Patent Docs

Merck KGaA v. Integra Lifesciences I, Ltd. (2005)

Merck v. Integra: The Supreme Court Misses A Golden Opportunity

    By Kevin Noonan --

The Supreme Court missed an opportunity to bring some certainty to the law concerning the scope of the "safe harbor" provisions of 35 U.S.C. § 271(e)(1) in its recent decision in Merck KGaA v. Integra Lifesciences I, Ltd., which was decided June 13, 2005.

The case involved a patent infringement lawsuit against Merck for using Integra's technology.  Specifically, Merck developed new antitumor agents from "RGD" peptides that inhibit angiogenesis.  The Federal Circuit affirmed the District Court's decision that the work did not fall within the § 271(e)(1) safe harbor because it was not "reasonably related" to obtaining regulatory approval as required by the statute.  The Federal Circuit stated that Merck's work was too far "back down the chain of experimentation" leading to the discovery of new drugs to fall within the scope of the exemption.

The Supreme Court disagreed.  The Court found no statutory basis for making a distinction between preclinical and clinical activities.  The Court held that the plain wording of the statute made it "apparent" that the exemption "extends to all uses of patented inventions that are reasonably related to the development and submission of any information under the Food, Drug and Cosmetic Act]."  The Court asserted that "[t]here is simply no room in the statute for excluding certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which is could have been included."

The consequences of the Supreme Court's decision favor neither small biotech companies nor innovator pharmaceutical companies.  As construed by the Court, whether any particular activity falls within the § 271(e)(1) safe harbor will depend on the reasonableness of the relationship between the infringing activity and the development of information for submission to the FDA.  Thus, every activity using a patented compound will have been done (in retrospect) "with the intent to develop a particular drug," and the safe harbor's availability will decrease any incentive to license third party technology.  The profits from any such drug will provide ample incentive to litigate for small biotech companies whose compounds are used in drug development.  Unless Congress acts to better define the scope of § 271(e)(1), it is safe to predict that the Supreme Court's Merck decision will provoke more litigation involving the permissible use of patented technology in drug development.

Merck KGaA v. Integra Lifesciences I, Ltd. (2005)
Opinion by Justice Scalia

A more thorough discussion of this topic can be found in Dr. Noonan's article in the Fall 2005 issue of The Patent Lawyer.

The "Anti-Commons" Aren't So Tragic, After All

    By Kevin Noonan --

Several years ago, it became current among certain academic commentators to opine that patenting genes could become a "tragedy of the anticommons."  By this they meant that permitting gene patenting would restrict progress, inhibit academic freedom and prevent scientists from working cooperatively.  Significantly, most of these commentators had neither a science background nor any experience as patent attorneys.  Their warnings rang hollow to those who had either type of experience, but they had (and continue to have) influence with policymakers, Congressional aides, and the Patent Office.

As it turns out, they were wrong, at least with regard to academic freedom and cooperation.  In a revealing new study, LeRoy Walters of the Kennedy Institute of Ethics and Georgetown University and colleagues reports "consensus, diversity and flexibility in intellectual property management" (see Nature Biotechnology 24: 31-39 (2006)).  The authors found that research university practices were influenced primarily by market forces related to licensing opportunities, and also by guidelines from the National Institutes of Health.

Licensing provides substantial economic benefit to universities; for example, Columbia University received $370 million between 1983 and 2000 for the Axel patents.  The report reveals that universities actively promote licensing patent rights to for-profit companies, but that the licenses are rarely exclusive.  Indeed, the report finds that even exclusive licenses are limited, either due to "field of use" restrictions or serial "exclusive" licensing to different companies.  Large companies are much less likely to require an exclusive license than smaller start-up companies, who require exclusivity in order to attract investment.

Universities have increasingly used the concept of "shop rights" to retain a research exemption, even to exclusively-licensed technology, to permit their own scientists to practice licensed technology.  Many universities have expanded the scope of this exemption to permit scientists to transfer rights to practice a patented invention to scientists at other universities doing basic (non-commercial) research.  Inclusion of such terms has become more important since the Madey v. Duke decision by the Federal Circuit, which eliminated the illusion of a common-law research exemption.

