How to Claim your Biotech-Based Invention

1. How to Claim your Biotech-Based Invention Deborah Reynolds Detailee, TCPS1600 571-272-0734 Deborah.Reynolds@uspto.gov

2. How to Claim your Biotech-Based Invention • DNA or protein inventions (with a focus on utility) • Antisense nucleic acid inventions

3. What is the Invention? • The famous quote from Brenner v. Manson, 383 U.S. 519 (1966): • “[A] patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.”

4. Claim Analysis • Consider the following claim: An isolated and purified nucleic acid comprising SEQ ID NO 1.

5. Question • What does the application disclose? • Full Open Reading Frame (ORF) • Application further asserts that the encoded protein is a member of a family of proteins that is already known based upon amino acid sequence homology (i.e. comparison of entire sequence or determination of a consensus sequence).

6. The Protein • Two possibilities • The search may support the assignment of the protein to a particular family, or may be inconclusive. • The search may reveal that the protein more likely belongs to a family other than that asserted in the application.

7. Example • Example: • Applicant asserts that the protein is an interleukin receptor because it is 85% identical at the amino acid level with other IL-receptors. • A search confirms the asserted identity and that the next closest match is a 50% identity to beta-actin. • No reason to doubt assertion that the protein is an IL-receptor.

8. Example • Utility • Is there a well-established utility for IL-receptors? • No. Different receptors would have different functions and the artisan would have to determine such.

9. Example • Is the utility specific? • Maybe. The use would be particular to a general class of receptors, but the limited amount of information present would apply equally to all IL-receptors.

10. Example • Is the utility substantial? • No. The artisan would need to prepare, isolate, and analyze the protein in order to determine its function and use. Therefore, the invention is not in readily available form.

11. Example • In the absence of an alternative utility that meets the requirements of 35 U.S.C. §101, with these facts, the claimed invention would be rejected under 35 U.S.C. §101 as failing to have patentable utility.

12. Example • Is there an alternative utility? • Probe? • It is possible that the DNA encoding the protein would have utility as a probe. However, the probe must have a specific, substantial and credible utility under 35 U.S.C. 101.

13. Key Theme for Antisense Patent Examining • Structure-Function Relationships • Antisense Oligo+ • Target Nucleic Acid+ • Delivery Scheme+ • Cell Type+ • Organism= • Modulation of Target and/or Therapy

14. “Enablement” Requirement • Commonly cited unpredictable factors for antisense: • predicting target accessibility • target folding/structure • antisense/target protein interactions • lack of correlation between in vitro and in vivo • efficient delivery to cells and cell targeting for specific disorders • oligo affinity/stability in vivo • “modulation” of target • inhibition • up-regulation • in vitro (cell culture) results generally in vivo success • animal model shown is not art recognized

15. Gene Walk Conclusions • Probability of finding functional antisense oligo is high. • A broad claim to “An isolated antisense oligonucleotide that inhibits the expression of gene X” may be enabled by providing the sequence for gene X and gene walk data (no magic number) • Predictability of any single antisense being effective is low • claim to specific antisense oligonucleotide may require evidence of function • The current state of predictability for antisense may support that breadth/scope claimed is enabled • but this may also raise prior art issues depending on what was known at the time of filing

16. Obviousness • Broad antisense claims to known genes would be considered obvious if the prior art suggested inhibiting the gene and the gene sequence was known. • The current knowledge and level of skill in the art is high such that one of ordinary skill in the art would expect at least an antisense against every known gene (i.e. at mRNA initiation site), absent evidence to the contrary. • Narrow claims to specific antisense oligos may be free of the art, when there would be no motivation to modify the prior art to achieve the specific antisense sequence claimed.

17. Recommendations • Claim functional antisense oligos by specific sequence. • List results of “gene walk” • showing activity of each oligo • “gene walk” data may provide a representative number of species to enable/describe a broad generic claim, but there is no magic number

18. Recommendations • Provide objectiveevidence that in vitro results are representative of in vivo applicability. • Respond to examiner-cited unpredictable factors with objective evidence to the contrary. • Expert opinions are more favorably viewed when supported using objective evidence. • Provide objective evidence that a particular animal model is generally accepted as representative of disease or methods of treating, particularly for humans. • Objective evidence includes arguments, case law, journal articles, and experimental data and comparisons commensurate with the disclosure as filed.

19. Questions? Deborah Reynolds Detailee, TCPS1600 571-272-0734 Deborah.Reynolds@uspto.gov