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.,
`FRESENIUS KABI USA, LLC, and WOCKHARDT BIO AG,
`
`Petitioners
`
`v .
`ELI LILLY AND COMPANY,
`Patent Owner.
`
`Case IPR2016-003181
`U.S. Patent 7,772,209
`
`
`
`
`
`
`
`
`PETITIONER’S UPDATED EXHIBIT LIST
`
`
`1 Cases IPR2016-01429, IPR2016-01393, and IPR2016-01340 have been joined
`
`with the instant proceeding.
`
`
`
`
`
`
`
`
`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.,
`FRESENIUS KABI USA, LLC, and WOCKHARDT BIO AG,
`
`Petitioners
`
`v .
`ELI LILLY AND COMPANY,
`Patent Owner.
`
`Case IPR2016-003181
`U.S. Patent 7,772,209
`
`
`
`
`
`
`
`
`PETITIONER’S UPDATED EXHIBIT LIST
`
`
`1 Cases IPR2016-01429, IPR2016-01393, and IPR2016-01340 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
`
`12/14/2015
`
`12/14/2015
`
`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)
`
`12/14/2015
`
`1
`
`
`
`Exhibit
`No.
`
`Exhibit
`1009
`
`Exhibit
`1010
`
`Exhibit
`1011
`
`Exhibit
`1012
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`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
`(Ex. 2042 in IPR2016-00237, -240)2
`
`12/14/2015
`
`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
`
`
`2 Pursuant to the parties’ December 6, 2016 stipulation that the transcript of Dr.
`
`Steven Zeisel’s deposition in IPR2016-00237 and -240 may be filed in the above-
`
`captioned proceeding, cross-references to the corresponding exhibit numbers in
`
`IPR2016-00237, and -240 are provided. (Paper 48, Stipulation Regarding the
`
`Deposition of Dr. Steven H. Zeisel, M.D., Ph.D.)
`
`2
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`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
`
`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
`
`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
`
`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)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`Exhibit
`No.
`
`Exhibit
`1013
`
`Exhibit
`1014
`
`Exhibit
`1015
`
`Exhibit
`1016
`
`Exhibit
`1017
`
`Exhibit
`1018
`
`Exhibit
`1019
`
`Exhibit
`1020
`
`3
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Exhibit
`No.
`
`Exhibit
`1021
`
`Exhibit
`1022
`
`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)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`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
`
`Exhibit
`1025
`
`Exhibit
`1026
`
`Exhibit
`1027
`
`Exhibit
`1028
`
`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)
`
`4
`
`
`
`Exhibit
`No.
`
`Exhibit
`1029
`
`Exhibit
`1030
`
`Exhibit
`1031
`
`Exhibit
`1032
`
`Exhibit
`1033
`
`Exhibit
`1034
`
`Exhibit
`1035
`
`Exhibit
`1036
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`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)
`
`Carrasco et al., Acute Megaloblastic Anemia:
`Homocysteine Levels Are Useful for Diagnosis and
`Follow-Up, Haematologica, 84: 767- 768 (1999)
`
`European Patent Application No. 0 595 005 (Ex.
`1010 in IPR2016-00237, -240)
`
`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.)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`5
`
`
`
`Exhibit
`No.
`
`Exhibit
`1037
`
`Exhibit
`1038
`
`Exhibit
`1039
`
`Exhibit
`1040
`
`Exhibit
`1041
`
`Exhibit
`1042
`
`Exhibit
`1043
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`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
`
`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)
`
`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
`
`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
`
`6
`
`
`
`Exhibit
`No.
`
`Exhibit
`1046
`
`Exhibit
`1047
`
`Exhibit
`1048
`
`Exhibit
`1049
`
`Exhibit
`1050
`
`Exhibit
`1051
`
`Exhibit
`1052
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Center for Drug Evaluation and Research, Product
`Development under the Animal Rule: Guidance for
`the Industry (October 2015)
`
`A.H. Calvert & J.M. Walling, Clinical Studies with
`MTA, British J. Cancer (1998) 78 (Suppl. 3): 35-40
`
`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) (Ex. 1017 in IPR2016-
`00237, -240)
`
`Eli Lilly & Company, Alimta® Labeling (Revised
`Sept. 2013)
`
`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)
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`12/14/2015
`
`Exhibit
`1053
`
`Return of Service, Eli Lilly & Co. v. Sandoz Inc.,
`Case No. 1:14-cv-2008 (S.D. Ind. Dec. 29, 2014)
`
`12/14/2015
`
`7
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`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)
`
`12/14/2015
`
`Declaration of Laura Lydigsen in support of
`Petitioner’s Motion to Admit Pro Hac Vice Laura A.
