By Kevin E. Noonan —

The American Intellectual Property Law Association (AIPLA) filed an amicus brief in the Myriad case (Association of Molecular Pathology v. U.S. Patent and Trademark Office), in support of neither party but advocating reversal.  While making many of the arguments made by Myriad and other amici, the brief contains at least one definitive (albeit prescient) rebuttal of the arguments made by the Justice Department in its ill-advised brief (see "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief").

The brief presents the questions of 1) whether "purified, isolated DNA" ("transformed in structure and function from native DNA at great cost through significant human effort that identified them as being associated with an increased risk of certain cancers") should be deemed patent-ineligible as a "product of nature"; 2) whether genetic diagnostic method claims should be deemed patent-ineligible as being "nothing more than scientific principles or abstract mental steps"; and 3) whether "potential customers and their related associations" have standing to bring a declaratory judgment action of patent invalidity that would permit third party providers to sell "potentially infringing goods and services that the potential customers may wish to purchase?"  Before answering these questions, the brief sets forth several policy reasons why they should all be answered in the negative.  These include the benefits to the U.S. populace and economy provided by strong patent protection, and the historical understanding of the value of patents in American history (citing Jefferson and Lincoln).  The brief relates these historical antecedents with the current controversy by pointing out that the patent system has provided strong economic incentives to biotechnology and the development of treatments for diseases like cancer, "that have eluded effective treatments for generations, despite the dedicated effort of the medical, scientific, and other interested communities."  These interests, the brief argues, were ignored by the District Court, in a decision that "threatens more than just the members of the biotechnology industry whose business depends on purified/isolated DNA molecule patents."  The outcome is contrary to the Constitutional mandate, AIPLA argues, which is sufficient reason for the Federal Circuit to reverse.

Citing Bilski v. Kappos, the brief argues that Congress "has envisioned Section 101 as broad, flexible, and adaptable to new technologies and advances in knowledge," a stance extending from Jefferson at the beginning of the Republic through Diamond v. Chakrabarty, to today.  The beneficiary, AIPLA agues, has been the public, both from the invention itself (be it a "'better mousetrap' or a breakthrough in advanced medical science") as well as the general economic benefits of prosperity through a patent's role in "inspiring entrepreneurship, putting investment capital in the hands of innovators, and stimulating employment."  Patents make innovation "contagious," the brief argues, by dint of the required disclosure of the claimed invention, the "quid pro quo" that makes the disclosure available to competing innovators, "who can then use the patent disclosure to push the frontiers of science even further."  And the brief mentions the oft-forgotten (or disregarded) feature of patents that they expire, so that thereafter "all are free to enjoy, commercialize, and improve the claimed inventions."  In contrast to these advantages, the brief argues that the District Court's decision would have a "profound negative impact" on biotechnology if not reversed.  The brief uses to support this contention the powerful example of the effects on the stock market of some ill-considered words by a White House spokesman in 2000, that the U.S. and Great Britain would act to limit patent protection for the fruits of the Human Genome Project, which caused the stocks in "two relevant [genomics] companies" to plummet by 25-30%.  The District Court's decision represents a "step backward" based, in part, on the "visceral reaction" against corporate ownership of "one's personal genetic makeup" — something that gene patenting does not provide, they are quick to point out.

AIPLA's argument focuses on the utility of isolated DNA as a tool for "allow[ing] health care practitioners to identify individuals at significant risk of breast and ovarian cancer, tailor existing treatment options to ensure the highest likelihood of therapeutic success, and develop new anti-cancer treatments specifically designed to combat these devastating diseases."  These are "real-world" benefits that the patent laws were intended to promote, argues the brief.  Importantly, patent policies consistent with the Constitution are "blind to the raw materials from which significant technological advances spring."  Isolated DNA does not fall within the "few narrow exceptions" to patent-eligibility (laws of nature, natural phenomena and abstract ideas).  (The brief cites the precautionary injunction from Bilski that "[t]hose exceptions do not 'give[] the Judiciary carte blanche to impose other limitations that are inconsistent with the text and the statute's purpose and design.'")  The brief cites precedent — adrenaline and prostaglandins — for the principle that "naturally-occurring biological substances" that have been isolated and purified "to give them different characteristics and uses" is sufficient for such "natural products" to be eligible for patenting.  Insofar as there is a "products of nature" exception, the brief cites In re Bergy (and Judge Giles Sutherland Rich) for the principle that it is limited to "something preexisting and merely plucked from the earth and claimed as such."  Provided that the "product of nature" is rendered different from the natural product as it exists in nature "in some structural and functional manner as a result of human effort and ingenuity" it is patent-eligible, according to the AIPLA's reading of the relevant case law.