Finally, the cause of the supposed problem, the profusion of gene patents, seems to be fading.  The 39,000 DNA patents issued by the Patent and Trademark Office encompass only 20% of genes identified in human genomic databases.  Moreover, the number of gene patents granted per year has declined every year since 2001, a trend the authors indicate will continue.

Amgen Inc. v. Hoechst Marion Roussel, Inc. (Fed. Cir. 2006)

    By Kevin Noonan --

The peripatetic case of Amgen Inc. v. Hoechst Marion Roussel, Inc. has once again been reviewed by the Federal Circuit (decided August 3, 2006).  Once again the CAFC has failed to lay the several issues in the case to rest.  While affirming infringement and validity of two of the patents in suit, the Federal Circuit has remanded the matter once again to the District Court in view of its de novo claim construction, and perhaps predictably disagreed with the lower court and reversed a determination of infringement under the doctrine of equivalents.

The case has two interesting aspects.  First, citing the rubrics of Phillips the Federal Circuit came to its own determination of the meaning of the term "therapeutically effective amount" with regard to a claim for recombinant erythropoietin (EPO).  EPO is a naturally-occurring hormone that stimulates the body to produce red blood cells, and its absence (or insufficiency) causes anemia.  The standard clinical measure of anemia is the hematocrit, or the percent of whole blood comprised of red blood cells.  In construing the term "therapeutically-effective amount," the District Court had required that EPO falling within the scope of the claim containing the term increase hematocrit and have any other biological properties of naturally-occurring EPO.

The Federal Circuit disagreed, and in doing so provided a nice illustration that Phillips has not changed the Court's capacity for arriving at its own idiosyncratic construction.  The CAFC determined that the lower court had improperly focused on hematocrit, which is one of EPO's biological properties recited in the specification, to the exclusion of several others, including increasing stimulation of reticulocyte response, development of ferrokinetic effects, erythrocyte mass changes, and stimulation of hemoglobin.  The Federal Circuit noted in particular that the specification recited that the therapeutic properties of recombinant EPO "included" all of these, and that the specification further stated that recombinant EPO was therapeutically useful even if it lacked some but not all of these properties.

Of course, the CAFC seems to have not considered the fact that all of the recited properties are related to the clinical measurement of hematocrit, since they are all part of the biological developmental pathway leading to an increase in the number of red blood cells in blood.  Thus, by cherry-picking the language of the specification, the Court was able to arrive at a facially-reasonable claim construction that seems to run contra to clinical reality.  This portion of the matter has been remanded, for further consideration in view of the CAFC's claim construction, on the issue of invalidity over prior art references to EPO preparations that did not increase hematocrit but may have had one of the other recited biological properties.

The second issue is the doctrine of equivalents.  The "predicted" recombinant EPO protein contains 166 amino acids, but as produced naturally (and using HMR's recombinant process) EPO has only 165 amino acids.  The issue before the Federal Circuit was whether Amgen was entitled to assert claims to HMR's recombinant EPO as an equivalent.  The District Court twice found in the affirmative, and the Federal Circuit remanded in its first review so the lower court could consider the issue in view of Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 740-41 (2002).  The District Court having arrived at the same conclusion, infringement under the doctrine of equivalents, the Federal Circuit reversed, finding estoppel arising during prosecution.  Specifically, the CAFC held that preliminary amendments resulting in claim language reciting the 166 amino acid species were not made for reasons tangentially related to the asserted equivalent, as found below, but raised prosecution history estoppel that precluded asserting the claim against HMR's 165-amino acid species.  The Federal Circuit's holding was based in part on Amgen's cancellation of claim limitations related to "fragments" of the 166-amino acid species, and in part because it found erroneous the District Court's determination that the amendments were made to limit the species to human EPO (the CAFC noted that if Amgen had intended to so limit the claims the mere addition of the word "human" would have been sufficient).  Finally, the Federal Circuit rejected the notion that amendments made to avoid a double-patenting rejection were "tangential to patentability."

