Patent Docs

In Defense of the Patent System: How the Mainstream Media's Representation of it is "Broken"

By Andrew Williams --

The mainstream media continues its attack on the patent system.  This problem has become significant, because the average American does not appear to understand the purpose (and benefits) of the patent system.  With all of the misinformation being reported, it is no wonder that lay people have the perception that the patent system is "broken."  This blog has reported in the past about NPR's criticisms of the patent system, which have occurred on such shows as "This American Life" and podcasts as "Planet Money" (see "When NPR Podcasters Hit the Patent System").  We pointed out that one of the downsides of these various reports was that the NPR hosts and reporters did not appear to understand the patent system.  But, on the plus side (if it can be considered as such), these reporters did not hide the fact that they did not understand the system, and they certainly did not profess to be patent law experts.

A different tone has been taken in an article recently published on Wired.com by Patrick Hall entitled "Patent Law Broken, Abused to Stifle Innovation."  Mr. Hall's article is written from the perspective of an "expert" in the field, beginning with the axiomatic proposition that the system is not only broken, but that its abuse is stifling innovation.  However, a review of this article with even a minimal understanding of the patent system suggests that not only is Mr. Hall not actually an expert on the subject, but that he may even lack an understanding of even the most basic tenets of U.S. patent law.  This would not be so disconcerting but for the fact that his piece was published on a site that has a wide-reaching readership, and there was no indication or suggestion provided that the opinions expressed were just that -- opinions by someone who appears to believe that software patents are "bad."

To be fair, the focus of Mr. Hall's article is almost entirely on software patents (even though he does appear to suggest that mechanical patents, such as those that would cover automobiles, are absurd).  This software focus on its own might not be of much interest to the readership of this blog.  However, the provided "recommendations," and the criticisms provided as a whole, are not limited to software patents, and therefore could impact pharmaceutical, chemical, and biotech patents.  Moreover, the more public bashing that software and business-method patents take can only result in a detriment to the patent system as a whole, especially when this is the only exposure to the system that most Americans ever receive.

Mr. Hall's piece begins with the assumption that the patent system is broken.  However, any support for this proposition was anecdotal at best.  For example, the article complained that Apple received a patent for its glass staircase in 2003.  No explanation was given as to why such a patent was undeserved, but the clear implication was that there is a problem if companies are receiving patents on staircases.  No patent numbers were provided, so we are left assuming that the article was referring to Design Patent No. D478,999.  If Mr. Hall understood the difference between utility and design patents, it was not included in his article.  As explained on the Patent Office website, "[a] design patent protects only the appearance of the article and not structural or utilitarian features."  So, "a 'utility patent' protects the way an article is used and works (35 U.S.C. 101), while a 'design patent' protects the way an article looks (35 U.S.C. 171)."  Id.  Therefore, instead of the absurd proposition that Apple has patented the staircase, as the article suggests, Apple has instead simply protected the way its staircases look.

Mr. Hall's article also cited three "absurd" patents as evidence of a broken system:  the motorized ice cream cone, the banana suitcase, and the gas grabber (we are not supposed to ask about this last one).  There is apparently support for the proposition that these patents are absurd -- they were all featured on the "Patently Absurd" website.  But, Mr. Hall's article did not explain why he thought these patents were absurd (other than the fact that absurdity must be self-evident).  Looking at the first example, the motorized ice cream cone, it would appear at first glance that this is a patent to a novelty product.  But, is the article suggesting that novelty products are undeserving of patent protection?  And a simple web search reveals that at least someone was marketing such a device at some point (it was even featured on Katie Lee and Hoda, a video for which can be found with the same web search).  Is Mr. Hall suggesting a new category of inventions that are not patent eligible?  But fear not, if you want to create your own motorized ice cream cone, you can do so without threat of suit from U.S. Patent No. 5,971,829 -- that patent expired for failure to pay a maintenance fee around 2011.  Of course, this highlights one of the points that Mr. Hall's article fails to address -- obtaining and maintaining a patent can be an expensive proposition, and that if a patent is truly "absurd," it is unlikely someone is going through the cost and effort of obtaining or enforcing one.

As one of the most puzzling examples of how the "current" patent system is broken, Mr. Hall's article cites U.S. Patent No. 549,160, which issued in 1895 to George Selden.  This patent claims a "road-locomotive" with "a liquid hydrocarbon gas-engine of the compression type," or as the article puts it, an automobile.  As with the other examples, the article does not explain why a car should be underserving of patent protection.  But all is well, according to article, because Henry Ford allegedly successfully challenged this "absurd" patent in 1911.  Except that isn't quite what happened.  A simple Internet search that digs a little deeper than the Wikipedia page for Selden's patent reveals that his patent was never found to be invalid.  It is true that his patent was surrounded by controversy, but that was because his application was filed in 1879.  Mr. Selden was apparently able to keep his application pending for close to 20 years, until others had gotten into the business.  It appears that Mr. Selden was using a "submarine" patent more than half a century before Jerome Lemelson.  Mr. Selden's downfall occurred not because his patent was determined to be invalid, but rather the type of combustion engines that automobile manufacturers were using at the turn of the century were different than those use in 1879.  Therefore, Mr. Ford successfully appealed a finding of infringement.  Of course, such a "submarine" patent is not feasible anymore, both because almost every application is published after filing, and more importantly, the expiration date of patents are now limited by the filing date.  Therefore, under the patent system that actually exists today, Mr. Selden would have only have been able to assert his patent for a couple of years.  Not surprisingly, these subtleties are missing from Mr. Hall's article.

Mr. Hall's article culminates with "seven simple changes" to fix the patent system.  However, the article makes statements and assumptions about the patent system that are incorrect, but a layperson reading the article would have no idea that this is the case.  The starting point for these seven "fixes" were similar proposals for software patents offered by the "Defend Innovation" initiative of the Electronic Frontier Foundation ("the EFF").  Without taking a position on the EFF's proposals, we note that Mr. Hall's article's exposition on these fixes is not limited to software patents.  In fact, it is in the article's expounding of these proposals that the most confusion would be introduced for those unfamiliar with the patent system.  For example, the EFF has suggested that software patents be required to provide an example of the software code for each claim.  Patents already have a requirement that the claims be sufficiently enabled and described, in order to satisfy 35 U.S.C. § 112.  Mr. Hall's article, however, provides no indication that such a requirement exists.  Instead, the following question is posed:  "[d]o I deserve a patent for a hovering skateboard that I cannot create?"  The article gets the answer right ("Absolutely not"), but posing the question in the first place suggests to the reader that there is currently no enablement requirement.  Such a reader is therefore left with the impression that the Patent Office is issuing patents on "ideas" that the inventor has no idea how to implement.

As another example, the EFF has suggested that all patents and licenses be made public.  In fact, such a proposal to require the recordation of real parties-in-interest has been included in many of the legislative proposals that have been recently proposed (see "Congress Continues Efforts to "Reform" U.S. Patent Law").  However, Mr. Hall's article suggests that this proposal is necessary because, without it, no one would know that a particular patent existed.  "Otherwise," the article asks, "how can innovators know if they are infringing on a patent."  Such reporting leaves the lay-reader with the impression that issued patents (or even published applications) are not publically available.  Not only is this incorrect, it is counter to the purpose behind the patent system -- to provide a period of exclusivity in exchange for the disclosure of an invention.

Many of the other proposals are simply unworkable or impractical.  For example, the EFF had suggested a patent term for software patents no longer than five years from the date that the application was filed.  It is unclear how they derived that the ideal term for software patents is five years, but at least the EFF recognized that this proposal might cause a problem with international treaties.  Mr. Hall's article ignored this complication, and instead expanded the original proposal by suggesting that "[p]atent lengths should reflect the speed of innovation within individual industries."  No guidance is provided, however, as to how this "speed of innovation" is to be calculated.  In fact, if his proposal was codified, then there is no reason that the converse should not be applied -- that industries with slower innovation speeds be given patent terms longer than the current twenty years from filing date.  More importantly, Mr. Hall's article does not take into account the logistical nightmare of how to categorize into which industry a particular patent falls -- and who would be responsible for that determination.

The final proposal in the article is perhaps the most ironic.  The article reiterates the EFF's request that Congress hold hearings to determine whether software patents are beneficial to society.  However, the starting point of this article already assumed this conclusion -- that the system is broken, and is being abused to stifle innovation.  But if this is true, why should Congress waste its time with such a study?  Maybe the article's underlying premise is not as strong as it would lead the readers to believe.  The article refers to scholarly studies that apparently have concluded that patents do not, in fact, protect economically useful inventions.  However, no such study is cited or even mentioned.  Making such statements without providing support is irresponsible journalism.

Mr. Hall's article concludes with the statement that "[o]nly countries with enlightened legal institutions can sustain long-term economic growth, facilitate innovation, and benefit from the genius of resourceful creators."  On this point, the article is probably correct.  Nevertheless, this article provides mostly unsupported statements as fact, which leads the reader to assume that our country does not have such a legal institution.  There is nothing wrong with Mr. Hall having such an opinion, or even his putting his opinion on the internet.  However, when a media outlet such as Wired.com posts such an article, without disclaimer or qualification, it invites the reader to assume that the piece represents reality.  It is no wonder that public outrage over the patent system is mounting.  Instead, the mainstream media needs to apply a balanced approached to the issues, present the merits and weaknesses of both sides, and allow the readers to reach an informed conclusion for themselves.  Of course, this is probably too much to ask.

Why Does Myriad Think It Can Win BRCA Gene Lawsuits?

By Kevin E. Noonan --

Earlier this month, Myriad Genetics filed patent infringement lawsuits against Ambry Genetics (on July 9th) and Gene-by-Gene (on July 10th).  Filed with the complaint in the Ambry lawsuit was a Motion for Preliminary Injunction, and the brief supporting this motion sheds light on the arguments Myriad will assert in its lawsuit (against Ambry and, presumably Gene-by-Gene as well).

