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Jun 5, 2013

Patent Eligibility of Biological Methods and Compositions

Several recent Supreme Court cases are discussed.

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    Whatever decision is made in the Myriad case, it is sure to have an impact on certain sectors of the industry. [© beermedia - Fotolia.com]

    In the last year and a half, the Supreme Court of the United States (Supreme Court) and the Court of Appeals for the Federal Circuit (Federal Circuit) have issued several decisions that center on the issue of whether biological methods and compositions are eligible for patent protection under 35 U.S.C. § 101. This article updates the information on this topic provided in two previous articles in Industrial Biotechnology.1,2 We discuss these recent court decisions and their possible implications on the patent eligibility of claims directed to biological methods and compositions. We also comment on the recent oral argument held on April 15, 2013, in Association for Molecular Pathology et al. v. Myriad Genetics, Inc., et al. before the US Supreme Court.

  • Biological Methods

    In January of 2012, the Supreme Court issued the Mayo v. Prometheus decision.3 The claims at issue in the Mayo case were directed to methods of optimizing the therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder. The following is a representative claim from the Prometheus patent (emphasis added)4:

  • 1. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising

     (a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and

     (b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,

     wherein the level of 6-thioguanine less than about 230 pmol per 8×108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

  • One of the independent Prometheus' patent claims contained a single active step of determining the level of 6-thioguanine in a subject having immune-mediated gastrointestinal disorder and included similar “wherein” clauses.

    In its decision, the Supreme Court held that the Prometheus claims were invalid because they covered non-statutory subject matter. The Court began by stating that a patent may not “preempt the use of a natural law,” and warned that the addition of steps to “well-understood, routine, conventional activity” or “post-solution” activity will not save a claim directed to a natural law.5–7

    The Court indicated that “[a] patent must do more than simply state the law of nature while adding the words ‘apply it,’” and held that the Prometheus claims failed to meet this standard.8 Specifically, the Court interpreted the “administering” step to “simply refer…to the relevant audience,” the “determining” step as “simply…[telling] the doctor to determine the level of the relevant metabolites in the blood, through whatever process the doctor or the laboratory wishes to use,” and the “wherein” clauses as “simply…[telling] a doctor about the relevant laws…” and providing “at most, a suggestion that they should consider the test results when making their treatment decisions.”9–11 In view of this interpretation of the active steps and the “wherein” clauses in the Prometheus claims, the Supreme Court concluded that the steps together added “nothing to the law of nature.”12

    Since the Supreme Court's Mayo v. Prometheus decision, the Federal Circuit has issued two decisions relating to the patent eligibility of biological methods: Association for Molecular Pathology v. Myriad Genetics, Inc. et al. (Myriad) and PerkinElmer, Inc. v. Intema Ltd. (PerkinElmer).13,14 The Federal Circuit's prior decision in the Myriad case was vacated by the Supreme Court, and the case was remanded to the Federal Circuit for reconsideration in view of the Mayo decision. Two types of method claims were at issue in the Myriad case: claims directed to methods of detecting a germline alteration in the BRCA1 gene or screening a tumor sample that included a single active step of “analyzing” or “comparing” nucleic acid sequences; and a single claim directed to a method for screening potential cancer therapeutics that included an active step of growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer.

    As in its previous vacated decision, the Federal Circuit held that the claims directed to methods of detecting a germline alteration in a BRCA1 gene or screening a tumor sample were “outside the scope of § 101 because they claim only abstract mental processes” and were thus invalid.15 The Federal Circuit specifically noted that these Myriad claims, which are directed to “comparing” or “analyzing” two nucleic acid sequences, “do not apply the step of comparing the…nucleotide sequences in a process,” but rather, “the step of comparing the two DNA sequences is the entire process….”16

    In contrast to the claims that recited only a single active step of “analyzing” or “comparing” nucleic acid sequences, the Federal Circuit held that the claim directed to a method for screening potential cancer therapeutics was eligible for patent protection. The Federal Circuit noted that the transformed eukaryotic cells used in these methods were a “product of man, not of nature,” and set forth that “once one has determined that a claimed composition of matter is patent-eligible subject matter, applying various known types of procedures to it is not merely applying conventional steps to a law of nature.”17,18 According to the Federal Circuit's reasoning in the Myriad case, the recitation of the use of a patent eligible composition in a method claim also makes the method claim eligible for patent protection under 35 U.S.C. § 101.

    Although the Federal Circuit's reasoning on this matter may be encouraging to patent applicants and owners, the Supreme Court is currently reviewing the patent eligibility of isolated DNA (a biological composition) in this appealed case, and the Federal Circuit's reasoning on the patent eligibility of the screening method claim may be significantly weakened if the Supreme Court determines that only certain classes of biological compositions are patent eligible.19

    The other recent Federal Circuit case dealing with patent eligibility of biological methods was the PerkinElmer case. Claim 1 below is a representative claim at issue in the PerkinElmer decision (emphasis added)20:

  • 1. A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down's syndrome, the method comprising the steps of:

     (a) measuring the level of at least one screening marker from a first trimester of pregnancy by:

      (i) assaying a sample…; and/or

      (ii) measuring at least one first ultrasound screening markers from an ultrasound scan…;

     (b) measuring the level of at least one second ultrasound screening marker from a second trimester of pregnancy [the at least second screening marker and the at least first screening marker are different] by:

      (i) assaying a sample…; and/or

      (ii) measuring at least one second ultrasound screening markers from an ultrasound scan; and

     (c) determining the risk of Down's syndrome by comparing the measured levels…with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies.

