Proteomics and “Orphan” Proteomics and “Orphan” ReceptorsReceptors

Yvonne (Bonnie) EylerTechnology Center 1600

Art Unit 1646(703) 308-6564

yvonne.eyler@uspto.gov

What is Proteomics?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.

Why is Proteomics Important?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

• Pin-point targets for drug discovery

• Contributes to understanding of gene function

Proteomic MethodologiesProteomic Methodologies

• Analysis of protein expression patterns

• Analysis of protein Sequence Information

• Analysis of protein structure/function relationships

What is an “orphan” receptor?What is an “orphan” receptor?

• An “orphan” receptor is a receptor with no known biological function.

• An “orphan” receptor is a receptor with no known ligand.

PatentabilityPatentability

• 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

Expression PatternsExpression Patterns2D Gel2D Gel

SpecificationSpecification

• The specification discloses 2D gels of proteins present in prostate cancer cell lysates and normal cell lysates.

• A polypeptide located in a spot unique to prostate cancer cells was isolated and sequenced (SEQ ID NO: 1)

• SEQ ID NO: 1 has 45% homology to WOW, a G protein coupled receptor which is up-regulated in prostate cancer which binds ligand B.

• Blocking of WOW/ligand B binding inhibits prostate cancer growth.

An Example ClaimAn Example Claim

• An isolated polypeptide comprising SEQ ID NO: 1.

Utility ConsiderationUtility Consideration• The asserted utility for SEQ ID NO: 1

is for use in screening assays to identify agents which bind to it. The agents are then to be used to inhibit prostate cancer growth.

• The asserted utility is based on the 45% homology to WOW receptor.

Sequence Homology is Usually Sequence Homology is Usually Insufficient to Establish UtilityInsufficient to Establish Utility

• Receptor function cannot be reliably predicted from DNA or protein sequence homology

• Evolutionarily-related protein families may have both overlapping and distinct features

Example #1 of Homology being Example #1 of Homology being Insufficient Criteria for UtilityInsufficient Criteria for Utility

• Transforming Growth Factor (TGF-beta) Family

– OP-1 induces metanephrogenesis whereas closest related TGF-beta family members—BMP-2 and TGF-beta1—have no effect on metanephrogenesis under identical conditions

Example #2 of Homology Being Example #2 of Homology Being Insufficient Criteria for UtilityInsufficient Criteria for Utility

• Platelet-derived Growth Factor (PDGF) Family

– VEGF, a member of the PDGF family, is mitogenic for vascular endothelial cells but not for vascular smooth muscle cells

– PDGF is mitogenic for vascular smooth muscle cells but not for vascular endothelial cells

Example #3 of Homology Being Example #3 of Homology Being Insufficient Criteria for UtilityInsufficient Criteria for Utility

• Vertebrate growth hormone of 198 amino acids becomes an antagonist (inhibitor of growth) when a single amino acid is changed. Even 99% homology does not allow predictability in this instance.

Utility Considerations for the Utility Considerations for the Claim ExampleClaim Example

• SEQ ID NO: 1 is an “orphan” receptor with no known ligand and no known function.

• The asserted utility is based solely on sequence homology to a G protein coupled receptor.

• G protein coupled receptors are a large and diverse family of receptors with diverse functions and properties, having no well established utility based on family membership.

ConclusionConclusion• The claimed polypeptide would

not be found to have a specific, substantial, and credible asserted or well established utility.

Specification # 2Specification # 2• The specification still discloses 2D gels of prostate

cancer and normal cell lysates.

• The polypeptide of SEQ ID NO: 1 is an “orphan” receptor.

• 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.

An Example ClaimAn Example Claim

• An isolated polypeptide comprising SEQ ID NO: 1.

Utility ConsiderationUtility Consideration

• The asserted utility for SEQ ID NO: 1 is for use to diagnose prostate cancer.

Utility ConclusionUtility Conclusion• The asserted utility is specific to

the polypeptide of SEQ ID NO: 1.

• The asserted utility is substantial.

• The asserted utility is credible.

Written DescriptionWritten DescriptionConsiderationsConsiderations

An Example Claim SetAn 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.

Satisfying Written DescriptionSatisfying 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

Written Description AnalysisWritten Description Analysis

• 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.

ConclusionConclusion

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

EnablementEnablementConsiderationsConsiderations

Satisfying the Enablement Satisfying the Enablement RequirementRequirement

• Factors to be considered, Factors to be considered, In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988)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

Enablement AnalysisEnablement Analysis• 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.

ConclusionConclusion

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

SolutionSolutionClaim:

• An isolated polypeptide comprising SEQ ID NO: 1.

Proteomics and “Orphan” Proteomics and “Orphan” ReceptorsReceptors

Yvonne (Bonnie) EylerTechnology Center 1600

Art Unit 1646(703) 308-6564

yvonne.eyler@uspto.gov