In its introduction, Myriad reminds the Utah District Court what is at stake:  that the company had invested "over $500 million dollars" in developing and commercializing its BRCA1 and BRCA2 genetic diagnostic tests.  These tests have "revolutionized patient care and provided medical diagnosis and treatment options never thought possible," providing a test "of superior reliability and accuracy" and that "has saved, and continues to save, countless lives."  Myriad continues to have many claims in its franchise (515 in 24 patents), including the ones specifically recited in its complaint.  Finally, Myriad takes the position (one not completely supported by the Supreme Court's express language) that the Court "found that, unlike isolated human genes, synthetic DNA is man-made and is not a product of nature.  Plaintiffs' remaining patent claims covering BRCA1 and BRCA2 gene testing, including those at issue here, pertain to synthetic DNA or methods-of-use, which were not affected by the Court's decision, and remain valid and enforceable."

The Statement of Facts provides access to the company's background on its website and recites one important aspect of Myriad's business:  as a result of its 16 years and one million patients tested, Myriad has "an extensive database of genetic variant information . . . [that] has allowed Myriad Genetics to further improve its test quality by ensuring that over 97% of the patients tested with BRACAnalysis®, who receive a report identifying a genetic variation, will be informed as to the clinical significance of the variant."  And the company emphasizes the pioneering nature of its work:

Myriad Genetics has also invested heavily in creating from scratch the market for breast/ovarian cancer genetic testing, including conducting extensive clinical studies in support of medical industry guidelines regarding hereditary cancer predisposition testing, developing a market of insurance reimbursement, both public and private, for such testing, and promoting physician and patient education surrounding the importance of hereditary cancer awareness and testing.

This section of the brief also references Ambry's activities specifically relevant to Myriad's patented technology (in particular, four tests identified as BreastNext, BRCAPlus, CancerNext and OvaNext) and Ambry's announcement that it would begin to provide BRCA testing.  This announcement contained the information that Ambry would offer its BRCA tests for $2,280 (compared with Myriad's $4,040), a "significant" price drop, and asserted that "[w]hile Ambry's tests do not offer the accuracy, quality and reliability of Myriad Genetics' integrated BRACAnalysis® test, they present a significant competitive threat as third-party payors, rather than patients and their health-care providers, frequently decide where testing will be performed and such payors are often not well-informed about the competitive quality of such tests."

Turning to the nature of the testing, Myriad tells the District Court that the difference in its claimed probes and PCR primers are that they comprise "synthetically created complementary DNA molecules" that differ from the genomic DNAs claimed in the claims invalidated by the Supreme Court because "they are not naturally occurring,[ r]ather, they are synthetic, laboratory-created DNA carefully designed by man to achieve specific performance metrics."  (While this is one interpretation of the Court's decision it is not the only one; indeed, the Court's basis for distinguishing patent-eligible cDNA and patent-ineligible genomic DNA was not on the basis of it being synthetic versus naturally occurring but that cDNA cannot be found in nature, a subtle but real difference.)  Nevertheless, Myriad contends that "[c]reating synthetic DNA sharing sequence similarity with any particular gene requires an application of detailed knowledge from the discovery of that gene's structure," thereby placing its primers in that portion of the opinion that indicates that "applications" of the knowledge of the BRCA genes may be patent-eligible.

The legal section of the brief sets forth the requirements for obtaining a preliminary injunction:  that there is a likelihood (not a certainty) that the patentee would be successful on the merits of the patent infringement suit; that the harm the patentee would suffer from infringement would be "irreparable" and not adequately compensated by money damages; that the balance of the hardships between the parties favors granting the injunction; and that the injunction would be in the public interest.  The brief proceeds to set forth arguments for each of these prongs (albeit thinly for the hardship balance).

Myriad's arguments for the likelihood it will succeed on the merits depend in large part but not entirely on Section III of the Supreme Court's decision regarding the availability of patent protection to Myriad based on applications of its discovery of the human BRCA genes:

[T]his case does not involve patents on new applications of knowledge about the BRCA1 and BRCA2 genes.  Judge Bryson [of the Federal Circuit] aptly noted that, "[a]s the first party with knowledge of the [BRCA1 and BRCA2] sequences, Myriad was in an excellent position to claim applications of that knowledge.  Many of its unchallenged claims are limited to such applications."  Id. at 2120 (citing Ass'n for Molecular Pathology, 689 F. 3d at 1349) (emphasis added).

Other arguments include reference to its earlier (in the 1997 timeframe) "cease and desist" activities against the University of Pennsylvania and other academic labs, and that those earlier enforcement efforts "settled within a year of filing."  "Not one of those infringers raised a serious contention as to the validity of Myriad's patents, and their quick exit from the market is indicative of the validity of those patents," according to this section of the brief.

Additionally, Myriad takes advantage of the ACLU's decision to focus its efforts on the isolated DNA claims, rather than the genetic diagnostic method claims, to assert that this failure supports the statutory presumption that the claims the company are now asserting are valid.

Turning to claims for probes and primers, the brief takes away any sting or disapprobation that could be associated by losing at the Court, stating that "there was nothing untoward about Myriad having sought and obtained patent protection over these newly discovered and isolated genes.  Myriad's actions were consistent with decades of patent practice and patent law, which the Supreme Court refined with its decision."  Further, the brief asserts that the Court's decision "reject[ed] the argument that any synthetic DNA sharing any sequence similarity to natural DNA is ineligible for patenting, despite the fact '[t]he nucleotide sequence of cDNA is dictated by nature, not by the lab technician'":

That may be so, but the lab technician unquestionably creates something new when cDNA is made.  cDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived.  As a result, cDNA is not a "product of nature" and is patent eligible under §101, except insofar as very short series of DNA may have no intervening introns to remove when creating cDNA.  In that situation, a short strand of cDNA may be indistinguishable from natural DNA.  Id. at 2119 (emphasis added).

Thus, according to Myriad, all the claims it is now asserting "either require the use of inventive DNA synthesized in a laboratory based upon knowledge about the BRCA1 and BRCA2 genes (e.g., gene-specific probes, primers and arrays) [] or pertain to such synthetic DNA compositions themselves, and these compositions are patent-eligible under the Court's Myriad decision."

Finally, addressing the patent eligibility of genetic diagnostic method claims the brief bootstraps the (undisturbed) Federal Circuit decision that Claim 20 of Myriad's '282 patent (relating to drug screening methods) are patentable, analogizing the rationale for that decision (the non-naturally occurring nature of the recombinant cells recited in that method) to Myriad's argument that the primers and probes in its asserted claims are patent eligible under the Court's Myriad decision.  (This argument does not address evidence that the primer and probe claims are invalid under other sections of the statute, inter alia, § 102 or § 103; see "Academic Amici Refute ACLU Falsehoods in Gene Patenting Debate".)  The Court's Mayo decision is distinguished in a footnote:  "Myriad discovered a new biomarker, created new reagents and techniques that could now analyze this new biomarker, and invented new methods of determining a patient's risk of breast and ovarian cancer using these reagents and techniques."

The brief then sets forth Myriad's evidence that Ambry is infringing the asserted claims.  The specific acts Myriad asserts are infringing are three:  "(1) preparation of synthetic DNA samples for BRCA1 and BRCA2 sequencing and analysis; (2) sequencing of BRCA1 and BRCA2; and (3) large rearrangement analysis of BRCA1 and BRCA2."  Myriad asserts that the process(es) used by Ambry begin with DNA isolated from a patient sample that is fragmented and BRCA gene sequences enriched (using "RainDance PCR Target Enrichment") and then PCR amplified with BRCA gene-specific (exon-specific) primers to produce synthetic DNA molecules that can then be sequenced.  Conceding that the primers and probes used in these processes "use natural DNA as inspiration," Myriad argues that "the primer molecules themselves are entirely man-made; they are synthesized in a laboratory" which is enough in Myriad's view to make these compositions patent-eligible.  Moreover, the amplified PCR fragments are themselves "100% synthetic" insofar as they are produced in a laboratory and do not exist in nature per se.

Myriad's brief then sets out claim charts for many of its asserted claims (and makes arguments for all claims Myriad is asserting in the litigation).

Myriad also addresses the extent to which practice of "new" sequencing methods fall within the scope of its claims from several sequencing generations ago.  The answer for Myriad is simple:  the sequence of the BRCA gene exons "includes nucleotide position numbers 2201, 2731, 2430, 4427, 3232, 3667, and 4956" (the positions of mutations indicative of a risk for breast or ovarian cancer), and thus are infringing.  And the brief reminds the District Court that Ambry also performs traditional Sanger sequencing (the state of the art when the Myriad patents were filed).

Finally, the brief addressed Ambry's large rearrangement analysis, which involves either "(1) multiplex ligation-dependent probe amplification ('MLPA') analysis or (2) chromosomal 'microarray' analysis."  The MPLA assay requires the use of "synthetic BRCA1 and BRCA2-specific probes" which are entitled to the same patent-eligibility status that Myriad argues the District Court should confer on synthetic DNA primers.  The chromosomal microarray analysis "necessarily requires hybridization of the synthetic DNA created from a patient's sample DNA to a BRCA1- or BRCA 2-specific probe" which should infringe a patent-eligible claim according to the same rationale.

On balance, Myriad's arguments are based almost in their entirety on the patent-eligibility and patentability of its claimed primers and probes and methods of use thereof.  These arguments are certainly open to different interpretations and Myriad's success, in its preliminary injunction motion and at trial will depend on how the Utah District Court (and presumably the Federal Circuit) will interpret the Supreme Court's decision in this regard.  Myriad's assertion of this interpretation of the Court's Myriad decision also suggests that the company may once again be the impetus for the Supreme Court to revisit the scope of its "product of nature" patent ineligibility doctrine.