  • The Federal Circuit held that the claims at issue in the PerkinElmer case were not eligible for patent protection, because they recite a “mental process of comparing data to determine a risk level” and that no action “beyond the comparison is required.”21,22 With respect to the individual steps in the claims, the Federal Circuit held that the “measuring” step “merely tell[s] the users of the process to measure the screening markers through whatever known method they wish,” the “assaying” step “could be performed without transforming the [sample],” and the “determining” step is a mental step and the statistical information is “well-understood, conventional information.”23–25 The Federal Circuit further stated that the concept of “two markers are better than one” is considered a “mental step” or “abstract idea.”26 The court also noted that “[a]s in Mayo, there is no requirement that a doctor act on the calculated risk” and “[t]here is at most a suggestion.”27 This final comment suggests that the Federal Circuit could find a method claim that includes mental steps or conventional steps, but also requires an active step, eg, by a physician, to be eligible for patent protection under 35 U.S.C. § 101 in the future.

  • Biological Compositions

    In addition to the method claims discussed above, the Federal Circuit also decided the eligibility for patent protection of Myriad's biological composition claims (following remand from the Supreme Court). Exemplary composition claims at issue in the Myriad case are shown below (emphasis added)28:

  • 1. An isolated DNA encoding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO: 2.

    2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO: 1.

  • Claim 1 corresponds to the genomic sequence of the BRCA1 gene (including introns), and claim 2 corresponds to a complementary DNA (cDNA) sequence that encodes the BRCA1 polypeptide.

    The Federal Circuit began by noting that the Supreme Court's Mayo v. Prometheus case does not control “the question of patent eligibility of…[composition] claims.”29 The Federal Circuit then asked whether the claim is directed to “[a] product of human ingenuity ‘having a distinctive name, character, [and] use’”30 or a composition that is “‘markedly different,’—[has] a ‘distinctive’ chemical structure and identity from those found in nature.”31 The Federal Circuit held that the Myriad composition claims met this test as “[t]he isolated DNA molecules…are not found in nature….[,] [but are] man-made, the product of human ingenuity.”32 The court noted that “[isolated DNA] is manipulated chemically so as to produce a molecule that is markedly different from that which exists in the body.”33 The court also found that the isolated DNA claimed in Myriad can be used for different purposes, and is a different molecule than the same nucleic acid sequence present in a chromosome or in chromatin.

  • The Supreme Court's View

    These Federal Circuit decisions set the stage for the oral arguments before the Supreme Court in the Myriad case presented on April 15, 2013. As can be expected, the different Justices had different views and concerns that they expressed during the oral arguments. For example, Justice Alito appeared to agree with the Federal Circuit's conclusion that isolated DNA has a different form and use than genomic DNA present in a cell. Justice Alito specifically commented that “[i]solated DNA has a very different function from the [genomic] DNA as it exists in nature. And although the chemical composition may not be different, it certainly is in a different form.”34 However, Chief Justice Roberts appeared to take a different view, commenting that “[h]ere you're just snipping, and you don't have anything new, you have something that is a part of something that has existed previous to your intervention.”35 In a similar vein, Justice Sotomayor asked, “I always thought that to have a patent you had to take something and add to what nature does. So how do you add to nature when all you are doing is copying its sequence?”36

    Despite their differences, several of the Justices seemed to agree that claims directed to cDNAs are patent eligible, because these nucleic acid sequences are not naturally found in a human cell. For example, Justice Sotomayor distinguished cDNA from isolated genomic DNA, stating that “[cDNA] is artificially created in the laboratory, so it's not bound [sic, found] in nature. It's not taking a gene and snipping something that's in nature.”37

    It is also noteworthy that Justices Kennedy, Alito, Scalia, and Kagan all brought up concerns about business incentives for the biotechnology industry. Justice Kagan asked “[w]hy shouldn't we worry that Myriad or companies like it will just say, well, you know, we're not going to do this work anymore?”38 Justice Scalia similarly inquired, “[w]hy would a company incur massive investment if it cannot patent.”39 Justice Alito commented that “if patent eligibility is denied here it will prevent investments that are necessary for the development of new drugs or it will lead those who develop the new drugs, new diagnostic techniques, to keep those secret, not disclose them to the public.”40

    Thus, during the oral hearing, the Court raised many different views and concerns, making it difficult to predict how the Court will decide the case. However, given the Justices' comments, we would not be surprised if they decide that cDNA and recombinant DNA are eligible for patent protection because they are created by man's manipulations, but that genomic DNA, even if isolated, is not eligible for patent protection, because it is not markedly different from naturally occurring DNA. If the Court decides the case in this way, we also expect that in future cases expression vectors or recombinant algae, fungi, or bacteria that are not found in nature would also be patent eligible. On the other hand, new strains of bacteria or fungi, eg, isolated from some bit of water, soil, or mud, would not be eligible for patent protection under Section 101.

    The Supreme Court is predicted to issue its decision in the Myriad case by the end of its term in June. In the meantime, many pundits will make predictions on the outcome. However, biotech patent applicants and owners alike can only wait for the decision, which, depending on its outcome, can have a major impact on certain sectors of this industry.


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