NC State Bbs 201 Intro To Biopharmaceutical Science April 3 20091. Introduction to Biopharmaceutical Science
Intellectual Property
(BBS 201)
April 3, 2009
Presented by:
Stan Antolin
Smith Moore Leatherwood LLP
300 N. Greene St., Suite 1400
Greensboro, NC 27401
T: 336-378-5516
© 2009 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED.
2. Biotechnology & Intellectual Property
• A problem – osteoarthritis
• Intellectual property
• Osteoarthritis – finding a cure for
• Biology – a basic review
• Developing patent protection
• Summary
3. Osteoarthritis — Aggrecan
• Articular cartilage
– Cushions bones of the
knee
– Degradation erosion
eventually bones of the
joint grind or rub
together
• Aggrecan
– Major extracellular
component of articular
cartilage
– Responsible for
providing
compressibility and
elasticity
– Loss implicated in the
degradation of articular
Deluzio, Queen's University, Kingston, ON. Canada cartilage
Peprotech Korea Limited.
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4. Osteoarthritis — Aggrecanase
– Capable of cleaving
aggrecan at the
glu373-ala374 bond
– Could contribute to
aggrecan cleavage
in osteoarthritis
– Could be
synthesized by
osteoarthritic human
articular cartilage
J Biol Chem. 2008 Jan 18; 283(3):1501-7
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5. Osteoarthritis — Aggrecanase
Aggrecanase
– Difficult to isolate and purify
– Poor stability
– Generally low expression
levels
– Difficult to develop inhibitors
and treatment therapies to
treat diseases that involve
aggrecan cleavage
J Biol Chem. 2008 Jan 18; 283(3):1501-7
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6. Osteoarthritis — Aggrecanase
• Aggrecanase
– Identify novel forms with improved stability
– Develop ways to
• Produce large amounts
• Isolate aggrecanase
• Purify aggrecanase
• Investigate aggrecanase role in disease
states
8. Intellectual Property: An Overview
Recognizing ownership in ideas generated by
creative thinkers.
– FDA Exclusivities
(US Food and Drug Administration)
– EMEA Exclusivities
(European Medicines Evaluation Agency)
– Trademark or Service Mark
– Copyright
– Trade Secret
– Patent
9. FDA Exclusivities — IND & NDA or BLA
Time to develop a drug = 10–15 year
Investigational New New Drug Application (NDA) /
Drug Application (IND) Biologic License Application (BLA)
Cost to develop a biologic Cost to develop a drug
2006 = $1.2 billion 2006 = $1.3 billion
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10. Trademarks and
Service Marks
– Trademark (goods)
– Service mark (services)
– Words, names, symbols,
designs, or combinations
– Source and quality
– Standard:
• Priority of use and
• Likelihood of confusion
– Duration:
• Infinite life tied only to use
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11. Trade Secrets
– Protect business or technical information
– Actual or potential commercial value
• unknown or unascertainable through
~ Independent development or
~ reverse engineering, and
– Maintained secret using reasonable effort under the circumstances
• Infinite protection as long as secret OR have tried to keep it that way
– Once out, no protection if no reasonable efforts.
• Need to have a confidentiality procedure in place, and follow that
procedure, before the trade secret is disclosed to ANYONE.
