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2. 2 Biotechnology Inventions: Genes & Life Forms and the Impact of Patenting on Upstream Science Nancy J. Linck, Ph.D., J.D. Deputy General Counsel Intellectual Property & Trade WIPO Open Forum on the Draft SPLT Geneva, March 3, 2006

3. 3 The United States’ Patent System Served our country well for more than 200 years, despite attacks from time to time and “sky is falling” warnings “Promoted the progress of … the useful arts” as our constitution charged the U.S. Congress to do It is a strong, enduring system that can be improved but is certainly not “broken”

4. 4 Current Issues Under U.S. Law Patentable Subject Matter 35 USC § 101 Utility 35 USC § 101 Enablement 35 USC § 112 Written Description 35 USC § 112

5. 5 35 USC § 101 Inventions Patentable “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter … may obtain a patent therefor, subject to the conditions and requirements of this title.”

6. 6 Patentable Subject Matter Chakrabarty 1980 Is the claimed invention a process, machine, manufacture, or composition of matter? “As with Fulton’s steamboat ‘folly’ and ‘Bell’s telephone toy,’ new technolgies have historically encountered resistance. But if our patent laws are to achieve their objective, extra-legal efforts to restrict wholly new technologies to the technological parameters of the past must be eschewed.” Chakrabarty (CCPA, Markey, J.)

7. 7 Patentable Subject Matter U.S. Supreme Court & Chakrabarty Section 101 is couched in “expansive” terms to give “ingenuity” a liberal encouragement Statutory subject matter “include[s] anything under the sun made by man” Ananda Chakrabarty’s bacterium containing genetically modified plasmids useful to degrade hydrocarbons are patentable subject matter

8. 8 The § 101 Utility Requirement Is the claimed invention a useful process, machine, manufacture, or composition of matter? Under the U.S. Patent and Trademark’s guidelines, the utility must be (1) specific, (2) substantial, and (3) credible

9. 9 An Example of a “Specific” Utility Disclosure of a specific biological activity and a reasonable correlation to a disease condition

10. 10 What is NOT a “Specific” Utility? Claim to a polynucleotide useful as a gene probe or chromosome marker is not specific unless a specific DNA target is disclosed A general statement of diagnostic utility of an unspecified disease is not specific enough Language such as “may prove useful” or a useful invention “may arise” are especially damaging to this test

11. 11 What is a “Substantial” Utility? A “substantial utility” defines a “real world” use A therapeutic method of treating a known or newly discovered disease An assay for identifying compounds that have a “substantial utility” An assay that measures the presence of a material which has a correlation to a predisposition to the onset of a particular disease condition

12. 12 What is NOT a “Substantial” Utility? Utilities that require or constitute carrying out further research to identify or reasonably confirm a “real world” context Basic research such as studying the properties of the claimed product or its mechanism of action Method of treating an unspecified disease

13. 13 The Use Must Be Credible A small degree of utility is sufficient—only total incapacity merits rejection Rare basis for rejection—seldom upheld by courts Mere identification of pharmacological activity of a compound relevant to an asserted pharmacological use provides an “immediate benefit to the public” Nelson v. Bowler (CCPA 1980)

14. 14 Unsuccessful Credibility Challenges Synthetic prostaglandins modeled on naturally occurring, bioactive prostaglandins plus tests showing relative activity (Nelson v. Bowler) Pharmaceutical compositions for treating leukemia in which active ingredient was structural analog to known anticancer agent and data showed comparable activity (In re Jolles 1980)

15. 15 Evaluation of Evidence Related to Utility Data from animal testing is relevant to asserted human therapeutic utility if there is a “satisfactory correlation” between the effect on animals and humans Do not need to prove correlation with statistical certainty If no previous treatment or cure, the PTO will carefully review for credibility

16. 16 In re Fisher 421 F.2d 1365 (Fed. Cir. 2005) Test case: Claimed 5 expressed sequence tags (ESTs) that encode proteins and protein fragments in maize plants Recited 7 utilities: serving as a molecular marker for gene mapping, measuring level of mRNA to study gene expression, providing a source for primers for use in PCR, identification of polymorphism, isolating promoters, controlling protein expression, and locating genetic molecules of other plants and organisms

17. 17 In re Fisher The PTO’s Rejection No specific and substantial utility but instead generally applicable to any EST No known use for the proteins produced as final products Utilities that require or constitute carrying out further research to identify or reasonably confirm a “real world” use are not substantial utilities Board of Appeals affirmed and Fisher appealed

18. 18 In re Fisher Basis for Federal Circuit’s Affirmance Court equated “practical utility” and “real world utility” with “substantial utility”—must show “a significant and presently available benefit to the public” and cannot require further research to identify or reasonably confirm utility Blessed the PTO Guidelines as “comport[ing] with this court’s interpretation of the utility requirement of § 101” No evidence that ESTs had been used for any of the asserted utilities

19. 19 In re Fisher Basis for Federal Circuit’s Affirmance Court analogized this case to earlier ones Process for preparing compounds of unknown use (Brenner v. Manson (S.Ct. 1966)) New steroidal compounds with two possible utilities (In re Kirk (CCPA 1967)) Compounds useful as intermediates in preparing steroids of no known use but similar in chemical structure to those with pharmcological activity (In re Joly (CCPA 1967))

20. 20 In re Fisher Majority’s Conclusions Granting a patent to Fisher “would amount to a hunting license because the claimed ESTs can be used only to gain further information about the underlying genes and the proteins encoded for by those genes.” The application “does not meet the utility requirement … because Fisher does not identify the function for the underlying protein-encoding genes” –No “immediate, well-defined real world benefit”

21. 21 In re Fisher Judge Rader’s Dissent ESTs are research tools, patentable under § 101 Similar to a microscope—both supply information about a molecular structure and advance research Research is conducted in small steps, usually requiring further research The Proper tool for assessing contributions of a claimed advance is 35 U.S.C. § 103, not § 101

22. 22 35 USC §112 Specification “The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same ….”