For those keeping score, the Federal Circuit in its two decisions has affirmed the District Court's judgment that two of Amgen's patents are not invalid and are infringed, also affirmed that another Amgen patent is invalid, reversed a finding of infringement under the doctrine of equivalents (but affirmed that this patent is also not invalid), and for one patent remanded the issue of invalidity to the District Court while affirming that if valid this patent is also infringed.  As noted in Judge Michel's dissent (over the claim construction issue), the District Court is now in position to decide whether to grant an injunction, keeping HMR's competing EPO product off the market until at least the expiration of two of Amgen's patents.  For the parties, that may be (or have to be) enough.

Amgen Inc. v. Hoechst Marion Roussel, Inc. (Fed. Cir. 2006)
Panel: Chief Judge Michel, Senior Circuit Judge Clevenger, and Circuit Judge Schall
Opinion by Circuit Judge Schall; dissenting-in-part opinion by Chief Judge Michel

This article was originally published on Patently-O on August 13, 2006.

Falkner v. Inglis (Fed. Cir. 2006)

    By Donald Zuhn --

In an appeal from a decision of the Board of Patent Appeals and Interferences, the Federal Circuit affirmed judgment for Appellees (Inglis et al.) in an interference involving vaccines comprising modified viral vectors.  In particular, the subject matter of the interference concerned vaccines comprising a poxvirus vector having a deleted or inactivated essential gene, wherein the modified poxvirus is capable of producing infectious viral particles when grown in a host cell modified to produce the absent essential viral gene product.  In contrast with the vaccines of the invention, traditional vaccines had been prepared by deleting or inactivating inessential genes in the viral vector, since the deletion or inactivation of essential genes made it difficult to produce vaccines in commercial quantities.

On appeal, Appellants (Falkner et al.) reiterated several arguments made before the Board, each concerning the common issue of whether Appellees had adequately described and enabled a poxvirus-based vaccine.  Specifically, Appellants argued that because Appellees did not identify any essential poxvirus genes or the inactivation of any such genes, Appellees had not sufficiently described and enabled vaccines comprising a poxvirus vector having a deleted or inactivated essential gene.

With respect to the Board's determination that Appellees had sufficiently described vaccines comprising poxvirus vectors having modified essential genes, the Federal Circuit noted that there was undisputed testimony before the Board that at the time of filing of Appellees' earliest application, the DNA sequence of the poxvirus genome and the locations of essential poxvirus genes had been disclosed in the scientific literature.  Adhering to the well-established rule that "[a] patent need not teach . . . what is well known in the art," the CAFC held that "there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure."  In affirming the Board's determination that Appellees adequately described the invention, the Federal Circuit concluded that because "accessible literature sources clearly provided, as of the relevant date, [poxvirus] genes and their nucleotide sequences (here "essential genes"), satisfaction of the written description requirement does not require either the recitation or incorporation by reference (where permitted) of such genes and sequences."

Falkner v. Inglis (Fed. Cir. 2006)
Panel: Circuit Judge Gajarsa, Senior Circuit Judge Archer, and Circuit Judge Dyk
Opinion by Circuit Judge Gajarsa

This article was originally published on Patently-O on June 1, 2006.

Invitrogen Corp. v. Clontech Laboratories, Inc. (Fed. Cir. 2005)

    By Donald Zuhn --

In an appeal from a District Court judgment invalidating more than two hundred claims in three Invitrogen patents as being anticipated under § 102(g)(2), the Federal Circuit vacated the District Court's invalidity judgment and remanded the case for further proceedings, holding that the District Court misapplied the law of appreciation when determining the date of conception for researchers at Columbia University.  The Federal Circuit, however, affirmed the District Court's rulings on enablement, written description, and infringement.

The patents at issue relate to a genetically modified version of the enzyme reverse transcriptase, which has use in the field of molecular biology.  Naturally-occurring (or unmodified) reverse transcriptase possesses both DNA polymerase and RNase H activities, the former permitting the enzyme to synthesize a DNA copy (cDNA) of a messenger RNA (mRNA) template, and the latter permitting the enzyme to degrade the mRNA template following cDNA synthesis.  In contrast, the modified enzyme lacks RNase H activity, and therefore, is unable to degrade the mRNA template following cDNA synthesis, allowing researchers to reuse the mRNA template to create additional cDNA copies.