12. Copyrights
– Protect “original works of authorship”
– Idea expressed in a tangible form
– Life of author plus 70 years
Registration: Receive the exclusive right to:
• Protection is automatic but • Reproduce
registration allows you to sue • Create derivative works
infringers and receive statutory
• Distribute
damages plus attorneys’ fees
• Perform
• Easy and inexpensive
• Display the work publicly
13. Patents
– Protect inventions
• standard: useful, novel, and non-obvious
• Duration: 20 years from date of filing
What A patent protects: EXCLUDSIONARY right :
• Utility • EXCLUDE others from making,
– Machine using, selling, offering for sale,
– Process or importing in the U.S. The
product or process of the claim
– Article of manufacture
– Composition
Do not receive right :
– An improvement thereof
• To make or use the product or use
• Design (14 years from grant) the process of the claim
• Plant
14. The Patent Bargain
Inventor receives :
• Right to EXCLUDE others from making, using, selling,
offering for sale, or importing in the US
• Does NOT give the owner any right to make or use
Public receives:
• Disclosure of the best way to solve a problem
• Right to use that solution once the inventor’s rights are
exhausted
15. Design Patents
Protects the appearance of an invention
• Does not protect structural or functional features
Duration is fourteen years from grant date
There is only one claim
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16. Plant Patents
• Protects asexually reproduced plant
varieties
• Duration is 20 years from date of
application
• There is only one claim in a plant
application
17. Utility Patents
“Anything under the sun that is made by man” (Almost)
– Machine
– Process
– Article of manufacture
– Composition
– An improvement thereof
Diamond v. Chakrabarty, 447 U.S. 303 (1980),
19. International Patent Protection
Patents are Territorial: Each Country Gets An Application.
Different Laws: Variations of the Same Application.
Treaties: PCT and Paris
Regional Patent Offices: WIPO, EPO, OAMPI, EAPO . . . .
United States: Everywhere Else:
– First to Invent – First to File
– Publication One Year – No Prior Publication
in Advance
20. Utility Patents
Utility patents are the most
common type of patent granted
by the USPTO.
Duration: 20 years from
date of application
(Plus Up to 5 years FDA
Exclusivity)
21. Aggrecan Monomer — Aggrecanase
• Aggrecanase
– Identify novel forms
with improved
stability
– Develop ways to
• Produce large
amounts
• Isolate
aggrecanase
• Purify
aggrecanase
• Investigate
aggrecanase role
in disease states
Peprotech Korea Limited. 18; 283(3):1501-7
J Biol Chem. 2008 Jan
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22. Truncated Aggrecanase
Aggrecanase
X X
TSP TSP
partial or complete
thrombospondin (TSP)
deletion can
stabilize aggrecanase
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24. Courtesy: U.S. Department of Energy Genome Program
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24
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25. Primary (a), secondary
(b), tertiary and
quaternary (c) structure
of HCC
Nature Structural Biology 8, 316 - 320 (2001)
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26. Eukaryotes Transcription mRNA
Courtesy: National Human Genome Research Institute.
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27. DNA is transcribed into RNA and
RNA is translated into Protein
Courtesy: National Human Genome Research Institute.
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28. Degeneracy
of the Genetic
Code
Of the 64 codons, 61 specify one
of the 20 amino acids. The other
3 codons are chain-terminating
codons and do not specify any
amino acid. AUG, one of the 61
codons that specify an amino
acid, is used in the initiation of
protein synthesis.
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28
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29. Eukaryotes Transcription mRNA
Courtesy: National Human Genome Research Institute.
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30. Reverse Transcriptase (RT):
mRNA cDNA
• Reverse transcriptase (RT)
& DNA polymerase used to
make a complimentary DNA
(cDNA) strand
– Contains no introns
– Complimentary to a
mRNA
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31. Truncated Aggrecanase
X X
TSP TSP
partial or complete
thrombospondin (TSP)
deletion can
stabilize aggrecanase
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32. Truncated Aggrecanase
X X TSP
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33. Biopharmaceutical Production Process
Insert gene into
DNA vector
Transfer into host cell
Express desired protein
Grow cells in
bioreactors
Extract, Purify, Dilute
Kleinberg M, et al. Am J Health-Syst Pharm. 2004;61:695-708. protein therapeutic
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34. Protecting Nucleic Acid Sequence
1. An isolated DNA comprising the sequence set forth
as SEQ ID NO: 33.
2. A cDNA comprising the sequence of
SEQ ID NO: 33.
3. An isolated nucleic acid comprising the nucleotide
sequence of SEQ ID NO: 33, or
a degenerate variant of SEQ ID NO: 33.
