By Kevin E. Noonan —
One of the arguments advanced by the plaintiffs in Association of Molecular Pathology v. U.S. Patent and Trademark Office ("Myriad") is that a pernicious effect of permitting patents on genes and genetic diagnostic methods is that women cannot obtain a "second opinion" of the results of genetic tests showing mutations in BRCA1 or BRCA2 genes. Whether this in fact makes any clinical difference is open to debate: while plaintiffs argue that there could be false negative results from Myriad's testing (insofar as all mutations are not assayed), there has been no specific allegation that there have been any such false negative results. Nevertheless, the District Court included this argument, and the contentions of the parties regarding it, in its decision:
Plaintiffs contend that as a result of the patents-in-suit, BRCA1/2 genetic testing is one of the very few tests performed as part of breast cancer care and prevention for which a doctor or patient cannot get a second confirmatory test done through another laboratory. Love Decl. ¶12. In particular, women who receive a positive result cannot confirm the lab's findings or seek a second opinion on the interpretation of those results. Ledbetter Decl. ¶23; Ostrer Decl. ¶11. According to Myriad, absent any doubts regarding the accuracy of the original test, resequencing the patient's genes by another laboratory would be an unnecessary waste of resources, and Myriad has never prohibited a second interpretation of the results of its diagnostic tests. Critchfield Decl. ¶64; Reilly Decl. ¶¶54,55. In addition, there are multiple laboratories available to conduct confirmatory BRCA1/2 testing pursuant to patent licenses granted by Myriad, including both the University of Chicago Genetic Services Laboratory and Yale Diagnostic Laboratories. Critchfield Decl. ¶62. That confirmatory testing, however, it limited to the confirmation of certain, specific positive test results; the remaining types of positive test results as well as all negative test results are excluded from such testing services. Matloff Decl. ¶¶9,10.
Association of Molecular Pathology v. U.S. Patent and Trademark Office, 669 F. Supp. 2d 365 (S.D.N.Y. 2010). The District Court made no rulings on this basis ("[w]hether the patents at issue impact the testing for BRCA1/2 mutations favorably or unfavorably is an issue of factual dispute not resolvable in the context of the instant [summary judgment] motions"), but regardless of the persuasiveness of the argument on the District Court's decision, the argument certainly resonates with the public (see "'60 Minutes' and 'Newshour' Take Different Approaches to Covering Gene Patenting Story").
As mentioned in the District Court's decision, Myriad does permit some "confirmatory" testing under license, behavior that indicates such testing may be appropriate under at least some circumstances. Presumably such testing (which is "confirmatory") is done for patient samples that have had been tested using Myriad's patented methods, covered by at least one of the method claims invalidated by the District Court:
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.
(U.S. Patent No. 5,709,999);
1. A method for screening a tumor sample from a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises gene comparing a first sequence selected form the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic alteration in the BRCA1 gene in said tumor sample.
(U.S. Patent No. 5,710,001);
1. A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject.
(U.S. Patent No. 5,753,441);
1. A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequences identifies a mutant BRCA2 nucleotide sequence.
2. A method for diagnosing a predisposition for breast cancer in a human subject which comprises comparing the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue sample from said subject with the germline sequence of the wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject indicates a predisposition to said cancer.
(U.S. Patent No. 6,033,857).
Presumably, confirmatory testing (in order to be infringing) is performed substantially the same way as the original testing, and is performed on the same sample (whether blood, cheek swab, or other source) from the same patient and assaying the same genes (BRCA1 or BRCA2). This raises the question of whether the principle of patent exhaustion is relevant to this situation, wherein the patient as the purchaser of Myriad's services (performing the patented test) can obtain a second test without further authorization from the patent licensee.
