Patenting and Commercializing Biomarker Technologies May 14, 2015 Connie Ding, J.D.
Stacy A. Williams, Ph.D.
Stites & Harbison, PLLC
UT Research Foundation
DIAGNOSTIC/PROGNOSTIC ASSAY PATENT PROSECUTION STRATEGIES Connie Ding STITES & HARBISON May 14, 2015
Examples of Diagnostic/Prognostic Assay • The presence or absence of – specific sequences or polymorphisms – certain antibodies and/or antigens – drug metabolites
• Expression levels for particular gene or gene product • Activity of specific enzymes
Patent Eligible Subject Matter • 35 U.S.C. §101 –Ineligible subject matter – Abstract ideas – Laws of nature/natural principles – Natural phenomena (including products of nature/natural products)
December 2014 USPTO Eligibility Guidance • Step 2A: Markedly different characteristics from its natural state – “product of nature” • Step 2B: “significantly more”
Patent Eligible Subject Matter-AntibodyUSPTO Examples • Claim 1. An antibody to Protein S. (Ineligible) • Claim 2. The antibody of claim 1, wherein the antibody is a murine antibody comprising complementarity determining region (CDR) sequences set forth as SEQ ID Nos: 7-12. (Eligible) • Claim 3. The antibody of claim 1, wherein the antibody comprises a variant Fc domain. (Eligible) – At least one amino acid modification relative to a wild-type Fc domain
Patent Eligible Subject Matter-Nucleotides – USPTO Examples • Claim 1. Isolated nucleic acid comprising SEQ ID NO: 1. (Ineligible) • Claim 2. Isolated nucleic acid comprising a sequence that has at least 90% identity to SEQ ID NO: 1 and contains at least one substitution modification relative to SEQ ID NO: 1. (Eligible) • Claim 3. The isolated nucleic acid of claim 1, further comprising a fluorescent label attached to the nucleic acid. (Eligible) • Claim 4. A vector comprising the nucleic acid of claim 1, and a heterologous nucleic acid sequence. (Eligible) – “heterologous” is defined as nucleic acid sequence that do not naturally occur.
Patent Eligible Subject Matter-Process claims • Additional examples are being developed • Screening/Diagnostic claims are not addressed in detail in the 2014 Interim Eligibility Guidance • The law in this area is unclear
Patent Eligible Subject Matter-Process Claims • University of Utah Research Foundation v. Ambry Genetics (Dec. 2014) – preliminary injunction – the Defendants have “convincingly succeeded in raising a substantial questions as concerning the subject matter eligibility of each of these claims”. • U.S. 5,747,282 (primer claims--ineligible subject matter) – Claim 16. A pair of single-stranded DNA primers for determination of a nucleotide sequence of a BRCA1 gene by a polymerase chin reaction, the sequence of said primers being derived from human chromosome 17q, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of the BRCA1 gene. – Claim 17. The pair of primers of claim 16 wherein said BRCA1 gene has the nucleotide sequence set forth in SEQ ID NO:1.
Patent Eligible Subject Matter-Process Claims • University of Utah Research Foundation v. Ambry Genetics (Dec. 2014) • U.S. 5,837,492 (primer claims--ineligible subject matter) – Claim 29. A pair of single-stranded DNA primers of at least 15 nucleotides in length for determination of the nucleotide sequence of a BRCA2 gene by a polymerase chain reaction, the sequence of said primers being isolated from human chromosome 13, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA comprising all or at least 15 contiguous nucleotides of the BRCA2 gene. – Claim 30. The pair of primers of claim 29 wherein said BRCA2 gene has the nucleotide sequence set forth in SEQ ID NO:1.
Patent Eligible Subject Matter – Strategies • Physical assay – Novel assay – specific use of the particular gene – Well understood, routine and conventional activities previously known to the industry—not enough to qualify as “significantly more”
• Administering step – Compound, antibody, pharmaceutical composition, etc.
Patent Eligible Subject Matter – Strategies • Narrow claims to a specific disease – E.g. a subset of a specific type of cancer
• More than one markers – Show correlation among markers
Written Description and Enablement – 35 U.S.C. §112 • Whether a person of ordinary skill in the art could practice claimed invention without “undue experimentation” • High level of unpredictability – diagnostic assays • Multiple working examples and detailed protocols to support claims
• Polymorphisms • Various polymorphic sequences in detail
• Expression level • In vitro v. in vivo data • mRNA v. Proteins levels • Mouse v. Human
Recently Allowed Claims Example • • • • • •
•
1. A method for diagnosing obstructive sleep apnea in a subject, comprising: (a) providing a biological sample from the subject; (b) determining an amount in the sample of a Urocortin III peptide; (c) determining an amount in the sample of a Uromodulin peptide, an Orosomucoid 1 peptide, a Kallikrein 1 peptide, or a combination thereof; (d) comparing the amount of the Urocortin III peptide in the sample, if present, to a control level of the Urocortin III peptide, (e) comparing the amount of the Uromodulin peptide, the Orosomucoid 1 peptide, the Kallikrein 1 peptide, or the combination thereof in the sample, if present, to a control level of the Uromodulin peptide, the Orosomucoid 1 peptide, the Kallikrein 1 peptide, or the combination thereof; and (f) diagnosing the subject as having obstructive sleep apnea, or a risk thereof, if there is a measurable increase in the amount of the Urocortin III peptide and if there is a measurable increase in the amount of the Uromodulin peptide, a measurable increase in the amount of the Orosomucoid 1 peptide, a measurable decrease in the amount of the Kallikrein 1 peptide, or the combination thereof in the sample as compared to the control levels,
Recently Allowed Claims Example (cont’d) •
wherein determining the amount in the sample of the Urocortin III peptide and the amount in the sample of the Uromodulin peptide, the Orosomucoid 1 peptide, the Kallikrein 1 peptide, or the combination thereof comprises determining the amount in the sample using mass spectrometry (MS) analysis, immunoassay analysis, or both,