Under this standard, isolated and purified DNA molecules are patent-eligible according to the brief.  As claimed, they are "new chemical compounds that do not exist in nature and have been adapted for new uses as diagnostic tools and probes."  The brief grounds this argument in the new utility of the isolated DNA, therein "[a]rmed with knowledge resulting from the use of the claimed purified/isolated DNA molecules in the claimed methods, cancer patients can determine whether or not to undergo certain medical procedures, and healthy individuals can opt for preventative techniques that may ward off the onset of cancer," supporting this analysis by Judge Rich's statements in Bergy that the bacterial cultures were required for the practice of the indisputably patent-eligible methods for producing lincomycin.  The brief then cites the District Court opinion that there was "[u]ndisputed evidence" that the isolated DNA was a chemical compound that was structurally and functionally different from DNA as it exists as a component of a chromosome.  Accordingly, AIPLA argues, these differences were enough to impart patent-eligibility on isolated human DNA.

The brief particularly points out that the District Court focused on the similarities between isolated DNA and DNA in its unisolated state in a chromosome of the "essential characteristics" (the infamous "physical embodiment of [genetic] information" standard) rather than the differences between isolated and native DNA.  There is "no legal basis" for thus "arbitrarily and categorically excluding such DNA-derived invention" from patent-eligibility.  The brief argues that the "shared essential characteristics" test cannot stand, since there will always be some similarities between a product derived from nature and the "natural product," and thus that patent-eligibility would always fail by focusing on the similarities rather than the differences:  "it therefore becomes all too easy to focus on one shared characteristic, while ignoring all the other differences, even salient, fundamental differences."  And of course it is all too easy to "cherry-pick" these properties, rather than consider the claims "as a whole" (the proper standard).  The brief argues that the District Court "selectively assign[ed] dispositive importance to one shared characteristic of the claimed purified/isolated DNA molecules and discount[ed] all the differences" in arriving at its decision, an analytical process rejected by the Bergy Court (which precedent is binding on the Federal Circuit unless and until overturned by the en banc Court).

The brief also argues that the District Court improperly granted summary judgment, since the question of whether isolated DNA was "transformed from their natural state to possess a different structure and new function" was a genuine issue of material fact when "all reasonable inferences [are decided] in favor of the non-movant Myriad."

Turning to the method claims, the brief argues that the District Court misapplied Bilski, particularly in view of the Supreme Court's clarification as to the role of the "machine-or-transformation" test in deciding patent eligibility of method claims.  The question is whether Myriad's claims completely preempt an abstract idea, and AIPLA argues they do not.  Rather, the method claims at issue are "applications[s] of a law of nature" consistent with the Supreme Court's holding in Diamond v. Diehr, "utiliz[ing natural processes] in a series of specific steps" that constitute patent-eligible subject matter, citing Prometheus Labs, Inc. v. Mayo Collaborative Servs.  In addition, the brief asserts that the method claims "inextricably" depend on the isolated DNA which require "substantial physical and chemical transformations" that would satisfy the Bilski test.  The brief sets forth the steps required to practice the method claims of U.S. Patent Nos. 5,710,001; 5,709,999; 5,753,441; and 6,033,857, which include "the transformative steps of drawing blood or removing a tissue sample from a subject, extracting BRCA DNA or RNA from the biological sample, and detecting alterations in the subject's BRCA nucleotide sequence in order to analyze the BRCA DNA, RNA or cDNA made from an mRNA of the sample."  Regarding the extent of transformation, "the extraction process radically alters the structure and function of the native DNA, creating a new chemical compound that does not exist in nature."  Even the comparison steps are transformative:  "such comparisons cannot be made by the naked eye but instead require sophisticated biotechnological methods of sequencing nucleic acids and/or detecting alterations that involve chemical or physical transformation."  The case for patent-eligibility of the screening method claim of U.S. Patent No. 5,747,282 is even easier to make, wherein the brief recites that "administration of a potential cancer therapeutic to a cell that contains an altered BRCA gene involves both the insertion of that gene into a cell and the biological effect of the test agent on cell growth."  Thus, even under the Federal Circuit's more restrictive "machine or transformation" test, the brief argues, Myriad's method claims are patent-eligible because they do not merely recite "only [] the abstract mental process of 'comparing' or 'analyzing' gene sequences" as the District Court had erroneously determined.

The brief then makes several policy arguments why the Federal Circuit should reverse the District Court's decision.  These include the principle that courts should not lightly "adopt[] changes that disrupt the settled expectations of the inventing community," citing Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 28 (1997).  Congress is the proper venue for plaintiffs to effect changes in the Patent Law, not the courts, because "[f]undamental alterations in these rules risk destroying the legitimate expectations of inventors in their property.  Id."  "To change so substantially the rules of the game now could very well subvert the various balances the PTO sought to strike when issuing the numerous patents which have not yet expired and which would be affected by our decision," citing Festo.

It is here that the brief presciently provides the most succinct answer to the DOJ's wrong-headed foray into the unfamiliar waters of patent law.  It arises in Footnote 19, which discusses President Clinton's attempts to forestall the highly negative effects of White House remarks that patent protection would not be available for the products of the Human Genome Project:

In a widely publicized comment, President Clinton noted that the people "with the skills and the experience to draw the line in the right place" were in a position to formulate criteria for patent-eligibility of gene-based inventions.  BIO Praises Clinton Reassurances Regarding Gene Patents and PTO Leadership, BIOTECH Patent News (Apr. 1, 2000), available at http://www.allbusiness.comltechnology 538104-1.html.  Indeed, the government agency specifically charged with that task, the Patent Office, has in fact already drawn that line in the right place, in its Utility Examination Guidelines.

