Flook, Diehr, Bilski, and Mayo do not directly apply, as those were method claims embodying laws of nature, not composition or manufacture claims directed to isolated "products of nature."  The brief goes somewhat astray in making this argument categorically, i.e., based on the statutory category of invention rather than, for example, on the differences in scope of the two types of claims.  This is nicely illustrated by the Myriad claims at issue, which are limited to DNA molecules that encode a specific amino acid sequence.  Unlike the broad reach of claims to a "law of nature," Myriad's claims are extremely narrow.  Think:  if a putatively infringing DNA molecule encodes a protein that differs by even a single amino acid, that DNA molecule does not literally infringe.  This point is even sharper when it is recognized that the one amino acid difference could be a valine to isoleucine change, which is equivalent to the addition or subtraction of a single methylene group – (-CH₂-) –  in a protein molecule comprising 60,000-100,000 atoms.  Never has so small a change had so large an effect on claim scope, and yet the AIPLA misses the opportunity to inform the Court that petitioners' claims about the scope of preemption occasioned by permitting isolated human DNA to be patented are grossly exaggerated.  Also in this section of the brief the AIPLA appears to agree that Myriad's claims may not even be patentable, a curious position for a brief in favor of patent eligibility.  Mayo showed clearly that the Court believes that its Section 101 jurisprudence is "well established" and a better vehicle for preventing patenting of claims that should not be patented -- why give them a reason to think that Myriad's claims might not be worth the effort?

The brief's section on preemption is where questions are raised about the focus of the brief and its potential vel non for persuasiveness.  First, rather than addressing the argument, the brief takes the position that "broad patent eligibility" is necessary, thereby to a degree conceding to petitioners the point that these claims broadly preempt use of human genes for research.  The brief then posits the existence of an "experimental use exception" for basic research that, frankly, does not exist.  While there are some 19th Century district court cases that support the proposition, for most, the Federal Circuit's decision in Madey v. Duke Univ., 307 F.3d 1351, 1361-62 (Fed. Cir. 2002), foreclosed any such broad protection against patent infringement liability for university research.  This is because the Federal Circuit recognized that university research was not for "philosophical experiments" or "gratifying a philosophical taste, or curiosity, or for mere amusement."  The brief correctly identifies the "safe harbor" provisions of the Hatch-Waxman Act, codified under 35 U.S.C. § 271(e)(1), but while broadly interpreted by the Supreme Court (Medtronic v. Eli Lilly & Co., Merck v. Integra) this is of limited usefulness for most inventions including isolated human DNA.  And the brief's citation of In re Rosuvastatin Calcium Patent Litig., __ F.3d___, 2012 WL 6217356, at *12 (Fed. Cir. Dec. 14, 2012), misses the mark because while "patenting does not deprive the public of the right to experiment with and improve upon the patented subject matter" and "[i]t is not necessary to wait for the patent to expire before the knowledge contained in the patent can be touched," the case does not stand for the proposition that a three-judge panel of the Court sua sponte created a research exception sufficient to protect university research on isolated, patented human DNA.  (It is somewhat amusing that one of the citations set forth in the brief to support the existence of a experimental use exception is L.C. Bruzzone, The Research Exemption: A Proposal, 21 AIPLA Q.J. 52 (1993), which is, on its face, a proposal.)  The better argument, of course, is that there has never been patent infringement litigation against basic research, even by Myriad:  indeed, more than 10,000 research papers have been published since the BRCA gene patents were granted.  This statistic is much more persuasive than an argument that bolsters the proposition that basic science research is at risk of patent infringement liability but for the tenuous existence of a experimental use/research exemption.

Finally, as has been discussed in previous posts, it is a waste of paper to argue to this Court deference to Congress on such matters, particularly when it is inaction, rather than affirmative action, that is the basis for the argument.

Oral argument is set for April 15th, and Patent Docs will be posting on additional amicus briefs in the interim and oral argument in due course.

Myriad Sets Forth Its Case to the Supreme Court

By Kevin E. Noonan --

Myriad Genetics filed its responsive  brief with the Supreme Court last Thursday in AMP v. Myriad Genetics ("the Myriad case").  It is a certainly a serviceable brief that makes the patent law arguments that need to be made and cites at least some of the precedent that should be cited.  But reading the brief leaves nothing so much as the impression that Myriad has squandered its opportunity to submit a brief the Supreme Court would listen to.

The brief begins by expanding on the Question Presented by Petitioners (and for which certiorari was granted, i.e., "Are human genes patentable") to the following:

Did the Federal Circuit correctly apply 35 U.S.C. § 101 to conclude that these particular molecules are "product[s] of human ingenuity 'having a distinctive name, character [and] use,'" particularly where the general legal rule followed by courts for 30 years has been to allow such patent claims, where the U.S. Patent and Trademark Office ("USPTO") has issued similar patents since at least 1982 and confirmed in the 2001 Utility Guidelines that such isolated molecules are patent-eligible as human-made inventions under § 101, where investors and technology companies have placed significant reliance in these settled property rights over the last 30 years, where the alternative dividing line is indefensible under law or science, and where the challenged claims do not preempt or preclude the use of alternative technologies to identify a patient's cancer predisposition?

The brief then makes many of the points that have been made by Myriad and its amici throughout this litigation:  that the scope of Section 101 of the Patent Act is broad, the Federal Circuit came to the correct decision, the requirements in Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980), are controlling precedent and Myriad's claims satisfy these requirements, and that the government's and Petitioner's arguments and interpretations of the law are incorrect.  The brief emphasizes the distinctions between isolated DNA and DNA as it exists in nature, and the new utilities imparted upon isolated DNA as the result of its isolation.  Myriad distinguishes claims to isolated human DNA from the unpatentable claims in Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948) (properly stating that Funk Bros. was a case about "invention," i.e., non-obviousness and not patent-eligibility), and relies heavily on the Court's interpretation of the scope of Section 101 in J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred International, Inc., 534 U.S. 124 (1996).  The brief makes the following analogy (among many):

No one would doubt the patent-eligibility of a newly-created chemical composition that, when applied in a laboratory to a person's blood or tissue sample, could detect a mutation genetically predisposing her to a risk of breast or ovarian cancer, thereby allowing her to take proactive measures to prolong her life even before cancer actually strikes.  That is what Myriad's patented molecules are -- and they were never available to the world until Myriad's scientists applied their inventive faculties to a previously undistinguished mass of genetic matter in order to identify, define, and create the isolated DNA molecules.

Myriad argues that there are other provisions of the Patent Act that can properly cabin claims to their proper scope, and that what Section 101 requires is "invention," drawing a parallel with analogous concepts in copyright law (specifically, "the eligibility threshold of copyright law, which requires authorial 'originality' -- defined as a "minimal level of creativity."  Feist Pub., Inc. v. Rural Tel. Serv. Co., 499 U.S. 340, 358-59 (1991)).

