Broadening the Scope of the Claims in Gene Therapy Applications

1. Broadening the Scope of the Claims in Gene Therapy Applications Deborah Reynolds Detailee, TCPS1600 571-272-0734 Deborah.Reynolds@uspto.Gov

2. Topics • Gene Therapy, a little background • Claims Analysis • Analysis of the Disclosure • Correlation of Evidence • How to overcome the rejection

3. Gene Therapy • Ex-vivo gene therapy • Cells transfected with gene in vitro and then administered to the patient • In-vivo gene therapy • Polynucleotide is administered directly into the patient

4. Gene Therapy • Traditionally • Replacement of a defective gene • Currently • Replacement of a defective gene • Vaccine immunization • DNA immunization • Anti-sense therapy • Supplying any therapeutic expression product

5. Obstacles for Gene Therapy • Stable expression of encoded gene • Host immune responses to vectors • Targeting vectors to specific cells • Specificity of vector expression • Representative animal models • Recognition of Immunogenic Epitopes which provide a therapeutic benefit

6. Scope of Enablement • “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).

7. Claim Interpretation • The claims are to be given their broadest reasonable interpretation that is consistent with the specification • Limitations and examples appearing in the specification do not generally limit what is covered by the claims

8. Intended Use Limitation • When a compound or composition is limited by a particular use, enablement of that claim should be evaluated based on that limitation. MPEP 2164.01(c) • Prior art evaluation may or may not turn based upon an intended use. The language used and where it occurs in the claim must be considered. See Eaton Corp. v. Rockwell International Corp., 66 USPQ2d 1271 (CA FC 2003).

9. Types of Claims • Products • A product, in order to be enabled must be disclosed such that there is at least one enabled method of making, and at least one enabled method of using the claimed product

10. Types of Claims • Methods • In order for a method claim to be enabled, each step must be enabled including all materials used therein

11. Foundation for Examiner’s Analysis • Determine what each claim as a whole covers • Broadest reasonable interpretation in light of and consistent with written description - In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997) • Preamble and transition phrases are treated under common usage

12. Gene Therapy Claims • Examination considerations • Sufficient administration • Sufficient expression • Art recognition of animal model • Phenotypic change correlated to the disease

13. Examiner Analysis of Gene Therapy Claims • Evaluate claims on: • Scope of the vector • (Adenoviral, retroviral, naked DNA, liposomes) • Scope of delivery • (IM, IV, sub Q, ID, oral, tissue specific target) • Scope of treatment • (Cancer, vaccine, viruses, hereditary, etc.) • Scope of molecule(s) delivered • (Related to disease being treated?) • Potential for ineffective in vivo responses • (Against vector, against cells, against host)

14. MPEP § 2164.05 • "In making the determination of enablement, the examiner shall consider the original disclosure and all evidence in the record, weighing evidence that supports enablement against evidence that the specification is not enabling."

15. MPEP § 2164.03 • "The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements...However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims.”

16. Working Examples • Working examples. • Compliance with enablement requirement does not turn on whether an example is disclosed. • Specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without undue amount of experimentation, in re Borkowski, 164 USPQ 642 (CCPA 1970). • A single working example in the specification for a claimed invention is enough to preclude a rejection which states that nothing is enabled since at least one embodiment is enabled.

17. Ex parte Maas, 9 Uspq2d 1746 • "Substantiating evidence may be in the form of animal tests which constitute recognized screening procedures with clear relevance to utility in humans. See Ex parte Krepelka, 231 USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein."

18. Ex parte Maas, 9 Uspq2d 1746 • "First, although appellants' specification describes certain in vitro experiments, there is no correlation on this record between in vitro experiments and a practical utility in currently available form for humans or animals. It is not enough to rely on in vitro studies where, as here, a person having ordinary skill in the art has no basis for perceiving those studies as constituting recognized screening procedures with clear relevance to utility in humans or animals" (emphasis added)

19. Ex parte Balzarini, 21 Uspq2d 1892 • "There is no evidence of record that experimental animal models have been developed in this area which would be predictive of human efficacy."

20. Cross v. Iizuka, 224 USPQ 739 • "Cross is arguing that there must be a rigorous correlation of pharmacological activity between the disclosed in vitro utility and an in vivo utility to establish practical utility. We, however, find ourselves in agreement with the Board that, based upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence."

21. Means to Obviate the Enablement Rejection • Has a reasonable basis to question the enablement been established? See MPEP 2164.04 • Applicants may submit argument and/or evidence that the disclosure as filed is enabled. See MPEP 2161.05 • Help us draw the correlations between your data and the real world utility