Gene Patents (Part 5 – the Law)
This is the fifth in a series of articles on the Myriad Genetics case. Here are the links to the previous articles in the series:
The previous posts in this series attempted to provide sufficient background in molecular biology to enable the non-specialist patent practitioner to understand the issues in Association for Molecular Pathology v. U.S. Patent and Trademark Office, No. 2010-1406) (Fed. Cir. July 29, 2011) (“the Myriad Genetics case”). We now return to the case with this background in mind.
It will be useful to begin by looking at some representative composition claims of the underlying patents, as did the majority in Myriad Genetics. Claims 1, 2, and 5 of U.S. Patent N0. 5,747,292 (“the ‘282 patent) are:
1. An isolated DNA coding 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.
5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.
The USPTO uses sequence identifiers (SEQ IDs) to unambiguously identify the nucleotide or protein sequence in a macromolecule. The ‘282 patent identifies SEQ ID NO:1 as being of the molecular type cDNA and having a length of 5914 base pairs. Further, the ‘282 patent identifies SEQ ID NO:2 as being of the molecular type protein and having a length of 1863 amino acids. Simple math (each amino acid requires 3 nucleotides in a cDNA) indicates that only 5589 base pairs would be required in a cDNA to encode the protein of SEQ ID NO:2. Although the ‘282 patent also includes sequence id’s to smaller and larger molecules (85 sequence id’s total), none of these sequence id’s is directly claimed in the ‘282 patent.
The ‘282 patent also includes in its Specification a number of important definitions. For example, “coding for” in claim 1 would be defined by “Encode. A polynucleotide is said to ‘encode’ a polypeptide if, in its native state or when manipulated by methods well known to those skilled in the art, it can be transcribed and/or translated to produce the mRNA for and/or the polypeptide or a fragment thereof.” (‘282 patent, column 19 lines 1-5). Further, “isolated” is defined as a nucleic acid “which is substantially separated from other cellular components which naturally accompany a native human sequence or protein, e.g. ribosomes, polymerases, many other human genome sequences and proteins. The term embraces a nucleic acid sequence or protein which has been removed from its naturally occurring environment and includes recombinant or cloned DNA isolates and chemically synthesized analogs or analogs biologically synthesized by heterologous systems.” (‘282 patent, column 19 lines 8-18)
Under the above definitions, claim 1 encompasses all polynucleotides which can be transcribed or translated into the polypeptide of SEQ ID NO:2. As the reader will know from the previous posts in this series, this includes the full gene or open reading frame that encodes the BRCA1 polypeptide, as well as smaller portions of the open reading frame such as cDNAs resulting from removal of the introns from the gene. Claim 2 is much narrower than claim 1, claiming only the 5914 base pair sequence of SEQ ID NO:1, presumably the cDNA resulting from reverse transcription of mRNA with the introns removed. Claim 5 is really no narrower than claim 1, since it claims “at least 15 nucleotides” and thus encompasses a genus of all polynucleotides that “encode” the BRCA1 polypeptide from 15 nucleotides in length up to the full open reading frame. All other terms of the above claims are self-defining to one of ordinary skill in the art.
The Federal Circuit’s decision in the Myriad case was by a three-judge panel. Judge Lourie wrote the opinion of the Court, with Judge Moore concurring in part and Judge Bryson concurring in part and dissenting in part.
Judge Lourie held that “the challenged claims to isolated DNAs, whether limited to cDNAs or not, are directed to patent-eligible subject matter under Section 101.” (Association for Molecular Pathology at 39) Judge Moore joined the majority opinion with respect to claims to isolated cDNA sequences and concurred in the judgment with respect to the other sequences. He wrote separately to explain his reasoning. Judge Bryson concurred with respect to the patentability of the cDNA claims but dissented with respect to the gene claims, finding them to not be patent-eligible.
