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.

By Kevin E. Noonan —

Myriad Genetics filed its appellant's brief in Association of Molecular Pathology v. U.S. Patent and Trademark Office last Friday, joined by the Directors of the University of Utah Research Foundation (Lorris Betz, Roger Boyer, Jack Brittain, Arnold B. Combe, Raymond Gesteland, James U. Jensen, John Kendall Morris, Thomas Parks, David W. Pershing, and Michael K. Young).  This is the first step in an appeal that awaits a large number of anticipated amicus briefs and appellees' briefs from plaintiffs (supported by the American Civil Liberties Union and the Public Patent Foundation).  There are also rumors that the Government will weigh in, but it is unclear whether it will be in favor or in opposition to the verdict below.

Myriad's brief begins with an attack on the plaintiffs' standing to bring the lawsuit, something expressly litigated during the District Court case (see "Round One Goes to the ACLU").  Myriad lost below, but has a chance to win reversal on this procedural issue.  Under this scenario, should Myriad prevail, the Federal Circuit would not reach the merits of the District Court's decision that isolated human DNA is not patent-eligible subject matter.  This would make it more likely that a certiorari petition would be limited to the procedural question, thus delaying any reconsideration of the patent-eligibility questions.  In view of the fact that the patents-in-suit expire between December, 2014 and March, 2017, any delay in a final resolution of the case on the merits works in Myriad's favor.

Myriad attacks both the District Court's conclusion that the plaintiffs had standing as well as the way the Court applied the relevant jurisdictional test.  Citing Medimmune, Inc. v. Genentech, Inc., 549 U.S. 118, 127 (2007), Myriad argues that the District Court erred in misapplying the "all the circumstances" test, because plaintiffs had failed to show "that there is a substantial controversy, between parties having adverse legal interests, of sufficient immediacy and reality to warrant the issuance of a declaratory judgment" (unless otherwise noted, all emphases are as set forth in the brief).  Myriad cites as error the District Court's application of the test in view of its assertion that, after Medimmune, "there is now an ease of achieving declaratory judgment jurisdiction," reminding the Court that it has held that "a lowered bar does not mean no bar at all."  Hewlett-Packard Co. v. Acceleron, LLC, 587 F.3d 1358, 1361-62 (Fed. Cir. 2009).  Contrary to this precedent, Myriad argues that "[t]he court's application of the 'all the circumstances' test eliminated any meaningful threshold for declaratory judgment jurisdiction by allowing any plaintiff with 'the ability and desire' to infringe . . . the right to challenge the patent's validity based solely on subjective fears of suit."  Myriad and the plaintiffs "do not have 'adverse legal interests,'" Myriad argues, because none of the plaintiffs have alleged that (recently) Myriad had any contact with any of them concerning the patents-in-suit nor did any of the plaintiffs "inform[] Myriad about their 'ability and desire' to infringe" these patents.  Plaintiffs did not allege any "affirmative act" by Myriad, which the brief states is required under post-Medimmune Federal Circuit precedent, citing SanDisk Corp. v. STMicroelectronics, Inc., 480 F.3d 1372, 1380-81 (Fed. Cir. 2007).  The brief analogizes the situation to the one in Prasco, LLC v. Medicis Pharm. Corp., 537 F.3d 1329, 1339 (Fed. Cir. 2008), where "the totality of the circumstances analysis in the instant case is that which has not occurred."  The District Court skirted this jurisdictional requirement, according to Myriad, by holding that such a requirement (for "a specific, affirmative act directed towards the plaintiff") would be contrary to the "all the circumstances" test.  This decision was erroneous, Myriad argues, as being contrary to Federal Circuit (SanDisk) and Supreme Court (MedImmune) precedent (on the grounds that the Supreme Court found the "touchstone" of an "adverse legal interest" to be "threatened [patent] enforcement action").  The brief also argues that the District Court's finding that the plaintiffs had standing is contrary to the Federal Circuit's decision in Hewlett-Packard Co. that "a communication from a patent owner to another party, merely identifying its patent and the other party's product line, without more, cannot establish adverse legal interests between the parties, let alone the existence of a 'definite and concrete' dispute."