It bears repeating:  "the government agency specifically charged with that task, the Patent Office, has already in fact drawn that line in the right place."  This argument, while not specifically developed in the brief, adds yet another reason to reverse the District Court:  failure to find that the Office's grant of "gene patents" was arbitrary and capricious agency action, thereby not entitled to Chevron deference in the exercise of its particular area of expertise.

Similarly, the brief argues that it is Congress, not the courts, that is the proper venue for arguing the "moral and ethical policy considerations" underlying the plaintiffs' challenge to patenting isolated DNA.  "[W]hile important," these issues "go beyond the social objective set forth [in the Patent Clause of the Constitution]" they argue.  This principle is even more applicable in instances, such as here, where Congress has spoken, broadly, on the scope of patent-eligible subject matter:  in such instances, "the courts should not arbitrarily narrow the scope of the patent laws based on their own balancing of ethical and moral considerations."  Here, the AIPLA argues that the District Court raised the concerns of "certain segments of the public who claim they might be adversely affected by the patents' existence" over the "rewards to society as a whole from encouraging progress in science and technology" that results from "the limited exclusionary power of patents."  The brief dismisses plaintiffs' complaint that the patents increase costs of patented diagnostic tests as being "a natural — indeed, even intended — consequence of the Framers' decision to provide patents on inventions and discoveries."  To allow such considerations to determine patent eligibility fails to recognize that the patented inventions here are what made the diagnostic tests possible in the first place, the brief argues, reminding the Court that "there has never been a 'medical treatment/diagnostics' exception in the statute," and insofar as Congress has intended to remedy disparities in health care availability, it has enacted laws (Hatch-Waxman and the Biologics Price Competition and Innovation Act are cited) to address these concerns.  (And, the brief notes, Congress did not "abrogate or limit[] the rights of innovators in biotechnological medical advances" in the latter Act.)  Simply put:

Addressing the alleged economic or social impact of Myriad's patents in the context of a patent challenge brought by patients and researchers is to engage in a moral and ethical inquiry that is not the proper subject of the patent statute, but is a matter for the public forum provided by Congress.

Finally, the brief argues that the "customer" plaintiffs (the individual breast cancer patients and their organizations) lacked standing and should have been dismissed from the lawsuit.  Under the "all the circumstances" test of Genentech, Inc. v. MedImmune, Inc., these plaintiffs did not allege actions of sufficient reality and immediacy to bring a declaratory judgment action against Myriad.  None of Myriad's activities were directed to any of these plaintiffs.  At best, their asserted desire to "purchase" the potentially infringing services that the other plaintiffs may provide would make them "at best only potential inducers of infringement," which status is insufficient to confer standing, citing Prasco, LLC v. Medicis Pharm. Corp.  The brief also cites as insufficient the District Court's finding that these plaintiffs "may very well understand the precise nature of, and be prepared to take advantage of, the services of a potential infringer were the latter not prevented from offering those services by a third party's assertion of its patent rights" as satisfying the standing requirement that a party had "undertaken 'meaningful preparation to conduct potentially infringing activity'" under the test enunciated in Cat Tech LLC v. TubeMaster, Inc., 528 F.3d 871, 880 (Fed., Cir. 2008).  "[M]ere contemplation" is not enough, the brief argues because it is "simply too tenuous" a basis for this finding.  Considered with the parties' allegations reversed, the brief argues it is "doubtful" that Myriad would be able to succeed in an action against the consumer plaintiffs for inducing infringement under the facts alleged, arguing that "potential purchasers of non-existent products do not have proper declaratory judgment standing," citing Ours Tech., Inc. v. Data Drive Thru, Inc., 645 F. Supp. 2d 830, 840 (N.D. Cal. 2009).  And while the consumer party plaintiffs "have a worthy and commendable interest in the outcome of this case," Federal Circuit precedent "has long held that the public interest merits of the patentability issues raised in this case do not confer jurisdictional standing," citing Indium Corp. of Am. V. Semi-Alloys Inc., 781 F.2d 879, 884 (Fed. Cir. 1985).

The brief ends with a cogent explication of the dangers presented by the District Court's decision:

In its attempt to be sensitive to the social implications of this case, the District Court impermissibly expanded its declaratory judgment jurisdiction to cover an "advisory opinion" for anyone merely expressing the desire to purchase a patented product or utilize a patent method, including non-existent products and services.  However, this decision, if affirmed, presents a very real concern for other federal courts and patent holders.  The dramatic expansion of federal declaratory judgment jurisdiction to those without a real and immediate interest in the litigation will open all patents to challenge by anyone asserting a "public" interest.  This has never been permitted by the controlling authorities and could not have been the intent of Congress in permitting declaratory judgment actions.

Briefing Update:  Patent Docs has learned of one additional amicus brief that has been filed in this appeal:

• Gilead Sciences, Inc. and BioGenerator, in support of Defendants-Appellants and urging reversal (brief)

We thank our readers for bringing this brief to our attention and note that we are interested in securing copies of any other amicus briefs that may be filed in this appeal.