`Lydigsen as Backup Counsel
`
`2/25/2016
`
`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)
`
`Cover page for Certified electronic copy of File
`History for U.S. Patent No. 7,772,209
`
`Declaration of Laura A. Lydigsen
`
`Supplemental Declaration of Ron D. Schiff, M.D.,
`Ph. D.
`
`12/12/2016
`
`12/12/2016
`
`12/12/2016
`
`12/12/2016
`
`12/12/2016
`
`12/12/2016
`
`Transcript of October 31, 2016 Telephone Hearing
`
`11/9/2016
`
`Exhibit
`No.
`
`Exhibit
`1054
`
`Exhibit
`1055
`
`Exhibit
`1056
`
`Exhibit
`1057
`
`Exhibit
`1058
`
`Exhibit
`1059
`
`Exhibit
`1060
`
`Exhibit
`1061
`
`Exhibit
`1062
`
`8
`
`
`
`Exhibit
`No.
`
`Exhibit
`1063
`
`Exhibit
`1064
`
`Exhibit
`1065
`
`Exhibit
`1066
`
`Exhibit
`1067
`
`Exhibit
`1068
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Printout of website
`http://www.nlm.nih.gov/services/ctphases.html,
`dated January 10, 2001 from Internet Archive
`Wayback Machine
`
`Cross Examination of Bruce Chabner from Trial
`Transcript Volumes VI and VII dated August 26-27,
`2013 from Eli Lilly and Company v. Teva Parenteral
`Medicines, Inc., et al. Civil Action No. 1:10-cv-
`01376
`
`Thomas G. Roberts et al., Trends in the Risks and
`Benefits to Patients with Cancer Participating in
`Phase 1 Clinical Trials, JAMA, Vol. 292, No. 17,
`2130-2140 (November 3, 2004)
`
`Wyndham H. Wilson, Phase I and Pharmacokinetic
`Study of the Multidrug Resistance Modulator
`Dexverapamil with EPOCH Chemotherapy, Journal
`of Clinical Oncology, Vol. 13, No. 8, 1985-1994
`(August 1995)
`
`12/22/2016
`
`Not Filed
`
`Not Filed
`
`Not Filed
`
`Demonstratives prepared by Dr. Ratain for trial in Eli
`Lilly and Company v. Teva Parenteral Medicines,
`Inc, et al. Civil Action No. 1:10-cv-01376
`
`12/22/2016
`
`Worzalla et al., LY355702 and LY355703, new
`cryptophycin analogues with antitumor activity
`against human tumor xenografts, Abstract 1516,
`Proceedings of the American Association for Cancer
`Research, Eighty-Eighth Annual Meeting, Volume
`38 (March 1997)
`
`Not Filed
`
`9
`
`
`
`Exhibit
`No.
`
`Exhibit
`1069
`
`Exhibit
`1070
`
`Exhibit
`1071
`
`Exhibit
`1072
`
`Exhibit
`1073
`
`Exhibit
`1074
`
`Exhibit
`1075
`
`Exhibit
`1076
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Robert H. Allen et al., Diagnosis of Cobalamin
`Deficiency I: Usefulness of Serum Methylmalonic
`Acid and Total Homocystein Concentrations,
`American Jounral of Hematology 34:90-98 (1990)
`[Duplicate of previously filed Exhibit 1050]
`
`L. Paz-Ares et al., A Phase II Study of the Multi-
`Targeted Antifolate, MTA (LY231514), in Patients
`with Advanced Transitional Cell Carcinoma (TCC)
`of the Bladder, Absract 1307, Proceedings of the
`American Society of Clinical Oncology, Thirty-
`Fourth Annual Meeting (May 16-19, 1998)
`
`Not Filed
`
`12/22/2016
`
`Printout from www.accessdata.fda.gov regarding
`Neupogen
`
`12/22/2016
`
`Neupogen® (Filgrastim) Package Insert, issued April
`2, 1998
`
`12/22/2016
`
`Deposition of Bruce Chabner taken April 23, 2013 in
`Eli Lilly and Company v. Teva Parenteral Medicines,
`Inc., et al. Civil Action No. 1:10-cv-01376
`
`Not Filed
`
`Deposition of Bruce Chabner taken November 10,
`2016 in IPR2016-00318.
