`Patent 7,772,209
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`SANDOZ INC.,
`APOTEX INC., APOTEX CORP.,
`EMCURE PHARMACEUTICALS LTD.,
`HERITAGE PHARMA LABS INC.,
`HERITAGE PHARMACEUTICALS INC.,
`GLENMARK PHARMACEUTICALS, INC., USA,
`GLENMARK HOLDING SA,
`GLENMARK PHARMACEUTICALS, LTD.,
`MYLAN LABORATORIES LIMITED,
`TEVA PHARMACEUTICALS USA, INC.
`and FRESENIUS KABI USA, LLC,
`
`Petitioners
`
`v .
`ELI LILLY AND COMPANY,
`Patent Owner.
`
`Case IPR2016-003181
`U.S. Patent 7,772,209
`
`
`
`
`
`
`
`
`PETITIONER’S UPDATED EXHIBIT LIST
`
`
`1 Cases IPR2016-01340 and IPR2016-01429 have been joined with the instant
`
`proceeding.
`
`
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Description
`
`U.S. Patent No. 7,772,209
`
`File History of U.S. Patent Application
`No. 11/776,329, which issued as U.S. Patent No.
`7,772,209 on August 10, 2010
`
`Findings Of Fact And Conclusions Of Law
`Following Bench Trial August 19, 2013, in Eli
`Lilly & Co. v. Teva Parenteral Medicines, Inc.,
`Case No. 1:10-cv-1376, Dkt. 336 (S.D. Ind.
`March 31, 2014)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
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`12/14/2015
`
`12/14/2015
`
`12/14/2015
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`12/14/2015
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`12/14/2015
`
`Exhibit
`No.
`
`Exhibit
`1001:
`
`Exhibit
`1002:
`
`Exhibit
`1003:
`
`Exhibit
`1004:
`
`Exhibit
`1005:
`
`Exhibit
`1006:
`
`Declaration of Ron D. Schiff, M.D., Ph.D.
`
`12/14/2015
`
`U.S. Patent No. 5,217,974
`
`C. Niyikiza, et al., MTA (LY231514): Relationship
`of vitamin metabolite profile, drug exposure, and
`other patient characteristics to toxicity, Annals
`Oncology 9 (Suppl. 4): 125-140, Abstract 609P,
`(1998)
`
`Exhibit
`1007:
`
`Hilary Calvert, An Overview of Folate
`Metabolism: Features Relevant to the Action and
`Toxicities of Antifolate Anticancer Agents,
`Seminars Oncology, 26: 3-10 (1999)
`
`Exhibit
`1008:
`
`Textbook of Small Animal Medicine (John K. Dunn
`ed. 1999)
`
`Exhibit
`1009:
`
`Sidney Farber, et al., Temporary Remissions in
`acute leukemia in children produced by folic acid
`antagonist, 4-aminopteroylglutamic acid
`(aminopterin), New Eng. J. Med., 238(23): 787-793
`
`
`
`2
`
`
`
`Exhibit
`No.
`
`Exhibit
`1010:
`
`Exhibit
`1011:
`
`Exhibit
`1012:
`
`Exhibit
`1013
`
`Exhibit
`1014
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Sarah L. Morgan, et al., Supplementation with Folic
`Acid during Methotrexate Therapy for Rheumatoid
`Arthritis, Annals Internal Med., 121: 833-841 (1994)
`
`12/14/2015
`
`G.B. Grindey, et al., Reversal of the toxicity but not
`the antitumor activity of Lometrexol by folic acid,
`Am. Ass’n Cancer Res., 32: 324, Abstract 1921
`(1991)
`
`Laurane G. Mendelsohn, et al., Preclinical and
`Clinical Evaluation of the Glycinamide
`Ribonucleotide Formyltransferase Inhibitors
`Lometrexol and LY309887, in Anticancer Drug Dev.
`Guide: Antifolate Drugs Cancer Therapy, (Ann L.
`Jackman, ed.) Ch. 12: 261-80 (1999)
`
`12/14/2015
`
`12/14/2015
`
`John F. Worzalla, et al., Role of Folic Acid in
`Modulating the Toxicity and Efficacy of the
`Multitargeted Antifolate, LY231514, Anticancer Res.,
`18: 3235-3240 (1998)
`
`12/14/2015
`
`L. Hammond, et al., A Phase I and
`Pharmacokinetic (PK) Study of the Multitargeted
`Antifol (MTA) LY231514 with Folic Acid, Proc.