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35. Protecting Amino Acid Sequence
1. A polypeptide comprising the amino acid
sequence of SEQ ID NO: 13.
2. A truncated aggrecanase comprising the
sequence set forth as SEQ ID NO: 13.
3. An amino acid comprising SEQ ID NO: 13,
wherein the polypeptide cleaves aggrecan.
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36. Requirements for Patentability
• Patentability over the prior art
– Novelty
– Non-obviousness
• Disclosure requirements
– Utility
– Specification
• Enablement
• Best mode
• Written description
36
37. Patentability over the Prior Art —Novelty
• single reference
• discloses every element of
claimed invention
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38. Abbaszade, I. et al. J. Biol. Chem. 1999;274:23443-23450
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39. Patentability over the Prior Art —
Non-obviousness
• Multiple references
• Predictability
• Motivation to combine
• Teach or suggest claimed invention
• Reasonable expectation of success
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40. Patentability over the Prior Art —
Non-obviousness
Sites of cleavage of aggrecan monomer by aggrecanase
Tortorella, M. et al. J. Biol. Chem. 2000;275:25791-25797
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42. Patent Summary
Patentability over the prior art
– Novelty
– Non-obviousness
• Disclosure requirements
– Utility
– Specification
• Best mode
• Enablement
• Written description
43. Patent Summary
• Specification
– Best mode
– Enablement
• Teach one skilled in the art
• Make and use the claimed invention
• Without undue experimentation
• Disclose nascent technology
– Written description
• Demonstrate applicant’s possession of the claimed invention
• Provide disclosure of structure, formula, chemical name, or
physical properties
43
44. Ways of Recognizing Ownership in Ideas
Generated by Creative Thinkers:
– FDA exclusivities
(US food and drug administration)
– EMEA exclusivities
(European medicines evaluation agency)
– Trademark or service mark
– Copyright
– Trade secret
– Patent
45. Thank you
Stan Antolin
stan.antolin@smithmoorelaw.com
T: 336-378-5516
F: 336-433-7591
© 2009 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED.
46. Intellectual Property Overview
Links
• United States Patent Office (USPTO):
– www.uspto.gov
– FAQs: http://www.uspto.gov/main/faq/index.html
– Trademark Search Engine:
http://www.uspto.gov/ebc/tess/index.html
– Patent Search Engine: http://www.patentfetcher.com/
– Patent Search Engine: http://www.google.com/patents
– Trademarks Basic Information:
http://www.uspto.gov/web/offices/tac/doc/basic/
• NC State Trademarks available at:
http://www.ncs.ncsu.edu/trademark/index.html
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47. Why IP Is Important Links
• Bessen, James E. & Meurer, Michael J.,The Private
Costs of Patent Litigation, available at
http://ssrn.com/abstract=983736
• USPTO 2007 Annual Report available at
http://www.uspto.gov/web/offices/com/annual/index.html
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48. Patent Primer Links
• USC: http://www.gpoaccess.gov/uscode/index.html
• CFR: http://www.gpoaccess.gov/cfr/index.html
• MPEP: http://www.uspto.gov/web/offices/pac/mpep/mpep.htm
• USPTO’s general design patent page
http://www.uspto.gov/web/offices/pac/doc/general/design.htm
• USPTO’s general plant patent page
http://www.uspto.gov/web/offices/pac/doc/general/plant.htm
• USPTO’s general treaties and foreign patents page
http://www.uspto.gov/web/offices/pac/doc/general/treaties.htm
• Bessen, James E. and Meurer, Michael J., The Private Costs of Patent
Litigation, available at http://ssrn.com/abstract=983736
• Article on the AIPLA survey regarding cost of litigation.
