Rebecca Rae Anderson, J.D., M.S., C.G.C. University of Nebraska Medical Center College of Public Health

Dilbert’s I.P. experience

SACGHS Office of Science Policy – NIH Secretary’s Advisory Committee on Genetics, Health and Society Gene Patents and Licensing Practices and Patient Access to Genetic Tests (Public Consultation Report March 2009) Appendix 1 : Case Studies Duke University Center for Genome Ethics, Law & Policy

What we’ll discuss: Can you really patent a gene? What is a genetic patent, anyway? How have genetic patents affected clinical genetics? What can we expect in the future?

Can you really patent a gene? Article 1 Section 8 Congress shall have power... to promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries.

Can you really patent a gene? 37 USC§101. Inventions Patentable. Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.

Can you really patent a gene?

Patent number Inventors Current owners Field of art Filing history Abstract

‘487 Inventors & Assignees

‘487 Timeline

‘487 Abstract

‘487 Drawings

‘487 Enablement

‘487 Claims

2. A purified normal CFTR RNA A purified... cDNA. 4. A purified DNA molecule... Comprising a DNA sequence encoding an amino acid sequence depicted in Fig A detectably labeled normal CFTR probe, comprising... At least 16 contiguous nucleotides A normal CFTR probe...

‘487 Claims

‘487 Figure: CFTR Sequences

~4,400 sequence patents by 2007

What’s the fuss? Monopoly? Anti-commons? Hold-outs? Cross-blocking? Defensive patents? Gendia What’s the fuss?

Adam Brandejs art installation ca.2006 What’s the fuss?

Canavan – Miami Children’s Retrospective royalties $25 per test (later $12.50) Few academics (<100 assays) One large commercial lab Salon.com Who owns your DNA? Jonathan & Amy GreenbergJudith Tsipis, M.S.

Greenberg v. Miami Children’s 264 F Supp 2d 1064 (S.D. Fla. 2003) Lack of informed consent Breach of fiduciary duty Unjust enrichment Fraudulent concealment Conversion Misappropriation of trade secrets

Canavan – Miami Children’s "My understanding from the hospital was we needed to file the patent just so I could work with the gene myself," says Matalon, who has since moved to the University of Texas hospital system, where he continues to work on Canavan disease. "I had nothing to do with their licensing decision and I got no penny from any patent.” Salon.com Who owns your DNA? Dr. Reuben Matalon

Science, Aug 2004

Hereditary Deafness Athena GeneDX Connexin 26 35delG A1555G D50N -- KID Pediatrix newborn screen Connexin 26 Sublicense 

BRCA Myriad 70’s Ph.D: Utah Population Database 200,000 Mormon families 1.6 million descendents of original 10,000 settlers Linked w/ Utah Cancer Registry 40,000 hits Dr. Mark Skolnick

BRCA Myriad BRCA1 co-inventors at University of Utah, NIH Assigned to University of Utah Exclusively licensed to Myriad BRCA2 purchased by Myriad from OncorMed Sole provider of BRCA1 – 2 sequencing in US Begins w/ full gene sequencing $3120 Mutation-specific for family members $300 Aggressive enforcement

BRCA Myriad Slow uptake of new technology? Large deletions found by French group Now part of Myriad package Inability to get ‘second opinion’? Inflated prices / lack of access? Suppression of research? At-cost sequencing for investigators: $1200 Undue advantage in finding new mutations

BRCA1-2 – Myriad Inflated cost? BRCA13581,155 BRCA24784,193 APC42108,353 MLH11957,359 MSH21680,098 MSH62523,807 GeneAmpliconsSize

BRCA1-2 – Myriad cost per amplicon BRCA1-2Full seq (2)82Myriad$3,120$38.05 FAPFull seq (1)42Baylor Boston Harvard Huntington U Pennsylvania Mayo Myriad (44 amplicons) $1,675 $1,500 $1,200 $1,360 $1,300 $1,795 $39.88 $35.71 $28.57 $32.38 $30.95 $40.80 HNPCCFull seq (3)60Baylor Boston City of Hope Harvard Huntington Mayo Myriad U Pennsylvania Quest Diagnostics $3,200 $2,995 $ $2,700 $1,800 $3,100 $2,950 $2,840 $4,760 $53.33 $49.92 $77.44 $45.00 $30.00 $51.67 $49.17 $47.33 $79.33

Medibic Life Sciences

Discoveries (vs. inventions) not patentable Genes are products of nature Shouldn’t patent core of personhood Patent on gene sequence is overbroad Contrary to indigenous law / 13 th amendment Patents are delaying medical research Sequence per se has little utility Sequence per se inherently useful Scope should be limited to methods, applications Scope should be limited to disclosed uses Sequences are now routine and thus obvious Patent genes only when completely characterized Reject computer-based conjectural gene functions Remedies? Challenge Rules Fed Register 66(4) Jan 5, 2001

PTO self-correction? The claimed invention in Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), was an isolated nucleic acid molecule. The claim stated that the nucleic acid encoded a particular polypeptide. The encoded polypeptide was identified in the claim by its partially specified sequence, and by its ability to bind to a specified protein. A prior art patent to Valiante taught the polypeptide... In view of Valiante's disclosure of the polypeptide, and of routine prior art methods for sequencing the polypeptide and isolating the nucleic acid molecule, the Board found that a person of ordinary skill in the art would have had a reasonable expectation that a nucleic acid molecule within the claimed scope could have been successfully obtained.

Remedies? Challenge Claims Impermissible subject matter Prior art Insufficient description Total patents: 74 Total claims: 1167 Total claims with problems: 448 Cumulative problems: 667 Patents on human genes: an analysis of scope and claims Science 307: (2005) Paradise, Andrews, Holbrook

Remedies? Challenge Scope Public policy arguments to Congress Mandatory licensing Exclusion of diagnostic use Changes would be prospective only Statutory / constitutional arguments to courts Natural phenomena, mental processes, abstract ideas Invalidation effective retrospectively

What’s Persuasive in court? Drafter’s intent Precedent (earlier cases) Reasoning by analogy Chemical moieties? Plant extracts I claim this substance I can’t claim any substance w/ aromatic hydrocarbon Alphabet? I copyright an article I can’t copyright a word

Assoc Molecular Pathology et al vs. USPTO, Myriad Genetics et al Not patentable subject matter Naturally occurring genes Association between mutation and disease Contrary to constitutional enabling clause Doesn’t promote progress of science Contrary to first amendment protections of freedom of thought, academic inquiry, exchange of knowledge and ideas

5,747,282 Claims 1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2. 5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

5,693,473 Claims 1. An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers in SEQ. ID. NO:1.

5,837,492 Claims 6. An isolated DNA molecule coding for a mutated form of the BRCA2 polypeptide set forth in SEQ ID NO:2, wherein said mutated form of the BRCA2 polypeptide is associated with susceptibility to cancer.

6,033,857 Claims 1. A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequences identifies a mutant BRCA2 nucleotide sequence.

5,710,001 Claims 1. A method for screening a tumor sample from a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises gene comparing a first sequence selected form the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic alteration in the BRCA1 gene in said tumor sample.

5,747,282 Claims 20. A method for screening potential cancer therapeutics which comprises: growing a transformed 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.