By Donald Zuhn —

In a brief filed on November 30, Plaintiffs-Appellees in Association for Molecular Pathology v. U.S. Patent and Trademark Office argue that they have standing; that Myriad's BRCA1/2 isolated DNA claims are invalid under 35 U.S.C. § 101 because they cover laws of nature, natural phenomena, physical phenomena, and products of nature; that Myriad's process claims are invalid under § 101 because they cover laws of nature and abstract ideas; and that Myriad's claims are unconstitutional under the First Amendment.

Plaintiffs-Appellees begin their brief by arguing that while "Myriad asserts that 'isolated' genes are so different that they constitute a human invention," "Myriad's entire business is premised on the knowledge that the 'isolated' genes are the same as the genes in the body."  The brief also contends that "Myriad has sued or threatened every lab to ever offer clinical BRCA1/2 sequencing and forbids any lab from giving patients a second opinion," and that "[t]his well-known, intimidating campaign of patent assertion has created a substantial chilling effect, and caused leading researchers, clinicians, and patients to abandon BRCA1/2 genetic testing despite having the complete capability and desire to do so."  According to the brief, "[v]irtually the entire medical community has joined Plaintiffs because these patent claims stifle vital clinical and research practices to the detriment of women's health and scientific progress."

In characterizing Myriad's isolated DNA claims, Plaintiffs-Appellees state that the claims:

[R]each DNA with introns (non-coding regions) and DNA without introns.  Each claim may also reach cDNA, and "recombinant or cloned DNA isolates as well as chemically synthesized analogs or analogs synthesized using biochemical systems."  All of the claims reach BRCA1/2 genes that are as little as 55% or 60% similar to the genes listed in the patents.  Because polypeptides can be made by DNA with different sequences, those claims defined as DNA that codes for a polypeptide each reach multiple DNA sequences.

In addition, each of the claims covers small segments of DNA.  Claims 5 and 6 of Patent '282 explicitly claim any DNA having as few as 15 nucleotides that make up BRCA1.  Undisputed evidence in the record establishes that this would reach much of the human genome.

(Note: Internal citations have been omitted unless otherwise indicated.)  As for Myriad's method claims, the brief contends that they "cover the abstract idea of looking at DNA sequences and thinking about their significance," and "[a]s such, they do not constitute patentable subject matter."

With respect to the isolated DNA claims, the brief attempts to draw a parallel between the subject matter of Myriad's claims and gold, stating that:

Under Myriad's view, any naturally-occurring thing that is "isolated" from its natural environment becomes patentable because once separated, it is definitionally different in structure and function.  Thus, "isolated" gold, i.e. gold removed from the streambed, would become patentable because it is structurally different — no longer integrated into the gravel or sand — and functionally different — potentially useful for jewelry-making.  But even if those distinctions are true, the "isolated" gold is still gold and a natural phenomenon.  Myriad also argues that "isolated DNA" cannot perform some of the functions of DNA.  But "isolated" gold can no longer comprise the sediment that influences the stream's channel, flow, and ecology once it leaves the stream.  It is still gold, and if redeposited into the water, it will settle into the streambed and perform its original functions.

According to Plaintiffs-Appellees, "Myriad appears to argue simply that DNA outside the body is structurally different because it is not surrounded by the body," but "[a]sserting that removing DNA renders it structurally different is the equivalent of asserting that isolating gold or a leaf from a tree makes it different."

While the brief acknowledges that "DNA is a chemical," it argues that "to suggest that they are chemicals like any other is simply incorrect."  Instead, the brief states that "DNA is foremost an informational molecule," and contends that "[n]o other known molecule has the ability to store vast quantities of information and to transmit that information through self-replication."

Turning to the first of Plaintiffs-Appellees' four arguments — that they have standing — the brief states that:

Viewing all the circumstances in this case — including all the facts regarding the ability of Plaintiffs to immediately undertake potentially infringing activity and Myriad's affirmative acts of asserting the patents-in-suit — while keeping in mind the purpose of the DJ Act, leads to the unmistakable conclusion that DJ jurisdiction exists.

