1. 1 1 AIPLA Firm Logo American Intellectual Property Law Association Politics, Health Care, Subject Matter Eligibility, & Patent Preemption Mercedes K. Meyer, Ph.D. April 2013 These materials are public information and have been prepared solely for educational and entertainment purposes to contribute to the understanding of U.S. intellectual property law and practice. These materials reflect only the personal views of the speaker and are not individualized legal advice. It is understood that each case is fact-specific, and that the appropriate solution in any case will vary. Therefore, these materials may or may not be relevant to any particular situation. Thus, Drinker Biddle & Reath LLP and the speaker cannot be bound either philosophically or as representatives of their various present and future clients to the comments expressed in these materials. The presentation of these materials does not establish any form of attorney-client relationship with Drinker Biddle & Reath LLP and the speaker. While every attempt was made to insure that these materials are accurate, errors or omissions may be contained therein, for which any liability is disclaimed.

2. 2 2 AIPLA Firm Logo Where do we stand? Method claims – Lab Corp., Classen, Prometheus & Myriad –Personalized medicine Have Akamai and McKesson helped? Composition claims - Gene claims under fire –Gene Claims – Myth v. Fact Politics & Health Care in the U.S.

3. 3 3 AIPLA Firm Logo 35 USC 101 § 101: –Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. The Exceptions to Eligibility: –Law of nature (naturally occurring correlates) MPEP §2106.01 –Algorithm –Abstract idea –AIA § 33 (a). Notwithstanding any other provision or law, no patent may issue on a claim directed to or encompassing a human organism See also MPEP § 2105 and 1077 Off. Gaz. Pat. Off 24 (1987) – multicellular organisms including animals are patent eligible.

4. 4 4 AIPLA Firm Logo American Intellectual Property Law Association Treatment Method Claims Status Check

5. 5 5 AIPLA Firm Logo We saw it coming - Lab Corp. Lab Corp.. v. Metabolite Laboratories, Inc., 548 U.S. 124 (2006) Certiorari was dismissed as improvidently granted. Claim 13 (still valid): – A method for detecting a deficiency of cobalamin or folate in warm-blooded animals comprising the steps of: assaying a body fluid for an elevated level of total homocysteine; and correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.

6. 6 6 AIPLA Firm Logo Personalized Medicine Obtain biological sample. Measure biomarker with diagnostic. –Metabolites, single & multiple biomarkers, genes, alleles, polymorphisms Correlate biomarker with therapy. Administer therapy. –The problem was that no therapy had to be administered in the Prometheus claims. THE DIVIDING LINE

7. 7 7 AIPLA Firm Logo Prometheus – Claim 1 USPN 6,355,623 1. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising: –(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and –(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder, –wherein the level of 6-thioguanine less than about 230 pmol per 8x10 8 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and –wherein the level of 6-thioguanine greater than about 400 pmol per 8x10 8 red blood cells indicates a need to decrease the amount of said drug subsequently ad ministered to said subject. INELIGIBLE SUBJECT MATTER

8. 8 8 AIPLA Firm Logo USPN 6,638,739 – Classen Immunization Schedule = Patent Eligible 1. A method of immunizing a mammalian subject which comprises: –(I) screening a plurality of immunization schedules, by (a) identifying a first group of mammals and at least a second group of mammals, said mammals being of the same species, the first group of mammals having been immunized with one or more doses of one or more infectious disease-causing organism-associated immunogens according to a first screened immunization schedule, and the second group of mammals having been immunized with one or more doses of one or more infectious disease-causing organism-associated immunogens according to a second screened immunization schedule, each group of mammals having been immunized according to a different immunization schedule, and (b) comparing the effectiveness of said first and second screened immunization schedules…., –(II) immunizing said subject according to a subject immunization schedule, ….

9. 9 9 AIPLA Firm Logo And finally, Myriad All of the method claims except for claim 20 of the USPN ‘282 were patent ineligible. –20. A method for screening potential cancer therapeutics which comprises: growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic. –“…at the heart of claim 20 is a transformed cell, which is made by man, in contrast to a natural material.”

10. 10 AIPLA Firm Logo American Intellectual Property Law Association Akamai & McKesson Game Changers?

11. 11 AIPLA Firm Logo The Tension How do you write a method claim that is patentable and enforceable? –The origin of the claims in Prometheus and Lab Corp. was to claim the essential components of the invention that generally only require one actor in order to practice the process. 35 USC § 271 (b) for induced infringement is difficult to prove. Direct infringement under § 271 (a) is easier to prove. –Claims were written for proving direct infringement.

12. 12 AIPLA Firm Logo American Intellectual Property Law Association Myriad – DNA Claims

13. 13 AIPLA Firm Logo Myriad The Question: “Are human genes patentable?” April 15, 2013 S. Ct. hearing Claim construction is not an inviolable prerequisite to a eligibility determination under § 101

14. 14 AIPLA Firm Logo Myriad: USPN 5,747,282 1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2. Gene? 2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1. cDNA? 5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1. Fragment of a gene? 6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2. Fragment of a cDNA? 7. An isolated DNA selected from the group consisting of: –(a) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having T at nucleotide position 4056; –(b) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having an extra C at nucleotide position 5385; –(c) a DNA having the nucleotide sequence set forth in SEQ ID NO: 1 having G at nucleotide position 5443; and, (d) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having 11 base pairs at nucleotide positions 189-199 deleted. cDNA variants?

