Isolated unaltered natural DNA is not patent eligible; man-made DNA (such as cDNA) that is distinguishable from natural DNA, remains patent eligible.
The opinion of the US Supreme Court issued on June 13th, 2013 (http://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf) relating to Myriad Genetics' patent of BRCA genes is breaking news and is suggested to have a major impact on gene patenting.
Summary
The Supreme Court ruled that isolated unaltered, natural deoxyribonucleic acid (DNA) sequences are not patentable based on section 101 of the US patent act (35 U.S.C. §101), irrespective of the industrial application and inventiveness of such DNA.
The Supreme Court also ruled that (man-made) cDNA that is distinguishable from natural DNA satisfies the requirements of patent eligibility.
Section 35 U.S.C. §101 of the US patent act governs what is to be regarded patent eligible subject matter. It basically rules that process, machines, manufactures, or compositions of matter and improvements thereof are patentable, while laws of nature, natural phenomena, and abstract ideas are not.
As a result, the most broad claims of Myriads patents, which would provide Myriad the exclusive right to isolate an individual's BRCA1 and BRCA2 genes, are judged invalid since they relate to a naturally occurring segment of DNA being not patent eligible under 35 U. S. C. §101.
Background
Myriad has based a number of patents on its discovery of the position of two genes encoding polypeptides BRCA1 and BRCA2, respectively, which are highly relevant in predicting an individual's risk of developing breast and ovarian cancer. More specifically, Myriad claimed that their research has revealed several mutations in BRCA1 and BRCA2 that are associated with increased risk of developing breast and ovarian cancer. By analysis of the DNA sequence of the BRCA 1 and/or BRCA 2 genes, specifically the mutations, one is able to assess a predisposition for developing breast and ovarian cancer.
After Myriad found out that several entities offered BRCA testing services to women, Myriad filed patent infringement suits against these entities. Some years later, several entities, including medical patients, advocacy groups and other doctors filed a lawsuit seeking a declaration that Myriads patents would be invalid under 35 U.S.C. §101.
The first instance district court judged the product claims reading on the BRCA1 and BRCA2 invalid because they covered products of nature. The US Court of Appeals for the Federal Circuit later reversed the decision, finding that isolated DNA and cDNA are patent eligible, since they would be different than DNA in its natural, non-isolated, form. The Supreme Court granted a petition for certiorari and issued an opinion on June 13th, 2013.
Claims at issue
Nine product or composition claims from three of Myriad patents relating to BRCA1 and BRCA2 (US 5,693,473, US 5,693,473 and US 5,837,492) were at issue in this case. Claims 1, 2, 5 and 6 of US 5,747,282 are regarded as representative by the Supreme Court, and copied in below:
- An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO: 2 (note: SEQ ID NO: 2 represents the amino acid sequence of a typical BRCA1 polypeptide).
- The isolate DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO: 1 (note: SEQ ID NO: 1 represents the cDNA sequence of a typical BRCA1 polypeptide).
- ....
- ....
- An isolated DNA having at least 15 nucleotides of the DNA of claim 1
- An isolated DNA having at least 15 nucleotides of the DNA of claim 2.
The Supreme Court now ruled that claim 1 is invalid as it falls within the "law of nature exceptions" of 101, for reason that Myriad did not create or alter the genetic information or the structure of the DNA. It was argued by the Supreme Court that Myriads principle contribution was uncovering the precise location of the sequences of the BRCA1 and BRCA2 genes. Isolation is regarded by the Court as the pure breaking of chemical bonds. The Court ruled the claim does not rely on the chemical changes that result from the breaking of this chemical bonds but focusses on the genetic information of the BRCA1 gene, i.e. the sequence, not the molecule, is what is actually claimed. This is further elucidated by the remark that Myriad would resist to a would-be infringer using the BRCA gene and one additional nucleotide pair.
The statement that Myriad only identified the location of the BRCA genes seems to underestimate the contribution of Myriad to BRCA testing, as Myriad claims to have also identified the role of mutations in the gene in risk of developing breast and/or ovarian cancer. The Supreme Court nevertheless ruled that such extensive research efforts cannot save the claim from being excluded from patentability because the DNA would nevertheless relate to a natural phenomenon.
The US Court of Appeals for the Federal Circuit based their decision mainly on the previous decision of the Supreme Court (Mayo v. Prometheus 566 U.S. ___ 2012) judging a method for determining a personal effective dose of a specific medicament based on metabolite levels to be measured as patent illegible as it is considered "a newly discovered law of nature". In Mayo v. Prometheus, the court ruled that Laws of nature are basic tools of scientific and technological work. Without the exception there would be considerable danger that the grant of patents would "tie up" the use of such tools and thereby "inhibit future innovation and premised upon them." The Court also mentions in this respect the decision of Diamond v. Chakrabarty, 477 U.S. ___ (1980) in which it is stated that products of nature are not created and manifestations ... of nature are free to all men and reserved exclusively to none".
The Supreme Court does not deny that Myriad found an important and useful gene, but stresses that "groundbreaking, innovative or even brilliant discovery does not by itself satisfy the §101 inquiry, i.e. even though highly inventive and industrially applicable, if an invention is considered as a natural phenomenon or a law of nature, it remains unpatentable.
The Supreme Court ruled that cDNA does not occur in nature, and therefore meets the requirement of 35 U.S.C. §101 and is patent eligible. Should the cDNA molecule meet further requirements (such as novelty and inventiveness over the prior art), a claim relating to cDNA is allowable.
The Supreme Court further ruled that cDNA is not patent eligible "insofar as very short series of DNA may have no intervening introns to remove when creating the cDNA. In that situation, a sort strand of cDNA may be indistinguishable from natural DNA." This implicates that short sequences of cDNA are patent eligible if these are distinguishable from natural DNA, like the sequences of the above indicated claim 5. Short sequences such as claimed in the above indicated claim 6 are only patent eligible if not occurring in nature for instance because these sequences in nature comprise an intron sequence which is not included in the claimed sequence.
Importantly, claims not at stake before the Supreme Court are claims relating to DNA in which the order of naturally occurring nucleotides has been altered, to a replicative cloning vector, to expression system or to host cells comprising the indicated isolated DNA sequences, to methods for producing BRCA1, to methods for screening or to kits for detecting mutations in the BRCA genes and primer pairs for to be used in PCR the BRCA gene.
Impact of the decision in US patent law and on biotech
The breadth of the (compromise) decision remains to be awaited and is depending on how lower courts will explain and apply the decision. It has to be concluded that what is regarded by the Supreme Court as patentable subject matter and what is not, is still quite subjective. The level of modification seems to be decisive as both isolated DNA (isolated by breaking specific chemical bonds to release the DNA from the genome) and cDNA (isolated DNA from which intron sequences have been removed, or DNA prepared in vitro from mRNA) do not occur in nature. Anti gene-patenting lobbyists may plead that both need not necessarily be the result of a technician creating something, but both can be predicted from knowledge of nature once the location of the gene has been discovered. Furthermore, the reason of a sequence being the subject of the claim rather than the molecule itself seems not to have been applied consistently as this does seem to apply for both claim 1 and claim 2, while the Court comes to a completely different outcome for said claims.
What if the reasons are extended beyond DNA: e.g. many naturally occurring proteins and polypeptides are patented in US. Time will tell.
As the Supreme Court ruled that modifying genes by excluding intron sequences resulting in cDNA is sufficient modification to judge it as patent illegible, even though nature has dictated intron positions, there are still possibilities for patenting of DNA sequences. Man-made constructs such as cloned genes, expression constructs, vectors, DNA probes and assays (should) still satisfy the standards of patent eligibility.
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