The brief also assails the District Court's decision insofar as it was grounded in the plaintiffs' "subjective perceptions" of an apprehension of suit.  Specifically, Myriad objects to the claim that "it is widely understood within the research community that Myriad has taken the position that any BRCA1/2 related activity infringes its patents and that Myriad will assert its patent rights against parties engaged in such activity," calling it "rumor and innuendo."  "The mere existence of a potentially adverse patent does not cause an injury nor create an imminent risk of an injury," Myriad argues, citing Prasco, and goes on to say that, post-MedImmune, "the law does 'not hold that a patent can always be challenged whenever it appears to pose a risk of infringement,'" citing Innovative Therapies, Inc. v. Kinetic Concepts, Inc., 599 F.3d 1377, 1382 (Fed. Cir. 2010).  Instead of such chimerical fears and apprehensions, Myriad argues that case law demands that "a 'controversy must be based on a real and immediate injury or threat of future injury that is caused by the defendants — an objective standard that cannot be met by a purely subjective or speculative fear of future harm,'" citing Prasco.

Myriad also argues that the plaintiffs failed the second prong of the MedImmune test, that the controversy must be "real, imminent, and traceable to defendants," again citing Prasco, because Myriad had taken "no action towards plaintiffs threatening suit."  The only actual "specific affirmative acts" Myriad had taken had been letters and other "communications" with three of the plaintiffs Drs. Kazazian, Ganguly, and Ostrer "from May 1998 to June 1999," as well as "an alleged exchange of phone calls between some [unidentified] Myriad employee and Dr. Matloff in 2005."  The passage of time is sufficient, Myriad argues, to rob any controversy of "sufficient immediacy and reality," citing MedImmune.  According to Myriad, the District Court "dismissed" the "staleness" of this conduct by attributing a requirement for greater immediacy with the "now-defunct 'apprehension of suit' test."  Not so, according to Myriad, since an "apprehension of suit" is properly one of the "totality of the circumstances" that courts should consider in making jurisdictional determinations.  (Although Myriad supports this position with pre-MedImmune Federal Circuit precedent, thereby weakening its impact.)  Drawing an analogy with laches, Myriad argues that "a patentee's ten-year silence presumptively extinguishes any reasonably objective fear of suit."  Myriad also brings to the Court's attention some interesting behavior by the plaintiffs (whether at the ACLU or PubPat's instigation is unknown), whereby Dr. Matloff contacted an unidentified Myriad employee in 2005 by telephone "regarding 'whether it was permissible for [Yale Laboratory] to perform genetic screening of BRCA genes.'"  Fortunately, the District Court did not rely upon this purported incident in its jurisdictional decision-making, since as Myriad points out, to do so would permit "anyone [to] manufacture jurisdiction by initiating phone calls or letters to a patentee; the patentee would be left with an untenable choice — grant permission to infringe or face a declaratory-judgment suit."

Similarly unavailing to plaintiffs in satisfying this second prong of the jurisdictional test were "ten-year-old litigation and licensing activities," according to the brief.  The District Court used evidence of these activities to find that Myriad had engaged in a "continuing course of [litigious] conduct over a period of several years."  True or not, Myriad argues that the Court "fails to explain how such aged conduct created a 'substantially immediate' controversy with plaintiffs."  Specifically, neither of the two patent cases cited by the District Court in support of its conclusion were against any of the plaintiffs here, and although Myriad concedes that the Court has held that "prior litigation is a circumstance to be considered in assessing the totality of circumstances," the Court has also held that "the fact that [patentee] had filed infringement suits against other parties for other products does not, in the absence of any act directed toward [plaintiff], meet the minimum standard discussed in MedImmune," citing Innovative Therapies, 599 F.3d at 1382.  Under this standard, neither the prior litigations nor licensing efforts — amounting to "a single 1998 letter sent to nonparty Dr. Nayfield" — satisfy the jurisdictional standard, contrasting the situation here with cases where the Federal Circuit has held prior litigation conduct to support declaratory judgment jurisdiction (including Hewlett-Packard Co.; Sony Elecs., Inc. v. Guardian Media Techs., Ltd., 497 F.3d 1271, 1285 (Fed. Cir. 2007); and SanDisk Corp.).

Myriad finishes this portion of its brief by arguing that the District Court's jurisdictional decision was outside the proper scope of Article III of the Constitution by providing an advisory opinion.  The Declaratory Judgment Act was intended to provide a party "with 'an equal start in the race to the court house, not a headstart,'" citing Kerotest Mfg. Co. v. C-O-Two Fire-29-Equip. Co., 342 U.S. 180, 185 (1952), and in the absence of any "suggestion of infringement by anyone for over a decade," a headstart is precisely what plaintiffs have sought (and, unfortunately for Myriad, obtained).  Myriad characterizes the case for what indeed it is:  "[i]n sum, this is a manufactured controversy with recruited plaintiffs having no dispute with Myriad beyond a desire to assist two public-advocacy groups' effort to use the courts to dictate public policy on DNA patents.  That sort of "abstract" dispute is not enough for declaratory-judgment jurisdiction.  Aetna Life Ins. Co. v. Haworth, 300 U.S. 227, 240 (1937).