`Am. Soc’y Clinical Oncology, 17: Abstract 866
`(1998)
`
`12/14/2015
`
`Exhibit
`1015
`
`L. Hammond, et al., A phase I and pharmacokinetic
`(PK) study of the multitargeted antifolate (MTA,
`LY231514) with folic acid (FA), Annals Oncology, 9:
`129, Abstract 620P (1998)
`
`12/14/2015
`
`Exhibit
`1016
`
`C. Niyikiza, et al., LY231514 (MTA): Relationship of
`vitamin metabolite profile to toxicity, Proc. Am.
`Ass’n Cancer Res., 17: 558a, Abstract 2139 (1998)
`
`12/14/2015
`
`
`
`3
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
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`12/14/2015
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`12/14/2015
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`12/14/2015
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`12/14/2015
`
`Exhibit
`No.
`
`Exhibit
`1017
`
`Exhibit
`1018
`
`Exhibit
`1019
`
`Exhibit
`1020
`
`Exhibit
`1021
`
`Exhibit
`1022
`
`R. Thödtmann, et al., Preliminary Results of a Phase
`I Study with MTA (LY231415) in Combination with
`Cisplatin in Patients with Solid Tumors, Seminars
`Oncology, 26 (2, Suppl. 6): 89-93 (1999)
`
`U.S. Patent No. 5,563,126
`
`Ernest Beutler & James K. Weick, Blood and
`Neoplastic Disorders, in Current Clinical Practice
`(Messerli, ed., 1987), Ch. 1: 291-302
`
`Lars Brattström, Vitamins as Homocysteine-
`Lowering Agents, J. Nutrition, 126: 1276S-1280S
`(1996)
`
`Chuan Shih, et al., LY231514, a Pyrrolo[2,3-
`d]pyrimidine-based Antifolate That Inhibits Multiple
`Folate-requiring Enzymes, Cancer Res., 57, 1116-
`1123 (1997)
`
`G. Robbin Westerhof, et al., Carrier- and Receptor-
`Mediated Transport of Folate Antagonists Targeting
`Folate-Dependent Enzymes: Correlates of
`Molecular-Structure and Biological Activity, Am.
`Soc’y Pharmacology Experimental Therapeutics, 48:
`459-471 (1995)
`
`Exhibit
`1023
`
`F. G. Arsenyan, et al., Influence of Methylcobalamin
`on the Antineoplastic Activity of Methotrexate,
`Pharmaceutical Chemistry J., 12(10): 1299-1303
`(1978)
`
`Exhibit
`1024
`
`File History of U.S. Patent Application
`No. 11/288,807, Abandoned
`
`
`
`4
`
`
`
`Exhibit
`No.
`
`Exhibit
`1025
`
`Exhibit
`1026
`
`Exhibit
`1027
`
`Exhibit
`1028
`
`Exhibit
`1029
`
`Exhibit
`1030
`
`Exhibit
`1031
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`U.S. Food & Drug Administration, Approved Drug
`Products with Therapeutic Equivalents Evaluations
`(30th ed. 2010)
`
`Z.P. Sofyina, et al., Possibility to Increase the
`Antitumor Effect of Folic Acid Antagonist with the
`Help of Methylcobalamine Analogs, Sci. Center
`Oncology 1:72-78 (1979)
`
`Victor Herbert, The Role of Vitamin B12 and Folate
`in Carcinogenesis, Advances Experimental Med.
`Biology, 206: 293-311 (1986)
`
`Glenn Tisman, et al., Overcoming Colon Cancer
`Resistance to Hepatic Artery Infusional 5FUdR
`Chemotherapy with Folinic Acid, Clinical Res.,
`33(2): 459A (1985)
`
`J.D. Kinloch, Maintenance Treatment of Pernicious
`Anaemia by Massive Parenteral Doses of Vitamin
`B12 at Intervals of Twelve Weeks, Brit. Med. J., 1:99-
`100 (1960)
`
`D. Wray, et al., Recurrent Aphthae: Treatment with
`Vitamin B12, Folic Acid, and Iron, Brit. Med. J.,
`2:490-93 (1975)
`
`J. Tamura, et al., Immunomodulation by Vitamin
`B12: Augmentation of CD8+ T Lymphocytes and
`Natural Killer (NK) Cell Activity in Vitamin B12-
`Deficient Patients by Methyl-B12 Treatment, Clin.
`Experimental Immunology, 116:28-32 (1999)
`
`12/14/2015
`
`12/14/2015
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`12/14/2015
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`12/14/2015
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`12/14/2015
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`12/14/2015
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`12/14/2015
`
`Exhibit
`1032
`
`Carrasco et al., Acute Megaloblastic Anemia:
`Homocysteine Levels Are Useful for Diagnosis and
`Follow-Up, Haematologica, 84: 767- 768 (1999)
`
`12/14/2015
`
`
`
`5
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`
`
`Exhibit
`No.