15. 15 AIPLA Firm Logo Politics: Sec. 27 of AIA SEC. 27. STUDY ON GENETIC TESTING. (a) IN GENERAL.--The Director shall conduct a study on effective ways to provide independent, confirming genetic diagnostic test activity where gene patents and exclusive licensing for primary genetic diagnostic tests exist. (b) ITEMS INCLUDED IN STUDY.--The study shall include an examination of at least the following: –(1) The impact that the current lack of independent second opinion testing has had on the ability to provide the highest level of medical care to patients and recipients of genetic diagnostic testing, and on inhibiting innovation to existing testing and diagnoses. –(2) The effect that providing independent second opinion genetic diagnostic testing would have on the existing patent and license holders of an exclusive genetic test. –(3) The impact that current exclusive licensing and patents on genetic testing activity has on the practice of medicine, including but not limited to: the interpretation of testing results and performance of testing procedures. –(4) The role that cost and insurance coverage have on access to and provision of genetic diagnostic tests. Results 9 months after enactment – June 2012 No study results

16. 16 AIPLA Firm Logo Thanks for your attention! Questions? Mercedes K. Meyer, Ph.D., J.D. Drinker Biddle & Reath LLP 1500 K Street, NW Suite 1100 Washington, DC 20005 +1-202-842-8821 Mercedes.Meyer@dbr.com www.drinkerbiddle.com

17. 17 AIPLA Firm Logo Prometheus – Claim 1 USPN 6,680,302 1. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising: –(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and –(b) determining a level of 6-thioguanine or 6-methyl-mercaptopurine in said subject having said immune-mediated gastrointestinal disorder, –wherein a level of 6-thioguanine less than about 230 pmol per 8x10 8 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein a level of 6- thioguanine greater than about 400 pmol per 8x10 8 red blood cells or a level of 6-methyl-mercaptopurine greater than about 7000 pmol per 8x10 8 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject. INELIGIBLE SUBJECT MATTER

18. 18 AIPLA Firm Logo Rewriting Claim 1 from the ‘623 Patent Perhaps a patentable alternative? –A method of administering 6-thiopurine to a patient in need thereof for treating an immune-mediated gastrointestinal disorder, comprising the step of administering a therapeutically effective amount of the drug that produces a level of 6-thiopurine no less than 230 pmol and no more than 400 pmol per 8x10 8 red blood cells in blood from the patient.

19. 19 AIPLA Firm Logo USPN 5,783,283 – Classen Patent Ineligible 1. A method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals, which comprises immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens, according to said immunization schedule, and comparing the incidence, prevalence, frequency or severity of said chronic immune-mediated disorder or the level of a marker of such a disorder, in the treatment group, with that in the control group.

20. 20 AIPLA Firm Logo Resources –Akamai Technologies Inc. v. Limelight Networks Inc. (Fed. Cir. 2012); McKesson Technologies Inc. v. Epic Systems Corp., 692 F.3d 1301 (Fed. Cir. 2012) –Ass’n for Mol. Path. et al. v. Myriad Genetics, Inc., 689 F.3d 1303 (Fed. Cir. 2012) –Bancorp Services, L.L.C. v. Sun Life Assur. Co. of Canada, 687 F.3d 1266 (Fed. Cir. 2012) –Coliainni et al., “Impact of gene patents and licensing practices on access to genetic testing and carrier screening for Tay-Sachs and Canavan disease.” Genet. Med. 12(4 Suppl): S5-S14 (2010) available at: http://www.ncbi.nlm.nih.gov/pubmed/20393311.http://www.ncbi.nlm.nih.gov/pubmed/20393311 –HHS Draft Report on Gene Patents: http://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Consultation%20Draft%203%209%202 009.pdf http://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Consultation%20Draft%203%209%202 009.pdf –HHS Report on Access to Medical Testing: http://oba.od.nih.gov/oba/sacghs/reports/SACGHS_patents_report_2010.pdf http://oba.od.nih.gov/oba/sacghs/reports/SACGHS_patents_report_2010.pdf –Laboratory Corp. of America Holdings v. Metabolite Laboratories Inc., 548 U.S. 124 (2006) –Classen Immunotherapies Inc. v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011) –Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S.Ct. 1289 (2012) –MPEP: http://www.uspto.gov/web/offices/pac/mpep/index.htmlhttp://www.uspto.gov/web/offices/pac/mpep/index.html –Public Consultation Draft Report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests.” 74 F.R. 11730 –Recent Examiner Training and Developments Under 35 USC §101 (Sep. 5, 2012): http://www.cabic.com/bcp/090512/BIO_9_2012_101_Train_Update(HANDOUT)_TC1600.pdf http://www.cabic.com/bcp/090512/BIO_9_2012_101_Train_Update(HANDOUT)_TC1600.pdf –Smartgene Inc. v. Advanced Biological Lab., SA (D.D.C. Mar. 30, 2012) Case 1:08-cv- 00642-BAH – claims found ineligible in view of Prometheus.