And the brief reminds the Court that the USPTO has been granting patents on isolated DNA (and the Federal Circuit upholding them) since 1982 as an application of the broad interpretation of patent eligibility enunciated by the Court in Chakrabarty.  Myriad emphasizes efforts by the PTO to ensure that the scope of claims granted on isolated DNA was appropriate, for example, as having "specific, substantial and credible" utility," citing both the 1995 (Utility Examination Guidelines, 60 Fed. Reg. 36,263 (July 14, 1995)) and 2001 (Utility Guidelines. 66 Fed. Reg. 1092 (Jan. 5, 2001)) versions of the Office's Utility Guidelines.  In this regard, Myriad cites numerous precedent to support the statement that "isolates or extracts of natural products may be patented"; examples include digitalis (U.S. Patent No. 1,898,199), rapamycin (U.S. Patent No. 3,929,992) and (perhaps infelicitously) the HIV virus (U.S. Patent No. 5,135,864), among others.

Myriad's response to the government's position is that it is inconsistent with the government's previous position permitting patents on isolated DNA in "[o]ver thirty years of precedent."  Myriad criticizes the government for arguing that the "line" should be drawn between cDNA (patent eligible) and "other isolated DNA molecules (not)."  The line has been drawn elsewhere under established government (PTO) practice, and this "'established general legal rule' -- not to mention the enormous reliance interests and property rights arising from that practice -- is far more worthy of respect than the arbitrary line now being offered as a mere litigating position by the United States" says Myriad, citing Bowen v. Georgetown Univ. Hosp., 488 U.S. 204, 212 (1988).

These arguments are followed in the brief by an argument related to the "[c]ountless companies and investors [that] have risked billions of dollars to research and develop advances under this promise of stable patent protection," followed almost immediately by a disquisition on the differences between isolated DNA and how it exists in nature, and a brief history of "the little biotech company that could" (i.e., Myriad) and the benefits to human health that resulted from the availability of patent protection (although it does not explain how claims to isolated, full-length BRCA1 and BRCA2 genes are relevant to genetic diagnostic testing, then or now).  The brief does Myriad a great service in getting before the Court some of the facts regarding the credit Myriad is amply due in providing genetic diagnostic testing for breast and ovarian cancer and setting forth the reality (as opposed to Petitioners' fantasies) regarding the true costs of the tests and the number of women for whom Myriad's BRCA gene tests are available.  As has been noted by others, Myriad also informs the Court that its "gene patents" have not impeded research, citing the evidence that "since the patents issued, over 18,000 researchers have conducted studies on BRCA1/2 genes, published over 8,000 papers, and conducted over 130 clinical trials."

Turning to Petitioner's arguments, the brief catalogs the many ways that Plaintiffs have mischaracterized the evidence and the law in making their arguments.  This starts, according to Myriad, with focusing on the similarities between isolated and naturally occurring human DNA, because there will always be such similarities with any naturally occurring product.  What is relevant, according to Myriad, are the differences, because it is in the differences that will be illustrated "whether a claimed composition is ''a product of human ingenuity 'having a distinctive name, character and use'' from a natural product," citing Chakrabarty.  The brief uses an analogy plucked from the opinion below to make this point:

A patent-eligible baseball bat, though shaped and formed by human hands, will share the characteristics of the wood embedded in the tree from which the bat was formed.  But the fact that the bat shares the properties of natural wood does not make the resulting, human-made product ineligible for patenting.

And the brief addresses in this regard Petitioner's "information content" argument, i.e., that Myriad's claims are unpatentable because the sequence of the isolated DNA and the DNA as it exists in nature are identical, pointing out that that to be useful the sequence of the DNA:

[I]n combination with the inventors' scientific work and ingenuity in characterizing and defining the molecule's starting and end points, the severing of covalent bonds, and the removal of the specific defined molecule from other materials in its native environment to create new functionality as a probe or primer.  Only because of the addition of human invention do these molecules exist to help patients chart their own course of medical treatments.

(In a short section, the brief also addresses the 1st and 14th amendment arguments with regard to the absence of any threat to a woman's access to information regarding her health.)  Perhaps the most apt application of these principles comes in the brief's argument that, assessed as Petitioner would have patent eligibility assessed, Chakrabarty's bacterium would not have been sufficiently different from naturally occurring Pseudomonas bacteria to be eligible for patenting.

Myriad also has "its day in court" by taking the opportunity to illustrate the fanciful nature of the litigation, citing quotes from lawyers representing the ACLU and the Public Patent Foundation (PubPat) that they were just looking to "sue somebody" over patents to isolated DNA and that the goal was to "rend[er] invalid patents on many other genes . . . .  We just had to pick one case as our case."  However tempting, this portion of the argument, and indeed the entire first section of the brief, is devoted to Myriad's failed attempt below to convince the lower court that the one plaintiff found by the Federal Circuit to have standing (Dr. Harry Ostrer) in fact does not, either by virtue of a lack of "immediacy" in the threat to his activities posed by Myriad's 1998 letter offering a license to Myriad's patents to his then employer, NYU, or by virtue of his move from NYU to Montefiore Hospital at the Albert Einstein College of Medicine (which had never received a "cease and desist" or license offer letter).  This portion of the brief goes over the same ground trod extensively below, and one that the Court dismissed sub silentio by not including it as a basis for granting certiorari (albeit as part of Petitioners' Questions Presented that the Federal Circuit had been overly exclusive in finding a lack of standing among the various Plaintiffs).  If only by emphasizing this argument by primacy of placement Myriad seems to have made a misjudgment on why the Court granted cert. and what it was interested in deciding.

Even ignoring this strange choice in presenting the order of its arguments, the real problem with the brief is that it seems tone deaf to the tenor of this Supreme Court.  Its emphasis on deference -- to the USPTO or earlier precedent, including especially the Federal Circuit's decision below -- ignores frank and explicit statements and signals from this Court that deference is not on its menu.  The brief seemingly ignores the difference between the Chakrabarty Court's understanding of its role as a coequal branch:

Our task, rather, is the narrow one of determining what Congress meant by the words it used in the statute; once that is done our powers are exhausted.  Congress is free to amend §101 so as to exclude from patent protection organisms produced by genetic engineering.  Compare 42 U.S.C. §2181, exempting from patent protection inventions "useful solely in the utilization of special nuclear material or atomic energy in an atomic weapon."  Or it may choose to craft a statute specifically designed for such living things.  But, until Congress takes such action, this Court must construe the language of §101 as it is.

Diamond v. Chakrabarty.

And this Court's:

[W]e must recognize the role of Congress in crafting more finely tailored rules where necessary.  Cf. 35 U.S.C. §§161–164 (special rules for plant patents).  We need not determine here whether, from a policy perspective, increased protection for discoveries of diagnostic laws of nature is desirable.

(i.e., if Congress does not agree with us they can "craft[] more finely tailored rules").  (Indeed, some members of the Court indicated recently at oral argument in Shelby County v. Holder that the Court need not defer to a 98-0 vote in the Senate reauthorizing the Section 5 of the Voting Rights Act.)

