Proteomics Examination

1. Proteomics Examination Yvonne (Bonnie) Eyler Technology Center 1600 Art Unit 1646 (703) 308-6564 yvonne.eyler@uspto.gov

2. What is a Proteome? • All the proteins expressed by a genome. • “Functional Proteome” = all the proteins produced by a specific cell in a single time frame.

3. Why is the Proteome Important? • It is the proteins within the cell that: • Provide structure • Produce energy • Allow communication • Allow movement • Allow reproduction • Proteins provide the structural and functional framework of cellular life

4. What is Proteomics? • Proteomics refers to the systematic analysis of protein profiles of entire cells, tissues, organisms, or species. • It represents the protein counterpart to the analysis of gene function.

5. Proteomics vs Genomics • DNA sequence does not predict if the protein is in an active form • RNA quantitation does not always reflect corresponding protein levels • Multiple proteins can be obtained from each gene (alternative splicing) • Genomics cannot predict post-translational modifications and the effects thereof • DNA/RNA analysis cannot predict the amount of a gene product made (if and when) • DNA/RNA analysis cannot predict events involving multiple genes

6. Why is Proteomics Important? • Identification of proteins in normal and disease conditions • Investigating epidemiology and taxonomy of pathogens • Analysis of drug resistance • Identification of pathogenic mechanisms • Reveals gene regulation events involved in disease progression • Promise in novel drug discovery via analysis of clinically relevant molecular events • Contributes to understanding of gene function

7. Proteomic Methodologies • Analysis of protein expression patterns • Analysis of protein Sequence Information • Analysis of protein structure/function relationships

8. Proteomic Methodologies • Complex protein mixtures are separated by 2-D gel electrophoresis • Then individual proteins are isolated from spots and are identified by using mass spectrometry • Individual proteins are sequenced, followed by database searches • Bioinformatics

9. Proteomics Examination

10. Patentability • Patent Statutes • 35 USC 101, Utility • 35 USC 102, Anticipation • 35 USC 103, Obviousness • 35 USC 112, 1st Paragraph, enablement • 35 USC 112, 1st Paragraph, written description • 35 USC 112, 2nd Paragraph

11. Protein Expression Pattern

12. Disclosure # 1 • The specification discloses 2D gels of proteins present in prostate cancer cell lysates and normal cell lysates. • The specification points to several spots indicating proteins expressed in prostate cancer that are not present in normal cells. • The specification distinguishes between these protein spots by isoelectric point and molecular weight. • No further information is provided.

13. Example Claim • An isolated polypeptide which is diagnostic of prostate cancer, wherein the polypeptide is identified by 2D gel electrophoretic comparison of proteins present in prostatic cancer cells as compared to normal prostatic cells.

14. Patentability Considerations-Written Description • 112 1st paragraph written description • Can one skilled in the art reasonably conclude the inventor had possession of the claimed invention at the time the application was filed?

15. Satisfying Written Description • Weigh factual considerations in view of level of skill and knowledge in the art • Complete or partial structure • Physical and/or chemical properties • Functional characteristics • Correlation between structure and function • Method of making • Combinations of the above

16. No structure of the polypeptide is provided in the specification Physical properties of the polypeptide are disclosed, ie molecular weight and pI The biological function of the polypeptide is not disclosed Method of making is not disclosed, only a method of isolating from a specific population of undefined cells. Written Description Analysis An isolated polypeptide which is diagnostic of prostate cancer, wherein the polypeptide is identified by 2D gel electrophoretic comparison of proteins present in prostatic cancer cells as compared to normal prostatic cells.

17. Conclusion • Applicant was not in possession of the claimed isolated polypeptide.

18. Solution • Claim a method of diagnosing prostate cancer that relies upon a particular pattern of polypeptide expression.