The brief's arguments regarding the remaining prongs are much less specific for genetic diagnostic patenting.  Regarding the irreparable injury prong, Myriad recites "at a minimum" the following harms it anticipates would arise from the Court denying its motion:  "(1) price erosion and the loss of the benefit of Myriad's established pricing strategy; (2) the loss of market share; (3) reputational injury; and (4) loss of the benefit of the remaining limited term of patent exclusivity and Myriad's business plans for that period, as well as the inability to fully obtain its reliance interest obtained by disclosing its discovery and investing hundreds of millions of dollars to commercialize that discovery in exchange for a limited exclusive right," citing Federal Circuit precedent on the relevance of these factors.  Robert Bosch LLC v. Pylon Mfg. Corp., 659 F.3d 1142, 1152-54 (Fed. Cir. 2011) (however, this was a decision in the context of a permanent injunction, where infringement had been established).  Ambry's purported cost for its test ($2,280) is "deeply discounted" from Myriad's cost ($4,040; a 46% discount).  Myriad identifies the fact that "third-party payors (such as insurers and/or HMO's) are primarily responsible for deciding whether they will reimburse or pay for testing, rather than the physician or the patient" to raise the risk of price erosion, because "[t]hose payors will exert pressure on Myriad to lower its prices in response to Ambry, and Myriad would be forced to do so in some instances" (and this could get worse if other competitors entered the marketplace).  In addition, Myriad argues that it is not the only entity that would be harmed:  the brief asserts that Myriad has paid about $57 million to licensors, which include universities and research hospitals, for whom losing this revenue stream "will [negatively] impact their ability to fund ongoing programs and new endeavors."

Myriad's arguments regarding market share have some of the flavor of marketing itself:  "[t]hrough its hard work and dedication, Myriad was able to finalize this invention, secure licenses from the patent owners, and develop a superior BRCA1 and BRCA2 test that not only created the market from scratch, but exhibits superior methodology and unparalleled reliability."  Ambry's activities amount to "free-riding" on this effort, and Myriad will lose market share from Ambry's lower prices not due to any advantages or benefits to patients but because "Ambry's significantly discounted prices will result in some third-party payors insisting that patients choose Ambry over Myriad solely because of cost and regardless of the fact that Myriad offers a superior, far more reliable product, and even if patients or physicians prefer to use Myriad."  The evidence of the superiority of Myriad's tests are based on the information Myriad has acquired from "over 1,000,000 patients tested" and the consequence that "Myriad [] provide[s] a clinically meaningful result for over 97% of the variants identified, as opposed to approximately 70% using the publicly available database."  (The argument regarding relative quality of the Myriad and Ambry tests are further developed in the public interest section of the brief.)  These considerations are relevant to the irreparable harm prong of the test because "Myriad has set its prices to reflect the higher quality of Myriad's test, including the significant investments made in discovering the sequences of the BRCA1 and BRCA2 genes, developing necessary technology to perform testing, building the market and analyzing and characterizing variants in a proprietary database" that results in these advantageously superior patient diagnostic outcomes.

Finally, regarding reputational harm, the brief asserts that "Myriad's years of experience and its built-in quality checks, including the fact that it has developed proprietary DNA base calling software, have resulted in a near perfect accuracy rate.  Ambry's failure rate, in contrast, may be as high as 4%  . . . Myriad has been able to further improve its test quality by ensuring that its percentage of 'variants of unknown significance' is less than 3%, compared to 25% to 30% in public databases."  Ambry's entry into the marketplace creates a risk to Myriad, because "[i]f Ambry is allowed to continue selling its tests, which have a higher error rate than Myriad's and will result in many more 'variants of unknown significance,' consumers will receive inconclusive or even flatly incorrect results from those tests.  However, because consumers generally are not well-informed about the different test providers, in part because third-party payors often select the provider based on cost, those consumers are likely to associate those flawed results with Myriad."  This outcome would be avoided if Ambry and others are kept from the marketplace until Myriad's patents have expired, because Myriad "has had no time or opportunity to distinguish its BRACAnalysis® test and associated testing quality from competitors as it would if its competitors were barred from entry until the patents' expiration."  Myriad has relied on its patent exclusivity to have the time to "finalize" its strategy for distinguishing its tests from competitors but "is not prepared to implement those plans immediately, which it would need to do in order to combat the effect of Ambry's testing."  And Myriad's is not the only reputation at risk, because permitting Ambry's less accurate testing to be used on patients "would also indirectly damage the reputation of the other patent owners, several of which are respected research universities or hospitals."

The "balance of the hardships" section of the brief is the shortest, amounting to no more than an assertion that Ambry will suffer no harm, while the harm to Myriad will be to "[a] significant part" of its business.

Finally, the public interest section directly addressed the contrast between public benefits that may be derived from lower prices and the public detriment that Ambry's purportedly lower quality tests would produce.  "While competition may serve the public interest in the short term, the mere existence of a lower-priced, lower quality option available from an infringer does not necessarily advance the broader public interest," according to Myriad.  In addition, "the public has a greater interest in acquiring new technology through the protections provided by the Patent Act than it has in buying 'cheaper knock-offs'."

The argument that Ambry's testing poses a risk to the public is Myriad's first and foremost argument.  "[T]he public interest at issue goes far beyond incentivizing invention.  Precluding Ambry from selling its less accurate test is critical, as allowing Ambry to proceed results in significant public risk over the status quo where Myriad provides testing of very high quality, accuracy and affordability."  Moreover:

As discussed above, Myriad used its years in the market to perfect its testing processes.  This work resulted in a near-perfect accuracy rate.  Ambry's published accuracy rate of 96-99% means that as many as 4% (or 1 in 25) of patients tested with Ambry products will receive either a false negative or a false positive.  The false negative result, of course is of the utmost concern.  Assuming such an error rate, allowing Ambry into the market will result in more patients believing incorrectly that they are not at elevated risk, and not taking preventative measures that they otherwise would take.  Conversely, a patient receiving a false positive may well elect preventative measures such as surgery when in fact there is no elevated risk.  This untenable result can and should be avoided by issuance of an injunction.

According to Myriad, the public interest requires patients to receive Myriad's tests "because of Myriad's exclusive access to its proprietary and extensive database of known genetic variants when making a comparison with a patient test sample," which permits Myriad to provide "definitive" results for more than 97% of patients, as compare with 70-75% of patients whose risk for breast or ovarian cancer are assessed using Ambry's tests.  And, ironically in view of the "second opinion" genetic testing aspects of AMP v. Myriad (and Congressional attention), Myriad argues that:

Thus, Ambry will inform 25-30% of patients tested that they have a genetic variant, but will give them no further information about the clinical implications of that variant.  Because insurance will not reimburse for a second, repetitive test, most patients will not be able to be tested again.  Thus, those patients and their medical providers will be left to guess at an appropriate course of treatment.  Some patients, knowing they have a genetic variant of unknown significance, will assume the worst and undertake unnecessary prophylactic measures, including potentially surgery, even though the underlying variant may be benign.  Allowing Ambry to proceed with its intent to enter the marketplace would be injurious to the public interest, and Ambry should be enjoined from doing so.

For better or worse, we live in a world that Myriad made.  In 1997, genetic diagnosis of cancer risk was in its infancy; traditional genetic linkage analysis had been successfully performed for diseases like Huntington's disease and other rare genetic diseases.  While some academic researchers had identified genes involved in cancer, these were typically loss-of-function mutations in several (~5-6) genes.  BRCA gene analysis was different, because it predicted with ~90% certainty that an affected woman would develop breast or ovarian cancer.  These biological consequences suggested radical prophylactic methods for prevention, each of which involved medical and personal costs.

Myriad was thus in the position of having to convince doctors that their test was beneficial and was sufficiently predictive to justify both the diagnosis and the treatment.  It also required that Myriad establish a network of genetic counselors capable of interpreting the genetic information and counseling affected women (and in the context of there being the "variations on unknown significance" that occurred at much higher frequency then than it does 16 years later).  And it required Myriad to lobby governments and private payers that the cost of Myriad's test was justified by the lower medical costs of prevention (which were not inconsiderable) than treatment of breast or ovarian cancer (because the personal costs were not the payers' problem and the alleviation of which not their perceived responsibility).

Myriad asserts that it spent about half a billion dollars to establish its business including all these ancillary costs on top of the scientific and technology costs.  Myriad did not spend this money due to altruism; like it or not, basing a society on the principle of "from each according to her abilities, to each according to her needs" was tried, famously, in the Twentieth Century with disastrous results.  But if we turn the clock back and let major medical centers in New York, and Boston, and San Francisco, and New Haven, and Bethesda develop BRCA testing, is there any hope or realistic expectation that women in Appalachia, or Oklahoma, or rural communities throughput the country would have had better, or even equivalent access to such testing?

Myriad says it has tested over one million women.  Is the fact that in our Imperfect healthcare system some women have not been able to get tested enough to desire a world where either that number or the demographic distribution thereof is significantly lower?  That outcome is hardly an example of promoting progress.

Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc. (Fed. Cir. 2013)

By Andrew Williams --

A claim term that can have different meanings or values depending on the method used to measure it renders the claim indefinite because it is impossible for a potential infringer to discern the boundaries of the claim.  This is because it is not possible to determine whether potential infringing activity will fall within the scope of the claims.  This principle of patent law was reaffirmed by the Federal Circuit last week in Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc.  The Court held that because the claim term "molecular weight" can be calculated at least three different ways, resulting in three different values, the asserted claims that included this value were invalid as indefinite.  However, the Court also held that at least some of the claims that included this term, but which explained in the claim how to calculate "molecular weight," were correctly found to be definite.  In addition, the Court determined that there was insufficient evidence to overturn the lower court's determinations that the asserted claims were enabled, not obvious, and infringed.  The impact, therefore, was that Teva's injunction of the various ANDA filers was maintained, but the issue of the length of the injunction was remanded to the lower court.