While neither party disputed the District Court's determination that Invitrogen had reduced a modified reverse transcriptase lacking RNase H activity to practice in January of 1987, Invitrogen did find fault with the lower court's ruling that Drs. Stephen Goff and Naoko Tanese, two researchers at Columbia University, had conceived of such an enzyme before Invitrogen had reduced the enzyme to practice.  Drs. Goff and Tanese had begun their work in 1984 by preparing a panel of bacterial mutants having modified reverse transcriptase genes.  The panel included two mutants that the Columbia University researchers would later show possess modified reverse transcriptase lacking RNase H activity.  However, due to limitations in the assays that Drs. Goff and Tanese were using to measure RNase H activity, they were unable to conclusively establish that any of the mutants possessed modified reverse transcriptase lacking RNase H activity at the time the mutant panel was prepared.  In March of 1987, Drs. Goff and Tanese used a new assay that they had developed to finally establish that two of the mutants from their panel possessed the modified enzyme.  They were also able to correlate the results obtained with their new assay with their late 1986 sequencing analysis of the mutants.

Following a series of pre-trial motions regarding the issues of conception, enablement, written description, and infringement, the District Court determined, inter alia, that Drs. Goff and Tanese (a) had conceived of a genetically modified reverse transcriptase lacking RNase H activity either in December of 1984 when they had isolated mutants possessing modified reverse transcriptase, or in January of 1986 when they had sequenced the reverse transcriptase genes in these mutants; (b) had actually reduced their invention to practice in March of 1987 when they established that two mutants from their panel possessed modified reverse transcriptase; and (c) were diligent in reducing their invention to practice, and did not abandon, conceal, or suppress it.  However, despite these rulings, the District Court refused to find that the work of Drs. Goff and Tanese anticipated Invitrogen's patents under § 102(g)(2), arguing that anticipation posed factual questions requiring resolution on a claim by claim basis.

Stating that conception "require[s] more than unrecognized accidental creation," and instead "requires that the inventor appreciate that which he has invented," the Federal Circuit found that the District Court erred by establishing Drs. Goff and Tanese's conception before January of 1987 and granting partial summary judgment for Clontech.  Relying on decisions of its predecessor Court, which "require some connection between the physical result (the invention) and the belief (by the inventor)," the Federal Circuit determined that the record was inconsistent with the District Court's notion that Drs. Goff and Tanese set out to create a modified reverse transcriptase or appreciated in 1984 that their mutant panel contained two mutants possessing modified reverse transcriptase.  Rather, the Federal Circuit believed that this case "fit[] squarely within the unrecognized, accidental duplication cases."

However, while the Federal Circuit determined that the evidence excluded both dates of conception proposed by the District Court, the Federal Circuit also found that Dr. Goff's deposition testimony precluded it from finding that the District Court abused its discretion in refusing to grant partial summary judgment for Invitrogen on the issue of conception.  In particular, Dr. Goff had testified that he had formed a suspicion in late 1986, based on his difficulties analyzing the mutants, that two of the mutants possessed modified reverse transcriptase lacking RNase H activity.  Because a reasonable fact-finder presented with Dr. Goff's testimony could conclude that the evidence preceding the researchers' March 1987 testing might suffice, under the applicable standard, to corroborate Dr. Goff's suspicions about the two mutants, the Federal Circuit vacated the District Court's invalidity judgment and remanded the case for further proceedings.

Invitrogen Corp. v. Clontech Lab., Inc. (Fed. Cir. 2005)
Panel: Chief Judge Michel and Circuit Judges Rader and Gajarsa
Opinion by Circuit Judge Gajarsa

This article was originally published on Patently-O on November 20, 2005.

Ex parte Bandman (B.P.A.I. 2004)

    By Donald Zuhn --

In an appeal from a final rejection of claims 3, 6, 7, 9, and 12 of U.S. Application No. 09/915,694, the Board of Patent Appeals and Interferences reversed the rejection of the claims under both the written description and enablement requirements of 35 U.S.C. § 112, first paragraph, and entered a new ground of rejection under 35 U.S.C. § 112, second paragraph, for claim 12.