Turning to the substance, Myriad makes what are now well-known arguments for the patentability of human (and indeed any) DNA.  New to the argument is the citation of Bilski v. Kappos for the proposition that the Supreme Court continues to recognize that Congress has "plainly contemplated that the patent laws would be given wide scope," citing Diamond v. Chakrabarty, 447 U.S. 303, 308 (1980), and that "[t]his breadth 'ensure[s] that 'ingenuity should receive a liberal encouragement,'" Bilski v. Kappos, 130 S. Ct. 3218, 3225 (2010) (quoting, through Chakrabarty, 5 Writings of Thomas Jefferson 75-76 (H. Washington ed. 1871)).  Isolated DNA is "unquestionably" a "composition of matter," or, in the alternative, "a new and useful improvement" on naturally occurring DNA.  The brief cites the U.S. Patent and Trademark Office's 2001 Utility Examination Guidelines for the proposition that isolated human DNA ("a gene") "is a chemical compound and is patentable if all the statutory requirements are met."  The brief also cites 35 U.S.C. § 103(b) as evidence that Congress has given its imprimatur to patenting isolated human DNA (specifically, wherein § 103(b)(3)(A)(i) specifies that "nucleotide sequences" would be a category of "patenting starting compositions" encompassed by the statute.  Myriad draws an analogy to how the Supreme Court majority considered the effects of 35 U.S.C. § 273(a)(3) on the question of whether a "business method" was patentable in Bilski v. Kappos:

In Bilski, the Supreme Court concluded that § 273(a)(3) and its definition of "method" as including "a method of doing or conducting business" demonstrated that Congress did not view business methods as categorically ineligible for patenting.  130 S. Ct. at 3228-29.  Section 103(b) similarly confirms that Congress viewed "nucleotide sequences" as appropriate subjects for patents; at minimum, it shows that Congress knows how to legislate in this area.  Accord 141 Cong. Rec. S15220, S15222 (Oct. 17, 1995) (statement of Sen. Hatch) ("[t]he U.S. patent on the starting materials — typically a new DNA molecule, a genetically altered host cell, or a vector — can prevent others from using them in the United States in any way").

The brief also argues that isolated DNA does not fall within the three recognized exceptions to broad patent eligibility, "laws of nature, physical phenomena, and abstract ideas."  The brief sets forth an extensive argument that Supreme Court precedent does not contain a "categorical" prohibition of patenting "products of nature."  This section includes an explication of the commonly-cited precedents (American Wood-Paper Co. v. Fibre Disintegrating Co., 90 U.S. 566 (1874) (cellulose); Cochrane v. Badische Anilin & Soda Fabrik, 111 U.S. 293 (1884) (alizarine dye); American Fruit Growers, Inc. v. Brogdex Co., 283 U.S. 1 (1931) (borax-coated oranges); Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948) (mixed bacterial cultures); In re Kratz, 592 F.2d 1169, 1174 (C.C.P.A. 1979) (2-methyl-2-pentenoic acid); In re Bergstrom, 427 F.2d 1394, 1401 (C.C.P.A. 1970) (prosaglandins); and Chakrabarty), distinguishing those cases the District Court used to support its decision (because inter alia the precedent was based not on categorical patent-ineligibility but on unpatentability for obviousness, etc.) and arguing that the District Court had misread this precedent.  Specifically, the brief argues that the Chakrabarty decision did not impose a requirement that to be patent-eligible a composition of matter must have "markedly different characteristics," making essentially a textual argument regarding how the Supreme Court set forth the applicable precedent.  "'Markedly different' is a fine term for judges to use when describing the particular facts of a particular case, as in Chakrabarty, but it surely was not meant as a legal standard to govern all future cases decided under the statute," Myriad argues.  This is particularly egregious error when a court, as the District Court here, uses such a "dubious standard" to "dismiss[] all the factual showings about the substantial differences between isolated BRCA DNA molecules and native DNA [by] concluding as a matter of law that the isolated molecules were not 'markedly different.'"  Myriad performs a similar deconstruction of the decision in Funk Bros., arguing that that decision was based not on patent-ineligibility but on lack of "invention," today known as obviousness.  (Cleverly, the brief turns Judge Dyk's dissent in Intervet Inc. v. Merial Ltd. to its advantage, arguing that the unpatentability of "the leaves of a plant" is founded not on patent ineligibility but on lack of novelty or obviousness.)