The brief's reliance on deference to the PTO's decisions granting gene patents and the rules it has implemented to do so (like the 2001 Utility Guidelines) lose much of its force in view of the brief filed by the government, that these practices were inconsistent with law and these patents should not have been granted.  While the brief notes that the PTO did not join the brief (and the unprecedented nature of this omission), the Court is certain to be familiar with the concept of the "unified Executive" and thus likely to come to the conclusion that the PTO is stubbornly resisting its comeuppance in a hidebound application of incorrect law.  The brief might have more aptly noted that it is this type of changing positions that is not due deference, as argued recently in Par Pharmaceuticals' brief in FTC v. Actavis:

"[W]hatever deference you are entitled to is compromised by the fact that your predecessors took a different position."  Transcript of Oral Argument at 44, Kiobel v. Royal Dutch Petroleum, No.10-1491 (Oct. 1, 2012) (Roberts, C.J.)

Such a citation might have given the Court pause regarding whether the government's position was persuasive, but the opportunity to make that case was lost.

Similarly, the brief focuses on applications of all the other sections of the Patent Act -- §§ 102, 103, 112 -- in making its arguments, with the rationale that these sections are more appropriate or more flexible or more nuanced in their application to the question before the Court.  This type of argument was made in Mayo, by the government, and rejected:

The Government does not necessarily believe that claims that (like the claims before us) extend just minimally beyond a law of nature should receive patents.  But in its view, other statutory provisions -- those that insist that a claimed process be novel, 35 U. S. C. §102, that it not be "obvious in light of prior art," §103, and that it be "full[y], clear[ly], concise[ly], and exact[ly]" described, §112 -- can perform this screening function.  In particular, it argues that these claims likely fail for lack of novelty under §102.

This approach, however, would make the "law of nature" exception to §101 patentability a dead letter.  The approach is therefore not consistent with prior law.

*  *  *

These considerations lead us to decline the Government's invitation to substitute §§102, 103, and 112 inquiries for the better established inquiry under §101.

(emphasis added).

The fact is that the Supreme Court doesn't consider patent questions like you or I, and patent lawyers would do well to recognize and adapt to that fact.  This brief does not, and its persuasive punch before the Court is likely much reduced as a consequence.

Finally, the Court should have put to bed any comprehension that the "settled expectations" or "economic investment" arguments, such as the brief's argument that "[c]ountless companies and investors have risked billions of dollars to research and develop advances under this promise of stable patent protection," will have much traction, in finding more persuasive the arguments of consumers rather than producers of technology and rejecting the position of respondent and amici like the Biotechnology Industry Organization in Mayo:

Patent protection is, after all, a two-edged sword.  On the one hand, the promise of exclusive rights provides monetary incentives that lead to creation, invention, and discovery.  On the other hand, that very exclusivity can impede the flow of information that might permit, indeed spur, invention, by, for example, raising the price of using the patented ideas once created, requiring potential users to conduct costly and time-consuming searches of existing patents and pending patent applications, and requiring the negotiation of complex licensing arrangements.  At the same time, patent law's general rules must govern inventive activity in many different fields of human endeavor, with the result that the practical effects of rules that reflect a general effort to balance these considerations may differ from one field to another.

The ACLU and PubPat have prevailed -- at the District Court and the court of public opinion -- by making this case about everything but patent law.  While in a different time it might have been sufficient to emphasize patent law in this argument, that time has passed (at least for now).  The Court has evinced a concern that its decisions now may inhibit future progress (a salient concern, in view of the Constitutional imperative that patents and patent law "promote the progress"), as noted in Bilski v. Kappos:

It is important to emphasize that the Court today is not commenting on the patentability of any particular invention, let alone holding that any of the above-mentioned technologies from the Information Age should or should not receive patent protection.  This Age puts the possibility of innovation in the hands of more people and raises new difficulties for the patent law.  With ever more people trying to innovate and thus seeking patent protections for their inventions, the patent law faces a great challenge in striking the balance between protecting inventors and not granting monopolies over procedures that others would discover by independent, creative application of general principles.  Nothing in this opinion should be read to take a position on where that balance ought to be struck.

Emphasizing the negative consequences on progress and innovation of a decision in the ACLU's favor would have provided the Court with greater motivation to pause before taking a broad, sweeping and unnecessary position on where the balance should be struck on patenting isolated human DNA.  Myriad's brief gives the Court no basis for doing so.

United States Asks Supreme Court to Affirm on cDNA, Reverse on Isolated, Unmodified DNA

By Donald Zuhn --

In an amicus brief filed last month in Association for Molecular Pathology v. Myriad Genetics, Inc., the United States asks the Supreme Court to affirm the judgment of the Federal Circuit that cDNA is patent-eligible and reverse the judgment of the appellate court that isolated but otherwise unmodified DNA is patent-eligible.  The government argues that:

Synthesized genetic materials such as cDNA are patent-eligible subject matter because they do not occur in nature but instead are the product of significant human creativity.  By contrast, isolated but otherwise unmodified DNA is not patent-eligible.  The public's ability to study and use native DNA would be unduly compromised if changes caused by the extraction of naturally-occurring substances from their native environments were sufficient to trigger patent-eligibility.  And while the process of isolating DNA entails physical changes, those changes do not significantly alter the structure or function of the relevant DNA segments.

The government explains that "[c]reating cDNA requires significant manipulation and alteration of naturally occurring genetic materials rather than simply the extraction of those materials from their native environment," adding that "[i]ssuing patents on cDNA creates no risk of preempting other uses of the raw materials from which cDNA is created."  However, the brief argues that "isolated but otherwise unmodified genomic DNA" molecules -- like DNA molecules claimed in Myriad's patents -- are not patent eligible because "[t]he process of isolation does not transform those molecules into human-made inventions."  Thus, "[i]solated DNA . . . is not patent-eligible because it has merely been "isolated" -- i.e., extracted from its cellular environment and separated from extraneous material -- rather than significantly altered by human intervention."

To prevent claims to isolated DNA from preempting the use of the underlying native DNA, the government contends that "the mere act of culling a natural product from its environment to exploit its preexisting natural qualities -- however useful those qualities may be -- should be treated as insufficient to create patent-eligible subject matter."  In explaining the government's change in position on DNA molecules -- before the district court, the government had noted that "the USPTO's position" on whether "DNA molecules" are patent-eligible "remains as set forth in its utility guidelines" -- the brief states that:

The district court's judgment in this case, however, prompted the United States to reevaluate whether such patents are consistent with the settled principle that patent protection does not extend to products of nature.  Based on that review, the United States concluded that, although the PTO has properly issued patents on cDNA and other synthesized genetic materials, isolated DNA is not patent-eligible subject matter.

In reassessing its position, the government looked to the Supreme Court's decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc.  Although Mayo concerned process claims rather than composition claims, the government argues that the decision "provides useful guidance for determining whether particular modifications to a naturally occurring substance are sufficient to render the modified substance patent-eligible."  And while "[n]ot every nuance of Mayo's process-claim analysis applies directly to patents directed to compositions of matter," the brief argues that "the law-of-nature and product-of-nature exceptions to Section 101 do, however, reflect the same basic principle:  a person should not receive a patent for simply discovering the existence and useful properties of something that already exists in nature."

