Patents and Clinical Genetics

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

Dilbert’s I.P. experience

SACGHS Office of Science Policy – NIH

Secretary’s Advisory Committee on Genetics, Health and SocietyGene 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 8Congress shall have power . . . to promote the progress of science and useful arts, by securing for limited times toauthors 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?

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

‘487 Claims2. A purified normal CFTR RNA . . .

3. A purified . . . cDNA.

4. A purified DNA molecule . . . Comprising a DNA sequence encoding an amino acid sequence depicted in Fig 1 . . .

5. A detectably labeled normal CFTR probe, comprising . . . At least 16 contiguous nucleotides . . .

6. A normal CFTR probe . . .

‘487 Claims

‘487 Claims

‘487 Figure: CFTR Sequences

~4,400 sequence patents by 2007

Monopoly?

Anti-commons?

Hold-outs?

Cross-blocking?

Defensive patents?Gendia

What’s the fuss?

Adam Brandejsart installationca.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? 3-7-2000

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? 3-7-2000

Dr. Reuben Matalon

Science, Aug 2004

Hereditary Deafness

Athena

GeneDXConnexin 26

Connexin 26

35delGA1555G

D50N -- KID

Pediatrix newborn screen

Connexin 26

Sublicense

BRCA1-2 -- Myriad

70’s Ph.D: Utah Population Database200,000 Mormon families1.6 million descendents of original 10,000 settlersLinked w/ Utah Cancer Registry40,000 hits

Dr. Mark Skolnick

BRCA1-2 -- Myriad

BRCA1 co-inventors at University of Utah, NIHAssigned to University of Utah Exclusively licensed to MyriadBRCA2 purchased by Myriad from OncorMedSole provider of BRCA1 – 2 sequencing in USBegins w/ full gene sequencing $3120Mutation-specific for family members $300Aggressive enforcement

BRCA1-2 -- Myriad

Slow uptake of new technology?Large deletions found by French groupNow part of Myriad package

Inability to get ‘second opinion’?

Inflated prices / lack of access?

Suppression of research?At-cost sequencing for investigators: $1200Undue advantage in finding new mutations

BRCA1-2 – MyriadInflated cost?

BRCA1 35 81,155BRCA2 47 84,193APC 42 108,353MLH1 19 57,359MSH2 16 80,098MSH6 25 23,807

Gene

Amplicons

Size

BRCA1-2 – Myriadcost per amplicon

BRCA1-2

Full seq (2)

82 Myriad $3,120 $38.05

FAP Full seq (1) 42 BaylorBostonHarvardHuntingtonU PennsylvaniaMayoMyriad (44 amplicons)

$1,675$1,675$1,500$1,200$1,360$1,300$1,795

$39.88$39.88$35.71$28.57$32.38$30.95$40.80

HNPCC Full seq (3) 60 BaylorBostonCity of HopeHarvardHuntingtonMayoMyriadU PennsylvaniaQuest Diagnostics

$3,200$2,995$4646.16$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 patentableGenes are products of natureShouldn’t patent core of personhoodPatent on gene sequence is overbroadContrary to indigenous law / 13th amendmentPatents are delaying medical researchSequence per se has little utilitySequence per se inherently usefulScope should be limited to methods, applicationsScope should be limited to disclosed usesSequences are now routine and thus obviousPatent genes only when completely characterizedReject computer-based conjectural gene functions

Remedies? Challenge Rules

Fed Register 66(4)1092-1099 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 matterPrior artInsufficient description

Total patents: 74Total claims: 1167Total claims with problems: 448Cumulative problems: 667

Patents on human genes: an analysis of scope and claims Science 307:1566-7 (2005) Paradise, Andrews, Holbrook

Remedies? Challenge Scope

Public policy arguments to CongressMandatory licensingExclusion of diagnostic useChanges would be prospective only

Statutory / constitutional arguments to courts

Natural phenomena, mental processes, abstract ideasInvalidation effective retrospectively

What’s Persuasive in court?

Drafter’s intentPrecedent (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 articleI can’t copyright a word

Assoc Molecular Pathology et al vs. USPTO, Myriad

Genetics et alNot patentable subject matter

Naturally occurring genesAssociation 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 Claims1. 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 4184-4187 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 Claims1. 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 Claims1. 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 Claims20. 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.