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

• "IPO Files Amicus Brief in AMP v. USPTO," November 2, 2010
• "AMP v. USPTO — Briefing Update," November 1, 2010
• "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief," October 31, 2010
• "Myriad Files Appeal Brief in AMP v. USPTO," October 28, 2010

By Donald Zuhn —

In an amicus brief filed last Friday with the Federal Circuit in Association of Molecular Pathology v. U.S. Patent and Trademark Office, the Intellectual Property Owners Association (IPO) sets forth the organization's views regarding "two issues of vital importance to the proper functioning of the patent system."  In response to the first issue of how immediate and substantial a controversy must be in order to create declaratory jurisdiction standing sufficient to challenge the validity of a patent, the IPO contends that an actual controversy of sufficient immediacy and reality is required, that such controversy was not present in the instant case, and therefore that the plaintiffs lacked standing in the instant case to bring a declaratory judgment action for invalidity.  With respect to the second issue of whether isolated DNA qualifies as patentable subject matter under 35 U.S.C. § 101, the IPO asserts that it does.  (For the sake of full disclosure, it should be noted that the IPO amicus brief was co-authored by Patent Docs author Kevin Noonan.)

On the issue of standing, the IPO begins by citing Prasco, LLC v. Medicis Pharm. Corp., 537 F.3d 1329, 1339 (Fed. Cir. 2008), for the proposition that "a case or controversy must be based on a real and immediate injury or threat of future injury that is caused by the [patentee]."  The brief next compares the facts in Association of Molecular Pathology with those in Prasco and SanDisk Corp. v. STMicroelectronics, Inc., 480 F.3d 1372 (Fed. Cir. 2007), noting that:

In contrast to the patentee in SanDisk, Myriad has not taken any affirmative action toward the plaintiffs that would create an actual controversy of sufficient immediacy and reality to warrant declaratory judgment jurisdiction.  Like the plaintiffs in Prasco, there is no evidence that Myriad either (i) had any plans to assert its patents against any of the plaintiffs or (ii) had any knowledge that any of the plaintiffs were even considering engaging in any type of infringing activity with respect to the claims at issue.

Addressing cease-and-desist letters sent by Myriad to two of the plaintiffs (Dr. Ostrer and Dr. Kazazian) on May 21, 1998; May 29, 1998; and August 26, 1998, the IPO argues that "these decade-old letters should not be considered to be sufficiently immediate to show a justiciable controversy, particularly when there is no evidence that Myriad has taken any other actions against these two plaintiffs in at least 10 years."  As for the researcher, non-researcher, and organization plaintiffs, the IPO concludes that each group "expressed at most a vague and unsubstantiated notion of being ready to engage in some undefined conduct that may or may not infringe Myriad’s patents at some undetermined time in the future."

The brief contends that the District Court's decision expands declaratory judgment jurisdiction such that "literally anyone might ask any federal court to invalidate any claim of any unexpired patent."  Under the District Court's approach to declaratory judgment jurisdiction:

[A]ny corporation, association or individual might attack almost any patent as a form of protest or to seek leverage against the patentholder.  Indeed, the present case appears to be just such a form of social protest against the principle of gene patents, based on nothing more than an unsubstantiated intent or desire to be free of the commercial constraint of well-established patent rights.

On the issue of the patent-eligibility of isolated DNA, the IPO notes that in Diamond v. Chakrabarty, 447 U.S. 303 (1980), "[t]he [Supreme] Court fashioned a straightforward test of whether a manufacture or composition of matter was patent-eligible:  it must demonstrate the hand of man, something that is 'a product of human ingenuity ‘having a distinctive name, character [and] use.'"  Describing the process by which DNA is "ioslated," the brief explains that:

In isolating the claimed DNA, an inventor typically identifies a cell that expresses a gene, obtains the mRNA from the cell and enzymatically converts it into DNA before it can be isolated.  The enzymatic conversion is performed by a viral enzyme called reverse transcriptase that is absent from cells that have not been infected by a virus that produces the enzyme.  Significantly, DNA copies of mRNAs encoding isolated human DNA do not exist without human intervention, i.e., prior to their synthesis by a researcher.

In view of this process, the IPO contends that claims to isolated human DNA satisfy the Chakrabarty requirement that patent-eligible subject matter show the hand of man.

The IPO argues that the District Court's decision, which concerns human DNA, "applies with equal force to isolated DNA from other organisms," and warns that "[b]anning patenting of isolated DNA from all known organisms would have widespread and deleterious effects on human health, nutrition, and progress."  The IPO also notes that patents on isolated human DNA support the development of biologics, and that "[i]f the district court’s decision that patents on isolated human DNA are directed to patent-ineligible 'natural products,' then biologics perforce would be patent-ineligible as well."  The brief also outlines how the District Court's decision, if affirmed, would adversely impact the personalized medicine industry by removing patents needed to promote investment and development.  Finally, the brief contends that "[a]bsent patent protection [for isolated human DNA and patents on diagnostic uses of genetic information], and under the circumstances of multigenic causation (or at least association) of common diseases, the impetus will be to develop and protect this nascent technology using, inter alia, trade secret protection."  The brief concludes that:

If the standard for patentable subject matter applied by the District Court were adopted, it could render broad categories of important inventions patent-ineligible, including most biologic drugs, antibodies, antibiotics, hormones, metabolites, proteins, and genetically-modified organisms and food.  This in turn would have a devastating effect on the viability of large portions of the biotechnology, pharmaceutical and other industries, industries that are built upon the availability of valid and enforceable patent protection for the fruits of their costly and risky research efforts.

