No Longer Under the Sun

BRCA Gene PAtents Held not PAtentABle in tHe Us

On Monday March 29th, 2010, in a highly anticipated decision, the U.S. District Court of the Southern District of New York ruled in favour of the plaintiffs in Association of Molecular Pathology et al v. U.S. Patent and Trademark Office et al., No. 09-CIV4515 (“BRCA”), granting partial summary judgment and finding the claims in several patents on BRCA1 and BRCA2 invalid for encompassing non-statutory subject matter. The plaintiffs included the American Civil Liberties Union (ACLU), various medical organizations, the Public Patent Foundation (PUBPAT), breast cancer and women’s groups, and various doctors, researchers and individuals diagnosed with breast cancer. The defendants included the United States Patent and Trademark Office (USPTO) and Myriad and the University of Utah Research Foundation. Defendant Myriad owns or licenses the seven patents that were at issue. The subject patents included claims directed to 1) isolated DNA containing all or portions of the BRCA1 and BRCA2 gene sequence and 2) methods for “comparing” or “analyzing” BRCA1 and BRCA2 gene sequences to identify the presence of mutations correlating with a predisposition to breast or ovarian cancer or screening for potential cancer therapeutics. Both types of claims were found invalid for including unpatentable subject matter.

The Court rejected Myriad’s argument that purification of naturally occurring compounds that do not exist in nature in pure form renders such compounds patent eligible. According to the Court, purification of a product of nature, without more, cannot transform the product into patentable subject matter - the claimed invention must possess “markedly different characteristics.” The Court found that “in light of DNA’s unique qualities as a physical embodiment of information,” structural and functional differences cited by the defendants between native and the claimed isolated DNA do not render the claimed DNA “markedly different.” Isolated DNA “containing” naturally occurring sequences were found unpatentable.

In addition to impacting patenting of isolated nucleic acids corresponding to naturally occurring gene sequences, this decision may be problematic for claims directed to primers and/or probes. The Court, in rejecting Myriad’s argument that isolated DNA is markedly different since it may be used as a probe or primer, indicated that the basis for this utility is primarily a function of the nucleotide sequence identity between native and isolated BRCA1/2 DNA (BRCA, page 131). It is unclear on the above reasoning if chimeric or optimized (e.g. codon optimized) nucleic acid molecules and/or labeled primers and probes whose utility is primarily a function of the nucleotide sequence identity between the native and modified sequence, will similarly be found unpatentable in the event that the decision is upheld.

According to the Court, the decision is directed to naturally occurring DNA sequences and does not impact the patent eligibility of other isolated naturally occurring biomolecules. The Court explicitly stated that its decision did not extend to other molecules occurring naturally in the body and capable of conveying information, such as adrenaline (BRCA, page 124).

Contested diagnostic method claims were found invalid under the “machine or transformation” test pronounced In re Bilski 545 F.3d 943 (Fed. Cir. 2008). The Court found that because “the claimed comparisons of the DNA sequence are abstract mental processes,

they also constitute unpatentable subject matter.” The Court distinguished the in-suit claims, to therapeutic claims found allowable in Prometheus Laboratories Inc. v. Mayo Collaborative Services (Case No. 2008-1403 (Fed. Cir. 2009). In Prometheus, the “determining” step had been found to be transformative since determining the levels of the claimed metabolites in a subject necessarily involves a transformation as those levels cannot be determined by mere inspection. The Court added that the “determining” step in Prometheus was construed to include the extraction and measurement of metabolite concentrations. The subject claims in contrast were directed to “comparing” and “analyzing” gene “sequences.” The Court acknowledged, while the purpose of the claimed method was, for example, to “detect a germline alteration in a BRCA1 gene,” the method actually claimed was “analyzing a sequence of a BRCA1 gene.” “Analysing” a sequence and/or “comparing” a sequence can arguably be carried out by mere inspection e.g. where the sequences have already been determined, suggesting an unfortunate choice of claim terms may have provided a technical argument to ground invalidity of these claims. Claim terms “from a human subject” or “from a nontumor sample” were found to specify the identity of the DNA or RNA sequence to be “analysed” or “compared” and not as establishing a physical transformation associated with obtaining DNA from those sources. The Court alluded to claim elements that would be allowable suggesting diagnostic method claims using isolated DNA, if carefully crafted, are patentable subject matter in the U.S.

More surprisingly, a method claim to identifying potential cancer therapeutics by utilizing cells modified to comprise an altered BRCA1 gene, was also invalidated on the ground that it sought to patent a basic scientific principal even though it arguably included transformative steps. The basic scientific principle according to the judge is “that a slower rate of cell growth in the presence of a compound indicates that the compound may be a cancer therapeutic.”

The claim in question however employs a “transformed” eukaryotic host cell containing an “altered BRCA1 gene” and involves growing the transformed eukaryotic host cell in the presence and absence of a compound suspected of being a cancer therapeutic, determining the rate of growth of the host cell in the presence and absence of the compound and comparing the growth rate of the host cells, wherein a slower rate of growth of the host cell in the presence of the compound is indicative of a cancer therapeutic. The claim would seem more accurately described as an application of a particular fundamental principle, e.g. the application being to cells comprising an altered BRCA1 gene, which according to the judge’s own recitation of dicta, is patent eligible under the Bilski machine or transformation test (BRCA, page 136).

The constitutional claims against the USPTO were dismissed without prejudice, as the claims were held invalid as containing nonpatentable subject matter. The Court noted that “a decision by the Federal Circuit or the Supreme Court affirming the holding … would apply to both the issued patents as well as patent applications and would be binding on all patent holders and applicants as well as the USPTO.”

The immediate effects of the decision may be circumscribed – the decision is for now limited to the Southern District of New

York and to the specific patent claims at issue in the case. Whether the decision will have any affect on Myriad’s position in the marketplace is also unclear. Although 15 claims in seven

BRCA patents owned or licensed by

Myriad were found invalid, the remaining 164 claims in these patents were not. Further, Myriad licenses or owns 16 other patents relating to its

BRCA tests that were not challenged.

The decision may however open flood-gates to additional gene patent challenges. Not surprisingly, Myriad has already announced its intention to appeal the decision to Court of Appeals for the

Federal Circuit. If upheld, this decision could jeopardize issued patents that claim isolated nucleic acids that contain naturally occurring sequences and methods using these nucleic acids that do not meet the Bilski machine or transformation test. The invalidity of the method claims could however be short lived. The U.S. Supreme Court is expected to hand down its decision in Bilski any day now. If overturned, the basis for invalidity of the BRCA method claims would no longer exist calling into question the longevity of the BRCA decision.

In any case, the decision appears to move away from the long held view that “any thing under the sun” is patentable in the U.S. For now at least, the invalidated BRCA gene patent claims are sheltered from the sun.

Carmela DeLuca, Ph.D. (Exp. Med.), J.D. is an associate lawyer with Bereskin & Parr LLP’s Biotechnology and Pharmaceutical Practice group. Carmela can be reached in Toronto at 416.957.1619 or cdeluca@bereskinparr.com.

Micheline Gravelle, B.Sc., M.Sc. (Immunology) is the leader of Bereskin & Parr LLP’s Biotechnology and Pharmaceutical Practice group. Micheline can be reached in Toronto at 416.957.1682 or mgravelle@bereskinparr.com.

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