`
`Reply Declaration of Ron D. Schiff, M.D., Ph.D.,
`dated December 21, 2016
`
`Letter from Lilly to FDA re LY231514 (MTA,
`MultiTargeted Antifolate); IND # 40,061 Serial No.
`207 Briefing Document for March 1 meeting to
`Discuss Vitamin Supplementation in the Ongoing
`Mesothelioma Registration Trial, (February 16,
`2000)(TX-913)
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`10
`
`
`
`Exhibit
`No.
`
`Exhibit
`1077
`
`Exhibit
`1078
`
`Exhibit
`1079
`
`Exhibit
`1080
`
`Exhibit
`1081
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Letter from Lilly to FDA re IND 40,061 – MTA
`(LY231514) Serial No. 195 Supplementation with
`Folic Acid and Vitamin B12 to Reduce Toxicity in
`Patients Receiving LY231514, (December 3,
`1999)(TX-330)
`
`Paul A. Bunn, Incorporation of Pemetrexed (Alimta)
`Into the Treatment of Non-Small Cell Lung Cancer
`(Thoracic Tumors), Seminars in Oncology, Vol 29,
`No 3, Suppl 9, 17-22 (June 2002)
`
`Luis Paz-Ares et al., Review of a Promising new
`Agent – Pemetrexed Disodium, Cancer supplement,
`Vol. 97, No. 8 2056-2063 (April 15, 2003).
`
`James Henry and Mary Mader, Recent Advances in
`Antimetabolite Cancer Chemotherapies, Annual
`Reports in Medicinal Chemistry, Vol. 39, 161-172
`(2004).
`
`Nannan Lu et al., Superior antimetastatic effect of
`Pemetrexed-loaded gelatinase-responsive
`nanoparticles in a mouse metastasis model, Anti-
`Cancer Drugs, Vol 23 No 10 1078-1088 (2012)
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`11
`
`
`
`Exhibit
`No.
`
`Exhibit
`1082
`
`Exhibit
`1083
`
`Exhibit
`1084
`
`Exhibit
`1085
`
`Exhibit
`1086
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`12/22/2016
`
`Affidavit of Christopher Butler and printout of
`websites from the Internet Archive Wayback
`Machine
`www.lillytrials.com/faq.shtml, dated 10/28/2001
`www.lillytrials.com/faq.shtml, dated 10/28/2001
`www.lillytrials.com/docs/terminology.html, dated
`2/6/2006
`www.lillytrials.com/docs/terminology.html, dated
`4/28/2006
`www.nlm.nih.gov/services/ctphases.html, dated
`10/11/2001
`
`Axel Hanauske et al, Pemetrexed Disodium: A
`Novel Antifolate Clinically Active Against Multiple
`Solid Tumors, The Oncologist, 6:363-373 (2001).
`
`12/22/2016
`
`Briefing Document (February 16, 2000) (TX76).
`
`12/22/2016
`
`Letter from Lilly to FDA re IND 40,061 – MTA
`(LY231514) Serial No. 195 Supplementation with
`Folic Acid and Vitamin B12 to Reduce Toxicity in
`Patients Receiving LY231514, (December 3, 1999)
`(TX333).
`
`Deposition of Steven H. Zeisel taken November 22,
`2016 in Neptune Generics, LLC et al. v. Eli Lilly&
`Company IPR2016-00237 and IPR2016-00240,
`which is filed in this proceeding pursuant to the
`parties’ stipulated agreement. Paper 48.
`
`12/22/2016
`
`12/22/2016
`
`Exhibit
`1087
`
`Michael Murray, Encyclopedia of Nutritional
`Supplements: The Essential Guide for Improving
`Your Health Naturally, Prima Publishing pp. 10-11,
`119-136, 431-432 (1996).
`
`12/22/2016
`
`12
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`LY231514 (ALIMTA): Impact of Folic Acid and
`Vitamin B12 Supplementation on Safety, (June, 4,
`2001) (TX379)
`
`Exhibit
`1089
`
`Leukine® Sargramostim Package Insert, revised
`June 2002.
