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Moving Beyond the Myriad Fallout:The Validity of “Gene Patents”

Rochelle Cooper DreyfussPauline Newman Professor of LawNew York University School of Law

Open Science Summit 2010July 30, 2010

Berkeley, California

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Recent developments: Supreme Court

1. Lab Corps. v. Metabolite Laboratories, 548 U.S. 124, 126 (2006)(Breyer, J. dissenting from denial of cert.) “[S]ometimes too much patent protection can impede rather than

‘promote the Progress of Science and useful Arts’”

2. Bilski v. Kappos (U.S. Supreme Court June 28, 2010)Kennedy (for Roberts, Thomas, Alito and Scalia)

“The Court’s precedents provide three specific exceptions to §101’s broad patent-eligibility principles: ‘laws of nature, physical phenomena, and abstract ideas.’”

Kennedy (for Roberts, Thomas, Alito)“It is important to emphasize that the Court today is not commenting on the patentability of any particular invention, let alone . . . the above-mentioned technologies [including advanced diagnostic medicine techniques]. . .”

3. Prometheus Laboratories, Inc. v. Mayo Collaborative Services, 581 F.3d 1336 (Fed. Cir. 2009), GVR (June 29, 2010).

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Open Questions1. Analysis of a case involving an abstraction

- M-or-T is not the sole test: is it a safe harbor?2. Laws of Nature

- advanced diagnostic medicine technique?- all diagnostic medicine techniques?

3. Physical Phenomena- associations?

4. Products of Nature- isolated genes?

--- last three issues all raised by Association for Molecular Pathology v. USPTO (S.D.N.Y. March 29, 2010).

- patents on isolated BRCA sequences and mutations- patents on associations between BRCA mutations and breast cancer

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Hints:J. Kennedy: quoting from Gottschalk v. Benson: “A contrary holding

‘would wholly pre-empt the mathematical formula and in practical effect would be a patent on the algorithm itself.’”

“Allowing petitioners to patent risk hedging would preempt use of this approach in all fields”

J. Stevens: “the Court excludes processes that tend to pre-empt commonly used ideas”

“Morse’s patent on electromagnetism for writing would preempt a wide swath of technological developments”

J. Breyer: “allowing individuals to patent these fundamental principles would ‘wholly pre-empt’ the public’s access to the ‘basic tools of scientific and technological work.’”

Patents should not come too early in scientific development in order to permit competitive development of new prospects for invention

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Problem: how do you know when patenting is too early?

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Sample Patents

Example 1, Breast Cancer. Patent 5,709,999 (filed August 12, 1994, granted January 20, 1998, estimated expiration date: January 20, 2015):

[Claim] 1. A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 . . . which comprises analyzing a sequence of a BRCA1 gene . . . from a human sample . .

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Example 2, Scoliosis. Patent 7,655,403 (filed December 2, 2006, estimated expiration date: December 2, 2026).

[Claim] 1. A method for determining if a human patient has a predisposition to idiopathic scoliosis comprising: obtaining a nucleic acid sample from the patient; assaying the sample to identify the nucleotide present at single nucleotide polymorphism rs4738824; and determining that the patient has a predisposition to idiopathic scoliosis when there is at least one G allele present at single nucleotide polymorphism rs4738824 relative to a human patient that has two A alleles present at single nucleotide polymorphism rs4738824.

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Example 3, Breast Cancer. Patent 5,747,282 (filed August 12, 1994, granted May 5, 1998, estimated

expiration date: May 5, 2015):

[Claim] 1. An isolated DNA coding for a BRCA1 polypeptide . . . .

[Claim] 2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1 [the coding sequence for BRCA1].

[Claim] 5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

[Claim] 6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2.

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Empirical Evidence

SACGHS Report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests, http://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Report%20Approved%202-5-20010.pdf.

Robert Cook-Deegan & Christopher Heaney, Gene patents and licensing: case studies prepared for the Secretary's Advisory Committee on Genetics, Health, and Society (April 2010), http://journals.lww.com/geneticsinmedicine/toc/2010/0400.

