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ACLU, Myriad Separately Ask Appeals Court for Rehearing in BRCA Patent Case

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This article has been updated from a version posted Aug. 30 to include details from the defendants' petition.

Plaintiffs and defendants in a suit seeking to overturn Myriad Genetics' BRCA patents have filed separate briefs with the US Court of Appeals for the Federal Circuit seeking a rehearing of the case.

The appeals court in early August overturned a lower court's decision in ruling that isolated gene sequences claimed in Myriad's patents are not products of nature and are therefore patentable. The court also determined, however, that several of the company's method claims that describe "comparing" and "analyzing" gene sequences were invalid (PGx Reporter 8/3/2011).

In response, both plaintiffs and defendants in the case, Association for Molecular Pathology et al. v. US Patent and Trademark Office et al., have requested a rehearing by the three judges of the appeals court.

Last week, plaintiff-appellees — including AMP, the American College of Medical Genetics, the American Society for Clinical Pathology, the College of American Pathologists, and other organizations and individuals — filed a petition for a panel rehearing on the grounds that the appeals court failed to consider whether the DNA fragments claimed in Myriad's patents are products of nature.

The petition, filed by the plaintiffs' legal representatives at the American Civil Liberties Union and the Public Patent Foundation, also charged that the court wrongly denied standing to two of the plaintiffs in the case — ACMG and Ellen Matloff, a genetic counselor at Yale.

Meantime, defendant-appellants, including Myriad and directors of the University of Utah Research Foundation, which holds the BRCA patents and licenses them to Myriad, filed a separate petition for a rehearing with the court on Aug. 29.

In their petition, the defendants argue that the only plaintiff that the appeals court found to have standing in the case, Harry Ostrer, no longer has standing since he has moved to a new institution that does not have a dispute with Myriad over the BRCA patents.

While Myriad's lawyers claim that the appeal should be dismissed as "moot" due to the plaintiff's lack of standing, they request that the panel uphold its decision on the patentability of isolated DNA.

Myriad's petition does not address the appeals court's invalidation of its method claims.

'Markedly Different'?

The ACLU/PubPat petition claims that the appeals court "erred" in deciding that gene fragments described in Myriad's patents are "markedly different" from what exists in nature and therefore patentable because it failed to consider two points: "that the language of the patents defines the function, not the structure, of the patented genes and gene fragments;" and that "gene fragments with the altered chemical structure identified by the court exist in nature."

Further, the petition argues that the majority of the court — Judges Alan Lourie and Kimberly Moore — "relied on facts not in the evidentiary record and failed to consider other, relevant facts clearly establishing that the claimed fragments are products of nature as a matter of both fact and law."

Specifically, the plaintiff-appellees state, the court erred in emphasizing the chemical nature of DNA fragments, which led it to conclude that the breaking of a covalent bond during the process of isolating a gene creates a DNA fragment that is chemically different from a naturally occurring DNA molecule as a result of human intervention.

The brief counters that the composition claims in Myriad's patents are "not defined by chemical structure," but are instead "defined by function" — namely, they encode a particular protein or fragment of a protein. That function, the plaintiffs state, is "created by nature, not by Myriad."

Secondly, the petition notes that "DNA fragments identical to those claimed in the patents appear in the body," citing as examples the fact that DNA fragments are created "every time gametes are produced during the normal process of meiotic recombination as well as during the cellular process by which cells make copies of themselves" and when DNA experiences a double-strand break. They also cite the fact that fragments of fetal genomes have been shown to be present in maternal plasma, and that DNA fragments, including fragments of BRCA genes, can be found in the blood of cancer patients.

In all these cases, the brief argues, "covalent bonds have been broken and terminations altered in nature, creating fragments similar to or identical to the BRCA1/2 genes."

The plaintiffs also note that the court was in error if it "considered the existence of the multiple
DNA fragments that exist in the body and concluded they … are patentable because the scientist determined the length or composition of the isolated fragment," since scientists do not control the size or composition of fragments when isolating a gene.

"In short, the chromosomal fragments/chemicals in the bottom of Myriad’s test tubes are no more the result of human decision-making than the fragments/chemicals created when there is a naturally occurring double strand break or in the blood of pregnant women or cancer patients," the petition states.

The plaintiffs also cite a study published last year by researchers at Duke University that found that 15-mer fragments of the BRCA1/2 genes are ubiquitous throughout the human genome (PGx Reporter 3/24/2010), in which case a scientist "isolating any human gene cannot take steps to ensure that she will not infringe Myriad’s patents because some of the fragments/chemicals that occur may be identical to those that are fragments of the BRCA1/2 genes."

The court "overlooked these facts because it relied on scientific facts and/or arguments that were not supported by the record," the brief states. In particular, it notes that Myriad did not refer to chemical terms such as "covalent bonds" or "hydroxyl termination points" in its arguments before the New York Southern District Court and that these terms are not used in any of the patent claims.

Standing to Sue

In addition to its arguments regarding the court's interpretation of the chemical nature of DNA, the petition also seeks a rehearing on the grounds that it failed to acknowledge "undisputed facts" that would give two additional plaintiffs — ACMG and Ellen Matloff — standing to challenge Myriad's BRCA patents.

The briefing notes that gene patenting is "germane to ACMG's purpose" and that the one plaintiff the court found to have standing, Harry Ostrer, is a member of ACMG. As a result, "ACMG therefore has organization standing," the petition states.

As for Ellen Matloff, director of cancer genetic counseling at the Yale Cancer Center, the petition claims as "incorrect" the appeals court's assertion that "none of the plaintiffs" besides Ostrer and two others "allege that Myriad directed any letters of other communications regarding its patents at them."

Rather, Matloff's declaration "makes clear that she personally had conversations with Myriad in which she was told by Myriad that she and geneticists at Yale would violate Myriad’s patents if they performed the tests that she wanted to perform."

Under the court's previously determined standard that a plaintiff would have standing if Myriad directed “any … communications regarding its patents at them,” Matloff has grounds to sue, the petition argues.

Myriad's petition also raises the issue of standing, but argues the opposite point — that none of the plaintiffs have standing to sue, including Ostrer. The defendants' argument is based on Ostrer's move from New York University to Montefiore Hospital and the Albert Einstein School of Medicine of Yeshiva University, which "eliminates his asserted controversy with Myriad," the brief states.

Specifically, Myriad had sent a letter to Ostrer's lab at NYU in 1998 offering to license the BRCA patents, which the plaintiffs argued had prevented him from performing the test at NYU. Ostrer's departure from NYU, the defendants claim, eliminates the controversy that existed between Myriad and NYU and does not create a controversy between Myriad and Montefiore.

Furthermore, Myriad's counsel argues, the plaintiffs have failed to establish that "Montefiore will even permit Dr. Ostrer to conduct clinical BRCA sequencing, or that Dr. Ostrer controls the Montefiore labs such that he would be able to perform the sequencing he 'wish[es] to engage in.'"

Citing legal precedent, the petition asserts that the appeal should be dismissed as moot because Ostrer's departure from NYU means that the "relief sought" in the suit "would not 'make a difference to the legal interests of the parties (as distinct from their psyches, which might remain deeply engaged with the merits of the litigation).'"

The defendants further claim that because the case is made moot due to Ostrer's "unilateral action," the court's decision to uphold Myriad's patent claims "should not be vacated" because such judgments "should be vacated only where mootness arises through no fault of the parties (such as external causes or mere 'happenstance')."

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