Judge Lourie’s opinion discusses the law of patentability of isolated DNA molecules, and I refer the reader to his opinion for the details. In summary, the Supreme Court’s opinions in the Chakrabarty and Funk Brothers cases are controlling. Chakrabarty’s holding was that a claim to “a non-naturally occurring manufacture or composition of matter — a product of human ingenuity ‘having a distinctive name, character [and] use” is patent-eligible under 35 U.S.C. 101. In contrast, the bacteria in Funk Brothers were found to be non-patent eligible under that statute, the difference being that Chakrabarty’s bacteria had “markedly different characteristics from any [bacterium] found in nature” based on the efforts of the patentee. According to Judge Lourie, the distinction rests on a “change in the claimed composition’s identity compared with what exists in nature.” Judge Lourie applied this law to the facts of the Myriad case, finding that because isolated DNA had covalent bonds in its backbone chemically severed, “BRCA1 and BRCA2 in their isolated state are not the same molecule as DNA as it exists in the body; human intervention in cleaving or synthesizing a portion of a native chromosomal DNA imparts on that isolated DNA a distinctive chemical entity from that possessed by the native DNA.” He rejected the plaintiff’s argument that, because the isolated DNAs have the same nucleotide sequence as native DNAs, they do not have any “markedly different” characteristics. For Judge Lourie, the information content of the DNA is not what makes a DNA markedly different from another: rather, it is the molecule’s chemical structure and not its function.
Judge Moore’s concurrence is aimed more directly at the chemical nature of the DNA sequences claimed. He pointed out that DNA is a chemical polymer that is “no different than any other well known polymer, for example, nylon.” Polymerization of the 4 mononucleotides “results in a molecule with a different ionic charge, different chemical bonds, and a different chemical composition, as compared to the monomers in aggregate.” Like Judge Lourie, Judge Moore takes a position that it is not the information content of DNA that is significant for patentability, but rather its chemical structure: “just because the same series of letters appears in both the chromosome and an isolated DNA sequence does not mean they are the same molecule.” He found the cDNA claims such as claim 2 of the ‘282 patent to be patentable under 35 USC 101. He expressed greater concern for the genomic DNA claims such as claim 1. In exploring these differences, he focused on the utility of the claimed DNAs. He found the short sequences of claim 2 to have clear utility in diagnostic testing as primers and probes, stating that “the body does not naturally engage in this type of testing….” However, he also found that the longer DNA sequences as claimed in claims 1 and 5 do not have such utility. He stated: “Whether an isolated gene is patentable subject matter depends on how much weight is allocated to the different structure as compared to the similarity of the function to nature.” Under this test, he implies, the longer DNA sequences would not be patentable because, although they are structurally different from naturally-occurring DNA, they do not have a significantly different function. However, he declines to rule the longer DNA sequences unpatentable because of the settled expectations of the scientific community created by the thousands of gene patents that have been issued by the U.S. Patent and Trademark Office.
Judge Bryson’s opinion takes a stronger position against the gene claims, finding that they are not directed to patentable subject matter, while concurring that the cDNA claims are patentable. His concern is that upholding patentability of the gene claims may preempt methods for whole-genome sequencing. Although the isolated genes have a different chemical structure from those found in the body, the “only material change made to those genes from their natural state is the change that is necessarily incidental to the extraction of the genes from the environment in which thay are found in nature.” He sees this isolation process as not significantly different from extracting a mineral or taking a cutting from a wild plant. For Judge Bryson, “there is no magic in a chemical bond that requires us to recognize a new product when a chemical bond is created or broken, but not when other atomic or molecular forces are altered.” There is no difference in terms of patentability between breaking a chemical bond and separating a cutting of a wild plant by scissors. The claimed genes have merely been isolated “according to nature’s predefined boundaries, i.e., at points that preserve the ability of the gene to express the protein for which it is coded.” Here, of course, he is referring to the removal of introns from the naturally-occurring gene to produce a cDNA. I refer the reader to Part 2 of this series. Thus, he concludes, claims to the short cDNA sequence are patentable under 35 U.S.C. 101, but claims such as claims 5 and 6 are not. He supports this position by noting that claim 6 would cover each BRCA1 exon, and also the cDNA of “more than 4% of human genes.”