Briefing Update:  Patent Docs has learned of three additional amicus briefs that were filed by last Friday's deadline:

• American Intellectual Property Law Association (AIPLA), in support of reversal, but in support of neither party (brief)
• Christopher M. Holman and Robert Cook-Deegan, in support of neither party (brief)
• Rosetta Genomics, Ltd., Rosetta Genetics, Inc., and George Mason University, in support of Defendants-Appellants, supporting reversal (brief)

We thank our readers for bringing these additional briefs to our attention and note that we are interested in securing copies of any other amicus briefs that may be filed in this appeal.

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

• "AMP v. USPTO — Briefing Update," November 1, 2010
• "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief," October 31, 2010
• "Myriad Files Appeal Brief in AMP v. USPTO," October 28, 2010

By Donald Zuhn —

On October 22, Defendants-Appellants Myriad Genetics, Inc. and ten Directors of the University of Utah Research Foundation filed their brief in Association of Molecular Pathology v. U.S. Patent and Trademark Office (see "Myriad Files Appeal Brief in AMP v. USPTO").  Pursuant to Rules 29(e) and 31(a)(2) of the Federal Rules of Appellate Procedure, amicus curiae briefs in support of Defendants-Appellants were due on Friday, October 29 (7 days after Defendants-Appellants' brief was filed), Plaintiffs-Appellees' brief must be filed within 40 days after Defendants-Appellants' brief is filed (Wednesday, December 1), and amicus curiae briefs in support of Plaintiffs-Appellees (or in support of neither party) must be filed no later than 7 days after Plaintiffs-Appellees' brief is filed (Wednesday, December 8).  As of last Friday's deadline, five amicus briefs have been filed:

• Alnylam Pharmaceuticals, Inc., in support of Defendants-Appellants, supporting reversal (brief)
• Biotechnology Industry Organization (BIO) and the Association of University Technology Managers, supporting reversal (brief)
• Genetic Alliance, supporting reversal, but not in support of either party (brief)
• The Intellectual Property Owners Association (IPO), in support of neither party (brief)
• United States, in support of neither party (brief)

Patent Docs provided a summary of the United States amicus brief on Sunday (see "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief") and we will be providing summaries of the remaining briefs over the next two weeks.  We are also interested in securing copies of any other amicus briefs that may be filed in this appeal.

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

• "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief," October 31, 2010
• "Myriad Files Appeal Brief in AMP v. USPTO," October 28, 2010
• "AMP v. USPTO — Briefing Schedule Update," August 22, 2010
• "Uh-oh: It Looks Like Judge Dyk Has Been Drinking the ACLU's Kool-Aid®," August 11, 2010
• "FCBA Submits Amicus Brief on Motion for Recusal in AMP v. USPTO," August 9, 2010
• "Appellees Move for Recusal of Chief Judge Rader in AMP v. USPTO Appeal," July 19, 2010
• "Facts, Perhaps the Antidote to the Anti-gene Patenting Plague," July 18, 2010
• "AMP v. USPTO after Bilski v. Kappos," July 6, 2010
• "Myriad Appeals AMP v. USPTO Decision," June 16, 2010
• "AMP v. USPTO: What Everyone Else Is Saying – Part II," June 8, 2010
• "AMP v. USPTO: What Everyone Else Is Saying," April 6, 2010
• "'60 Minutes' and 'Newshour' Take Different Apporaches to Covering Gene Patenting Story," April 5, 2010
• "AMP v. USPTO: What the Parties Are Saying About the Decision," April 1, 2010
• "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims," March 30, 2010
• "Round One Goes to the ACLU," March 29, 2010
• "Debating Gene Patents – Round Four," February 10, 2010
• "Newsweek = Newspeak on Gene Patenting," February 8, 2010
• "Everybody Knows — The Boston Globe Weighs in on Gene Patenting," February 1, 2010
• "The USPTO Asks out of Gene Patenting Case (Again)," January 19, 2010
• "Top Stories of 2009: #4 to #1," January 4, 2010
• "Gene Patenting: Australian Potpourri," December 28, 2009
• "Science Progress Article Examines Impact of Gene Patents on Research," December 21, 2009
• "Gene Patenting Debate Continues – Round Three," December 17, 2009
• "BRCA Patent Suit to Continue in Southern District of New York," November 2, 2009
• "Empirical Research Fails to Support Gene Patenting Ban," October 22, 2009
• "The Tragedy of a Bad Idea," August 25, 2009
• "Gene Patenting Debate Continues – Round Two," August 4, 2009
• "The Unwanted Consequences of Banning Gene Patenting," June 16, 2009
• "Falsehoods, Distortions and Outright Lies in the Gene Patenting Debate," June 15, 2009
• "Gene Patenting Debate Continues," June 9, 2009
• "Association for Molecular Pathology v. U.S. Patent and Trademark Office," May 17, 2009
• "Court Report: Special Edition," May 13, 2009