Claims 3 and 12 of the '694 application, which were representative of the subject matter on appeal, recite, inter alia, an isolated polynucleotide encoding a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 1 (claim 3) and an isolated polynucleotide comprising a naturally occurring polynucleotide sequence at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 (claim 12).

The Examiner had rejected claims 3, 6, 7, 9, and 12 for failing to comply with the written description requirement, asserting that the specification provides only a single representative species -- the polynucleotide of SEQ ID NO: 2, and fails to disclose any structure-function relationship in this species.  The Examiner had also rejected claims 3, 6, 7, 9, and 12 for failing to comply with the enablement requirement, asserting that because the specification does not teach the specific amino acids and structural motifs in the proteins encoded by the claimed polynucleotides that are essential for protein activity (specifically, malate dehydrogenase activity), the amount of experimentation required to make the claimed polynucleotides was undue.  Appellants contended that because the claims at issue recite polynucleotides having a naturally occurring polynucleotide sequence, or that encode a polypeptide having a naturally occurring amino acid sequence, "through the process of natural selection, nature will have determined the appropriate amino acid sequences [i.e., those retaining malate dehydrogenase activity]."

With regard to the written description rejection, the Board noted that "[t]he written description requirement . . . does not require a description of the complete structure of every species with a chemical genus" (Ex parte Bandman, No. 2004-2319, slip op. at 3 (B.P.A.I. January 6, 2005)).  The Board also compared the circumstances of the instant case with those faced by the Federal Circuit in Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316 (Fed. Cir. 2002).  In Enzo Biochem, the Federal Circuit determined that an "[a]dequate written description may be present for a genus of nucleic acids based on their hybridization properties, 'if they hybridize under highly stringent conditions to known sequences because such conditions dictate that all species within the genus will be structurally similar'" (Ex parte Bandman, No. 2004-2319, slip op. at 4 (B.P.A.I. January 6, 2005) (citing Enzo Biochem, Inc., 296 F.3d at 1327)).  In the instant case, the Board determined that the genus of molecules defined by the claims was similarly limited and reversed the Examiner's written description rejection.

With regard to the enablement rejection, the Board disagreed with the Examiner's assertion that in order to satisfy this requirement, the specification must provide guidance regarding the specific amino acid residues that are tolerant to change without affecting malate dehydrogenase activity.  Instead, the Board deemed persuasive Appellants' argument that because the claims were limited to naturally occurring sequences, nature will have determined the amino acid residues that are tolerant to change (i.e., naturally occurring variants will presumably retain malate dehydrogenase activity).  In particular, in reversing the Examiner's enablement rejection, the Board determined that the Examiner had not provided sufficient evidence that a naturally occurring polypeptide that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or a polypeptide encoded by a naturally occurring polynucleotide sequence that is at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 would not retain malate dehydrogenase activity.

Although the Board reversed both the written description and enablement rejections, it also entered a new ground of rejection for claim 12 under 35 U.S.C. § 112, second paragraph.  The Board found that the specification provided no guidance that would allow one of ordinary skill in the art to determine, with a reasonable degree of confidence, whether a polynucleotide sequence that is at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 occurs naturally.  The Board concluded that the metes and bounds of claim 12 were unclear, and therefore, that the claim was indefinite.

Ex parte Bandman (B.P.A.I. 2004)
Panel: Administrative Patent Judges Smith, Grimes, and Green
Opinion by Administrative Patent Judge Green

This article was originally published on Patently-O on June 14, 2005.

In re Fisher: EST Utility Redux

    By Donald Zuhn --

On Tuesday, the Federal Circuit will hear In re Fisher, in which the Court will address the utility requirement for the first time since the Patent Office set forth revised Utility Examination Guidelines in January 2001.  Specifically, in Fisher, the issue of patentable utility is being raised with respect to nucleic acid molecules.  In commenting on the possible importance of this case, Harold Wegner has described Fisher as having "the potential of being either the single most important pharmaceutical patent case in recent years - or a yawn."  Amicus briefs filed by such well-known biotech and pharmaceutical companies as Affymetrix, Eli Lilly, and Genentech in support of the Board's decision in Ex parte Fisher suggest that it may be the former as opposed to the latter.