The Supreme Court has spoken with regard to exhaustion of method claims, in Quanta Computer, Inc. v. LG Electronics, Inc., expressly reversing a Federal Circuit decision that method claims could not fall within the scope of the patent exhaustion doctrine. The Court said in its decision that it had never treated composition and method claims differently, applying the "substantial embodiment" test to apply the patent exhaustion principle to method claims, citing earlier Supreme Court precedent including Ethyl Gasoline Corp. v. United States, 309 U.S. 436 (1940), and United States v. Univis Lens Co., 316 U. S. 241 (1942). The test is whether sales "substantially embody" the patents in suit; such sales exhaust the patent right to obtain further royalties. Controlling precedent (Univis) involved sales of eyeglass "blanks" for making patented compound lenses, and the products sold by the alleged infringers were the final eyeglasses containing lenses ground from the blanks sold by the patentee. In Univis, the Court opined that the lens blanks embodied essential features of the patented lenses and thus sales of the blanks exhausted patent rights in the finished lenses.
In Quanta. defendants were makers of computers comprising both patented and non-patented components. LG Electronics licensed the patents-in-suit (U.S. Patent Nos. 4,939,641; 5,379,379; and 5,077,733) to Intel, imposing a condition on its licenses with Intel that sales were not authorized to third parties that would mix Intel and non-Intel components, and further that Intel was under an affirmative obligation to inform its customers that such uses were not licensed. The patents-in-suit claimed methods for organizing read/write requests in computer cache and random access memory (the '379 patent); methods for prioritizing access of peripheral devices to the microprocessor via the computer bus (the '733 patent); and a system for "ensuring that the most current data are retrieved from main [RAM] memory by monitoring data requests and updating main memory from the cache when stale data are requested" (the '641 patent). It was undisputed that Quanta and the other defendants purchased patented microprocessors from Intel that fell within the scope of the LG patents, that they were aware of the restrictions and limitations placed on their use of these components by the license between LG and Intel, and that the defendants sold computer systems comprising Intel components operatively linked to non-Intel components.
The Supreme Court ruled that the components at issue, microprocessors and chipsets, "substantially embodied" the system and method claims of the patents-in-suit. It analogized these components with the lens blanks in Univis (where the patentee argued the lens blanks "did not fully practice the patents at issue" because they needed to be ground into lenses); in Quanta, the patented microprocessors and chipsets did not "function at all" until they were assembled into the final product (i.e., the computer comprising non-Intel components). "If [the Court's opinion stated], as in Univis, patent rights are exhausted by the sale of the incomplete item, then LGE has no postsale right to require that the patents be practiced using only Intel parts." The Court found Univis controlling, inter alia, because the "only reasonable and intended use [of the microprocessors and chipsets] was to practice the patent," just as the only "reasonable and intended use" of the lens blanks in Univis was to make the patented eyeglasses. Moreover, the microprocessors and chipsets embodied the essential features of the patented invention, since all that was required was to attach them to other conventional computer components in conventional ways (much as the lens blanks in Univis were converted to lenses using conventional grinding techniques not encompassed by the patent claims). A similar rationale may be applicable in the case of second opinions in the Myriad case. The test certainly "substantially embodies" the claimed methods, and the practice of the method on a patient sample (with the concomitant production of the patient's genotype) should by analogy with Univis and Quanta exhaust Myriad's patent rights. One distinction between the method claims here and in Univis and Quanta is that those sales involved tangible items (lens blanks and chip sets) that are used to practice the claimed methods. In that way the application of the method claims is ancillary to what is sold, whereas here the practice of the method is what is sold (and the genetic information is what is obtained). The only tangible aspect is the patient sample (and, for the purposes of this discussion, the unpatented reagents used to perform the tests), and the product of the testing (genetic information) is not patentable per se (see "Patenting Information").
Whether this analysis holds will depend on the situs of infringement: while the women as putative purchasers of the practice and results of the claimed methods may thereby be insulated from liability for inducing infringement, the question will be whether clinical labs practicing the claimed methods for these women are shielded from liability thereby.
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