ASSOCIATION FOR MOLECULAR PATHOLOGY, ET AL. v. MYRIAD GENETICS, INC., ET AL.

ASSOCIATION FOR MOLECULAR PATHOLOGY, ET AL. v. MYRIAD GENETICS, INC., ET AL. 1Each human gene is encoded as deoxyribonucleic acid (DNA) taking double helix shapeEach cross-bar in that helix consists of two chemically joined nucleotidesThe nucleotides code for amino acids exons, do not code intronsDNA can be extracted to isolate specific segmentsScientists can synthetically remove introns to create exons-only nucleotides, called complementary DNA (cDNA) Changes in genetic sequence are called mutations some are harmless but some can cause disease2Myriad discovered the precise location and sequence of BRCA1 and BRCA2 genesMutations in these genes can increase risk of breast and ovarian cancerDevelop medical test to detect mutations in patients BRCA1 and BRCA2 and to assess cancer riskMyriad sought and obtained many genes patents for isolated DNA and cDNA3Litigation HistoryLitigation HistoryDistrict Court 2010Petitioner Ostrer, along with medical patients, advocacy groups, and other doctors, filed a lawsuit seeking a declaration that Myriads patents are invalid under 35 U. S. C. 101.Myriads claims, including claims related to cDNA, were invalid because they covered products of nature.Litigation HistoryFederal Circuit 2011The Federal Circuit reverses 2-1, holding that genes are patentable.

Supreme Court 2012The Supreme Court granted the petition for certiorari, vacated the judgment, and remanded the case in light of Mayo Collaborative Services v. Prometheus Laboratories, Inc.

Litigation HistoryFederal Circuit 2012Federal Circuit affirmed its previous decision and reissued an almost identical decision.Petitioner Ostrer had standing. Both isolated DNA and cDNA were patent eligible under 101.

Supreme Court 2012Case returned to the Supreme Court to answer whether human genes are patentable.

Claims before the Supreme CourtClaimsClaim 1 asserts a patent on [a]n isolated DNA coding for a BRCA1 polypeptide, which has the amino acid sequence set forth in SEQ ID NO:2.Claim 2 claims [t]he isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1. SEQ ID NO:1 lists only the cDNA exons in the BRCA1 gene, rather than a full DNA sequenceClaim 5 of the patent claims a subset of the data in claim 1. In particular, it claims [a]n isolated DNA having at least 15 nucleotides of the DNA of claim 1.IssuesIssuesWhether the isolated DNA segment (BRCA1 and BRCA2 genes) constitutes an invention or discovery of new and useful composition of matter, or a new and useful improvement thereof (cf 101 of the US) , or, is it a product of nature/naturally occurring? 2. Whether the synthetically created cDNA (exons-only strands of nucleotides) constitutes an invention or discovery of new and useful composition of matter, or a new and useful improvement thereof (cf 101 of the US), or , is it a product of nature/naturally occurring?

MYRIADs ArgumentsOn isolated DNA sequence (BRCA1 and BRCA2 gene)1.extensive research location of the gene unknown until Myriad found it from among 8million nucleotide pairs2.isolating DNA from human genome involves breaking of the chemical bondsnew non-naturally occurring molecule is created On cDNA1. new exons-only molecule is createdNot naturally-occurring

Implications : If valid Myriad patents 1.Myriad will have exclusive right to isolate an individuals BRCA1 and BRCA2 genes (as well as any strand of 15 or more nucleotides within the genes).But isolation is necessary to conduct genetic testing2.Myriad will have exclusive right to synthetically create BRCA cDNA.

DECISIONSection 101 of the Patent Act"Whoever invents or discovers any new and useful . . . composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title." Implicit exceptionLaws of natureNatural phenomenaAbstract ideas MyriadDid not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes.Uncovered the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13 Description and ClaimsDescription: Detail of the "iterative process" of discovery by which Myriad narrowed the possible locations for the gene sequences that it sought.Claims: Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes Not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA.

cDNACreation of a cDNA sequence from mRNA results in an exons-only molecule that is not naturally occurringcDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived.

ScopeNo method claims before this Court. No new applications of knowledge about the BRCA1 and BRCA2 genes. No scientific alteration of the genetic codeANALYSISNon specificity of DNA sequencesCCS Database of 18,382 high-confidence genes *15mer gene: at least 1 other gene689 CCDS gene : BRCA1 geneNumber of matches decreased as the DNA sequence size increased; Even then, 99.999% of 15mers are repeated at least 2x in entire human genomeCross-kingdom exact matches of 15mers

Other cancer types carrying BRCA1 mutationsOvarian and breast cancers are only 2 of 21 total cancer types likely associated with BRCA1 mutations**

*Rosenfeld & Mason, Genome Medicine 2013, 5:27** The Cancer Genome Atlas data