As with most ANDA cases, it is important to have a grasp of the technology to understand the issues involved in this case.  The drug at issue in this case was Copaxone®, which is marketed by Teva for treating multiple sclerosis.  The active ingredient is copolymer-1, or glatiramer acetate, which is a polypeptide product that consists of four different amino acids (alanine, glutamic acid, lysine, and tyrosine).  Copolymer-1, however, is a mixture of individual polymer molecules with different constituent ratios, and different molecular weights.  Therefore, it is often expressed as "average molecular weight."  However, statistically speaking, there are at least three ways to calculate average molecular weight:  peak average molecular weight (M_p), number average molecular weight (M_n), and weight average molecular weight (M_w).  One way to measure "molecular weight" of these molecules is to use Size Exclusion Chromatography (SEC).  A simplistic way to think about SEC is as a technique that utilizes a column "sieve" that allows different size (or weight) molecules to leave (elute) the column at different times.  If the column is calibrated, you can determine the size or weight of the molecules in question depending on when they elute from the column.  The peak average molecular weight (M_p) is the molecular weight of the most abundant molecule in the sample, which occurs as the highest peak in the elution profile.  The number average molecular weight (M_n) is the combined total mass of all of the molecules in the sample divided by the total number of molecules.  Judge Moore, writing for the three-judge panel, chose to not define weight average molecular weight (M_w), instead referring to it as "still another average molecular weight measure that is calculated differently from M_p and M_n."  For readers that are curious, weight average molecular weight (M_w) is similar to number average molecular weight, except instead of dividing the sample by total number of molecules, you take into account the weight fraction of each molecule.  Therefore, the larger the molecule, the more "weight" it will have in the value.

There is a second way to express molecular weight, which was used in the patents-in-suit in the so-called "Group II" claims.  Claim 1 of U.S. Patent No. 6,054,430 is representative of these Group II claims:

    1. Copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 kDa to about 20 kDa, prepared by a process comprising the steps of:
    reacting protected copolymer-1 with hydrobromic acid to form trifluoroacetyl copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 kDa to about 20 kDa, wherein said reaction takes place for a time and at a temperature predetermined by test reaction, and
    treating said trifluoroacetyl copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 kDa to about 20 kDa with aqueous piperidine solution to form copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2kDa to about 20kDa.

In this case, the molecular weight is not expressed as a statistical measure, but rather the percentage of copolymer-1 molecules that fall within a defined range.  As a result, the measurement is not dependent on the type of calculation performed because it requires a determination of the actual values.

The procedural posture of this case is typical for an ANDA case (notwithstanding the fact that there appear to be generic companies on both sides of the "V").  Teva holds the NDA for Copaxone®, for which eight patents are listed in the Orange Book.  Several companies separately submitted Abbreviated New Drug Applications (ANDAs) to market generic versions of this drug.  Teva sued these companies for patent infringement, and at least seven of the eight Orange Book listed patents were asserted.  All seven of these patents shared the same specification, because they descended from the same parent, U.S. Patent No. 5,800,808 ("the '808 patent"), which was also asserted in this case.  This is significant because the '808 patent was filed on May 22, 1995, and therefore has a later expiration date than all of the other patents (seventeen years from date of issuance, or Sept. 1, 2015, instead of May 24, 2014, the expiration date of the remaining patents).  Thus, when the Court determined the claims of the '808 patent to be indefinite, it remanded the case to the lower court to determine the impact this would have on the length of the injunction.  As for the lower court's findings, it defined the term "molecular weight" in the Group I claims as peak average molecular weight (M_p), and rejected the argument that the term was insolubly ambiguous.  It also held that all of the asserted claims were infringed, and that they were not invalid for obviousness or lack of enablement.  The ANDA filers appealed.

Indefiniteness

The Appellants challenged the lower court's determination that "molecular weight" could be defined, because one of skill in the art would not understand which measurement (M_p, M_w, M_n, or something else) should be used.  The specification of the patents-in-suit was silent as to which measurement was appropriate, other than to describe the use of SEC (which can be used to obtain all three values).  Statements made in the prosecution history compounded the problem.  In response to an indefiniteness rejection in one of the patents, the patentees said that "[o]ne of ordinary skill in the art, upon reviewing the specification, would understand that 'average molecular weight' refers to the molecular weight at the peak of the molecular weight distribution curve," or M_p.  However, in response to an identical rejection in an earlier related application, the patentees said that ""[o]ne of ordinary skill in the art could understand that kilodalton units implies [sic] a weight average molecular weight," or M_w.

Teva argued that one skilled in the art would have understood that average molecular weight could only be M_p.  Teva asserted that use of SEC without more suggests M_p because determining M_n and M_w required additional calculations.  The Court appeared skeptical of this argument, because SEC can be used to calculate all three values.  Teva also downplayed the prosecution history by explaining that a skilled artisan would recognize that the statement in the earlier application was false -- because "kilodalton units" does not imply weight average.  Teva appears to have alleged that the second statement rectified the earlier misstatement.  However, there is no indication that the patentees in the later application retracted the earlier statement.  Therefore, the Court was left with two contradictory statements that could not be rectified.  As such, the claims in Group I were held to be indefinite.

However, the claims in Group II survived the invalidity challenge.  The Appellants argued that the claim term "molecular weight" was the same in all of the asserted claims, and therefore they should all rise and fall together.  However, the Federal Circuit pointed out that the use of the term "molecular weight" in these claims was not in reference to an average, but rather to a range, as shown in the representative claim above.  Therefore, because the claim had exact values instead of statistical measures, the scope was readily ascertainable.

Enablement

Appellants also alleged that the claims were not enabled because the specification did not specify how the SEC column should be calibrated, and therefore either self-standards or universal calibration could be used.  They argued that copolymer-1 is complex and exhibits an unpredictable behavior.  In fact, they pointed to Teva's difficulties in identifying an appropriate calibration method.

The Federal Circuit found no clear error with the fact finding of the lower court.  The lower court weighed the testimony of the experts, and found Teva's expert to be more convincing.  Moreover, there was no evidence that Teva's own alleged difficulties were based on faulty measurements as opposed to regulatory or scale-up issues.  As a result, the lower court's determination was affirmed.

Obviousness

Appellants also challenged the lower court's holding that the patents at issue would not have been obvious in view of the prior art.  The closest prior art reference disclosed compounds with a molecular weight higher than 10 kDa.  Appellants alleged that there was no evidence that copolymer-1 with a molecular weight less than 10 kDa exhibits an improved toxicity profile over the prior art.  However, the Federal Circuit found no error with the District Court's determination that there was a preference in the prior art for higher molecule weight compounds, and therefore it taught away from the claimed invention.  Also, the Court noted that Copaxone® was coextensive with the asserted claims.  Therefore, a nexus was presumed for purposes of the undisputed commercial success of the drug product, and Appellants had not rebutted this presumption.  As a result, because the Appellants failed to establish the obviousness of the claimed invention, the Federal Circuit affirmed.

Infringement

Finally, Appellants challenged the finding of infringement.  First, they challenged the Court's construction of the term "approximately" in relation to the molar ratio of the amino acid subunits.  However, "approximately" was not a claim term, but instead it was found in a claim term definition.  The term at issue was "copolymer-1" and the District Court construed it to mean "a mixture of polypeptides composed of alanine, glutamic acid, lysine, and tyrosine in a molar ratio of approximately 6:2:5:1."  As such, the application of the term "approximately" was part of the infringement analysis, not of claim construction, and therefore the standard of review was clearly error.

In making the infringement analysis, the lower court determined that a ratio of 6:2:5:1 was equivalent to a percentage ratio of 42.9%, 14.3%, 35.7%, and 7.1%.  In comparison, Mylan's ratio was 42.7%, 14.4%, 33.6%, 9.2% (the ratio for Sandoz was comparable, so only Mylan's product will be discussed here).  The court calculated that this aggregate difference was only 4.5%.  As compared with the prior art, which tolerated aggregate differences of 12%, it found the accused products to fall within the scope of the claims.  Appellants asserted that the relative proportions were important, not the aggregate.  Therefore, because Mylan's ratios were 4.6:1.6:3.7:1.0, the ratio of lysine to tyrosine was 3.7:1.0, and therefore deviated more than 16% from the ratio of 5.0:1.0.  The Federal Circuit agreed with Teva, however, that Appellants were performing a "mathematical sleight of hand."  In essence, they were normalizing the ratio to the least abundant amino acid, tyrosine, which will skew the results.  Ultimately, the Federal Circuit found that the lower court did not clearly err by looking at the aggregate percentage difference and finding it less than 5% from the ideal.

Finally, Appellants asserted that the Teva had disclaimed copolymer-1 compositions having M_w greater than 10kDa.  The basis for this assertion was that the patentees had compared the pending claims to a reference describing copolymer-1 with a minimum molecular weight of 10 kDa, stating that the then-pending claims cover copolymer-1 having a molecular weight of about 5 to 9 kDa.  Somewhat ironically, the Federal Circuit found that there was no a clear disavowal of the claim scope, because it was unclear that the patentees were referring to M_w.  Therefore, for almost the same reason that some of the claims were found to be indefinite, the Court found that there was no disavowal, and therefore infringement determination was affirmed.

Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc. (Fed. Cir. 2013)
Panel:  Chief Judge Rader, Circuit Judge Moore, and District Judge Benson
Opinion by Circuit Judge Moore

Court Report

By Sherri Oslick --

About Court Report:  Each week we will report briefly on recently filed biotech and pharma cases.

Cornerstone Therapeutics Inc. et al. v. Exela Pharma Sciences LLC et al.
1:13-cv-01275; filed July 24, 2013 in the District Court of Delaware

• Plaintiffs:  Cornerstone Therapeutics Inc.; Cornerstone Biopharma Inc.; EKR Therapeutics LLC
• Defendants:  Exela Pharma Sciences LLC; Exela Pharmsci Inc.; Exela Holdings Inc.

Infringement of U.S. Patent Nos. 7,612,102 ("Pre-mixed, Ready-to-Use Pharmaceutical Compositions," issued November 3, 2009) and 7,659,291 ("Methods of Treatment with Pre-Mixed, Ready-to-Use Pharmaceutical Compositions," issued February 9, 2010) following a Paragraph IV certification as part of Exela's filing of a supplemental NDA (under § 505(b)(2) of the Food, Drug and Cosmetic Act) to manufacture a generic version of EKR's Cardene® I.V. Premixed Injection (nicardipine hydrochloride premixed injection for intravenous administration, used for the short-term treatment of hypertension when oral therapy is not feasible or not desirable).  View the complaint here.