http://lawdepartmentmanagement.typepad.com/law_department_managem
ent/2005/03/costs_of_patent.html
• Ronald Schutz and Ken Hall, Strategies for Patent Holders Contemplating
Litigation, available at
http://www.rkmc.com/Strategies_for_Patent_Holders_Contemplating_Litigati
on.htm
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49. Patent Update Links
• Licensing
– MedImmune v. Genentech, available at http://www.supremecourtus.gov/opinions/06pdf/05-
608.pdf
– O'Connor, Sean M., Using Stock and Stock Options to Minimize Patent Royalty Payment
Risks After Medimmune v. Genentech, available at http://ssrn.com/abstract=977342
– http://www.law.com/jsp/article.jsp?id=1169806049217
• Injunctions
– eBay v. MercExchange, available at http://www.supremecourtus.gov/opinions/05pdf/05-
130.pdf
– Eric Wesenberg & Peter O'Rourke, The Toll on the Troll: The Implications of 'eBay v.
MercExchange‘, available at http://www.law.com/jsp/article.jsp?id=1147943132930
• Obviousness
– KSR v. Teleflex, available at http://www.supremecourtus.gov/opinions/06pdf/04-1350.pdf
– J. Matthew Buchanan, KSR International v. Teleflex Inc., fedcirc.us, available at
http://www.fedcirc.us/case-reviews/ksr-international-v.-teleflex-inc.html
– USPTO guidelines on examination in light of the KSR decision,
http://www.uspto.gov/web/offices/com/sol/notices/72fr57526.pdf
– Jay Sandvos, How KSR v. Teleflex should change your patent strategies, available at
http://www.edn.com/index.asp?layout=article&articleid=CA6442383
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50. Patent Update Links
• Patent Infringement:
– http://www.mwe.com/index.cfm/fuseaction/publications.nldetail/o
bject_id/2fc2350a-5379-42f7-a9f5-4faa65146c32.cfm
• Biotechnology:
– Janis K. Fraser, Ph.D., U.S. Gene Patents in Legal Limbo –– for
Now, available at
http://www.ipfrontline.com/depts/article.asp?id=18311&deptid=4
– Harold C. Wegner, Biotechnology Law Report, available at
http://www.liebertonline.com/doi/pdfplus/10.1089/blr.2007.9915
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51. Patent Update Links
• Software/Business Methods:
– Hung H. Bui, In Re Bilski, No. 2007-1130 (Fed. Cir. Feb. 15, 2008,
available at
http://www.ipfrontline.com/depts/article.asp?id=20898&deptid=7
– USPTO guidelines November 22, 2005, available at
http://www.uspto.gov/web/offices/com/sol/og/2005/week47/patgupa.htm
– Foundation for a Free Information Infrastructure, http://www.ffii.org/
– Non profit: http://www.spi.org/home.jsp
– Deputy Commissioner’s May 18, 2008 memo:
http://www.uspto.gov/web/offices/pac/dapp/opla/preognotice/section_10
1_05_15_2008.pdf
– Anti-software patent: http://www.out-law.com/page-9447
– ecommerce patents, Arner, Erika Harmon, Yoches, E. Robert, Recent
Developments of E-Commerce Patents: The Ever Precarious Nature of
E-Commerce Patent Protection in the U.S., available at
http://www.finnegan.com/resources/articles/articlesdetail.aspx?news=d3
faffe2-c076-49bc-bffa-b1c74d37a6a0
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52. Patent Update Links
• Evaluation:
– Intellectual Property valuation article:
www.ipmetrics.cc/IPVT.pdf
– Michael Fitzgerald, A Patent Is Worth Having, Right? Well,
Maybe Not, available at
http://www.nytimes.com/2007/07/15/business/yourmoney/15prot
o.html?_r=1&ref=yourmoney&oref=slogin
– Pro-trade secrets: http://www.jordasecrets.com/
– Checklist comparing trade secret and patent protection:
http://www.iphandbook.org/handbook/chPDFs/ch11/ipHandbook-
Ch%2011%2005%20Jorda%20Trade%20Secret%20Licensing.p
df
• Smith Moore Leatherwood, LLP: http://www.smithmoorelaw.com/
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