`
`Exhibit
`1090
`
`Teresa Alati et al., Augmentation of the Therapeutic
`Activity of Lometrexol [(6-R)5,10-
`Dideazatetrahydrofolate] by Oral Folic Acid, Cancer
`Research 56 2331-2335 (1996).
`
`Exhibit
`1091
`
`Declaration of Patrick J. Stover, Ph.D., dated
`December 22, 2016
`
`Exhibit
`No.
`
`Exhibit
`1088
`
`Exhibit
`1092
`
`Exhibit
`1093
`
`Exhibit
`1094
`
`Exhibit
`1095
`
`Exhibit
`1096
`
`Exhibit
`1097
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`Physicians’ Desk Reference , 53rd Edition, pages:
`137, 545, 963,964, 1649, 1666,1667, 1927-1928,
`2810-2812, 2913-2916, 3170, 3175, 3242 (1999)
`(TX-1374)
`
`Declaration of David B. Ross, M.D., Ph.D., M.B.I.,
`dated December 22, 2016.
`
`Charles Erlichman, et al., Phase I-Phase II Trial of
`N-Phosphonacetyl-L-Aspartic Acid Given by
`Intravenous Infusion and 5-Fluorouracil Given by
`Bolus Injection, JNCI, Vol. 68, No. 2, 227-231
`(February 1982)
`
`Lawrence Friedman et al., Introduction to Clinical
`Trials, Fundamentals of Clinical Trials, 3rd Edition,
`pp. 1-15 & 94-129 (1998).
`
`12/22/2016
`
`Hrishikesh Mehta et al., G-CSF and GM-CSF in
`Neutropenia, J Immunol; 195:1341-1349 (2015)
`
`12/22/2016
`
`Package Insert for Cystadane (betaine anhydrous for
`oral solution) powder, revised April 2010.
`
`12/22/2016
`
`13
`
`
`
`Exhibit
`No.
`
`Exhibit
`1098
`
`Exhibit
`1099
`
`Exhibit
`1100
`
`Exhibit
`1101
`
`Exhibit
`1102
`
`Exhibit
`1103
`
`Exhibit
`1104
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`D. Von Hoff et al., The complete phase Ib clinical
`trial: A method to accelerate new agent
`development, Abstract 2562, Supplement to Journal
`of Clinical Oncology, Vol. 25, No. 18S (June 20,
`2007).
`
`Lometrexol Plus Folic Acid in Treating Patients with
`Stage IIIB or Stage IV Non-Small Cell Lung Cancer,
`available at,
`https://clinicaltrials.gov/ct2/show/study/NCT000337
`22?term=ddathf&rank=1 regarding Tularik (last
`accessed Dec. 21, 2016)
`
`Excerpts from Cecil Textbook of Medicine, eds.
`James Wyngaarden and Lloyd Smith (1982).
`
`Worzalla et al., Effects of folic acid on toxicity and
`antitumor activity of LY231514 multi-targeted
`antifolate (MTA), Abstract 3198, Proc Am Assoc
`Cancer Res 38:478 (1997) (TX-1495).
`
`Beverly A Teicher, MTA (L Y23 15 14) in
`Combination Treatment Regimens Using Human
`Tumor Xenografts and the EMT-6 Murine Mammary
`Carcinoma, Seminars in Oncology, Vol 26, No 2,
`Suppl 6, pp 55-62 (April 1999).
`
`David G. Priest, Accumulation of Plasma Reduced
`Folates After Folic Acid Administration, Vol 26, No
`2, Suppl 6, pp 38-41 (April 1999).
`
`Beverly A Teicher, Treatment Regimens Including
`the Multitargeted Antifolate LY231514 in Human
`Tumor Xenografts, Clinical Cancer Research, Vol. 6,
`1016–1023 (March 2000).
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`14
`
`
`
`Exhibit
`No.
`
`Exhibit
`1105
`
`Exhibit
`1106
`
`Exhibit
`1107
`
`Exhibit
`1108
`
`Exhibit
`1109
`
`Exhibit
`1110
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`John Lindenbaum, Prevalence of cobalamin
`deficiency in the Framingham elderly population,
`Am J Clin Nutr, 60:2-11 (1994).
`Excerpts from Physicians’ Desk Reference For
`Nonprescription Drugs And Dietary Supplements,
`20th Edition, 403, 831, 842-843 (1999).