The District Court's decision that isolated human DNA was not patent-eligible "gave insufficient respect to the PTO's contrary determination, as well as to a long line of authority from this Court, its predecessor, and other respected jurists, holding that molecules that are newly isolated from natural products and useful are eligible for patents."  Even the Supreme Court properly defers to Congress to make these types of changes in longstanding practice Myriad argues, citing J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred International, Inc., 534 U.S. 124 (2001), and Bilski.  The brief distinguishes the prudent application of judicial restraint by the Supreme Court in J.E.M. Ag Supply with the District Court "dismissing out of hand" their arguments concerning the high degree of "public reliance" on the patent-eligibility of isolated human DNA.  (In a footnote, the brief recites the statistics that "[o]ver the past 29 years, the PTO has issued some 2,645 patents with claims to "isolated DNA," and over 50,000 patents containing at least one claim directed to a nucleic acid sequence, including those derived from humans, other animals, plants, bacteria, and so on).  As a result:

[B]y refusing to give any consideration to this historical practice, and the significant industries built up in reliance thereon, the district court disregarded almost 100 years of precedent, dating back at least to Judge Learned Hand's opinion in Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95 (S.D.N.Y. 1911), aff'd, 196 F. 496 (2d Cir. 1912).  In the face of this consistent and long-followed view of § 101's scope, plaintiffs' arguments are better addressed to Congress, not to the courts.  The Supreme Court has long held that courts "should not read into the patent laws limitations and conditions which the legislature has not expressed."  United States v. Dubilier Condenser Corp., 289 U.S. 178, 199 (1933).

The isolated BRCA1 and 2 genes are patent-eligible as claimed because the claims are directed at "a nonnaturally occurring manufacture or composition of matter" — "a product of human ingenuity 'having a distinctive name, character and use'" as required by Chakrabarty that "exist only because of the 'human ingenuity' [exercised] in discovering and isolating them."

And of course the brief alerts the Court to the deleterious consequences of "a sweeping exception to patent eligibility for 'products of nature' on 'truly 'new' and 'useful' discoveries, like pharmaceuticals derived from natural sources."  Here, Myriad distinguishes the isolated BRCA 1 and BRCA 2 genes as being "unavailable" to scientists for any use, including the "detection and treatment of breast and other cancers."  Even the District Court acknowledged that the isolated BRCA 1 and 2 genes had utility, a utility that the brief notes was "not available to the public" until the invention claimed in the patents-in-suit.

This section of the brief ends with Myriad's argument that the District Court improperly granted summary judgment because there remain questions of fact regarding "whether the characteristics of isolated DNA are 'markedly' different from those of native DNA" because "the meaning of 'markedly different' has never been developed in case law, [and thus] the court improperly viewed itself as free to draw the 'legal' conclusion that 'none of the structural and functional differences . . . between native BRCA DNA and the isolated BRCA DNA claimed in the patents-in-suit render the claimed DNA 'markedly different.'"

Finally, the brief addresses the patent eligibility of Myriad's method claims, which the District Court decided were patent-ineligible under the Federal Circuit's "machine-or-transformation" (MoT) test from In re Bilski.  Here, Myriad argues that the claims, properly construed, encompass a transformation step sufficient to satisfy the MoT test.  The brief notes that the Supreme Court, in holding that the MoT test was "useful" but not exclusive, specifically cited "advanced diagnostic medical techniques" as types of methods where innovation might be differentially harmed by an overly restrictive patent eligibility standard.  The brief notes that, even under the arguably more limited patent eligibility regime of the Federal Circuit's MoT test, the Court found patent-eligible the method claimed in Prometheus Laboratories, Inc. v. Mayo Collaborative Services, 581 F.3d 1336 (Fed. Cir. 2009), certiorari granted, judgment vacated, and remanded, 130 S. Ct. 3543 (2010).  In that case, the Court found transformative steps for assaying blood for the presence of thiopurine or its metabolites, since these steps involved physical or chemical transformations of levels that "cannot be determined by mere inspection."  Similarly, Myriad argues, its claimed methods involve "extracting, processing and analyzing a human tissue or blood sample using 'nucleotide sequences,' which are molecules."  (Myriad further argues that its claims "show an even stronger claim to patent-eligibility [because] the BRCA sequences were not known prior to Myriad's invention[, whereas] in Prometheus, by contrast, the method claims' transformative step involved the detection of old, known metabolites.)  The District Court improperly "read out" these "critical elements" of the claims, considering only those elements that were (in the District Court's view) "directed only to the abstract mental processes of 'comparing' or 'analyzing' gene sequences."  The District Court's error was in not considering the claims as a whole; "it is 'inappropriate to dissect the claims into old and new elements and then to ignore the presence of the old elements in the analysis,'" citing Diamond v. Diehr, 450 U.S. 175 (1981).  Rather than being mere "data gathering steps," as the District Court characterized them, Myriad argues that the sequencing steps are the transformative steps that satisfy the requirements for patent-eligibility.  (This argument illustrates the subjectivity introduced into the patent-eligibility determination by concepts like "(mere) data gathering steps" and "insignificant post-solution activity.")  The problem is the failure of the District Court to construe the claims:  "[u]nder a proper claim construction, the claims require the transformation of a human sample, and the transformation of the specific BRCA molecules in that sample," according to Myriad, illustrating the point with claim 1 of U.S. Patent 5,709,999:

1.  A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.

Myriad argues that, properly construed, this claim requires the steps of "first, in order to analyze the BRCA1 gene, RNA or a BRCA1 cDNA made from mRNA of the human sample, the sample must be transformed[: t]he BRCA1 gene and mRNA are within the patient's body and must be isolated from a patient's tissue sample in order to be sequenced."  Myriad's brief recites what this entails:  "the cells of the tissue sample must be broken open, and a sample of the DNA or RNA extracted.  . . .  Sequencing is accomplished using a diagnostic probe or primer to hybridize to the target DNA or RNA extracted from the sample to initiate a sequencing reaction."  The brief then sets forth the second step:  "the DNA or RNA of the tissue sample is transformed when a primer or probe is used to bind to and 'hybridize' the DNA or RNA isolated from the human sample; a new 'hybrid' DNA/DNA or DNA/RNA compound is formed, allowing its sequence to be analyzed."  As a consequence of these steps, Myriad argues, "the original human sample is no longer the same human sample, and the DNA and mRNA obtained from that sample are no longer the same DNA and mRNA from the original sample."  Myriad draws the conclusion that "[t]his is transformative under Supreme Court precedent," citing Gottschalk v. Benson, 409 U.S. 63, 70 (1972); Diamond v. Diehr; and Parker v. Flook.  Myriad characterizes these transformations as being "central to the purpose of the claim — detecting 'germline mutations in the BRCA1 gene and their use in the diagnosis of predisposition to breast and ovarian cancer.'"  A similar analysis yields the same conclusion for all the other method claims at issue.

The brief then discusses the basis for the District Court's error — construing "the term 'sequence' in the method claims as mere information (i.e., letters from the alphabet), rather than as a physical molecule."  This error was based on using what the Court considered the "plain meaning" of the term "sequence" devoid of any consideration of the disclosure of the specifications of the patents-in-suit, contrary to the mandates of Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005) (en banc), Myriad argues, supporting its construction of the claim term "sequence" to mean the molecule rather than "mere words on a page" with citations to the specifications.  And the brief also cites the District Court's invalidation of a method of screening claim (claim 20 of U. S. Patent 5,747,282):

20.  A method for screening potential cancer therapeutics which comprises:  growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

The brief specifically criticizes the District Court's reliance on "the essence of the claim" (which is not the proper approach for construing a claim), which gave the Court "license" (according to Myriad) to "entirely ignore the 'arguably' transformative steps . . . involv[ing] administering a substance to a cell in the expectation that the substance will slow [the cell's] growth.  If that is not transformative, nothing ever could be," Myriad asserts.  Citing the Supreme Court's reasoning in Bilski:

Under the plain statutory language, these methods are "new and useful process[es]" (again, their utility is stipulated), and these extraordinarily useful (indeed, lifesaving) methods are not mere "concepts," or "unpatentable abstract idea[s]," as was the method of hedging ruled ineligible in Bilski, 130 S. Ct. at 3231.  They are very real ways of diagnosing and treating cancers.  They are patent-eligible because patent protection is in accord with the "larger object of securing patents for valuable inventions without transgressing the public domain."  Id. at 3227.  Patents representative of this "Information Age," id., should not be invalidated because they involve the use of information.

Finally, in a sentence, Myriad dismisses the "alternative, constitutional arguments" raised by plaintiffs (and used by the District Court to deny motions to dismiss for standing and then discarded when the Court reached the merits), and termed the First Amendment arguments as "frivolous . . . because these patent claims do not impede speech or thought; they are, as shown above, new and useful compositions and methods critical to the ongoing fight against one of the most insidious diseases known to man."

Amicus briefs in support of Myriad or neither party are due tomorrow.