In contrast with isolated but otherwise unmodified genomic DNA, the government argues for the patent-eligibility of cDNA molecules.  In particular, the government states that:

With exceptions not relevant here (such as retroviruses that use cDNA-like structures to replicate themselves), cDNA molecules generally do not occur in nature, either in isolation or as contiguous sequences contained within longer natural molecules.   . . .  To create cDNA, a scientist therefore does not simply remove existing cDNA from its natural environment.

According to the government, "cDNA is thus analogous to the genetically modified bacterium in Chakrabarty."  Countering the petitioners' argument that cDNAs are not patent-eligible because they contain the same protein-coding information as DNA in the body, the government notes that:

[T]he properties of any product originally derived from nature, including the bacterium in Chakrabarty, can be traced to the operation of natural principles.  While the coding properties of cDNA molecules' exons are determined by nature, those properties operate within a molecule (a DNA strand with the regulatory and intron regions spliced out) that does not exist in nature and that has increased utility relative to naturally occurring genetic materials or isolated but unmodified DNA.  The fact that a cDNA incorporates nucleotide sequences whose significance is derived from nature therefore does not mean that the molecule as a whole is a product of nature.

As for Myriad's composition claims, the brief points out that "[a]bsent the 'isolated' limitation, claim 1 of the '282 patent, for example, would encompass the native BRCA1 gene in the human body, which 'cod(es) for a BRCA1 polypeptide'," and that "[i]n their pre-isolation form -- i.e., as a portion of a larger native gene within a cell -- the BRCA sequences clearly are products of nature."

In addressing Myriad's reliance on early lower-court decisions upholding patents on natural compounds that have been so refined and purified through human intervention as to become a substance different "in kind" from the natural product, the government explains that:

Those decisions indicate that certain purification processes -- i.e., processes that involve human manipulation of a substance that has been removed in impure form from its natural environment -- may sometimes result in an altered substance that has structural features and⁄or operative properties that render the product markedly different from the impure substance that occurs in nature.  For instance, cDNA could be thought of as a "purified" gene, as it incorporates into a single contiguous, synthetic molecule only the coding regions of the naturally occurring gene.  But isolated DNA reflects no such transformation.  [Rather], isolated DNA has simply been removed from its natural environment within the human body, with minor structural changes that have no effect on its intrinsic properties . . . .  To label the process of removing DNA from a cell "purification," and to hold the culled DNA segments patent-eligible on that ground, would "make patent eligibility depend simply on the draftsman's art," without reference to the nature and extent of the underlying transformation, or the consequences for the public's ability to use the underlying substance.

In response to the argument that Congress' failure to amend U.S. patent law to prohibit the patenting of isolated DNA implies congressional approval of such patents, the government argues that "[i]n these circumstances, Congress's failure to enact legislation abrogating the PTO's practice of issuing isolated DNA patents does not give rise to any inference of congressional endorsement of the PTO's interpretation."  The brief notes that "although bills relating to patents on genetic materials have occasionally been introduced in Congress, there is little 'evidence that Congress considered . . . the precise issue presented before the Court.'"  In particular, the government explains that "[b]ecause 'Congress takes no governmental action except by legislation,' and bills can be proposed and rejected for any number of reasons, none of these bills raises any inference that Congress approved the PTO's practice of granting patents on isolated DNA."

As for the "concern that invalidating patents on isolated DNA would unduly disturb the 'settled expectations' of biotechnology patent holders and investors," the government notes that "[a] patentee's legitimate expectations . . . are always tempered by the possibility that a court could subsequently disagree with the PTO and hold that the patent is invalid under Section 101 or other provisions of the Patent Act."  Finally, with respect to the argument that isolated DNA should remain patent-eligible in order to encourage biotech innovation, the government acknowledges that "[t]he prospect of patent protection for isolated genomic DNA has undoubtedly encouraged valuable discoveries," but counters that "[a]s between the reliance interests of patent holders whose research efforts may have been prompted in part by the PTO'ss patenting standards, and the public interest in avoiding undue restrictions imposed by patents that effectively preempt natural laws and substances, the interest of the public has consistently been given precedence."

Patent Docs plans to review a number of the briefs filed in this case, including the briefs on the merits filed by the petitioners and the respondents, as well as several of the amicus briefs that were filed.  According to the docket for this case on the Supreme Court website, amicus briefs have been filed by the Juhasz Law Firm, P.C., the American Medical Association et al., GeneDx and Law Professors, the National Women's Health Network et al., Federation Internationale Des Conseils En Propriete Intellectuelle, CLS Bank International, the United States, the International Center for Technology Assessment et al., Genformatic LLC, Academics in Law, Medicine, Health Policy and Clinical Genetics, James D. Watson, Ph.D., Fifteen Law Professors, Sigram Schindler Beteiligungsgesellschaft mbH, the AARP, Kali N. Murray and Erika R. George, the Institute of Professional Representatives Before the European Patent Office (EPI), the Ethics & Religious Liberty Commission of the Southern Baptist Convention and Prof. D. Brian Scarnecchia, Eric S. Lander, the American Intellectual Property Law Association, the Canavan Foundation et al., Professor Eileen M. Kane, Knowledge Ecology International, and InVitae Corporation.

On Monday, the Supreme Court set argument for this case for April 15, 2013.

Is It Time for Myriad to Concede in AMP v. Myriad for the Good of the Biotechnology Industry?

Will I lose my dignity?
Will someone care?
Will I wake tomorrow
From this nightmare?

"Will I," Rent

By Kevin E. Noonan --

The Supreme Court's grant of certiorari over the question "Are human genes patentable" had raised for many the specter of an uninformed generalist court rendering a decision containing dicta that would negatively affect biotechnology.  This possibility is real, in view of the voices raised against patenting human genes based on moral, policy, or ideological grounds.  While strongly felt, these sentiments are based, in large part, on a misunderstanding or mischaracterization of either the facts or the law, specifically patent law.  These misstatements include arguments based on patent claims somehow exerting an ownership interest in individual's DNA, or that isolated human nucleic acid claims preempt future research (in the face of thousands of published scientific journal articles published since the BRCA gene patents were granted), or that isolated DNA patents inhibit future technologies like personalized medicine.

This is an argument that might have been relevant 30 years ago, but at least two facts mitigate against resolving this issue now.  The first is that the day of the DNA patent claim is rapidly coming to a close.  These types of patents were first filed directed to specific genes encoding biologically relevant proteins having therapeutic benefits.  These include erythropoietin, tissue plasminogen activator, interferon, blood clotting Factors VIII and IX, and others.  (Indeed, one of the most compelling types of evidence not considered by any court in the Myriad case is the testimony of the tens or hundreds of thousands of patients whose lives have been saved or bettered by biotechnology drugs protected, in part, by so-called "gene patents.")  Myriad's BRCA gene patent claims are in this form, one of the reasons why these claims are not infringed by genetic diagnostic methods used today.