19. Patentability Considerations-Enablement 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, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

20. Factors to be considered, In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988) • Quantity of experimentation necessary • Amount of direction or guidance presented • Presence or absence of working examples • Nature of the invention • State of the prior art • Relative skill of those in the art • Predictability or unpredictability of the art • Breadth of the claims

21. Undue experimentation necessary to isolate and identify polypeptide. No guidance present regarding the structure of the polypeptide. No working examples of isolated polypeptide used to diagnose prostate cancer. The prior art does not teach polypeptide or it’s use to diagnose prostate cancer. The structure and function isolated polypeptide is unpredictable from the disclosure. An isolated polypeptide which is diagnostic of prostate cancer, wherein the polypeptide is identified by 2D gel electrophoretic comparison of proteins present in prostatic cancer cells as compared to normal prostatic cells. Enablement Analysis

22. Conclusion • Specification was not enabling for the claimed isolated polypeptide.

23. Solution • Claim a method of diagnosing prostate cancer that relies upon a particular pattern of polypeptide expression.

24. Patentability Considerations-Utility • Asserted utility • specific • substantial • credible • Well established utility

25. The asserted utility is to use the polypeptide to diagnose prostate cancer The asserted utility is specific The asserted utility is substantial The asserted utility is credible An isolated polypeptide which is diagnostic of prostate cancer, wherein the polypeptide is identified by 2D gel electrophoretic comparison of proteins present in prostatic cancer cells as compared to normal prostatic cells. Utility Analysis

26. Conclusion • The claimed invention has a specific, substantial, and credible asserted utility, i.e. for cancer diagnosis.

27. Disclosure # 2 • The specification discloses 2D gels of prostate cancer and normal cell lysates. • A polypeptide located in a spot unique to prostate cancer cells was isolated and sequenced (SEQ ID NO: 1) • Antibodies were generated to SEQ ID NO: 1 • The antibodies were used in a series of binding assays to demonstrate a clear correlation between presence of high levels of SEQ ID NO: 1 and prostate cancer.

28. An Example Claim Set • An isolated polypeptide comprising at least 10 contiguous amino acids of SEQ ID NO: 1. • An isolated polypeptide having at least 45% identity to the polypeptide of SEQ ID NO: 1.

29. Satisfying Written Description • Weigh factual considerations in view of level of skill and knowledge in the art • Complete or partial structure • Physical and/or chemical properties • Functional characteristics • Correlation between structure and function • Method of making • Combinations of the above

30. Physical properties of a single polypeptide are disclosed, ie molecular weight and pI by 2D gel electrophoresis and its sequence. The physical properties of polypeptides comprising 10 amino acids or of polypeptides having 45% identity to SEQ ID NO: 1 are not disclosed or known in the art. No biological function of the polypeptide of SEQ ID NO: 1 is disclosed. The isolated polypeptide is an “orphan” receptor. No structural to functional correlation is disclosed between core structural features needed to retain function in the two claimed genus of polypeptides. Written Description Analysis • An isolated polypeptide comprising at least 10 contiguous amino acids of SEQ ID NO: 1. • An isolated polypeptide having at least 45% identity to the polypeptide of SEQ ID NO: 1.

31. Conclusion • Applicant was not in possession of the claimed genus of isolated polypeptides.

32. Satisfying the Enablement Requirement • Factors to be considered, In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988) • Quantity of experimentation necessary • Amount of direction or guidance presented • Presence or absence of working examples • Nature of the invention • State of the prior art • Relative skill of those in the art • Predictability or unpredictability of the art • Breadth of the claims

33. No guidance regarding the critical structural features of the polypeptide of SEQ ID NO: 1. Which 10 amino acids are essential to functional and physical properties? Where over the length of the polypeptide may changes be made up to 45% identity and still retain functional and physical properties? There is no function for the isolated polypeptide. It is an “orphan” receptor. It is not predictable that the scope of the claimed polypeptides could be used to diagnose prostate cancer. Enablement Analysis • An isolated polypeptide comprising at least 10 contiguous amino acids of SEQ ID NO: 1. • An isolated polypeptide having at least 45% identity to the polypeptide of SEQ ID NO: 1.

34. Conclusion • The specification was not enabling for the scope the claimed isolated polypeptides.

35. Solution Claim: • An isolated polypeptide comprising SEQ ID NO: 1.

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