[authors: Michael R. Samardzija, Ph.D. and Karthika Perumal, Ph.D.]
The U.S. Court of Appeals for the Federal Circuit delivered a mixed verdict1 in the latest episode of the lawsuit against Myriad Genetics and the University of Utah Research Foundation over the patent eligibility of Myriad's patent claims on the BRCA1 and BRCA2 genes and the methods of utilizing these genes. Earlier this year, the Federal Circuit was asked to reconsider its July 2011 decision following the Supreme Court's decision in Mayo2 that found the medical diagnostic claims merely incorporating laws of nature are ineligible for patent protection. Last week's decision by the Federal Circuit was significantly similar to its July 2011 decision even after the application of the guiding principles from Mayo.
Dissection of the current opinion
The Myriad patent portfolio3 under dispute mostly involves four types of claims - two types of claims directed to DNA sequences as compositions of matter and two types of claims directed to methods of utilizing these sequences as diagnostic and screening tools.
Patent eligibility of nucleic acid sequences
The two types of composition claims are claims directed to 1) isolated cDNA sequences (isolated DNA sequences that are different from the naturally occurring sequences) and 2) isolated DNA sequences (sequences that are identical to naturally occurring sequences and range from short fragments to longer strands, including the full-length sequence). The three judges on the Federal Circuit panel agreed that the Supreme Court's earlier decision in Mayo does not control the question of patent-eligibility of these composition claims and that isolated cDNA sequences were patent eligible subject matter under § 101. But the panel's decision was split over the patent eligibility of isolated DNA sequences.
Judge Lourie in his majority decision did not distinguish the isolated cDNA and the isolated DNA compositions based on their sequence differences relative to the native sequence in the chromosomal DNA. Instead, he held all isolated DNA sequences, whether cDNA or not, are patent-eligible subject matter under § 101. While the isolated sequences may share the same informational properties as the native sequences, the isolated sequences are chemically distinct entities from the naturally occurring genes in the chromosomes. In her concurring opinion, Judge Moore distinguished between the two types of compositions but reached deep into the judicial history of patentability and the policy issues to concur with Judge Lourie's opinion on patent eligibility of the longer strands of isolated DNA sequences. In addition to judicial precedent, Judge Moore relied on the USPTO's policy and guidelines regarding the patent eligibility of isolated natural products, and on the lack of Congressional action despite Congressional awareness of the patents on human genes. She also expanded on Judge Lourie's concerns about upsetting the ‘settled expectations of the biotechnology industry' with respect to composition of matter claims directed to isolated gene sequences. Both Judge Lourie and Judge Moore stressed that Congress did not exclude isolated DNA sequences as patent-ineligible subject matter when it enacted a comprehensive patent reform legislation, the Leahy-Smith America Invents Act.
In his partial dissent, Judge Bryson restated his objections to allowing patents for purified or isolated versions of naturally occurring elements. He provided several visually vivid analogies, likening the isolation of a gene to the snapping of a leaf from a tree, "extracting a kidney from a host," and "extracting a slab of marble from the earth." He utilized the Supreme Court's analysis in Mayo to conclude that as the isolated DNA sequences are identical to the naturally occurring sequences, there is not sufficient inventive contribution. Therefore, he contends such sequences, irrespective of their length, should not be eligible for patent protection.
Patent eligibility of methods of utilizing the isolated nucleic acid sequences
A straightforward application of Mayo to the method claims did not change the previous Federal Circuit analysis. The Myriad patent portfolio had two types of methods claims: claims directed to methods of "comparing" or "analyzing" the BRCA sequences of a patient against the normal BRCA gene sequence,4 and a claim directed to a method of screening potential cancer therapeutics.5
The methods of "comparing" or "analyzing" sequences were found to be patent-ineligible subject matter. Claims in Mayo that were found invalid by the Supreme Court were directed to a method that comprised of "administering" a known drug and "determining" its level in the patient's blood. While the methods relied on transformation of the patient's body and blood, the claims were found to merely capture a law of nature - the relationship between concentrations of the thiopurine in the blood and the prospect of the administered dosage being ineffective or causing harm. The Supreme Court found no inventive step in the claimed method beyond the law of nature and routine conventional activity. Myriad's claims were exactly the kind that were admonished by the Supreme Court - claims that simply state a law of nature and add the words "apply it." Myriad's claims were directed to methods of comparing the nucleic acid sequences from tumor and normal cells or analyzing the sequences for gene mutations. No step of the claimed methods involved the extraction or sequencing or any processing of the BRCA nucleic acids. Unsurprisingly, the Federal Circuit held these claims of "comparing" or "analyzing" sequences invalid for claiming abstract mental processes.
But, Myriad had one claim directed to the method of screening for a cancer therapeutic by determining which compound decreases the growth rate of a host cell, containing the cancer-causing mutations of BRCA1 gene. In addition to the ‘determining' and ‘comparing' steps, the claims included two steps of growing the transformed cells in the presence and absence of a prospective therapeutic. All three members of the Federal Circuit panel found this claim to be patent-eligible because the "heart" of this method claim was a man-made transformed cell.
This decision by the Federal Circuit provides incremental guidance on the patent eligibility of medical diagnostic patents. Patent eligibility of claims that solely have comparing or determining elements associated with a natural correlation are likely in jeopardy. Claims that include steps involving the transformation of physical or informational elements appear to be in better shape to withstand a §101 attack. Additional steps such as novel testing techniques or testing reagents, or devices would strengthen medical diagnostic claims. But when pursuing claims that include more inventive steps, one should also keep in mind the limitations imposed by infringement theories when all steps are not performed by a single actor. When a naturally occurring biological element is identified as a diagnostic or prognostic tool, it is more important now to develop reagents or devices, which utilize the biological elements in a manner distinct from the naturally occurring state. Patent applicants would be well-advised to continue pursuing claims directed to isolated cDNA sequences, shorter fragments of the conserved regions of genes, and other nucleic acid sequences that are structurally distinct from the native chromosomal sequence. The split decision in Myriad leaves the question of patent eligibility of isolated DNA sequences open for further analysis by an en banc panel at the Federal Circuit or a direct review by the Supreme Court.
1 Association for Molecular Pathology et al. v. U.S. Patent and Trademark Office et al., No. 2010-1046 (Fed. Cir. Aug. 16, 2012). See Update: Chilling Assault on Personalized Medicine, Bracewell & Giuliani LLP (Sep. 9, 2009) for a description regarding the plaintiffs.
2 Mayo Collaborative Services v. Prometheus Laboratories, Inc. 132 S. Ct. 1289 (2012)(for a detailed discussion of Mayo and the particular facts and determinations involved, see Update: Can't Touch This - Supreme Court Finds Personalized Medicine Patent Claims Invalid, Bracewell & Giuliani LLP (Mar. 20, 2012)).
3 The patents-in-suit are U.S. Patent Numbers 5,693,473; 5,709,999; 5,710,001; 5,747,282; 5,753,441; 5,837,492; and 6,033,857.
4 Claim 20 of the '282 patent reads as follows:
20. A method for screening potential cancer therapeutics which comprises: growing a trans-formed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.
5 Representative method claims include claims 1 of the '999 patent:
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 Ta-bles 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.