Merck & Cie et al. v. Watson Laboratories, Inc. et al.
2:13-cv-01309; filed July 24, 2013 in the District Court of Nevada

• Plaintiffs:  Merck & Cie; Bayer Pharma AG; Bayer Healthcare Pharmaceuticals, Inc.
• Defendants:  Watson Laboratories, Inc.; Actavis, Inc.

Merck & Cie et al. v. Watson Laboratories Inc. et al.
1:13-cv-01272; filed July 23, 2013 in the District Court of Delaware

• Plaintiffs:  Merck & Cie; Bayer Pharma AG; Bayer HealthCare Pharmaceuticals Inc.
• Defendants:  Watson Laboratories Inc.; Actavis Inc.

The complaints in these cases are substantially identical.  Infringement of U.S. Patent No. 6,441,168 ("Stable Crystalline Salts of 5-methyltetrahydrofolic Acid," issued August 27, 2002) following a Paragraph IV certification as part of Watson's filing of an ANDA to manufacture a generic version of Merck's Beyaz® (drospirenone, 17α-ethinyl estradiol, and levomefolate calcium, used for oral contraception).  View the Delaware complaint here.

AbbVie Inc. v. Roxane Laboratories, Inc.
2:13-cv-00708; filed July 18, 2013 in the Southern District of Ohio

Infringement of U.S. Patent Nos. 8,268,349 ("Solid Pharmaceutical Dosage Form," issued September 18, 2012) and 8,399,015 (same title, issued March 19, 2013) following a Paragraph IV certification as part of Roxane's filing of an ANDA to manufacture a generic version of AbbVie's Norvir® (ritonavir, used to treat human immunodeficiency virus (HIV) infection).  View the complaint here.

Cumberland Pharmaceuticals Inc. v. Akorn Inc.
1:13-cv-01232; filed July 12, 2013 in the District Court of Delaware

Infringement of U.S. Patent No. 8,148,356 ("Acetylcysteine Composition and Uses Therefor," issued April 3, 2012) following a Paragraph IV certification as part of Akorn's filing of an ANDA to manufacture a generic version of Cumberland's Acetadote® (N-acetylcysteine  injection, used to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen).  View the complaint here.

Alcon Pharmaceuticals Ltd et al. v. Lupin Ltd. et al.
1:13-cv-01230; filed July 12, 2013 in the District Court of Delaware

• Plaintiff:  Alcon Pharmaceuticals Ltd; Alcon Research Ltd.
• Defendants:  Lupin Ltd.; Lupin Pharmaceuticals Inc.

Infringement of U.S. Patent No. 8,450,311 ("Pharmaceutical Compositions Containing a Fluoroquinolone Antibiotic Drug," issued May 28, 2013) following a Paragraph IV certification as part of Lupin's filing of an ANDA to manufacture a generic version of Alcon's Moxeza® (moxifloxacin hydrochloride, used to treat bacterial conjunctivitis).  View the complaint here.

Everett Laboratories, Inc. v. Acella Pharmaceuticals, LLC
1:13-cv-04294; filed July 12, 2013 in the District Court of New Jersey

Infringement of U.S. Patent No. 6,863,904 ("Compositions and Methods for Prophylactic and Therapeutic Supplementation of Nutrition in Subjects," issued March 8, 2005) based on Acella's manufacture and sale of its Choice-Tabs, an alleged copy of Everett's Strovite® One (prescription-only nutritional supplement).  View the complaint here.

Aptalis Pharma US Inc. et al. v. Sandoz Inc.
3:13-cv-04290; filed July 12, 2013 in the District Court of New Jersey

• Plaintiffs:  Aptalis Pharma US Inc.; Aptalis Pharma Canada Inc.
• Defendant:  Sandoz Inc.

Infringement of U.S. Patent Nos. 8,217,083 ("Mesalamine Suppository," issued July 10, 2012) and 8,436,051 (same title, issued May 7, 2013) following a Paragraph IV certification as part of Mylan's filing of an ANDA to manufacture a generic version of Aptalis' Canasa® (mesalamine rectal suppository product, used to treat active ulcerative proctitis).  View the complaint here.

Pegasus Laboratories, Inc. v. Weatherford Compounding Pharmacy
2:13-cv-02333; filed July 10, 2013 in the District Court of Kansas

Pegasus Laboratories, Inc. v. Diamondback Drugs, LLC
2:13-cv-02334; filed July 10, 2013 in the District Court of Kansas

The complaints in these cases are substantially identical.  Infringement of U.S. Patent Nos. 5,747,476 ("Treatment of Equine Protozoal Myeloencephalitis" issued May 5, 1998), 6,255,308 (same title, issued July 3, 2001), and 6,448,252 (same title, issued September 10, 2002), licensed to Pegasus, based on defendants' compounding and sale of a sulfadiazine and pyrimethamine producted used for the treatment of horses with EPM, similar to Pegasus' ReBalance® product.  View the Weatherford complaint here.

Conference & CLE Calendar

July 28-30, 2013 - 2013 Annual Meeting & Conference (National Association of Patent Practitioners) - San Diego, CA

July 29-30, 2013 - TTS North America*** (TTS Ltd., the University of California, San Francisco, and BayBio) - San Francisco, CA

July 30, 2013 - Are We Innovators, or Are We Trolls: The Slippery Slope of Defining A Patent Troll (McDonnell Boehnen Hulbert & Berghoff LLP) - 10:00 to 11:15 am (CT)

July 31, 2013 - Battling Patent Trolls: Leveraging New Executive Orders, AIA and Other Tools (Strafford) - 1:00 to 2:30 pm (EDT)

July 31 to August 2, 2013 - Advanced Patent Law Seminar (Chisum Patent Academy) - Seattle, WA

August 5-7, 2013 - Advanced Patent Law Seminar (Chisum Patent Academy) - Seattle, WA

August 8, 2013 - Analyzing and Adapting to the Supreme Court's Myriad Ruling (Technology Transfer Tactics) - 1:00 to 2:00 pm (Eastern)

August 8-11, 2013 - 2013 Annual Meeting (American Bar Association) - San Francisco, CA

August 21, 2013 - Inducement to Infringe in Hatch-Waxman Litigation: Lessons from Commil USA v. Cisco Systems and Bayer Schering v. Lupin for Pharma Patents (Strafford) - 1:00 to 2:30 pm (EDT)

August 22, 2013 - What are the Implications of CLS Bank Int'l v. Alice Corp. on Computer-Implemented Inventions? (McDonnell Boehnen Hulbert & Berghoff LLP) - 10:00 to 11:15 am (CT)

August 29, 2013 - AIA Impact on Section 102 and Prior Art: Navigating the Expanded Scope of Prior Art and the AIA Exceptions (Strafford) - 1:00 to 2:30 pm (EDT)

September 15-17, 2013 - 41st IPO Annual Meeting (Intellectual Property Owners Association) - Boston, MA

September 17-18, 2013 - FDA Boot Camp*** (American Conference Institute) - Boston, MA

September 18, 2013 - Conflicts in Patent Prosecution: Avoiding the Ethical Pitfalls Minimizing Risks of Malpractice Liability and Ethics Sanctions (Strafford) - 1:00 to 2:30 pm (EDT)

September 23-24, 2013 - International Congress on Paragraph IV Litigation*** (Momentum) - New York, NY

***Patent Docs is a media partner of this conference or CLE

TTS North America 2013

TTS Ltd., the University of California, San Francisco, and BayBio will be holding its 2013 edition of TTS North America this Monday and Tuesday, July 29-30, 2013, at the University of California, San Francisco, Mission Bay Campus in San Francisco, CA.  The TTS Global Initiative is the leading international meeting for biotech sector Industry-academia licensing, partnering, and technology transfer.  The TTS North America is the flagship summit of this key international initiative and community of leading technology transfer, licensing, IP, and early stage biotech innovation and venture professionals world wide.

A full program for TTS North America, including an agenda of each event's sessions and list of speakers can be obtained here.  Patent Docs author Dr. Kevin Noonan of McDonnell Boehnen Hulbert & Berghoff LLP will provide a presentation entitled "KOL Insight: The most important emerging trends & developments in biotech IP and their significance for TTOs and early stage biotech," and will also participate on a panel on "What crucial new developments in IP law and US legislation are of greatest concern to TTOs and early stage biotech and their investors?"

The registration fee for TTS North America is $599 (academic Innovators, university or Institute Technology Transfer Officers, non-governmental or non-profit organizations, and start-ups) or $999 (multinational, corporate, legal & consulting, and government).  Patent Docs readers who register using the Code CJS13 and select the "Academic Rate" will be able to secure a registration fee of $399.  Details regarding registration for the event can be found here.

Patent Docs and McDonnell Boehnen Hulbert & Berghoff LLP are partners of TTS North America.

International Congress on Paragraph IV Litigation

Momentum will be holding the International Congress on Paragraph IV Litigation on September 23-24, 2013 in New York, NY.  The conference will offer presentations on the following topics:

• An Examination of Recent Circuit and District Court Decisions and Trends in Paragraph IV Disputes
• FTC Keynote Address -- The Use of Reverse Settlement Payments to "Pay for Delay"
• Addressing Recent Trends in Citizens Petitions and Dissecting the Impact on Paragraph IV Litigation Strategies for Both Patentees and ANDA Filers
• In-House Roundtable -- Corporate Views on the Costs, Benefits and Strategies Behind Paragraph IV Litigation
• Judicial Perspectives on Paragraph IV Litigation -- View from the Bench
• How to Manage, Oversee and Coordinate Multi-Jurisdictional IP Litigation and Overcome Global Settlement Obstacles -- International Litigation Case Study
• Comparing and Contrasting the Divergent Litigation Pathways of Small vs. Large Molecule Products: Examining the Impact of Differing Regulatory Schemes, Challenges Created Under the AIA and Lessons Learned from Recent Biosimilars Litigation in the US & Abroad -- Focus on Biosimilars
• Impact of the AIA on Litigation Strategies for Branded and Generic Pharmaceutical Companies -- Spotlight Address
• Label "Carve-Outs" and Listing Strategies -- Practical Tips for Minimizing Downstream Exposure to Paragraph IV Challenges and Drafting Codes to Limit Carve -Out Opportunities
• Claim Construction and the Markman Hearing -- Practical Tips for Ensuring the Best Interpretation of Key Patent Claims and Obtaining the Results You Want from the Markman Hearing
• Effective Motion Practice in Paragraph IV Disputes -- When and How to Successfully Pursue and Respond to Motions for Summary Judgment and Preliminary Injunctions
• Special Litigation Considerations for Paragraph IV Disputes Involving Multiple ANDA Filers -- Litigation Management Strategy Discussion
• 180-Day Exclusivity and Forfeiture -- A Dissection of Key Filing Benchmarks and Timing Considerations for Counsel on Both Sides
• "At Risk" Launches -- Assessing the Pros and Cons of Launching During Litigation and Considering the Downstream Impact an "At Risk" Launch Can Have on Your Settlement Strategy
• Paragraph IV Appeals -- A Litigators Guide to Effectively Preserving Issues for Appeal and Keeping Your Case Alive Post -District Court
• Settlement Strategy Discussion -- Litigation Strategies for Negotiating a Paragraph IV Settlement that Will Withstand Government Scrutiny

In addition, two pre-conference workshops will be offered from 8:30 to 9:30 am on September 23, 2013.  The first workshop is entitled "Preparing for and Anticipating a Paragraph IV Challenge: Assessing the Business Risks and Legal Costs of a PIV Challenge," and the second is entitled "Paragraph IV Mock Trial: Inside a Real-Time Examination of a Company Witness, Inventor and Scientist."