The vast majority of gene patent applications, however, were filled as the result of the Human Genome Project.  These patents are limited in at least three ways.  First, the U.S. Patent and Trademark Office has established a policy that patents will be granted only if an applicant provided on the filing date specific, substantial, and credible utility for the protein encoded by the claimed DNA.  This provision prevents an applicant from obtaining patent exclusivity unless the applicant shows that she establishes utility, a requirement of the patent statute, of the encoded protein.  (This requirement is related to the policy enunciated in Brenner v. Manson, where claims to methods for making steroid molecules were invalidated based on failure to disclose a utility for the steroid molecules made using the methods.)  Second, certain researchers (notably, Sir John Shulston in England) made certain that the sequence results of the HGP were published in public databases as soon as possible; doing so placed the sequences in the prior art and precluded patentability for any application filed after the sequences were made public.  Finally, because almost all of these patents were filed at the turn of the century, and the term of these patents will expire no later than 20 years after application filing, the "problem" of gene patents will disappear no later than 2020 (and in many instances much earlier even if a patent can be obtained under the enhanced utility requirements).

Another reason why the ACLU's challenge is anachronistic (except for those meaning to make an ideological point) is that present and future technology, such as genetic diagnostic testing or personalized medicine, is not prevented or inhibited by claims to isolated DNA molecules encoding a specific human protein.  This is a consequence of the history of these type of claims for providing means for producing biologically relevant proteins like EPO and TPA.  The claims require that the DNA is isolated and that it encodes the full-length protein, as defined by specific amino acid sequence.  (For these reasons these claims are exceedingly narrow, and do not broadly preempt:  for example, such claims are not literally infringed if the encoded protein differs by a single amino acid, meaning that a difference of a single methylene group (the difference between a valine and an isoleucine residue) is enough to take a species outside the scope of the claim.)  Modern gene sequencing methods used for diagnostics neither isolate DNA nor produce a full-length DNA molecule encoding the protein.  Rather, sequencing is performed in such a way that fragments of the DNA are produced in a reaction mixture and sequenced without isolation; what is produced is the sequence, a characteristic of the DNA molecule that is not protected by the patent.  (This is why infringement of isolated DNA claims does not lie by using the sequence information to, inter alia, interrogate a DNA database.)  And the Myriad case has established that method claims directed to merely comparing an individual's gene sequence with a reference sequence and disclosing mutations identified as indicating a risk of disease, without more, are not patent eligible (under either Bilski v Kappos or Mayo v. Prometheus).

So there appears to be no sound policy reason for having the Supreme Court render a decision on the patent eligibility of human genes.  Sadly, there is seemingly no sound business reason for Myriad Genetics to have the Court decide this question either.  Myriad's counsel, Greg Castanias, argued in the first Federal Circuit oral argument that the plaintiffs did not have standing because there was no redressability to their claim.  Specifically, Mr. Castanias argued that even if the Court ruled in plaintiffs' favor, Myriad had other patent claims that would prevent Dr. Harry Ostrer and other plaintiffs from providing BRCA gene diagnostic tests.  In addition, while these patents were undoubtedly important when Myriad was establishing its diagnostics business they are less important now.  Fifteen years and thousands of genetic tests (apparently without any failures) later, the company's reputation, experience and extensive database is far more valuable than the claims at issue.

Under these circumstances, the question must be asked whether the prudent thing for Myriad to do is grant Dr. Ostrer a covenant not to sue on all the patents and claims involved in this litigation.  The result would be to render the issues before the Court moot; regardless of the perceived importance of the Question Presented, even the Supreme Court is limited by Article III of the Constitution and cannot render an advisory opinion on this issue.  Such an action by Myriad would not only prevent this case from being decided, it would preclude the Court from including in its opinion dicta on the patent eligibility of isolated DNA from other species (which may have importance in fields like agriculture or biofuels) or other "products of nature" that may provide the basis for biologic and other types of drugs.  In view of the seemingly complete lack of any practical reason for having the Supreme Court decide this issue, and the risks to the progress provided for a generation by the biotechnology industry, nothing other than a desire to be vindicated remains to support seeing this case through to its conclusion.  Frankly, in view of what is at stake, such vindication is simply not enough.

Top Three Stories of 2012

By Donald Zuhn --

Reflecting upon the events of the past twelve months, Patent Docs presents its sixth annual list of top biotech/pharma patent stories.  For 2012, we identified fifteen stories that were covered on Patent Docs last year that we believe had (or are likely to have) the greatest impact on biotech/pharma patent practitioners and applicants.  On Monday, Tuesday, and Wednesday we counted down stories #15 to #4, and today we count down the top three stories of 2012.  As with our other lists (2011, 2010, 2009, 2008, and 2007), links to our coverage of these stories (as well as a few links to articles on related topics) have been provided in case you missed the articles the first time around or wish to go back and have another look.  As always, we love to hear from Patent Docs readers, so if you think we left something off the list or disagree with anything we included, please let us know.

3.  Implementation of Leahy-Smith America Invents Act Continues

The U.S. Patent and Trademark Office began the year by publishing five notices of proposed rulemaking in January to implement various provisions of the Leahy-Smith America Invents Act.  Another four notices of proposed rulemaking and a practice guide for proposed trial rules were published in February.  Over the summer, the Office issued three more notices of proposed rulemaking and a guidance document on the first-inventor-to-file (FITF) provisions of the AIA.  In July, the Office began issuing final rules to implement AIA provisions, with the final rules corresponding to the notices of proposed rulemaking issued earlier in the year.  By mid-August, the Office had issued eight final rules and a patent trial practice guide.  The Office also held a roundtable in September to obtain public input on issues relating to the Office's proposed rules to implement the first-inventor-to-file provisions of the AIA.  In February, the Office started to exercise its new fee setting authority under the AIA by submitting a proposed fee schedule to the Patent Public Advisory Committee (PPAC), with the PPAC holding two public hearings on the proposed schedule.  In September, the PPAC issued a report on the proposed schedule, which the Director considered before publishing a notice setting and adjusting certain patent fees.  The publication of the proposed fee schedule initiated a 45-day comment period, which ended in November.  The Office is expected to publish a final notice on fees in the coming weeks, with the fee schedule taking effect 45 days after publication (to provide Congress with an opportunity to review the schedule).  Earlier in the year, the Office issued AIA-mandated reports on the prior user rights defense provisions of the AIA and on international patent protections for small businesses.  While the Office collected public comments on genetic diagnostic testing and held two public hearings on the matter, the Office was unable to meet the deadline for submitting its AIA-mandated report on genetic diagnostic testing to Congress (and, in fact, has scheduled a roundtable on January 10 to discuss the topic further).  The Office also opened its first satellite office in Detroit, and after considering public input on locations for additional satellite offices, announced that it would be opening three additional offices in Dallas, TX; Denver, CO; and California's Silicon Valley.  Throw in a series of AIA roadshows, webinars, and a Twitter chat, and it has been a busy year for the Office as it implements changes brought about by the AIA, and for applicants and practitioners as they try to keep up with these changes.  And FITF is only 72 days away.