The particular controversy presented in Fisher can be traced back as far as 1991, when a group of NIH investigators led by J. Craig Venter sought to protect thousands of DNA sequences corresponding to portions of expressed genes.  Venter called these gene fragments expressed sequence tags, or ESTs.  Venter's group sought to protect not only the ESTs themselves, but also the full-length sequences from which the ESTs were derived and the protein products encoded by the full-length sequences, without first determining the biological function of the encoded protein products.  In several applications filed on its ESTs, the NIH asserted a number of utilities, including the design of oligonucleotides for use in chromosomal analysis, PCR amplification, and recovering the corresponding full-length gene.  After receiving a second rejection on its initial filing, the NIH abruptly abandoned its attempts to protect the ESTs, and withdrew all of its pending EST applications from consideration.

While the withdrawal of these applications temporarily quieted the debate surrounding EST patentability, the Patent Office again stoked the fires of controversy in 1995, when it published new Utility Examination Guidelines.  The new Guidelines removed some of the obstacles to EST patenting by only requiring that an applicant assert a utility that was "specific" and "credible."  The new Guidelines had thus omitted the requirement that the assertion of utility also be "substantial," as set forth by the Supreme Court in 1966 in Brenner v. Manson.  In 1997, the Patent Office further declared that since ESTs were acknowledged to have utility apart from the full-length sequences from which they were derived, an applicant would no longer be prevented from securing protection for an EST by the failure to specify the function of the full-length sequence from which that EST was derived.

The Patent Office reversed course again in 2001 when it publishing revised Utility Examination Guidelines, reinstating the Brenner substantial utility prong.  The revised Guidelines now required that an applicant assert a specific and substantial utility for the claimed invention that would be considered credible by a person of ordinary skill in the art.  The Patent Office also issued Revised Interim Utility Guidelines Training Materials, which provided Examples indicating how the revised Guidelines were to be applied to thirteen different types of biochemical subject matter, including ESTs, as well as definitions of the three utility prongs.  In particular, the Training Materials defined "specific utility" as utility that is specific to the subject matter claimed, as contrasted with a general utility that would be applicable to the broad class of the invention; "substantial utility" as utility having a "real world" use; and "credible utility" as utility that is believable to a person of ordinary skill in the art based on the totality of evidence and reasoning provided.

In the appeal to be heard Tuesday, Appellants Dane Fisher and Raghunath Lalgudi (employees of Monsanto Co., the real party in interest) seek to reverse the Board's decision affirming the final rejection of a claim directed to five ESTs isolated from maize leaf tissue.  The five ESTs constitute only a small portion of the 4,013 sequences that Appellants originally claimed and an even smaller portion of the 32,236 sequences that Appellants disclosed in their application.  Appellants also asserted a number of utilities for the claimed ESTs in their application, including the use of the ESTs to identify polymorphisms (i.e., alternate forms, or alleles, of the claimed sequences), to design oligonucleotide probes or primers for use in isolating DNA sequences from other plants and organisms, and to measure mRNA expression levels in plant cells using microarray technology.

The Board, in Ex parte Fisher, analyzed Brenner and subsequent CCPA and CAFC decisions in In re Kirk, In re Ziegler, In re Jolles, Cross v. Iizuka, and In re Brana, and determined that "[r]ather than setting a de minimis standard, Section 101 requires a utility that is 'substantial'," or in the words of the Brenner court, "one that provides a specific benefit in currently available form."  The Board then examined Appellants' asserted utilities and determined that none of the claimed ESTs provided a specific benefit in its currently available form.  In particular, with regard to Appellants' assertion that the claimed ESTs could be used to measure mRNA expression levels in plant cells using microarray technology, the Board declared that "the asserted utility of the claimed nucleic acid - as one component of an assay for monitoring gene expression - does not satisfy the utility requirement of Section 101."