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The Duke Studies

1. breast/ovarian cancer2. colon cancer 3. hearing loss4. cystic fibrosis (CF)5. inherited susceptibility to Alzheimer disease6. hereditary hemochromatosis (HH)7. spinocerebellar ataxias (SCA)8. long QT syndrome (LQTS)9. Canavan disease10.Tay-Sachs disease

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1. Use of genetic diagnostics: multifarious

• Susceptibility to disease– prophylactic action

- BRCA mutations/mastectomies & hysterectomies

– other defensive activities - heart-related mutations/exercise, eating & drinking habits

• Treatment choices – hearing loss, medication

• Family planning– marital decisions (Ashkenazi Jews)– prenatal testing (Down’s syndrome)

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Use of genetic diagnostics (cont’d)• Pharmaceutical discovery and testing

– identifying populations for testing

• Developing new diagnostic methodologies– multiplex testing– whole genome sequencing (“personalized medicine”)– “SNPS” studies (23andme; deCODEme, Navigenics)

• Population studies– improved association studies

• Characterization of viruses and bacteria– creating vaccines and treatment

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2. Problems caused by patent-enabled exclusivity suggest inefficiencies:

- Insurance issues • e.g. lack of agreements with Medicaid

- Quality concerns• proficiency testing through sample sharing cannot be

performed• clinicians have no recourse if concerned about a lab or

result• patients cannot obtain second-opinion testing

- Terms of testing• prenatal tests• stored samples• small populations (Canavan disease)

- Failure to report out results to patients (SNPs) - Failure to rapidly incorporate the best science

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Deletions

intron intron intron

EXON 1 EXON 2 EXON 3 EXON 4

intron intron intron

EXON 1 EXON 2 EXON 3 EXON 4

Maternal Copy of Gene A

Paternal Copy of Gene ADeletion of Exon 3

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Innovation-related concerns:

- Research uses• exclusion of BRCA breast cancers• understanding disease at the molecular level

- Development of multiplex tests and whole genome sequencing

• patent thickets and hold out problems• double marginalization and high prices

- Use of data mining techniques

- Failure to report new mutations

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3. Findings: exclusivity unnecessary

• In no case studied was a test developed by an exclusive rights holder found to be the first to market

– associations largely found by academics and geneticists (“user innovators”)– funding through fees, government grants, patient advocacy group donations– cost of developing tests < $10,000

• Enforcement of exclusive rights was consistently used to narrow or clear the market of already available tests

• Where there is no patent protection, or licensing is nonexclusive, or existing patents are not enforced, widespread test development is observed

– cystic fibrosis – colorectal cancer predisposition– hearing loss

• In these cases, patients and clinicians have a wide array of choices– quality is assured– services are optimized– the latest science is incorporated into the testing protocols

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4. Conclusions

• The cost of patenting diagnostics does not outweigh the benefits

• In the genetics area, “inventing around” is not available to keep patent holders honest– markers are associated with high error rates– protein testing is not available for all applications

• The social harms of patenting are real and require immediate attention

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5. Policy Options

(1) Subject matter exclusions: a. diagnostics

b. genes

(2) New defenses to infringement

a. research defense

b. diagnostic defense

(3) New institutional arrangements

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(1) Subject matter exclusions: (a) diagnostics

SACGHS analysis: suggests that diagnostic associations do “preempt the field”

- many uses- inefficient exploitation- can’t invent around

- advances are made by user innovators, so patents unnecessary for development

SACGHS view (not a recommendation): simple diagnostics should not be patentable

they are laws of nature or physical phenomena

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(1) Subject matter exclusions: (b) products

SACGHS (implicitly): distinguished diagnostic and therapeutic usage

- patents not needed for developing diagnostics- value of the gene lies in its informational content, which is identical in nature and diagnosis- no opportunities for inventing around

- patents may be needed to finance the costly road to therapeutic application

- value of the gene depends on isolation- inventing around more likely- user innovators can’t bring these products to market

Other policy options pursued for patents on genesThese policy options could also be used if courts disagree about

the validity of diagnostic patents

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(2) Defenses to Infringement

SACGHS recommendations:1. The Secretary of Health and Human Services should support and work with the Secretary of Commerce to promote the following statutory changes:

A. The creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient care purposes.

B. The creation of an exemption from patent infringement liability for those who use patent-protected genes in the pursuit of research.

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Alternative diagnostic defense

Based on 35 USC § 287(c) for surgical methods:

– doctors would be primary infringers for using patented inventions in diagnosis

- remedies would not be available

- those selling kits would be contributorily liable- remedies would be available

Doctors could use “home brews” to supply

second opinions, fill unsatisfied demand

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(3) New Institutional Arrangements

a. Promote norms designed to improve access (codes of conduct). Examples:- NIH Best Practices for the Licensing of Genomic Inventions- OECD Guidelines for Licensing Genetic Inventions- AUTM, Nine Points to Consider in Licensing University Technology

b. Enhance Transparency (clearing houses, patent pools)

c. More proactive role for funders (NIH)- better tracking- clarify “march in” rights under the Bayh Dole Act- government-mediated access- sanctions for exclusive licensing without business justification

d. Advice to patent office on other issues of eligibility:- nonobviousness- written description (Ariad v. Lilly)