By Kevin E. Noonan —

The United States government (or at least that part of it constituting the Department of Justice) has filed an amicus curiae brief in the AMP v. USPTO case (Myriad) in which it advocates a change in policy regarding the patent-eligibility of isolated genomic DNA.  Written by two DOJ officers with little evident background in science, technology, or patent law (there are no USPTO lawyers on the brief), the brief makes a distinction between isolated DNA that is the subject of "human manipulation" (such as cDNA) that it argues is patent-eligible, and human DNA that has been merely "isolated," which should not be.  While seemingly poised to mollify (if not satisfy) all parties to the dispute, the seeming ignorance of the consequences of the patent-eligibility criteria espoused by the government on a wide range of fields important to "the national economy, to medical science, and to the public health" is disturbing as well as contrary to sound patent policy.

The brief characterizes the questions presented as (1) whether "human-engineered DNA molecules, such as cDNAs, are patent-eligible subject matter," and (2) whether "isolated but otherwise unmodified genomic DNA is patent-eligible subject matter."  These questions are not the ones presented to the Federal Circuit, if only because the District Court made no such distinction in its decision below:  isolated human DNA was not patent-eligible, according to the District Court, because it is "the physical embodiment of genetic] information."  The particular pin the DOJ has constructed upon which its rhetorical angels dance has no basis in the issues before the Federal Circuit.

One hint of where the DOJ went astray is evident in its discussion of molecular biology, where it explains that:

DNA can be extracted from the natural cellular environment in which it occurs through established laboratory techniques . . . .  A particular segment of DNA of interest, such as a gene, can then be excised from the extracted material.  The result of this laboratory process — a DNA molecule excised from the genome and separated from its cellular environment — is commonly termed "isolated DNA."

While on its face not manifestly incorrect, the simple phrase "through established laboratory techniques" ignores and trivializes the nature of what it takes to isolate human DNA that encode particular genes.  This is an error that at various times the USPTO and the Federal Circuit have made, but in the context of the brief's conclusions it is the basis for the fundamental misunderstanding that permits the DOJ to place the modifier "merely" before "isolated human genomic DNA."  The wide-ranging effect of this error is found immediately after this "explanation" of the process of isolating DNA, where as an example of such "merely" isolated genomic DNA the brief cites U.S. Patent No. 4,472,502, which claims a gene from Lactobacillus.  Perhaps the brief writers are not aware that bacteria and other microorganisms do not have their genes split into introns and exons as mammalian genes are.  The consequence of this ignorance is that in the regime they espouse, isolated DNA from microorganisms would perforce not be patentable, because it was merely "isolated."  While not relevant to the '502 patent (which long ago expired), what will be the effect on the economics of producing vaccines for the next pathogenic outbreak if the DNA comprising the vaccine cannot be protected?  The brief writers are clearly ignorant of the existence of the question, much less capable of proposing an answer.

The brief properly castigates the District Court for "erroneously cast[ing] doubt on the patent-eligibility of a broad range of manmade compositions of matter whose value derives from the information encoding capacity of DNA," specifically reciting "cDNAs, vectors, recombinant plasmids, and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops, created with the aid of such molecules — [they] are in every meaningful sense the fruits of human ingenuity and thus qualify as 'human-made inventions' eligible for patent protection under section 101," citing J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int'l, Inc., 534 U.S. 124, 130 (2001) (quoting Diamond v. Chakrabarty, 447 U.S. 303, 313 (1980)).  The "hand of man" is sufficiently evident for the government that such claims are patent-eligible.

The brief then goes on to argue that the District Court was correct in finding "that genomic DNA that has merely been isolated from the human body, without further alteration or manipulation, is not patent-eligible," based on the rationale that the unique chain of chemical base pairs that induces a human cell to express a BRCA protein is not a "human-made invention."  The brief also states that the "fact" that a disease is associated with a particular mutation is also not patent-eligible, being "simply a law of nature."  It must be noted that, like the District Court, the government's brief confuses a claim to a method for detecting the existence of a natural phenomenon with a claim to the phenomenon itself.  Also, Myriad's claims were further directed to a specific utility — identifying women at increased risk for breast or ovarian cancer — that is outside what was available in nature (i.e., the mutation existed but neither the women nor anyone who could therapeutically intervene was aware of it until the mutation was identified).  And in keeping with much of the debate on this issue, the government's conclusion is "supported" by an inapt analogy:  that isolated DNA is "no less a product of nature when that structure is 'isolated' from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth."  Which would be true, if isolated DNA was anything like cotton or coal, which of course it is not.  Similarly, the brief argues that chemical elements like lithium, pure ductile tungsten, uranium, and vanadium are not patent-eligible despite the fact that they do not occur naturally.  But isolated DNA is more similar to isolated and purified erythropoietin, or lincomycin, or adrenaline, purified preparations of which are and always have been eligible for patenting.

