Joan Ellis Ph.D. Member Dickinson Wright PLLC
The Myriad Decisions Have Not Been a Death Knell for the Biotechnology Industry
Companies must take the lessons from Association for Molecular Pathology v. Myriad Genetics, Inc. and apply them to their biotechnology inventions to ensure patent protection.
Scientists at Myriad discovered the location of the BRCA1 and BRCA2 genes on human chromosomes 17 and 13, associated those genes with a woman’s risk of developing breast and ovarian cancer, and determined their nucleotide sequences. The Association for Molecular Pathology challenged three of Myriad’s patents in district court. The case was eventually appealed to the Supreme Court who granted certiorari on the claims directed to isolated DNA. Justice Thomas delivered the majority opinion that held that human genes were unpatentable because “the location and order of the nucleotides existed in nature before Myriad found them.” 1
Importantly for the biotechnology industry, the Court indicated that the patentability of cDNA stood on a different footing. Since cDNA is devoid of introns normally present in eukaryotic genomes and is synthesized in the laboratory, it is not a product of nature and, therefore, patent eligible. The Court pointed out that it was not expressing an opinion on whether (1) DNA have a rearrangement of the naturally-occurring order of nucleotides; and (2) new methods of using naturally-occurring DNA, were patent eligible.
In December 2014, the Federal Circuit reviewed an appeal of other Myriad patents that claimed (1) a pair of single-stranded DNA primers, derived from chromosome 17q, that were to be used to determine the nucleotide sequence of BRCA1; and (2) methods of detecting a BRCA1 mutation in a patient.2
Myriad argued that DNA primers are synthetically created and have a different function than the naturally-occurring gene, and therefore are patent eligible under §101. However, the court found that the nucleotide sequence of the primers were identical to the naturally-occurring BRCA1 sequence and held that they were products of nature. Myriad also argued that the primers performed a function in vitro that did not occur when they are part of the naturally-occurring sequence. The court disagreed finding that the use of the primers in a polymerase chain reaction was not a “significantly new function” because “in nature complementary nucleotide sequences bind to each other.”3
The Federal Circuit also considered two method claims that were directed to screening the DNA of a human subject for an alteration of the BRCA1 gene.4 The court found that paragraph one of the claims described comparing wild-type BRCA1 nucleotide sequences with a patient’s DNA and determining whether there was a difference in the sequences. The court concluded that the steps of “comparing” and “analyzing” two nucleotide sequences were an unpatentable abstract idea. The second paragraph of the claims described hybridizing DNA and detecting the presence of a hybridization product. The court found that these steps were “well-understood, routine and conventional techniques” employed by scientists in the field and did “not add ‘enough’ to make the claims as a whole patent-eligible.”5
Claim Construction Post-Myriad
The Myriad decisions have not been the death knell for the biotechnology industry. This may partially be due to the fact that the Supreme Court indicated that many biotech inventions are still patentable. Below are examples of what is patent eligible in the post-Myriad era.
cDNA is still patent eligible. Thus, practitioners can direct cDNA claims to sequences that are derived from genes that naturally contain introns. Claims to cDNA must either include the full-length sequence or portions thereof that were separated by an intron in the naturally-occurring gene.
Claims to small DNA fragments that occur in the gene in its state (i.e., primers) will not be patentable.
Nucleotide sequences, proteins and peptides that are not identical to naturally-occurring genes and proteins may be patent eligible. Nucleotide sequences and proteins that have been altered by inserting, deleting and/or substituting nucleotides and amino acids, respectively, may satisfy §101. In The Univ. of Utah Research Foundation, the Federal Circuit confirmed that a DNA sequence having “a function that is similar to that found in nature” can be patent eligible provided it has a different structure. However, it is not yet clear how much a composition must differ from a naturally-occurring product to be patentable.
New methods of using old or known compositions may be patented. Even if a naturally-occurring nucleotide sequence or protein is not patent eligible, it may still be possible to obtain a patent on newly discovered methods of using them.
2 University of Utah Research Foundation v. Ambry Genetics, No. 2014-1362,-1366, slip op. at 7-8.
3 Id., slip op. at 9
4 Claim 7 is representative and reads as follows:
7. 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 BRCA1 cDNA of wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from the wild-type indicates an alteration in the BRCA1 gene is said subject,
_______wherein a germline nucleic acid sequence is compared by hybridizing a BRCA1 gene probe which specifically hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and detecting the presence of a hybridization product wherein a presence of said product indicates the presence of said allele in the subject.
Claim 8 further required that the patient’s DNA be amplified prior to hybridization with the wild-type BRCA1 gene and that the amplified DNA be sequenced. The court found that these two additional steps were also “well-understood, routine and conventional activit[ies] engaged in by scientists at the time of Myriad’s patent applications”.
5 Univ. of Utah Res. Fdn., slip op. at 17.
Joan Ellis ([email protected]), is a member in Dickinson Wright PLLC’s Washington, D.C. office. She focuses on patent prosecution and litigation with an emphasis in the chemical and life science fields.