In briefing the issues before the Federal Circuit, Appellants argue that the Board erred in concluding that an EST is "subject to a heightened standard of utility . . . that hinges upon some undefined 'spectrum' of knowledge about the function of the gene that corresponds to the EST."  Appellants also contend that the Board erred in concluding that the claimed ESTs lack patentable utility "despite the undisputed existence of eight scientifically useful applications for the claimed ESTs and a commercially successful industry built upon the sale and licensing of ESTs corresponding to genes of unknown function, just like those at issue here."  In arguing against the Patent Office's application of a "heightened standard" of utility in this case, Appellants note that the Patent Office has set forth "three substantially different constructions of the utility standard over the last decade alone," and that the Board has adopted a test "so ambiguous and impracticable that even the PTO cannot articulate with any reasonable certainty when the claimed ESTs - or any other EST - might be entitled to patent protection."  Appellants also contend that the Patent Office has applied the wrong test in determining whether there is an assertion of specific utility, since "the specific utility prong only requires the existence of an identifiable benefit for the claimed invention; it does not require a benefit that is unique to the claimed invention."

The Patent Office, on the other hand, denies that Appellants' ESTs have been subjected to a heightened standard, arguing instead that Appellants merely failed to assert a specific and substantial utility for the claimed ESTs that would be considered credible by a person of ordinary skill in the art.  In its brief, the Patent Office often focuses on Appellants' failure to satisfy the specific utility prong, arguing, for example, that Appellants' asserted utilities "would apply not only to the over 32,000 ESTs Fisher discloses, and to the over 600,000 ESTs disclosed in Monsanto's [six] related appeals, but also to any ESTs derived from any organism."  In particular, the Patent Office counters Appellants' argument that because each EST only specifically binds to its complement, the specific sequence of each EST makes its use as a probe or primer specific, by stating that "there is no specific reason for using the EST to bind its complement," and therefore, "[t]o the extent that more sequence data could be acquired by using the ESTs as probes, that result would likely be true for any scrap of DNA derived from nature."  Finally, in responding to Appellants' assertion that ESTs have a real world value as part of a multi-billion dollar industry, the Patent Office contends that "batches of ESTs of unknown significance are sold for the purpose of finding targets worthy of further development, not because the individual ESTs have any specific currently available benefit."

Dr. Zuhn's article "DNA Patentability: Shutting the Door to the Utility Requirement," which was published in the summer 2001 issue of the John Marshall Law Review, contains a more thorough discussion of the history of the utility requirement, particularly with respect to DNA sequences.

This article was originally published on Patently-O on May 2, 2005.

In re Crish (Fed. Cir. 2004)

    By Donald Zuhn --

In an appeal from a decision of the Board of Patent Appeals and Interferences, the Federal Circuit affirmed the rejection of claims directed to purified DNA molecules having promoter activity for the human involucrin gene (hINV) as unpatentable under 35 U.S.C. § 102(b).

After isolating and sequencing the promoter sequence for hINV in the plasmid pSP64λI-3 H6B, Appellants pursued claims directed to specific portions of the promoter sequence having promoter activity.  The claims were rejected under § 102(b) as being anticipated by one of Appellants' own publications, disclosing the approximate size and structure -- but not the sequence -- of the hINV promoter, and by a second publication, disclosing protein-binding sites on the hINV promoter.  In Appellants' own publication the plasmid pSP64λI-3 H6B was used to determine the structure of the hINV promoter, while in the second publication the plasmid pSP64λI-3 H/Hc was used to identify protein-binding sites on the hINV promoter.  Appellants appealed the Examiner's final rejection to the Board.

Appellants first asserted that even if the publications cited against their application used plasmids containing the same hINV promoter region, other workers had sequenced the hINV promoter region in the plasmid pSP64λI-3 H6B, and had obtained a sequence that differed significantly from the promoter sequence described in Appellants' application.  In addition, Appellants asserted that because neither prior art publication specifically disclosed the nucleotide sequence recited in their application, neither publication could anticipate their application.  The Board affirmed the Examiner's final rejection, concluding that Appellants had failed to demonstrate that the plasmids used in the prior art publications possessed hINV promoter sequences that differed from the sequence described in Appellants' application.  The Board also determined that although neither prior art publication disclosed the hINV promoter sequence, the plasmids described in each publication necessarily possessed an hINV promoter sequence that was identical to the sequence described in Appellants' application.

