the intellectual property landscape of the human genome

Kyle L. [email protected]

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The intellectual property landscape of the human genome

Kyle JensenPhD CandidateMIT Chemical Engineering

Fiona MurrayAssistant Professor Management of Technology Innovation & EntrepreneurshipMIT Sloan School of Management


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The “tragedy of the anti-commons” describes resource under-usage when many agents have rights to exclude

Tragedy of the commons Tragedy of the anti-commons

M. A. Heller, R. S. Eisenberg, Science 280, 698 (1998).


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There is some evidence for an anti-commons effect in the broader field of biotechnology

Patent

Use forward citations as a measure of

scientific progress

All publications from Nature Biotech 97-99

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FCjtF. Murray, S. Stern, NBER Working Paper 11465, 2005.


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Many suggest a genomic anti-commons effect exists; however, supporting evidence is limited and anecdotal

● Genomic anti-commons in a nutshell:

» IP rights, paired with exclusive licensing will increase transaction costs and

● Slow development of new medicines

● Stifle academic R&D

● Discourage downstream investment

● But, classic rationale for patent system is to promote investment, R&D

» Evidence for genomic anti-commons is ancedotal

Nuffield Council on Bioethics, The ethics ..., Tech. rep., London, UK (2002).T. Caulfield, E. Gold, M. Cho, Nat Rev Genet 1, 227 (2000)L. Andrews, Nat Rev Genet 3, 803 (2002)S. M. Thomas, M. M. Hopkins, M. Brady, Nat Biotechnol 20, 1185 (2002).M. Stott, J. Valentine, Nat Rev Drug Discov 3, 364 (2004).


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The growth in sequence-oriented IPR prompts many of the same questions for the human geome

No. sequences in Genbank No. sequences disclosedin issued US patents

1:50 scale

How much of the human genome is covered by IPR? By whom?

D. L. Wheeler, et al., Nucleic Acids Res 33 Database Issue, 39 (2005).


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To map patents to human genes we assembled a database of nucleotide sequences from issued US patents

● 686,864 sequences from Genbank

● +109,766 parsed from patent full-texts

● Only from patents with a valid sequence listing

D. L. Wheeler, et al., Nucleic Acids Res 33 Database Issue, 39 (2005).User Services, National Center for Biotechnology Information (2004). Personal communication.O. of Public Affairs, U.S. Patent and Trademark Office (2005). Personal communicationUSPTO, Patent FullText and FullPage Image Databases, http://www.uspto.gov/patft/index.html (2005).


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From this database, we extracted only sequences that are explicitly mentioned in the patent claims

● Natural language modeling using simple regular expressions

● Applicable only to claims using SEQ ID nomenclature


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An all-by-all homology search was used to determine which patented sequences correspond to human genes

Patent 1 sequences

Patent 2 sequences

Patent N sequences

USPTO Patent Sequences

796,630 sequences(82,395 claimed) from

30,048 patents

Gene 1 transcripts

NCBI RefSeq

495,772 sequences from 2,969 species

BlastnEval = 0.0>= 150 bp

Gene M transcripts

NCBI, The RefSeq Database, http://www.ncbi.nlm.nih.gov/RefSeq/ (2005).

K. D. Pruitt, T. Tatusova, D. R. Maglott, Nucleic Acids Res 33 Database Issue, 501 (2005).

Conflicts resolved by highest bit-score

X


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Our analysis show that 4,382 of the 23,688 genes in the human genome are claimed in granted U.S. patents

NCBI Map Viewer. Build 35.1 http://www.ncbi.nlm.nih.gov/mapview/ (2005).

D. Maglott, J. Ostell, K. D. Pruitt, T. Tatusova, Nucleic Acids Res 33 Database Issue, 54 (2005).


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Most genes are claimed in only a single patent; a few genes are covered by extensive IPR


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The most IP-protected genes tend to be involved in cancer and cellular processes such as signal transduction, cellular

differentiation, and cell proliferation

GeneID No. Patents Gene Name Locus Annotation

655 20 BMP7 20q13 bone morphogenetic protein 7

1029 20 CDKN2A 9p21 cyclin-dependent kinase inhibitor 2A

768 14 CA9 9p13-p12 carbonic anhydrase IX

672 14 BRCA1 17q21 breast cancer 1, early onset

6469 13 SHH 7q36 sonic hedgehog homolog

3084 13 NRG1 8p21-p12 neuregulin 1

3953 12 LEPR 1p31 leptin receptor

6004 11 RGS16 1q25-q31 regulator of G-protein signalling 16

3549 10 IHH 2q33-q35 Indian hedgehog homolog

959 10 CD40LG Xq26 CD40 ligand

7424 10 VEGFC 4q34.1-q34.3 vascular endothelial growth factor C

3557 10 IL1RN 2q14.2 interleukin 1 receptor antagonist

NCBI Map Viewer. Build 35.1 http://www.ncbi.nlm.nih.gov/mapview/ (2005).

D. Maglott, J. Ostell, K. D. Pruitt, T. Tatusova, Nucleic Acids Res 33 Database Issue, 54 (2005).


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The institutions with the most gene-oriented patents tend to be biotech or research institutes rather than larger pharmaceutical companies

No. Genes

2220

153

142

114

102

100

95

63

59

58Variations in assignee names across patents strongly effects this result. For example HGS is occasionally “Human Genome Sciences” instead of “Human Genome Sciences, Inc.” Also, this does not account formergers and acquisitions or subsidiary relationships. Assignee name standardization by EPO.

*

*

European Patent Office, INPADOC, http://www.european-patent-office.org/inpadoc/ (2005).


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Private US-based firms tend to own the most human gene IP


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Most genes have a single rights-holder; however a handful of genes have highly fragmented IPR ownership


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Our results suggest that disease-associated genes have heavier IP coverage than others

● Of 291 known cancer genes, 131 appear “patented”

» 45% vs. 18% background rate● Significant with p-value<0.01 based on binomial distribution

» Those that are patented, are more heavily patented than expected by chance

● Significant with p-value<0.01 based on chi-squared test

● Of 1,456 genes in Online Mendelian Inheritance in ManTM database 517 are “patented”

» 35% vs. 18% background rate● Significant with p-value<0.01 based on binomial distribution


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A patent density view of disease pathways reveals the IP barrier of various targets

Huntington's disease pathway


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Questions?

the intellectual property landscape of the human genome

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