`
`Exhibit
`1033
`
`Exhibit
`1034
`
`Exhibit
`1035
`
`Exhibit
`1036
`
`Exhibit
`1037
`
`Exhibit
`1038
`
`Exhibit
`1039
`
`Exhibit
`1040
`
`Exhibit
`1041
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`European Patent Application No. 0 595 005
`
`12/14/2015
`
`U.S. Patent No. 5,344,932
`
`Amended Joint Claim Construction Statement in Eli
`Lilly & Co. v. Teva Parenteral Medicines, Inc. et al.,
`No. 1:10-cv-1376 (S.D. Ind.), filed April 19, 2012
`(Dkt. 110)
`
`Excerpts from transcript of the trial on invalidity
`held between August 19 and August 29, 2013 in Eli
`Lilly & Co. v. Teva Parenteral Medicines, Inc., Case
`No. 1:10-cv-1376 (S.D. Ind.)
`
`E. Bajetta et al., Phase II study of pemetrexed
`disodium (Alimta®) administered with oral folic
`acid in patients with advanced gastric cancer,
`Annals of Oncology 14:1543-48 (2003).
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`Letter dated February 4, 2004 from Robert Temple to
`John Worzalla concerning NDA 21-462
`
`12/14/2015
`
`Johan B. Ubbink et al., Vitamin Requirements for the
`Treatment of Hyperhomocysteinemia in Humans, J.
`Nutrition 124:1927-1933 (1994)
`
`12/14/2015
`
`Anja Brönstrup et al., Effects of folic acid and
`combinations of folic acid on plasma homocysteine
`concentrations in healthy, young women, Am. J.
`Clin. Nutr. 1998:68:1104-10 (1998)
`
`J. B. Ubbink, The role of vitamins in the
`pathogenesis and treatment of
`hyperhomocyst(e)inaemia, J. Inherited Metabolic
`Disease, 20:316-25 (1997)
`
`12/14/2015
`
`12/14/2015
`
`
`
`6
`
`
`
`Exhibit
`No.
`
`Exhibit
`1042
`
`Exhibit
`1043
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`S. Sörenson et al., A systematic overview of
`chemotherapy effects in non-small cell lung cancer,
`Acta Oncologica 40(2-3):327-29 (2001)
`
`R. Thödtmann et al., Phase I study of different
`sequences of MTA (LY231514) in combination with
`cisplatin in patients with solid tumours, Annals
`Oncology, 9: 129, 618P (Abstract) (1998)
`
`12/14/2015
`
`12/14/2015
`
`Exhibit
`1044
`
`Complaint filed in Eli Lilly & Co. v. Teva Parenteral
`Medicines, Inc., No. 1:08-cv-335 (D. Del.) on June 5,
`2008
`
`12/14/2015
`
`Exhibit
`1045
`
`Calvert, MTA: Summary and Conclusions, Seminars
`in Oncology, 26 (2, Suppl. 6): 105-08 (1999)
`
`12/14/2015
`
`Exhibit
`1046
`
`Center for Drug Evaluation and Research, Product
`Development under the Animal Rule: Guidance for
`the Industry (October 2015)
`
`Exhibit
`1047
`
`A.H. Calvert & J.M. Walling, Clinical Studies with
`MTA, British J. Cancer (1998) 78 (Suppl. 3): 35-40
`
`Exhibit
`1048
`
`Exhibit
`1049
`
`Exhibit
`1050
`
`Center for Drug Evaluation and Research, Guidance
`for Industry: Single Dose Acute Toxicity Testing for
`Pharmaceuticals (August 1996)
`
`Center for Drug Evaluation and Research, E6 Good
`Clinical Practice: Consolidated Guidance (April
`1996)
`
`Robert H. Allen et al., Diagnosis of Cobalamin
`Deficiency I: Usefulness of Serum Methylmalonic
`Acid and Total Homocysteine Concentrations, Am. J.
`Hematology 34:90-98 (1990)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`Exhibit
`1051
`
`Eli Lilly & Company, Alimta® Labeling (Revised
`Sept. 2013)
`
`12/14/2015
`
`
`
`7
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Exhibit
`No.