For information regarding this and other related topics, please see:

• "USPTO Issues Final Rule Implementing Micro Entity Status," December 26, 2012
• "USPTO News Briefs," December 20, 2012
• "USPTO to Hold Roundtable on Genetic Diagnostic Testing," December 4, 2012
• "IPO Submits Comments on Proposed Fees," November 14, 2012
• "USPTO Holds Live Chat on AIA," November 13, 2012
• "USPTO News Briefs," October 30, 2012
• "PPAC Issues Report on USPTO Patent Fees Proposal," October 9, 2012
• "Rules Changes Implementing the Inventor's Oath or Declaration Provisions of the AIA," October 4, 2012
• "More on USPTO's Proposed New Fees - Part II," September 19, 2012
• "More on USPTO's Proposed New Fees," September 11, 2012
• "USPTO Proposes New Patent Fees and CPI Adjustments to Certain Fees," September 6, 2012
• "USPTO News Briefs," September 5, 2012
• "USPTO News Briefs," August 27, 2012
• "USPTO Issues Several Final Rules for Implementing AIA Provisions," August 15, 2012
• "USPTO Issues Final Rule to Implement Miscellaneous Post Patent Provisions of AIA," August 8, 2012
• "USPTO Issues Final Rule for Implementing Statute of Limitations Provisions for Office Disciplinary Proceedings," July 31, 2012
• "USPTO Issues Final Rule for Preissuance Submissions," July 25, 2012
• "USPTO to Open Three More Satellite Offices," July 2, 2012
• "Docs at BIO: Session on Prior User Rights as a New IP Option," June 20, 2012
• "USPTO Report on Genetic Testing Delayed," June 18, 2012
• "BIO International Convention 2012 Preview - Part III: BIO and the America Invents Act," June 14, 2012
• "USPTO Issues Proposed Rules for Implementing Micro Entity Status," June 4, 2012
• "USPTO News Briefs," May 23, 2012
• "USPTO Posts Comments on Genetic Diagnostic Testing," May 22, 2012
• "USPTO Posts Comments on Proposed Fees Changes," March 19, 2012
• "A Glimpse under the Hood: How the USPTO Proposes to Adjust Patent Fees," March 14, 2012
• "USPTO Proposes Fees Changes," March 1, 2012
• "USPTO News Briefs," February 20, 2012
• "USPTO Holds First Hearing on "Second Opinion" Genetic Testing," February 16, 2012
• "Patent Docs Author Testifies at Genetic Diagnostic Testing Hearing," February 16, 2012
• "USPTO to Hold Hearing on Genetic Diagnostic Testing," February 15, 2012
• "USPTO Proposes More Rules for Implementing AIA Provisions," February 13, 2012
• "USPTO Issues Proposed Rulemaking for Supplemental Examination Provisions of AIA," February 8, 2012
• "PPAC to Hold Public Hearings on Proposed Fee Schedule," February 1, 2012
• "Interpreting 35 U.S.C. § 102 under the America Invents Act," January 31, 2012
• "USPTO Proposes Rules Changes for Implementing AIA Provisions -- Oath or Declaration Provisions," January 30, 2012
• "USPTO News Briefs," January 26, 2012
• "USPTO News Briefs," January 18, 2012
• "USPTO Issues Report on Prior User Rights," January 17, 2012
• "USPTO Proposes Rules Changes for Implementing AIA Provisions -- Statute of Limitations Provisions for Office Disciplinary Proceedings," January 16, 2012
• "USPTO Proposes Rules Changes for Implementing AIA Provisions -- Preissuance Submissions Provision," January 12, 2012
• "USPTO Proposes Rules Changes for Implementing AIA Provisions -- Miscellaneous Post Patent Provisions," January 11, 2012

2.  Supreme Court Grants Certiorari in AMP v. Myriad

Six days after issuing its decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., the Supreme Court issued an Order granting the petition for writ of certiorari in Association for Molecular Pathology v. Myriad, vacating the judgment, and remanding the case back to the Federal Circuit for further consideration in light of the Mayo decision.  As we noted yesterday, the Federal Circuit decided on remand that claims to isolated human DNA satisfy the requirements of 35 U.S.C. § 101, with each member of the panel issuing opinions that tracked their earlier opinions (the Federal Circuit's decision placed #5 on our 2012 list of top stories).  In September, the American Civil Liberties Union (ACLU) and Public Patent Foundation (PubPat) again filed a petition for certiorari with the Supreme Court, which the Court granted on November 30.  The Court's grant was limited to the first question presented -- whether human genes are patent-eligible -- and the Court denied certiorari on the other two questions (thus letting stand the Federal Circuit's determination that screening methods using genetically transformed cells are patent-eligible under the Court's Mayo v. Prometheus precedent, and that a declaratory judgment plaintiff must cite actual injury to have standing).  The Supreme Court's grant of certiorari in AMP v. Myriad ensures that this case will be a top story again in 2013.

For information regarding this and other related topics, please see:

• "Supreme Court Grants Cert in AMP v. Myriad," November 30, 2012
• "Myriad Files Responsive Brief Opposing Certiorari," November 29, 2012
• "AMP v. Myriad Briefed and Distributed for Conference - Update," November 19, 2012
• "AMP v. Myriad Briefed and Distributed for Conference," November 13, 2012
• "Plaintiffs (Again) File Certiorari Petition in Myriad Case," September 25, 2012
• "Patent Eligibility and Biology," August 23, 2012
• "The Proper Scope of DNA (or 'Gene') Patent Claims," August 1, 2012
• "Myriad and Prometheus: Do Patents 'Preempt' Follow-On Research?" July 29, 2012
• "The Aussies Are At It Again," June 14, 2012
• "Supreme Court Remands Myriad Case," March 26, 2012

1.  Supreme Court Issues Decision in Mayo v. Prometheus

On March 20, the Supreme Court unanimously held in Mayo Collaborative Services v. Prometheus Laboratories, Inc. that claims directed to the relationship between the concentrations of blood metabolites and response to a therapeutic drug were invalid for "effectively claim[ing] underlying laws of nature themselves."  In the nine months since the Supreme Court issued its decision, applicants and practitioners have tried to gauge the impact of the decision and have asked whether claims perceived to be directed to "laws of nature" can, in fact, be written to pass Constitutional muster.  The U.S. Patent and Trademark Office responded to the Mayo decision by issuing preliminary guidance on the day after the decision, and then followed up with interim guidance in July.  It did not take the lower courts long to apply Mayo, with the District Court for the District of Columbia in SmartGene, Inc. v. Advanced Biological Laboratories SA invalidating diagnostic method claims in view of Mayo only ten days after the Supreme Court issued its decision.  In November, the Federal Circuit made its "first" attempt to implement the Supreme Court's jurisprudence on the scope of patent eligibility for diagnostic method claims in PerkinElmer, Inc. v. Intema Ltd. (we did not count the Federal Circuit's decision on remand in AMP v. Myriad, as the diagnostic method claims in that case had already been held patent-ineligible under the "machine-or-transformation" test set forth in In re Bilski).  As we wrote at the time, PerkinElmer stands as the most recent cautionary tale of how diagnostic methods claims must be crafted -- narrow, specific, encompassing particular assaying and detection steps, and encompassing some (any) patentable feature other than the naturally occurring correlation between a marker and disease.  Whether this will be sufficient to render the subject matter of such claims as patent-eligible remains an open question.