More apt are decisions of the Commissioner and Board regarding pine needle fibers and whatever was isolated in the Ex parte Berkman case, but the brief seems just as happy to agree with ancient PTO decisions as it is to disagree with the PTO's decision that isolated genomic DNA is patent-eligible (and, as the brief admits, after a statutorily-required notice and comment that fully addressed this issue directly and specifically, rather than being applied far after the fact on other "natural products").

The brief attempts to point out all the things that, in the brief writers' views remain patent-eligible if the line of demarcation should be drawn according to their inclination.  Thus, "[n]ew and useful methods of identifying, isolating, extracting, or using genes and genetic information may be patented (subject to the prohibition against patenting abstract ideas), as may nearly any man-made transformation or manipulation of the raw materials of the genome, such as cDNAs. . . .  Thus, the patent laws embrace gene replacement therapies, engineered biologic drugs, methods of modifying the properties of plants or generating biofuels, and similar advanced applications of biotechnology."  But what would qualify as an "engineered" biologic drug, if the touchstone of making such drugs is for them to be as similar to the protein as possible as it exists in nature?  The problem with their approach comes in the following sentence:  "[c]rossing the threshold of section 101, however, requires something more than identifying and isolating what has always existed in nature, no matter how difficult or useful that discovery may be."  Besides their own prejudices, the brief writers do not explain why, nor do they explain (if they are even aware) of the broad swath of heretofore patentable inventions would fall outside the scope of patent-eligibility using the same reasoning.

Insofar as it exhibits reasoning, the brief bases its argument on the idea, unsupported in the case law, that "products of nature" are not patent-eligible.  As many on this side of the debate have done before them, the brief bases its argument on Funk Bros. v. Kalo Inoculant Co., 333 U.S. 127 (1948).  Arguably overruled, or at least distinguished by the Supreme Court's Chakrabarty decision, the brief further cites the J.E.M. Ag Supply case for its "products of nature" argument, despite the fact that there the question was whether Congress had included plants within the ambit of utility patent protection (which is not the same issue the brief cites the case to support).  Regarding Funk Bros., it is informative to review Justice Frankfurter's concurring opinion for a fuller understanding of the reasoning behind Justice Douglas's majority opinion.  According to Justice Frankfurter:

Insofar as the court below concluded that the packaging of a particular mixture of compatible strains is an invention and as such patentable, I agree, provided not only that a new and useful property results from their combination, but also that the particular strains are identifiable and adequately identified.  I do not find that Bond's combination of strains satisfies these requirements.  The strains by which Bond secured compatibility are not identified and are identifiable only by their compatibility.  . . .  [The patentee] appears to claim that since he was the originator of the idea that there might be mutually compatible strains and had practically demonstrated that some such strains exist, everyone else is forbidden to use a combination of strains whether they are or are not identical with the combinations that Bond selected and packaged together.  It was this claim that, as I understand it, the District Court found not to be patentable, but which, if valid, had been infringed.  . . .  The consequences of such a conclusion call for its rejection.  Its acceptance would require, for instance in the field of alloys, that if one discovered a particular mixture of metals, which when alloyed had some particular desirable properties, he could patent not merely this particular mixture but the idea of alloying metals for this purpose, and thus exclude everyone else from contriving some other combination of metals which, when alloyed, had the same desirable properties.  In patenting an alloy, I assume that both the qualities of the product and its specific composition would need to be specified.  The strains that Bond put together in the product which he patented can be specified only by the properties of the mixture.

Id. at 133-34 (emphasis added).

This is the "phenomenon of nature" that the Funk Bros. Court held unpatentable:  a broad claim to any combination of these bacteria that had the desired properties.  As such, it is completely consistent with cases like O'Reilly v. Morse, where the Court precluded from patentability any application of electromagnetism for transmitting signals.  The Court properly proscribed from patentability such overbroad claims to what an inventor had not invented; these cases do not stand for a broad "product of nature" prohibition unless willfully misinterpreted.

The brief is replete with reasons why "mere" purification should not be sufficient to render a composition of matter patent-eligible, but they all are grounded in the idea that man has not created a "product of nature" and hence is not an inventor.  As Judge Rich pointed out in In re Bergy, this analysis misses the point:  by isolating something new and useful from nature, man provides the benefits required by the Constitution for the exercise of the Congressional power to grant a patent:  to "promote the Progress of Science and the Useful Arts."  The question is not whether anyone thinks that there is sufficient "invention" in a particular composition of matter or manufacture.  To be patent-eligible, the Constitutional requirements are what is required and all that is required (outside the bounds the Supreme Court has set for natural law, abstract ideas, and phenomena of nature).  A "natural product" may reflect natural law or phenomena of nature (but that is not surprising since all we have is nature) but that is not the same as claiming the phenomenon or natural law.