`
`Exhibit
`1052
`
`Rusthoven et al., Multitargeted Antifolate LY231514
`as First-Line Chemotherapy for Patients with
`Advanced Non-Small-Cell Lung Cancer: A Phase II
`Study, J. Clin. Oncology, 17 (4) 1194-99 (April
`1999)
`
`Exhibit
`1053
`
`Return of Service, Eli Lilly & Co. v. Sandoz Inc.,
`Case No. 1:14-cv-2008 (S.D. Ind. Dec. 29, 2014)
`
`Exhibit
`1054
`
`Exhibit
`1055
`
`Exhibit
`1056
`
`Exhibit
`1057
`
`Exhibit
`1058
`
`FDA, Electronic Orange Book: Approved Drug
`Products and Therapeutic Equivalence Evaluations
`Entry for Alimta®, available at
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/
`patexclnew.cfm?Appl_No=021462&Product_No=00
`1&table1=OB_Rx (last accessed Dec. 14, 2015)
`
`Declaration of Laura Lydigsen in support of
`Petitioner’s Motion to Admit Pro Hac Vice Laura A.
`Lydigsen as Backup Counsel
`
`Z.P. Sofyina, et al., Possibility to Increase the
`Antitumor Effect of Folic Acid Antagonist with the
`Help of Methylcobalamine Analogs, Sci. Center
`Oncology 1:72-78 (1979)
`
`Victor Herbert, The Role of Vitamin B12 and Folate
`in Carcinogenesis, Advances Experimental Med.
`Biology, 206: 293-311 (1986)
`
`J. Tamura, et al., Immunomodulation by Vitamin
`B12: Augmentation of CD8+ T Lymphocytes and
`Natural Killer (NK) Cell Activity in Vitamin B12-
`Deficient Patients by Methyl-B12 Treatment, Clin.
`Experimental Immunology, 116:28-32 (1999)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`2/25/2016
`
`Not filed
`
`Not filed
`
`Not filed
`
`Exhibit
`1059
`
`Cover page for Certified electronic copy of File
`History for U.S. Patent No. 7,772,209
`
`Not filed
`
`
`
`8
`
`
`
`Description
`
`Declaration of Laura A. Lydigsen
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Not filed
`
`Not filed
`
`Supplemental Declaration of Ron D. Schiff, M.D.,
`Ph. D.
`
`Transcript of October 31, 2016 Telephone Hearing
`
`11/9/2016
`
`9
`
`Exhibit
`No.
`
`Exhibit
`1060
`
`Exhibit
`1061
`
`Exhibit
`1062
`
`
`
`
`
`
`
`CERTIFICATE OF SERVICE
`
`Case IPR2016-00318
`Patent 7,772,209
`
`I hereby certify that true and correct copies of the foregoing document were
`served on November 9, 2016 via email to the following individuals at the email
`addresses below.
`
`Dov P. Grossman (Reg. No. 72,525)
`Williams & Connolly LLP
`725 Twelfth St. NW
`Washington DC 20005
`Direct Phone: 202-434-5812
`Facsimile: 202-434-5029
`dgrossman@wc.com
`
`David M. Krinsky (Reg. No. 72,339)
`Williams & Connolly LLP
`725 Twelfth St. NW
`Washington DC 20005
`Direct Phone: 202-434-5338
`Facsimile: 202-480-8302
`dkrinsky@wc.com
`
`Adam L. Perlman
`Williams & Connolly LLP
`725 Twelfth St. NW
`Washington DC 20005
`Direct Phone: 202-434-5244
`aperlman@wc.com
`
`James P. Leeds (Reg. No. 35,241)
`Eli Lilly and Company
`Lilly Corporate Center
`Indianapolis, IN 46285
`Direct Phone: 317-276-1667
`Facsimile: 317-277-6534
`leeds_james@lilly.com
`
`John C. Demeter (Reg. No. 30,167)
`Eli Lilly and Company
`Lilly Corporate Center
`
`
`
`
`
`
`
`
`
`Dated: November 9, 2016
`
`
`
`
`
`
`Case IPR2016-00318
`Patent 7,772,209
`
`Indianapolis, IN 46285
`Direct Phone: 317-276-3785
`Facsimile: 317-276-3861
`demeter_john_c@lilly.com
`
`
`
`
`
`/s/ Ralph J. Gabric
`Ralph J. Gabric (Reg. No. 34,167)
`Laura L. Lydigsen
`Bryan T. Richardson, Ph.D. (Reg. No.
`70,572)
`Joshua H. James (Reg. No. 72,568)
`Brinks Gilson & Lione
`NBC Tower – Suite 3600
`455 N. Cityfront Plaza Dr.
`Chicago, Illinois 60611