With respect to Plaintiffs-Appellees' ability to immediately undertake potentially infringing activity, the brief notes that "the medical professional Plaintiffs have the immediate ability and desire to provide BRCA screening," that "[t]he genetic counselor Plaintiffs similarly have the immediate ability and desire to begin assisting patients in seeking, receiving, and interpreting BRCA diagnostic testing," that "[t]he patient Plaintiffs . . . have the immediate ability and desire to receive that screening, whether it be to confirm test results received from Myriad, to obtain further analysis of a mutation reported by Myriad to have 'uncertain significance,' or to get a test that they cannot obtain through Myriad," and that "[t]he breast cancer and women's health advocacy organization Plaintiffs have the immediate ability and desire to begin assisting patients in seeking, receiving, and interpreting BRCA diagnostic testing."  As for Myriad's affirmative acts asserting the patents-in-suit, the brief states that "the record establishes that Myriad has sued or threatened every known lab to ever offer clinical BRCA testing, including the University of Pennsylvania lab directed and operated by two of the Plaintiffs, Drs. Kazazian and Ganguly."  The brief also states that "[t]he district court also found that Myriad has systematically and continuously sent threatening patent license letters and demanded license agreements from any academic or other institution wishing to perform BRCA diagnostic testing, including the NYU lab directed by plaintiff Dr. Harry Ostrer."

Plaintiffs-Appellees next argue that Myriad's BRCA1/2 isolated DNA claims are invalid under 35 U.S.C. § 101 because they cover laws of nature, natural phenomena, physical phenomena, and products of nature.  According to Plaintiffs-Appellees, "[t]he patenting of human genes violates long-established Supreme Court precedent that prohibits the patenting of laws of nature, natural phenomena, products of nature, and abstract ideas."  Citing Diamond v. Diehr, 450 U.S. 175, 185 (1981), and Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980), Plaintiffs-Appellees also suggest that "[c]ontrary to Myriad's assertion, the Court has described 'products of nature' as an exception, along with laws of nature, physical phenomena, natural phenomena, and abstract ideas."

The brief contends that "[t]hree Supreme Court cases are fundamental to the section 101 analysis":  Chakrabarty, where "[t]he Court considered whether the claimed product had 'a distinctive name, character [and] use' and 'markedly different characteristics from any found in nature'"; Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948); and American Fruit Growers, Inc. v. Brogdex Co., 283 U.S. 1 (1931).  Plaintiffs-Appellees argue that:

These seminal cases prohibit the patenting of a product of nature even if it has undergone some degree of change, does not appear naturally in that form in nature, and is novel or highly useful.  They also layout the key clues to applying section 101: whether the product has a distinctive name, character and use, Chakrabarty, 447 U.S. at 309-10; whether it has markedly different characteristics from any found in nature, id. at 310; and whether the patent is on "nature's handiwork" or covers qualities that are the work of nature. Id.; Funk Bros., 333 U.S. at 130.

Plaintiffs-Appellees distinguish "chemical molecules like water [that] can be described as H₂O, HOH, or OH₂ because they consist of any two hydrogen atoms and an oxygen atom," from DNA, which the brief states "is not described according to the sugars and phosphates of its backbone, but by its nucleotide sequence." "Because this blueprint is the defining characteristic of DNA and remains the same before and after isolation," Plaintiffs-Appellees contend that "isolated DNA has neither a distinctive name, character, and use from naturally-occurring DNA nor markedly different characteristics."

The brief also suggests that in view of the DOJ's amicus brief (see "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief"), the Federal Circuit need not defer to guidance from the USPTO (in the form of the Office's utility examination guidelines).  According to Plaintiffs-Appellees:

[T]he Utility Guidelines no longer represent the position of the United States.  After consultation with numerous federal agencies, including the PTO, U.S. Br. 1, the U.S. concluded that "isolated but otherwise unaltered genomic DNA is not patent-eligible subject matter under 35 U.S.C. § 101."  U.S. Br. 18.  If deference to the decisions of the United States is due, that deference now supports invalidation of the claims.