•
wherein the mass spectrometry (MS) analysis is selected from the group consisting of liquid-chromatography mass spectrometry (LC-MS), electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and
•
wherein the immunoassay analysis is selected from the group consisting of an enzyme-linked immunosorbent assay (ELISA) and an immunoturbidimetric assay
THANK YOU! Connie Ding Stites & Harbison, PLLC
[email protected] (901) 9691133
Commercializing Target and Biomarker Technologies May 14, 2015 Stacy A. Williams, Ph.D. UT Research Foundation
From Patenting to Commercialization While part of our mission is to protect university intellectual property, our ultimate goal is to find commercial partners for all viable inventions • Strongly committed to turning the invention into a marketed product • Possesses the financial and personnel resources to develop, manufacture, and sell the product • Willing to pay the university a fair price for the invention
How Valuable is Your Patent? Potential partners are looking for exceptional technologies backed by strong patents Valuable patents: • Generally have broader claims • Prevent competitors from “designing around” the invention • Cover products that are high-demand and profitable (currently and/or in the future) • Offer protection where the product’s market is located
Target and Biomarker Patents Targets and biomarkers themselves are not patent eligible (composition claims unlikely) What we can protect: • Kit or method claims • Novel materials for diagnostic assays • Novel drugs designed for target • Existing drugs for novel target
Talk to UTRF About Your Biomarker Ideas Patenting may be difficult, but UTRF can help. Types of biomarker technologies we typically work with: A. Diagnostic Assays – Predictors of propensity for or early diagnosis of a disease B. Patient response to therapeutics (companion diagnostics) C. Identification of novel drug targets
A. Novel Diagnostic Assays Increased levels of VOL1 are found in human colon cancer tissue samples and cells. You propose a novel assay for early diagnosis of colon cancer by detection of VOL1 in serum samples. • Is VOL1 known to be related to other forms of cancer? • Have you identified any other potential biomarkers? • Have you developed a novel reagent?
Patenting Your Diagnostic Assay Ways to improve your chances of obtaining a patent: • Markers that have never been associated with the disease or are not known to be related to the field • Identification of a cluster of markers that are highly predictive of the disease (i.e., a set of 5 proteins that predict 95% of cases) • Data using human patient samples • Creation of a novel reagent (antibody) for your diagnostic assay – allows for composition claims
Commercializing Your Diagnostic Assay
Novel lateral flow binding assay developed to detect MMP-9
Global Diagnostics Market in 2013: • $20.1 billion • Annual Growth Rate: 13.7%
Hot Areas of Interest for Companies: • Oncology • Cardiovascular Disease • Neurology • Infectious Disease • Autoimmune Disease
B. Companion Diagnostics Absence of VOL1 results in improved response to Mirapex in an RLS mouse model. You propose a novel assay for determination of patient response to Mirapex by detection of VOL1 in patient samples. • Is this an established mouse model? • How long has Mirapex been on the market? • Do you have data from human patient samples? • Can you develop a novel reagent or method?
Patenting Companion Diagnostics Similar Rules Apply • Markers that have never been associated with the disease or are not known to be related to the field • Identification of a cluster of markers that are highly predictive of the disease (i.e., a set of 5 proteins that predict 95% of cases) • Data using human patient samples • Creation of a novel reagent (antibody) for your diagnostic assay – allows for composition claims
Commercializing Companion Diagnostics The global companion diagnostics market was valued at $1.8 billion in 2013. It is expected to grow at a CAGR of 18.1% from 2013 to 2019 to $5.6 billion.
Valuable Biomarkers: • Predictive of patient response to drugs that are still early in development - Trend towards co-development of drug and diagnostic • Applications within a family of drugs • Oncology, Cardiovascular Disease, Neurological Disease
C. Novel Drug Target Increased levels of VOL1, a metalloproteinase, are found in a mouse model for schizophrenia. You propose that a selective antagonist for VOL1 can be used to treat the cognitive and behavioral defects in patients with schizophrenia and related diseases. • Can you or your collaborators develop an antagonist for VOL1? • Are there existing drugs that could be used? • Is this an established mouse model?
Patenting Target-Related Technologies Best Case Scenario • A novel chemical entity or biological against target (composition of matter claims) • Use of a known drug against target Method Claims • Use of an unspecified agonist/antagonist of a target to treat a disease • Method of screening for molecules that agonize/antagonize a target • Little commercial value
Commercializing Target Technologies Additional Data may be Needed • In vivo data using established mouse models • Data using research grade compounds Research Collaborations with Industry Interesting disease – autoimmune diseases, diabetes, neurological diseases, infectious diseases In-House Collaborations • Pharmaceutical Sciences • ORNL – computational modeling, if there is a crystal structure for your target
Talk to UTRF About Your Biomarker Ideas The pharmaceutical industry and UTRF are still interested in your biomarker inventions. Submit a technology disclosure: • When you have cell and/or animal data to validate your target
or biomarker
• Before you publish or present
utrf.tennessee.edu
Richard Magid, Ph.D.
[email protected] 448-1562
(General matters, entrepreneurship, and medical devices)
Lakita Cavin, J.D., Ph.D.
[email protected] 448-7825
(Legal matters and biological technologies)
Stefan Schweizer, Ph.D.
[email protected] 448-1146
(Chemical and pharmaceutical technologies)
Stacy Williams, Ph.D.
[email protected] 448-2181
(Biological and dental technologies)