In affirming the Board's decision, the Federal Circuit determined that the Board had reasonably concluded that the plasmids used in Appellants' prior publication and in Appellants' application were identical.  The Court next concluded, in addressing Appellants' first assertion, that it was irrelevant whether other workers had obtained a different sequence for the promoter region of hINV since Appellants could not rely upon the inability of another worker to correctly sequence the promoter region of the hINV gene from plasmid pSP64λI-3 H6B when they had accurately sequenced the promoter region themselves.  Finally, with regard to Appellants' second assertion, the CAFC determined that "[Appellants'] characterization that the pending claims cover a novel DNA sequence having promoter activity, whereas the references disclose only the starting material plasmid, is unsound," since "[t]he starting material plasmid necessarily contains the gene of interest, including the promoter region."

In re Crish (Fed. Cir. 2004)
Panel: Chief Judge Mayer and Circuit Judges Lourie and Dyk
Opinion by Circuit Judge Lourie

This article was originally published on Patently-O on January 3, 2005.

In re Wallach (Fed. Cir. 2004)

    By Donald Zuhn --

In an appeal from a decision of the Board of Patent Appeals and Interferences, the Federal Circuit affirmed the rejection of claims directed to isolated DNA molecules encoding TNF binding protein II (TBP-II) under the written description requirement of 35 U.S.C. § 112.

Appellants had purified TBP-II from urine and determined (a) the amino acid sequence of an N-terminal portion of the protein, (b) the protein's molecular weight, and (c) that the protein inhibited TNF activity.  Appellants then pursued, in separate divisional applications, claims directed to proteins having the partial sequence, molecular weight, and inhibitory activity described and claims directed to isolated DNA molecules encoding such proteins.  The DNA claims were rejected under § 112 as lacking an adequate written description in the specification.  Appellants appealed to the Board, which affirmed.

Appellants asserted that because the PTO had effectively conceded that claims to the TBP-II protein were adequately described in the specification, the claims to isolated DNA molecules encoding the TBP-II protein were therefore adequately described in the specification.  Specifically, Appellants argued that because the complete amino acid sequence of a protein is an inherent property of an isolated, fully characterized protein, and the determination of a protein's complete amino acid sequence puts one in possession of all DNA sequences encoding that protein (as a result of the unequivocal correspondence between amino acids and DNA codons in the genetic code), Appellants' full characterization of TBP-II (i.e., determination of its N-terminal amino acid sequence, molecular weight, and inhibitory activity) demonstrated possession of all DNA sequences encoding TBP-II.  The PTO countered that because Appellants' specification included neither the complete amino acid sequence of TBP-II nor any actual DNA sequence, and disclosed the sequence of only ten of the 185-192 amino acids that make up TBP-II, Appellants had not demonstrated possession of all DNA sequences encoding TBP-II.

The Federal Circuit noted that while "the state of the art has developed such that the complete amino acid sequence of a protein may put one in possession of the genus of DNA sequences encoding it," Appellants had not disclosed the complete amino acid sequence of TBP-II, but rather, had provided only a partial sequence of the protein.  In addition, the Court concluded that Appellants' possession of TBP-II "says nothing about whether they were in possession of the protein's amino acid sequence [since] Appellants have not provided any evidence that the full amino acid sequence of a protein can be deduced from a partial sequence and the limited additional physical characteristics that they have identified."  With respect to the DNA claims at issue, the CAFC determined that absent a description of the complete TBP-II amino acid sequence or any evidence of a "known or disclosed correlation between the combination of a partial structure of a protein, the protein's biological activity, and the protein's molecular weight, on the one hand, and the structure of the DNA encoding the protein on the other," the Board's decision to affirm the rejection of Appellants' DNA claims was proper.

In re Wallach (Fed. Cir. 2004)
Panel: Chief Judge Mayer and Circuit Judges Lourie and Gajarsa
Opinion by Circuit Judge Lourie

This article was originally published on Patently-O on August 11, 2004.

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