`(Ex. 1053 in IPR2016-00237, -240)
`
`Sydney Farber et al., The Action of Pteroylglutamic
`Conjugates on Man, Science, 619-621 (December
`19, 1947).
`
`Barry Shane and E.L. Robert Stokstad, Vitamin B12-
`Folate Interrelationships, Annu. Rev. Nutr., 5:115-
`141 (1985).
`
`W.F.J. Cuthbertson and Joan Lloyd, The Vitamin
`B12 Concentration in Liver Extracts and a Note on
`the Relationship Between Clinical Response and B12
`Dosage, Journal of Pharmacy and Pharmacology,
`Volume 1, Issue 1, 705-709 (September 1949).
`
`Janet Houghton et al., Relationship Between Dose
`Rate of [6RS]Leucovorin Administration, Plasma
`Concentrations of Reduced Folates, and pools of
`5,10-Methylenetetrahydrofolates and
`Tetrahydrofolates in Human Colon Adenocarcinoma
`Xenografts, Cancer Res. 15;50(12):3493-502 (June
`1990).
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`Exhibit
`1111
`
`Exhibit
`1112
`
`Yong-Shi Lu, Studies on the Polyglutamate
`Specificty of Thymidylate Synthase from Fetal Pig
`Liver, Biochemistry, 23, 6870-6876 (1984)
`
`D. Kelly et al., Increased folate catabolism in mice
`with ascetic tumours, Clinical Science, Vol. 65, No.
`3, 303-305 (September 1983).
`
`12/22/2016
`
`12/22/2016
`
`15
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`12/22/2016
`
`Exhibit
`No.
`
`Exhibit
`1113
`
`Exhibit
`1114
`
`Exhibit
`1115
`
`Exhibit
`1116
`
`Exhibit
`1117
`
`John Meenan et al., Epithelial Cell Folate Depletion
`Occurs in Neoplastic But Not Adjacent Normal
`Colon Mucosa, Gastroenterology, 112:1163-1168
`(1997).
`
`Carlos Krumdieck et al., A long-term study of the
`excretion of folate and pterins in a human subject
`after ingestion of 14C folic acid, with observations
`on the effect of diphenylhydantoin administration,
`Am J Clin Nutr, 31, 88-93 (January 1978).
`
`Mette Gaustadnes et al., Prevalence of Congenital
`Homocystinuria in Denmark, New England Journal
`of Medicine, Vol. 340, No. 10, p. 1512 (May 13
`1999).
`
`Leo Kluijtmans et al. The Molecular Basis of
`Cystathionine β-synthase Deficiency on Biochemical
`and Clinical Phenotype and on Response to
`Treatment, Am. J. Hum. Genet. 65:59–67 (1999).
`
`E.V. Quadros et al., Synthesis of Cobalamin
`Coenzymes by Human Lymphocytes In Vitro and the
`Effect of Folates and Metabolic Inhibitors, Blood,
`Vol. 48, No. 4 (October 1976).
`
`Exhibit
`1118
`
`E9 Statistical Principles for Clinical Trials
`(September 1998).
`
`Exhibit
`1119
`
`Exhibit
`1120
`
`Medical Review(s), Center for Drug Evaluation and
`Research: Approval Package for Application
`Number 21-462 (2004).
`
`Statistical Review(s), Center for Drug Evaluation
`and Research: Approval Package for Application
`Number 21-462 (2003).
`
`16
`
`
`
`Description
`
`Case IPR2016-00318
`Patent 7,772,209
`Filing Date
`
`Anand Karanad and Agnes Krozser-Hamati,
`Pernicious anemia, Post Grad Med, Vol. 91, No. 2,
`(February 1, 1992).
`
`Chuan Shih and Donald Thornton, Preclinical
`Pharmacology Studies and the Clinical Development
`of a Novel Multitargeted Antifolate, MTA
`(LY231514), Chapter 8, Anticancer Drug
`Development Guide: Antifolate Drugs in Cancer
`Therapy, ed. Jackman,(1999).
`
`12/22/2016
`
`12/22/2016
`
`Exhibit
`No.
`
`Exhibit
`1121
`
`Exhibit
`1122
`
`
`
`17
`
`
`
`CERTIFICATE OF SERVICE
`
`I hereby certify that true and correct copies of the foregoing document were
`served on December 22, 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: December 22, 2016
`
`
`
`
`
`
`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
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