The brief also argues that other precedent supports the conclusion that isolated DNA is not patentable.  Among the cases cited by Plaintiffs-Appellees are:  Ex parte Latimer, 1889 Dec. Comm'r Pat. 123 (1889) (purified pine needle fiber); Gen. Elec. Co. v. De Forest Radio Co., 28 F.2d 641 (3d Cir. 1928) (substantially pure tungsten); In re King, 107 F.2d 618 (C.C.P.A. 1939) (vitamin C purified from lemon juice); In re Merz, 97 F.2d 599 (C.C.P.A. 1938) (purified ultramarine); In re Marden (Marden II), 47 F.2d 958 (C.C.P.A. 1931) (purified vanadium); In re Marden (Marden I),47 F.2d 957 (C.C.P.A. 1931) (purified uranium).  As for lower court cases that Myriad relies on to support its position for patentability, the brief contends that those cases "did not squarely address subject matter eligibility under section 101 or are otherwise inapposite."  In a footnote, Plaintiffs-Appellees also argue that "Myriad's reliance on section 103(b)(1) to support the patentability of isolated DNA is similarly misplaced."  In particular, Plaintiffs-Appellees contend that "[t]he fact that Congress mentioned 'nucleotide sequence' in section 103(b)(1) — a statutory provision which deals with the obviousness of processes — does not support the notion that Congress intended isolated DNA to be patentable compositions.  An organism can be engineered to express a 'nucleotide sequence' that is not naturally-occurring."

Returning to the DOJ brief, Plaintiffs-Appellees note that "[a]micus United States argues that claims limited to cDNAs would not violate section 101."  While stating that this issue is not material to the case, the brief argues that "should this Court choose to reach the cDNA question, it should also invalidate claims on cDNA that is an exact copy of naturally-occurring mRNA."  In addition, the brief contends that "cDNA does exist naturally in the body through a naturally-occurring process in which RNA is reverse-transcribed into cDNA," and that "[s]ome of these cDNAs are then reinserted into the genome in the form of pseudo genes."

Plaintiffs-Appellees devote only a few pages of the brief to their final two arguments.  With regard to their argument that Myriad's process claims are invalid under § 101 because they cover laws of nature and abstract ideas, the brief states that "[c]onsidered as a whole, the method claims at issue here clearly cover a phenomenon of nature — whether two BRCA sequences are different or the same."  In particular, the brief contends that:

Claim 2 of '857 covers comparing a BRCA2 sequence from a sample with the wildtype sequence, wherein any alteration indicates a predisposition to breast cancer, and further illustrates the preemptive effect.  The claim does not specify which alterations are covered and makes the scientifically incorrect assumption that any alteration indicates cancer predisposition.  Thus, the claim exemplifies how a patent on a general correlation between a gene and disease monopolizes a law of nature.  A scientist who wants to identify which alterations in fact indicate a breast cancer predisposition will run afoul of the patent claim as soon as he or she compares two gene sequences and considers the significance of an alteration.

As for Myriad's argument that its process claims satisfy the transformation prong of the machine-or-transformation test, Plaintiffs-Appellees counter that in order to satisfy the test:

Myriad imports entirely new terms and processes into the claims' plain language.  Myriad argues that "sequence" should be understood as the isolated DNA molecule and that the method claims necessarily involve isolating, sequencing, and hybridization of DNA or genes using a primer or probe.  Yet, none of these processes is required by the challenged claims themselves and for that reason, they cannot be magically inserted.

The brief also points to dependent claims not involved in the suit, which do require hybridizing, amplifying, electrophoresing, and/or cloning.

Finally, with respect to Plaintiffs-Appellees' First Amendment argument, the brief states that:

None of the method claims purports to cover any specified process of comparing or analyzing gene sequences or testing therapeutics.  The only instructive part of these claims is that at the end, the medical professional thinks, "They are the same" or "They are different" or "They are different in a way that is significant."  In other words, it is the thought that is patented, not a particular process.  Enforcement of such a patent by a governmental actor, such as the Defendant University of Utah Research Foundation, would violate the First Amendment.