23. 23 35 USC §112 Two Separate and Distinct Requirements Written description: Inventor must have had “possession” of the claimed invention when the application was filed Enablement: The specification must teach how to make and use the claimed invention

24. 24 35 USC §112 Enablement If the examiner rejects a claim for lack of utility, then must also reject it for lack of enablement (cannot teach how to use if not useful) Typically, enablement is not a significant issue—focus is on written description

25. 25 35 USC §112 Written Description Prior to 1997, used to ensure applicants did not add essential disclosure to later-filed continuations or new claims (“new matter”) In 1997, also used to invalidate a patent for failure to show “possession” of the claimed invention (University of California v. Eli Lilly (Fed. Cir.)

26. 26 University of California v. Eli Lilly 119 F.3d 1559 (Fed Cir 1997) Relevant patent was filed in 1977 Key claim required “a nucleotide sequence having the structure of the reverse transcript of an mRNA of a [human], which mRNA encodes insulin” Prophetic example using the method used to obtain rat cDNA along with the amino acid sequences for human insulin A and B chains

27. 27 University of California v. Eli Lilly (continued ) Analysis: –No description of human cDNA (no relevant structure or physical characteristics) –Sequence information for rat is not sufficient –General process for making it plus protein sequence is not sufficient Conclusion: No possession

28. 28 University of California v. Eli Lilly (continued ) Genus claims to vertebrate and mammalian insulin cDNA for which rat insulin-encoding cDNA was sufficiently disclosed (one species) Held: Not sufficient to support the broad genuses—a broad statement such as “mammalian insulin cDNA” is not equivalent to a generic chemical claim—just a functional definition

29. 29 35 USC §112 Written Description The concept of “possession” is a difficult one: One skilled in the art must “immediately envisage” what is claimed from what is disclosed Highly fact-based inquiry, so must be decided on a case-by-case basis (tough to understand through earlier cases)

30. 30 What is Necessary to Show Possession? Description of an actual reduction to practice A showing that the invention was ready for patenting such as by disclosure of drawings or structural chemical formulae Specific identification of a deposit of a biological material

31. 31 Examples from Guidelines Assume: –The utility requirement is satisfied –The claimed invention is novel and nonobvious

32. 32 Lack of Written Description A claimed biomolecule sequence characterized only by a function without any known correlation between function and structure, even when it’s accompanied by a method for making the biomolecule sequence

33. 33 Lack of Written Description Genes A claim to “A gene comprising SEQ ID NO:1” where there is insufficient description of specific structures such as promoters, enhancers, coding regions, and other regulatory elements, and these structures are required in the description of the gene

34. 34 Lack of Written Description ESTs Claim: An isolated DNA comprising SEQ ID NO: 16. (A genus claim) Reduction to practice of SEQ ID NO: 16 but substantial variability among the DNAs Conclusion: No possession of the genus

35. 35 DNA Fragment Encoding a Full Open Reading Frame (ORF) Claim: An isolated and purified nucleic acid comprising SEQ ID NO: 2. 5000 members of cDNA library were sequenced and open reading frames identified One member having SEQ ID NO: 2 has a high level of homology to a DNA ligase Conclusion: In possession of the genus

36. 36 Hybridization Claim: An isolated nucleic acid that specifically hybridizes under highly stringent conditions to the complement of the sequence set forth in SEQ ID NO: 1, wherein said nucleic acid encodes a protein that binds to a dopamine receptor and stimulates adenylate cyclase activity.

37. 37 Hybridization (con’t) Hybridization techniques using a known DNA probe under highly stringent conditions were conventional in the art at filing SEQ ID NO: 1 is disclosed and there’s an actual reduction to practice of it Would not expect substantial variation within the genus Conclusion: Adequately described

38. 38 Allelic Variants Claim: An isolated allele of an isolated DNA that encodes protein X (SEQ ID NO: 2). Genus of DNAs that encodes protein X can be envisioned from one species by using a genetic code table but the genus of alleles cannot be due to lack of knowledge in the art. Conclusion: Not adequately described

39. 39 Protein Variants Claim: An isolated variant of an isolated protein having SEQ ID NO: 3. One member of the genus SEQ IDNO: 3 is described by a complete structure No limitations are put on substitutions, deletions, insertions and/or additions and no common features are described Conclusion: No “possession”

40. 40 Product by Function Claim: A protein comprising SEQ ID NO: 3 and variants thereof that are at least 95% identical to SEQ ID NO: 3 and catalyze the reaction of A to B Procedures for making variants are routine and an assay is described to identify which proteins will have claimed catalytic activity A single species is reduced to practice Conclusion: “Possession” established

41. 41 Other Examples www.uspto.gov: Synopsis of Application of Written Description Guidelineswww.uspto.gov See also Revised Interim Utility Guidelines Training Materials for more examples relating to the utility requirement

42. 42 Biotech Inventions: General Conclusions The line between what is sufficient and what is not is subjective and will change as the level of knowledge and skill in the art increases Broad claims will come under more scrutiny that narrow ones More detail about the claimed invention helps but may limit the value of the claim

43. 43 Impact of Patenting on Upstream Science Focus’s basic research Fosters discoveries that will serve the public such as cures and treatments for diseases Through partnerships under Bayh-Dole, promotes the development of such useful discoveries No negative impact shown—NRC data does not support their expressed concerns

44. 44 Thank you Any questions or requests for slides, write me at nlinck@bio.org For information about the Biotechnology Industry Organization (BIO), visit our website: www.bio.org