The agenda for the International Congress on Paragraph IV Litigation can be found here.  A complete brochure for this conference, including an agenda, detailed descriptions of conference sessions, list of speakers, and registration form can be obtained here.

The registration fee for the conference is $1,695 (the on-site registration fee is $1,895).  Those registering by August 5, 2013 will receive a $100 discount.  Those interested in registering for the conference can do so here.

Patent Docs is a media partner of the International Congress on Paragraph IV Litigation.

IPO Annual Meeting

The Intellectual Property Owners Association (IPO) will be holding its 41st Annual Meeting on September 15-17, 2013 in Boston, MA.  Among the presentations being offered at the annual meeting are:

• Recent Patent Case Law Update
• AIA: Looking Backward and Looking Forward
• Trends in Corporate IP Management – 2013 Corporate Benchmarking Survey Results
• 10 Things About Patent Licensing That You Don't Know, But Wish You Did
• Back To The Future: Trial Practice at the PTAB
• Biopiracy: Fact or Fiction? International Treaty Negotiations Could Affect Your Bottom Line and Your IP Rights
• Bad Faith Filings from an International Perspective
• Navigating the Uncertain Waters of Patent Damages and Injunctive Relief
• Recent Developments in International IP
• The Ins and Outs of Corporate Collaborations with Universities
• Trade Secret Enforcement
• Patent Ethics

In addition, the Hon. Kathleen O'Malley, Circuit Judge, U.S. Court of Appeals for the Federal Circuit will present the luncheon keynote on September 17.

A program for the meeting, including an agenda, descriptions of the scheduled sessions, and list of speakers, can be obtained here.

The registration fee for the meeting is $500 (government/academic), $975 (IPO members), or $1,475 (non-members).  Those interested in registering for the meeting can do so here.

Webinar on AIA Impact on Section 102 and Prior Art

Strafford will be offering a webinar/teleconference entitled "AIA Impact on Section 102 and Prior Art: Navigating the Expanded Scope of Prior Art and the AIA Exceptions" on August 29, 2013 from 1:00 to 2:30 pm (EDT).  Thomas L. Irving and Erika H. Arner of Finnegan Henderson Farabow Garrett & Dunner will provide guidance to patent counsel regarding the impact of the Leahy-Smith America Invents Act (AIA) on Section 102 and prior art, and offer best practices for utilizing prior art in patent applications.  The webinar will review the following questions:

• How has the AIA impacted the scope of prior art?
• What are the Section 102 exceptions and what is the impact on Section 103 art?
• What practices should counsel employ in order to utilize prior art?

The registration fee for the webinar is $297 ($362 for registration and CLE processing).  Those registering by August 2, 2013 will receive a $50 discount.  Those interested in registering for the webinar, can do so here.

Webinar on Inducement to Infringe in Hatch-Waxman Litigation

Strafford will be offering a webinar/teleconference entitled "Inducement to Infringe in Hatch-Waxman Litigation: Lessons from Commil USA v. Cisco Systems and Bayer Schering v. Lupin for Pharma Patents" on August 21, 2013 from 1:00 to 2:30 pm (EDT).  Thomas L. Irving, Dr. David P. Frazier, and Robert F. Shaffer of Finnegan Henderson Farabow Garrett & Dunner will provide patent counsel with guidance on claim and label language; to proactively coordinate patent, regulatory and clinical personnel; and to maintain consistency between claims and likely or actual label language throughout patent prosecution and label negotiation with the FDA.  The webinar will review the following questions:

• What can be learned from the AstraZeneca v. Apotex, Bayer Schering v. Lupin, and Commil USA v. Cisco Systems Inc. decisions?
• What are the best approaches to maintain consistency between claims and likely or actual label language?
• What steps can be taken to maintain the coordination of patent, regulatory and clinical personnel throughout the patent prosecution and label negotiation with the FDA?

The registration fee for the webinar is $297 ($362 for registration and CLE processing).  Those interested in registering for the webinar, can do so here.

Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir. 2013)

By Kevin E. Noonan --

It has long been a practice in prosecuting a patent application to keep a continuation application pending during the term of any granted patent.  This practice is advantageous because it permits the patentee to pursue specific claims in a later-filed application to a competitor's product that falls within the scope of the invention as disclosed in the specification.  Of course, this strategy requires that later-filed claims be disclosed in the specification as originally filed to satisfy the enablement and written description requirements of 35 U.S.C. § 112.  In re Ruschig, 379 F.2d 990 (CCPA 1967).

These considerations arose in the Federal Circuit's decision in Novozymes v. DuPont Nutrition Biosciences in a patent infringement lawsuit involving modified alpha-amylase enzymes.  Alpha-amylases are enzymes produced in microorganisms and higher plants and animals (including man) that catalyze the breakdown of certain polysaccharides.  The enzymes are used commercially, inter alia, in detergents, sugar refining, and ethanol production, but as enzymes are sensitive to elevated temperatures and pH extremes.  Novozymes' commercial embodiment of this enzyme is obtained from Bacillus licheniformis (BLA) and sold as Termamyl™.

Traditionally, alpha-amylases are stabilized against the deleterious effects of heat and extreme pH by complexing with calcium, which "represents an added cost and often imposes undesirable effects on industrial equipment."  In an effort to avoid these costs and undesirable effects, Novozymes "pursued two parallel strategies in attempting to identify promising mutation sites among the approximately 500 amino acids that make up a Bacillus alpha-amylase polypeptide:  rational protein design [which attempted to use knowledge and information on the effects of mutations in amino acid sequence on protein structure] and random mutagenesis [which did not]."  The priority application of the patent-in-suit at issue in this case disclosed 17 amino acid sequence positions identified by rational design and 16 positions identified by random mutagenesis that were candidates for amino acid changing mutations in two bacterial alpha-amylases:  the B. licheniformis species that comprised the company's Termamyl™ product and a species from B. stearothermophilus ("BSG"), as well as five other bacterial alpha-amylase species.  As disclosed in the specification of the priority document, these changes could involve substitution of the amino acid at each of these 33 positions with one of the other 19 naturally occurring amino acids, or could involve deletion of the amino acid at that position (a total of 20 possible changes for each of the 33 candidate positions).  Accordingly, the total number of variant B. licheniformis species disclosed generically in the priority document amounted to about 8.6 x 10⁴².  In fact, the specification of the priority document provided but two specific examples with actual experimental data.  However, many of the substitutions were found not to provide variant alpha-amylase enzymes having "improved stability at 'high temperatures (i.e., 70-120°C.) and/or extreme pH (i.e., low or high pH, i.e., pH 4-6 or pH 8-11), in particular at free (i.e., unbound, therefore in solution) calcium concentrations below 60 ppm.'"

DuPont's accused product was a B. stearotherophilus variant species having an amino acid sequence change at position 239 from a serine to a glutamic acid (abbreviated "S239Q").  As noted in the Federal Circuit opinion, "DuPont produced approximately 1,500 alpha-amylase variants with substitutions covering 150 of the 515 amino acid positions in the parent BSG enzyme.  . . .  DuPont then screened its panel of 1,500 variants for increased thermostability under low-calcium conditions and identified a variant substituted at position 239 [the S239Q variant] as the best performer."

In response, Novozymes filed a continuation application that resulted in the patent-in-suit, U.S. Patent No. 7,713,723; claim 1 is representative:

1.  An isolated variant of a parent alpha-amylase, wherein:
    (a) the variant has at least 90% sequence identity to SEQ ID NO: 6 [BSG alpha-amylase],
    (b) the variant comprises a substitution of serine at position 239 relative to the parent alpha- amylase, using the amino acid sequence of SEQ ID NO: 8 [BLA alpha-amylase] for determining position numbering, and
    (c) the variant has increased thermostability relative to the parent alpha-amylase, wherein thermostability is determined at pH 4.5, 90° C. and 5 ppm calcium and has alpha-amylase activity

(emphasis in opinion).

The District Court granted summary judgment of infringement against DuPont and denied DuPont's summary judgment motion of invalidity under 35 U.S.C. § 112 for failure to satisfy the written description requirement, based on there being disputed issues of fact.  (The Court also denied Novozymes' preliminary injunction motion on the grounds that there was considerable question of whether Novozymes would prevail on the merits in view of DuPont's invalidity challenge.)  The Court submitted to the jury the question of whether the claims were invalid under 35 U.S.C. § 112 for failure to satisfy the enablement or written description requirements, and the jury found (using a special verdict form) that the claims were not invalid, awarding Novozymes a judgment of more than $18 million.  The Court granted DuPont's JMOL motion, on the grounds that the specification did not provide an adequate written description of the invention as claimed, relying on both Federal Circuit and CCPA precedent including Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011); Billups-Rothenberg, 642 F.3d 1031, 1036 (Fed. Cir. 2011); Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004); Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320 (Fed. Cir. 2000); In re Ruschig, 379 F.2d 990 (CCPA 1967).