For information regarding this and other related topics, please see:

• "PerkinElmer Inc. v. Intema Ltd. (Fed. Cir. 2012)," November 20, 2012
• "Patent Eligibility and Biology," August 23, 2012
• "Chief Judge Rader (Not Surprisingly) Gets it Right about Chimerical 'Tragedy of the Anti-Commons,'" August 6, 2012
• "Myriad and Prometheus: Do Patents 'Preempt' Follow-On Research?" July 29, 2012
• "USPTO Issues Interim Guidance Regarding Mayo v. Prometheus," July 5, 2012
• "BIO International Convention 2012 Preview: BIO and the Prometheus Supreme Court Case," June 5, 2012
• "Do Diagnostic Method Claims Fall under the Safe Harbor of 35 U.S.C. § 287(c)?" April 11, 2012
• "SmartGene, Inc. v. Advanced Biological Laboratories SA (D.D.C. 2012)," April 10, 2012
• "USPTO Issues Preliminary Guidance on Mayo v. Prometheus," March 27, 2012
• "Mayo Collaborative Services v. Prometheus Laboratories -- What Should We Do? (or Can These Claims Be Saved?)," March 26, 2012
• "Mayo Collaborative Services v. Prometheus Laboratories -- What the Court's Decision Means," March 22, 2012
• "Mayo Collaborative Services v. Prometheus Laboratories -- What the Supreme Court Said," March 21, 2012
• "Early Reaction to Supreme Court Decision in Mayo v. Prometheus," March 20, 2012
• "Mayo Collaborative Services v. Prometheus Laboratories, Inc. (2012)," March 20, 2012

Image of New Year's Eve ball drop for 2012 in Times Square (above) by Replytojain, from the Wikipedia Commons under the Creative Commons Attribution-ShareAlike 3.0 Unported license.

Top Stories of 2012: #4 to #7

By Donald Zuhn --

Reflecting upon the events of the past twelve months, Patent Docs presents its sixth annual list of top biotech/pharma patent stories.  For 2012, we identified fifteen stories that were covered on Patent Docs last year that we believe had (or are likely to have) the greatest impact on biotech/pharma patent practitioners and applicants.  On Monday and Tuesday, we counted down stories #15 to #8, and today we count down stories #7 to #4 as we work our way towards the top three stories of 2012.  As with our other lists (2011, 2010, 2009, 2008, and 2007), links to our coverage of these stories (as well as a few links to articles on related topics) have been provided in case you missed the articles the first time around or wish to go back and have another look.  As always, we love to hear from Patent Docs readers, so if you think we left something off the list or disagree with anything we included, please let us know.

7.  Federal Circuit Interprets § 271(e)(1) Safe Harbor as Extending to Post-approval Activities

In a case involving whether certain post-approval activities fall within the "safe harbor" of 35 U.S.C. § 271(e)(1), a divided panel of the Federal Circuit in August vacated a preliminary injunction granted by the District Court, holding that acts taken after approval fell with the safe harbor.  According to the majority, it was significant that Congress had not (expressly) limited the scope of the safe harbor to the Food, Drug and Cosmetic Act but had "broadly" included within the scope of the safe harbor "any federal law" that "regulates the manufacture, use, or sale of drugs."  Thus, the majority rejected Momenta's contention that the process and quality control information obtained from Amphastar's infringement was not submitted to the FDA but was retained by defendants, as these "batch records" must be maintained "for at least one year after expiration of the batch" of generic enoxaparin and must be "readily available for authorized inspection" by the FDA."  The majority opinion states that "[w]e therefore hold that post-approval studies that are 'reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs' fall within the scope of the § 271(e)(1) safe harbor."  Momenta's request for rehearing en banc was denied by the Federal Circuit in November.

For information regarding this and other related topics, please see:

• "Momenta Pharmaceuticals Inc. v. Amphastar Pharmaceuticals, Inc.: 'The Rest of the Story,'" August 13, 2012
• "Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc. (Fed. Cir. 2012)," August 9, 2012
• "Chief Judge Rader (Not Surprisingly) Gets it Right about Chimerical 'Tragedy of the Anti-Commons,'" August 6, 2012

6.  Implementation of Biosimilar Regulatory Pathway Proceeds Despite Opposition

In February, the U.S. Food and Drug Administration published its long-awaited draft guidance on the development of biosimilar products.  The FDA's guidance consisted of three documents:  Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product, and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.  The FDA then spent the next few months collecting comments regarding the draft guidance, and in May held a hearing on the draft guidance, where researchers, payors, patient and physician groups, and industry advocates provided their thoughts on the FDA's first attempt to clarify the logistics as to the operation of the BPCIA.  The FDA's efforts to implement the BPCIA, however, did not push implementation of the biosimilar regulatory pathway up to #6 on this year's list.  No, it was the Supreme Court's landmark decision in June upholding the Patient Protection and Affordable Care Act (PPACA) -- of which the BPCIA is a part -- as constitutional under the taxation clause of the Constitution that lifted this topic to #6.  While the Supreme Court's decision in National Federation of Independent Business v. Sebelius did not constitute a direct challenge to the BPCIA, there were a handful of direct challenges to aspects of the BPCIA.  For example, President Obama took yet another shot at the 12-year data exclusivity period specified under the BPCIA in his 2013 budget proposal, calling for a modification of the length of exclusivity to facilitate faster development of generic biologics by "award[ing] brand biologic manufacturers seven years of exclusivity rather than 12 years under current law."  The same modification had been included in the President's 2012 budget proposal.  In addition, Abbott filed a Citizen Petition with the FDA in April, requesting that the agency refrain from accepting biosimilar applications under the BPCIA that cite reference products (biologics) for which a biologics license application (BLA) was submitted to the FDA prior to March 23, 2010 (when the PPACA was signed into law).  Interestingly, in a letter to the FDA, Rep. Anna Eshoo (D-CA), who was one of the principal authors of the BPCIA, stated that "[w]hile Abbott's Citizen Petition argues that pre-BPCIA approved biologic products cannot be subject to the law, l want to state very emphatically that it was Congressional intent for the new pathway to apply to biologics approved before and after the passage of the Affordable Care Act."  In October, the FDA sent a letter to Abbott noting that the agency "has been unable to reach a decision on [Abbott's] petition because it raises complex issues requiring extensive review and analysis by Agency officials."  The agency did not provide a date by which it would respond.