The brief makes no attempt to ignore or deny that this is a change in policy, noting that both the PTO and the NIH have granted or sought patents on isolated DNA.  However, it has likely not escaped the administration's attention that making this change by PTO fiat would implicate the Takings Clause of the Constitution in ways that getting a court mandate would not (see "'Takings' by Congress and the Courts").

"The fundamental question under section 101 is whether the inventor has created something through the application of human ingenuity or merely exposed something previously unappreciated in nature," according to the government's brief, citing J.E.M. Ag Supply, 534 U.S. at 134, and Chakrabarty, 447 U.S. at 313.  Drawing on its inapt analogies recited throughout the brief, the government argues that isolated human DNA is not patent-eligible just as "mined coal, separated cotton fibers, pure metallic lithium, ductile uranium, and other products of nature whose industrial value to mankind likewise arises when they are extracted from their naturally occurring environments."  In the real world, the policies the brief advocates are inconsistent, irrational, and irrelevant to the question of whether "genes" should be patentable.  The overwhelming majority of "gene patents" granted over the past 30 years have been directed to cDNA, a synthetic form of DNA produced enzymatically from cellular mRNA.  This type of DNA is patentable, according to the government, thus providing no comfort to plaintiffs and no substantial effect on the biopharmaceutical applications of biotechnology.  However, there is real danger that the bases for the government's arguments with regard to "merely isolated" human genomic DNA apply to all "natural products"; the same rationale that the government improperly applies to come to its conclusion that merely "isolated" DNA is not patent-eligible can be (and will be) applied to any other naturally-occurring substance, including antibodies, antibiotics, antisense and small interfering RNAs (siRNAs), hormones, metabolites, and proteins, precluding them from patentability, as set forth in an amicus brief from the Intellectual Property Owners Association:

These include any naturally-occurring chemical compound, including compounds isolated from petroleum and other sources of organic matter, the products of fermentation by microorganisms, and chemical compounds produced by microorganisms, plants or non-human animals that can be adapted for human use.  Taken to its logical conclusion, the district court's "natural products" ban on patent eligibility would extend even to inorganic matter, such as ultrapure silicon used to produce computer microchips, isolated metal products prepared from ore and other natural sources, minerals and glasses produced from silicon and other natural sources, and any other compound produced from any naturally-occurring source.

It is difficult to see the benefits to the public in a patent-eligibility standard that would exclude Blood Clotting Factors VIII and IX, insulin, human growth hormone, erythropoietin, tissue plasminogen activator, and all monoclonal antibodies.

One difference between the science-challenged Justice Department and the PTO is that patent officials understand how dependent human beings are to "products of nature" in producing new answers to basic medical challenges.  Declaring unpatentable such a vast swath of compounds with real-world applications, for what can only be misguided political reasons, is neither sound policy nor good politics.  It may be that many of the same people who contribute to the ACLU also support (and contribute) to the prevailing (for now) political party, but political pandering is no basis for making patent policy.  It is especially paradoxical for an administration that has promoted innovation as the means for overcoming the Bush-era recession, and is potentially disastrous for the future of fields like medicinal chemistry and biologic drugs.

The brief is almost Jesuitical in prescribing which angels are competent to dance on the head of its rhetorical pin.  It is easy for the uninformed to buy into the fiction that "genes" are merely rows of letters on a page — the trap laid by an equally scientifically challenged ACLU and fallen for by the District Court; this aspect of the case is argued in Myriad's opening brief.  Isolated DNA is a chemical compound, and the fact that it can be represented in sequence listings does not negate its essential nature.  And isolating this chemical compound effects a chemical change on the molecule that is profound:  rather than being covalently linked to the rest of the 3 billion nucleotides that make up a human genome, it is isolated and thus useful for human manipulation and exploitation.  This property, being affected by the hand of man, is the proper touchstone for patent-eligibility as enunciated in Diamond v. Chakrabarty; it shouldn't (but it might) take a Constitutional amendment for such a sound principle to have some repose against courts and ignorant politicians from trying to overturn it, to society's detriment.

The very property the government's brief argues makes isolated genomic DNA patent-ineligible applies with even greater force for all those other valuable and useful "products of nature."  Indeed, there is substantially less modification for these compounds, which are merely isolated (separated from other impurities) rather than chemically changed (by breaking covalent bonds that hold the DNA molecule together).  Simply put, the government's position will prevent protection (and thus retard commercialization) of any useful compound found in plants, microrganisms, animals, etc.  By this rationale, Banting and Best would not have been able to protect insulin; imagine the difference in the lives of millions of Americans (including Justice Sotomayor) if insulin had not been available to manage diabetes.

Myriad and several amici have based a substantial portion of their argument on the procedural question of whether plaintiffs have standing to sue, and if the Federal Circuit decides the appeal on this question the substantive issue of whether isolated human DNA, genomic or otherwise, is patent-eligible will be postponed.  The government's brief raises the additional question of whether the Commerce Department (and the Patent Office) will adopt, or be bound by, the poor policies contained in the brief, and whether the PTO will be required to impose the unnecessary preconditions for patent-eligibility that the government brief espouses.