The Federal Circuit affirmed, in an opinion by Judge Schall joined by Judge Bryson, with Chief Judge Rader dissenting.  The majority opinion rejected Novozymes' contentions that any deficiencies in the disclosure in its specification was ameliorated by the general understanding, knowledge and skill in the art, citing Snitzer v. Etzel, 465 F.2d 899 (CCPA 1972), and Union Oil Co. of California v. Atlantic Richfield Co., 208 F.3d 989 (Fed. Cir. 2000).  DuPont, in contrast, relied on In re Ruschig, arguing successfully that Novozymes' disclosure amounted to nothing more than an "invitation to experiment," and unsuccessfully at that, pointing out that Novozymes' "application fails to disclose a single alpha- amylase variant substituted at position 239 that actually exhibits increased thermostability, noting that the only disclosed substitution at that position (S239W) disclosed in the '723 priority application does not work as required by the '723 patent's claims."

The majority stated its holding expressly:  "no reasonable jury could find that the claims of the '723 patent meet the written description requirement of § 112, ¶ 1, and that the district court therefore correctly entered judgment as a matter of law invalidating those claims."  The opinion contrasts the specificity of the claims with the generic disclosure of the specification, noting that Novozymes provided only "generalized guidance listing several variables that might, in some combination, lead to a useful result."  This determination was mandated by "[n]umerous prior decisions" from both the CCPA and the Federal Circuit, citing most of the canonical precedent including In re Ruschig, Boston Scientific Corp. v. Johnson & Johnson, and Univ. of Rochester v. G.D. Searle & Co., and distinguishing Snitzer v. Etzel and Union Oil Co. of California v. Atlantic Richfield Co.  In the Snitzer case, the majority noted that the specification of the patent at issue provided disclosure of a small number of distinctly recited species, in stark contrast to the overwhelming number of species falling within the ambit of the '723 patent specification, while in the Union Oil case the specification "defined the claimed gasoline compositions in terms of various chemical and physical properties" and that "ordinarily skilled petroleum refiners would immediately appreciate that the qualitative chemical properties recited in the claims translated to specific, manifest compositions that would yield those properties."

The majority expressly found that the '723 specification, and the disclosure of the priority document, "contains no disclosure of any variant that actually satisfies the claims, nor is there anything to suggest that Novozymes actually possessed such a variant at the time of filing."  While the opinion recognizes distinctions between Novozymes' specification and the deficiencies in the specifications in the authorities it cites to support their opinion, "[o]n closer inspection these 'analogies fall flat.'"  "Taking each claim -- as we must -- as an integrated whole rather than as a collection of independent limitations, one searches the ['723 priority] application in vain for the disclosure of even a single species that falls within the claims or for any 'blaze marks' that would lead an ordinarily skilled investigator toward such a species among a slew of competing possibilities," according to the opinion, and "working backwards" from the claims (and the accused product) impermissibly "seeks to derive written description support from an amalgam of disclosures plucked selectively from the '723 priority application."  Even Novozymes' expert agreed with DuPont that "one could not know which, if any, individual substitutions at any of the seventeen sites selected by rational protein design would yield increased thermostability without actually making and testing the variants," and it was evident that the '723 specification and its priority document did not disclose the specifically claimed thermostable variant.  Further:

In this case, to actually possess the variant enzymes claimed in the '723 patent would have required Novozymes to confirm its predictions by actually making and testing individual variants or at least identifying subclasses of variants that could be expected to possess the claimed properties, which it did not do before filing the ['723 priority] application.  At best, the ['723 priority] application describes a roadmap for producing candidate alpha-amylase variants and then determining which might exhibit enhanced thermostability.  A patent, however, "is not a reward for the search, but compensation for its successful conclusion."  Ariad [Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010) (en banc)] (quoting University of Rochester, 358 F.3d at 930 n.10).  For that reason, the written description requirement prohibits a patentee from "leaving it to the . . . industry to complete an unfinished invention."  Id.

Chief Judge Rader dissented.  While his continued dissatisfaction with the written description requirement was evident ("[a]lthough a separate written description requirement, and the vague notion of "possession" that it embodies, still troubles me"), his dissent does not trod that old ground of disagreement with his brethren.  Instead, the Chief Judge contends that, having established a separate written description requirement it is a question of fact, and the jury deserves deference to its factual determinations that should not lightly be overturned by JMOL.  On the facts in this case, Chief Judge Rader finds substantial evidence (including expert testimony, the weight and persuasiveness of which being particularly within a jury's purview) supporting the jury's verdict and thus would let it stand:

[T]he jury received expert testimony, heard from skilled protein engineers, reviewed visual aids and publication excerpts, and examined the patent document as guided by those skilled in the art, over an eight day trial.  The jury was given a special verdict form asking whether DuPont had proven by clear and convincing evidence that the claims at issue were invalid for lack of written description.  . . .  The jury answered in favor of Novozymes, and substantial evidence supports this determination.

Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir. 2013)
Panel: Chief Judge Rader and Circuit Judges Schall and Bryson
Opinion by Circuit Judge Schall; dissenting opinion by Chief Judge Rader

BIO IPDx Symposium Highlights Uncertainty in Diagnostic Patenting

By James DeGiulio --

On July 22, BIO hosted the first IP and Diagnostics (IPDx) Symposium in Alexandria, Virginia, which was organized to open a dialogue regarding the latest developments in diagnostics and personalized medicine.  The symposium covered a wide range of topics in the field, including obtaining patent protection, regulatory & reimbursement, and business development & strategic deals.  Despite the range of topics, one unifying theme applying to all aspects of this burgeoning field is uncertainty.

Patent protection in diagnostics is crucial, for there is no market or data exclusivity attributed to diagnostic testing.  Industry members must attempt to predict at an early stage whether patent protection over a diagnostic can be achieved, and if the prediction is negative, the diagnostic may not be pursued.  This prediction has become much more difficult recently, and not unexpectedly at the forefront of the symposium discussion was the impact of the recent Supreme Court decisions in Mayo and Myriad.  The first panel, moderated by Patent Docs author Donald Zuhn of MBHB, was comprised of Patent Docs author Kevin Noonan of MBHB, Duane Marks of Roche Diagnostics, and Mary Till of the USPTO, with each panelist providing their recommendations on how to successfully navigate patent prosecution under the limitations imposed by these Court decisions.  Drafting claims to recite method of treatment steps or to include non-natural compositions (such as the transformed cells from claim 20 in Myriad) were two potential strategies discussed that may avoid § 101 scrutiny under Mayo and Myriad.

Of course, Myriad explicitly exempts cDNA from § 101 scrutiny, which came as a relief to many sectors of biotechnology, who consider cDNA as (arguably) the most commercially important aspect of so-called "gene patents."  However, the scope of the Myriad decision was the topic of debate between the panelists and audience members.  While there was agreement that the Myriad holding is not limited to human DNA, there was spirited disagreement regarding its long-term impact on patents claiming naturally occurring DNA.  On the one hand, it is true that the vast majority of patents covering human DNA are nearing the end of their lifespan, thus reducing the significance of the Myriad opinion here.  However, on the other hand, the biotechnology industry must consider the possible ramifications beyond human genes, particularly in sectors like biofuels that rely on lower-order organisms.  Since the genes of these lower-order organisms often lack introns, claims directed to their cDNA will not fall within the exception stated in Myriad.

Further, under Myriad, there are questions regarding the fate of isolated polypeptides, stem cells, and all other compositions based on natural products.  These compositions represent platform technologies for many biotech firms, and this uncertain climate is causing hesitation disclosing such technologies in patent applications.  The risk of failing to secure adequate patent protection may be too great.  The panelists noted the possibility that the biotechnology industry shifts away from patenting diagnostic products, moving instead towards the trade-secret and/or service provider model.  In this model, samples would be tested in-house, and the biotech company would keep the biomarker information and diagnostic algorithms as trade secrets.  This in-house testing model may also have the added benefit of avoiding any future FDA regulation of such diagnostic testing, which represents another unsettled issue in the field of diagnostics discussed at the Symposium.

In re Adler (Fed. Cir. 2013)

By Kevin E. Noonan --

Ever since the Supreme Court handed down its decision in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), both the U.S. Patent and Trademark Office and the courts have found it easier to render a decision that a claimed invention was obvious.  While how the USPTO and the courts have implemented the KSR obviousness standards have been the subject of some debate, occasionally there is a case that illustrates that the nuances of the Court's obviousness rubrics can be applied in such a way that comports with the "common sense" standard the Court elevated to an analytical tool in KSR.

Such an instance arose in the application of Doran Adler et al.  The case involved an appeal of a PTO determination that the claims of USSN 10/097,096 to applicants Doran Adler et al. were obvious.  The invention relates generally to methods and systems for detecting "pathologies of the gastrointestinal tract"; claim 57 is representative:

57.  A method for displaying in-vivo information, the method comprising:
    receiving at a data processor data generated by a swallowable in-vivo device transversing a GI tract, the data comprising a set of in-vivo images of the GI tract;
    the data processor comparing values of the received images to a reference value of blood and to a reference value of healthy tissue;
    the data processor causing to be displayed the imaged as a color video; and
    the data processor further, based on the comparison, causing to be displayed an indication of a position in the GI tract of a change in the level of red color content, the change correlating to the presence of blood.

Also at issue (but not separately argued) was a system claim (claim 63), substantially comprising a system for practicing the method of claim 57.  The cited prior art was the Meron (WO 00/22975) reference, which discloses a swallowable camera comprising a "means for sensing the presence of blood" combined with the Hirata reference (a scientific journal article) that discloses an endoscopic comparison of normal and healthy esophageal tissues based on colorometric analysis of esophageal varicies detected by comparing "color toner and red color sign."