For information regarding this and other related topics, please see:

• "Rep. Eshoo Expresses Views on Abbott's Biosimilars Petition in Letter to FDA," October 25, 2012
• "FDA Continues to Review Abbott Petition on Biosimilars," October 24, 2012
• "Affordable Care Act Survives Supreme Court Review Largely Unscathed, Clearing Way for Biosimilars," June 28, 2012
• "BIO International Convention 2012 Preview - Part II: BIO and Biosimilar Regulations throughout the World," June 12, 2012
• "House Passes User Fee Bill," May 31, 2012
• "Senate Passes User Fee Bill," May 29, 2012
• "FDA Holds Public Hearing on Biosimilar Draft Guidance," May 20, 2012
• "BIO Comments on FDA Biosimilars Guidance: Demand More Testing, Permit Fewer Differences," April 25, 2012
• "Abbott Asks FDA to Refuse Certain Biosimilar Applications," April 23, 2012
• "FDA Discusses Initial Considerations for Biosimilar Guidance Documents," February 27, 2012
• "President's Latest Budget Proposal Seeks Decrease of Data Exclusivity Period and Elimination of Pay-for-Delay Agreements," February 21, 2012
• "More on FDA Draft Guidelines for 'Follow-on' Biologic Drug Approval Pathway," February 14, 2012
• "FDA Publishes Draft Guidelines for Biosimilar Product Development," February 9, 2012

5.  Federal Circuit Confirms Patent Eligibility of Isolated DNA

In August, the Federal Circuit in Association for Molecular Pathology v. U.S. Patent and Trademark Office, decided on remand that, the Supreme Court's decision in Mayo v. Prometheus notwithstanding, claims to isolated human DNA satisfy the requirements of 35 U.S.C. § 101.  Each of Judge Lourie's majority opinion, Judge Moore's concurring opinion, and Judge Bryson's opinion concurring in part and dissenting in part substantially tracked their opinions when the panel first decided AMP v. USPTO.  Had the case ended here, the Federal Circuit's decision would have placed higher on our list (perhaps foreshadowing one of the stories to be discussed in the final installment of our Top Stories series).

For information regarding this and other related topics, please see:

• "Patent Eligibility and Biology," August 23, 2012
• "Association for Molecular Pathology v. United States Patent and Trademark Office (Fed. Cir. 2012)," August 16, 2012
• "AMP v. USPTO -- Federal Circuit Confirms Patent Eligibility of Isolated DNA," August 16, 2012
• "The Proper Scope of DNA (or "Gene") Patent Claims," August 1, 2012
• "Myriad and Prometheus: Do Patents 'Preempt' Follow-On Research?" July 29, 2012
• "Federal Circuit Hears Oral Argument in AMP v. USPTO Remand," July 23, 2012
• "Myriad Genetics Files Supplemental Brief in AMP v. USPTO," July 19, 2012
• "Supplemental Brief for Appellees in AMP v. USPTO," July 19, 2012
• "Biopharmaceutical Companies Weigh-In on Myriad Case," July 17, 2012
• "Health Care Professionals Contend That Isolated DNA and cDNA Are Patent Ineligible," July 16, 2012
• "Coalition of Amici File Brief in Support of Myriad," July 15, 2012
• "Dr. James Watson: Human Genes Should Not Be Patented," July 12, 2012
• "Scientist-Law Professor Files Amicus Brief in Myriad Case," July 11, 2012
• "U.S. Government: Mayo Decision Supports Prior Argument That Isolated Genomic DNA Is Not Patent Eligible," July 10, 2012
• "IPO Amicus Brief Argues for Patent Eligibility of Myriad's Isolated DNA Claims and Method Claim 20," July 9, 2012
• "Eli Lilly & Co. File Amicus Brief in AMP v. Myriad," June 27, 2012
• "Biotech Companies Send Letter on Myriad Case to Attorney General and Solicitor General," June 19, 2012
• "Parties and Amici File Briefs in Myriad Case," June 17, 2012
• "The Aussies Are At It Again," June 14, 2012
• "Federal Circuit Declines Invitation to Reconsider Standing Question," June 13, 2012
• "Plaintiffs Respond to Myriad's 'Suggestion' of Mootness or, Alternatively, Motion for Remand in AMP v. USPTO," June 10, 2012
• "Myriad Files Motion 'Suggesting' Mootness or Seeking Remand in AMP v. USPTO," May 30, 2012
• "Federal Circuit Sets Schedule for AMP v. USPTO," April 30, 2012
• "Supreme Court Remands Myriad Case," March 26, 2012

4.  Supreme Court Grants Certiorari in Monsanto v. Bowman

In October, the Supreme Court granted certiorari in Monsanto v. Bowman, against the advice of the U.S. Solicitor General.  In Bowman, Monsanto's complaint arose from farmer Bowman's "second planting" of herbicide resistant seed that was made using so-called "commodity seed" (seed sold by farmers to local grain elevators for commodity use, for example, as cattle feed).  After planting this seed, which was significantly cheaper than Roundup Ready® seed, farmer Bowman tested the crop for Roundup® resistance and found that substantial amounts of the seed were resistant.  He used Roundup® on these plantings and then replanted the seed.  The District Court granted summary judgment of patent infringement and entered judgment against farmer Bowman, and the Federal Circuit affirmed.  The question presented to the Supreme Court is:

Whether the Federal Circuit erred by (1) refusing to find patent exhaustion in patented seeds even after an authorized sale and by (2) creating an exception to the doctrine of patent exhaustion for self-replicating technologies?

For information regarding this and other related topics, please see:

• "Supreme Court Grants Certiorari in Monsanto v. Bowman," October 22, 2012
• "Bowman Responds to Solicitor General," September 12, 2012
• "Solicitor General Recommends the Supreme Court Deny Cert in Bowman v. Monsanto," August 30, 2012

Image of New Year's Eve ball drop for 2012 in Times Square (above) by Replytojain, from the Wikipedia Commons under the Creative Commons Attribution-ShareAlike 3.0 Unported license.

Supreme Court Grants Cert in AMP v. Myriad

By Kevin E. Noonan --

In a decision that should surprise no one, the U.S. Supreme Court granted certiorari today in Association for Molecular Pathology v. Myriad Genetics, Inc.  The grant was limited to the first question presented, whether human genes are patent-eligible, and the Court denied certiorari on the other two questions (thus letting stand the Federal Circuit's determination that screening methods using genetically transformed cells are patent-eligible under the Court's Mayo v. Prometheus precedent, and that a declaratory judgment plaintiff must cite actual injury to have standing).

The decision is unsurprising in view of the (relative) specificity of the question presented and the overwhelmingly one-sided nature of the amicus briefing (see "AMP v. Myriad Briefed and Distributed for Conference").  Later posts will discuss potential outcomes and stratagems for ensuring that the Court is fully informed on the facts rather than the rhetoric of gene patents. But one thing is certain:  anyone with skin in this game who sits on the sidelines should be ashamed.