The PTAB affirmed the Examiner's obviousness rejection, in a non-precedential decision by APJ Grimes, joined by APJ's Scheiner and Mills, finding that despite the absence of an express disclosure of the use of the Meron system to detect blood, the combination of Meron's teachings (that a video camera could be miniaturized and used to detect GI anomalies "that may be associated with bleeding" in the GI tract) with Hirata's disclosure that image comparison could be used to detect changes in the red color spectrum of the GI tract led to a conclusion of obviousness.

The Federal Circuit affirmed, in an opinion by Judge Wallach joined by Judges Prost and Reyna.  The panel cited specific findings of fact that the opinion held were supported by substantial evidence:

12.  Hirata discloses that color tone was analyzed by comparing the color tone of a defined varices region with the color tone of a defined normal esophageal region.

13.  Hirata discloses that the area of red color sign was also determined for a defined varices region.

14.  Hirata discloses that, using image processing, both color tone results and area of red color sign results could be used to select patients with varices that have a higher risk of rupture.

(It was uncontested that the Meron reference teaches a swallowable camera.)  The Court found that the Board did not err in its obviousness determination, and that the Board did not base its obviousness determination on grounds different from those relied upon by the Examiner (which would have entitled applicants to a rehearing on the merits).  As set forth in the panel's opinion:

The primary issue on appeal is whether the Board properly found that it would have been obvious in light of the prior art to compare reference values for healthy tissue and blood to determine whether images of the gastrointestinal tract showed "a change in the level of red color content" where that "change correlat[es] to the presence of blood," as articulated in the claims at issue.

The appellants argued that their claims embody two comparisons (between patient images and an image of healthy tissue or between patient images and blood).  The Court affirmed the PTO's conclusion that a "two-prong" assessment as advocated by appellants was merely a "predictable variation" on the combination of Hirata and Meron and thus unpatentable for being obvious, citing KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) ("If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.").  The opinion rejected appellants' attempts to distinguish the Hirata reference for failing to teach detection of blood, stating (in a footnote) that "substantial evidence supports the Board's finding that Hirata teaches identification of a pathology through red color image analysis of two reference values" wherein "one of ordinary skill in the art would understand that detecting areas with different red color values corresponds to blood."

The purported "new grounds of rejection" argument was predicated on appellants' contention that the Board's analysis "changed the thrust of the Examiner's rejection (Hirata's classification of red color signs); the opinion reproduces appellants' comparison between the Examiner's grounds of rejection and the rationale set forth in the PTAB's decision:

The court found that appellants did not identify "specific facts found by the Board but not by the examiner, nor [did they] illustrate[] how any such facts formed the basis of the Board's rejection."  Accordingly:

While the Board's explanation may go into more detail than the examiner's, that does not amount to a new ground of rejection.  See In re Jung, 637 F.3d 1356, 1365 (Fed. Cir. 2011).

In re Adler (Fed. Cir. 2013)
Panel: Circuit Judges Prost, Reyna, and Wallach
Opinion by Circuit Judge Wallach

Hatch-Waxman Watch: Safe Harbor Edition

By Andrew Williams --

Last week, two district courts dispensed with lawsuits based on the protections afforded by the safe harbor provision of the Hatch-Waxman statute.  Both of the cases relied heavily on the Federal Circuit case Momenta Pharm. v. Amphastar Pharm., 686 F.3d 1348 (2012).  In fact, one of the cases was the Momenta case back at the Massachusetts District Court.  The other case was in the Southern District of New York, and in that case, the dismissal occurred at the pleadings stage.  Because both cases looked to 35 U.S.C. § 271(e)(1), it is useful to review this provision, which reads:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

The Federal Circuit Momenta case interpreted this language broadly, stating that the "language unambiguously applies to submissions under any federal law, providing that the law 'regulates the manufacture, use, or sale of drugs.'"  Therefore, according to current Federal Circuit jurisprudence, the safe harbor is not limited to pre-approval activities (see Momenta); it is not limited to information that is actually submitted to the FDA, provided the FDA requires that records be maintained for possible inspection (see Momenta); and it is OK if the information has alternative uses, such as for fund raising or other business purposes (see Abtox, Inc. v. Exitron Corp., 122 F.3d 1019, 1030 (Fed. Cir. 1997)).  It is with this understanding that the lower courts proceeded.

Momenta Pharma., Inc. v. Amphastar Pharma., Inc., C.A. No. 11-11681-NMG

Last week, the U.S. District Court for the District of Massachusetts granted a summary judgment motion of non-infringement in favor of Amphastar (see Memorandum & Order).  This case involved generic versions of Aventis' product Lovenox (enoxaparin).  However, the patent-in-suit was owned by Momenta, another generic company, and related to methods for comparing generic enoxaparin to the branded version.  As a reminder, the procedural posture in front of the Federal Circuit was as an appeal of a preliminary injunction.  Because the Court found that the alleged infringing activity was protected by 35 U.S.C. § 271(e)(1), it vacated the injunction.  In fact, the Federal Circuit suggested that "the district court may want to consider whether Momenta's admission . . . makes this case amenable to summary judgment of non-infringement."  Nevertheless, the lower court stayed the case pending a petition for en banc appeal, and a petition for certiorari to the Supreme Court in Classen Immunotherapies, Inc. v. Biogen IDEC, another safe harbor case.  After both of those petitions were denied, the District Court lifted the stay, and Amphastar moved for summary judgment the next day.

Momenta's position regarding whether the safe-harbor provision applied in this case apparently did not change significantly.  First, it argued that the FDA did not mandate the use of its patented test, and therefore its use by Amphastar was entirely voluntary.  However, as the District Court pointed out, the Federal Circuit "explicitly" held that the safe harbor "'does not mandate the use of a non-infringing alternative when one exists."  Second, Momenta argued that the required record-keeping was not a "submission," and therefore fell outside the statute.  However, again, the Court noted the Federal Circuit's "express" holding that the FDA's requirement for maintaining records that might be inspected was sufficient to satisfy this requirement.  Finally, Momenta alleged that the use of this information during manufacturing was for commercial purposes, and therefore not "solely" for uses related to satisfying Federal Law.  However, the Federal Circuit found this argument to not be consistent with precedent, citing the Abtox case.  Therefore, the Massachusetts court simply applied the holding of Momenta to grant the summary judgment motion.

Momenta also argued that Amphastar was liable under 35 U.S.C. § 271(g), which states in part: "Whoever without authority imports into the United States or offers to sell, sells, or uses within the United States a product which is made by a process patented in the United States shall be liable as an infringer, if the importation, offer to sell, sale, or use of the product occurs during the term of such process patent."  This section of the statute is generally directed to importation of a product made by a U.S. patented method practiced abroad, and in this case, there was no allegation that Amphastar manufactured the drug product outside the U.S.  Instead, Momenta argued that the language of the statute does not require that the patented process be practiced inside or outside the U.S.  This ignores, however, another section of that provision that states it only applies when "there is no adequate remedy under this title for infringement."  Because 35 U.S.C. § 271(a) applies to the making or use of a patented invention within the U.S., the Court reasoned that 35 U.S.C. § 271(g) does not apply in this case.

At about the same time that Amphastar filed its Summary Judgment motion, Teva filed a motion to dismiss a similar action based on the same patents.  In almost an identical opinion, the Massachusetts District Court also dismissed this case (see Memoradum & Order).

Teva Pharma. USA, Inc. v. Sandoz Inc., Case No. 09 Civ. 10112 (KBF)

The U.S. District Court for the Southern District of New York also dispensed of two cases last week because of the Hatch-Waxman safe harbor provision (Mylan was defendant in the second case), but this time both cases were at the pleading stage.  Interestingly, Momenta was a co-defendant with Sandoz.  Therefore, the parties of this case were basically a mirror image of the Momenta v. Teva litigation that was dismissed in Massachusetts.  In other words, both parties were able to take advantage of the safe-harbor provision in the different litigations (or both parties were burned by it).

The products in question were generic versions of glatiramer acetate, which is sold under the name Copaxone to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis.  Glatiramer acetate is a mixture of polypeptides, and much like with Lovenox/enoxaparin in the Momenta case, the ANDA filers needed to demonstrate that their active ingredient was the same as the branded product.  Specifically, the ANDA filers needed to show that the polypeptides in their products have the same molecular weight characteristics as those in Copaxone.  Teva is the exclusive licensee to four patents that claim polypeptide markers and methods for using these markers to measure these molecular weight characteristics.

Because the fact pattern was so similar to Momenta, the defendants moved to dismiss for failure to state a claim.  The District Court did not, however, start with Momenta, but rather it underwent a similar analysis as the Momenta court.  First, it started with the text of statute, and it found the meaning to be plain and unambiguous.  As a result, the District Court did not need to consult the legislative history.  If it did, it might have discovered that the intent of Congress was that the statute was only meant to apply to pre-approval activity, as Chief Judge Radar explained in detail in the Momenta dissent.

The District Court then compared the case to Momenta, and found that the two cases had "striking similarities."  The Court concluded that the holding of Momenta and its fact pattern support dismissal in this case.  "Momenta allows for the elective use of patented technology as long as it serves to produce information required under federal law."  Teva had not alleged that Sandoz or Mylan activity was any different.

Instead, Teva attempted to differentiate this case by relying on another Federal Circuit case, Proveris Scientific Corp. v. Innovasystems, Inc., 536 F.3d 1256 (Fed. Cir. 2008).  In that case, Innovasystems was making and selling a product that could be used by generic drug manufactures to calibrate drug delivery devices.  Innovasystems had argued that when its product was used by its customers (the generic drug manufacturers), they were protected by the safe harbor provision, and therefore Innovasystems should also be protected.  The Federal Circuit rejected this argument, and pointed out that the "patented invention" of Innovasystems was not the type of "patented invention" to which § 271(e)(1) refers.  It was important that Innovasystems was selling the patented invention to others, and not developing information for submission to the FDA.  The District Court concluded that the present case was analogous to Momenta, and that Proveris was inapposite to the present facts.  Therefore,  the Court held, "without an exclusion for plaintiffs' patented product not being the type of "invention" that can fall within § 271(e)(1), plaintiffs failed to state a claim" for the relevant counts in the complaints (see Opinion & Order).