`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`Filed on behalf of: Breckenridge Pharmaceutical, Inc.
`
`By: Daniel R. Evans
`Registration No. 55,868
`MERCHANT & GOULD P.C.
`191 Peachtree Street, NE
`Suite 3800
`Atlanta, GA 30303
`Main Telephone: 404.954.5100
`Main Facsimile: 612.332.9081
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE
`
`PATENT TRIAL AND APPEAL BOARD
`
`BRECKENRIDGEG PHARMACEUTICAL, INC.
`
`Petitioner, v.
`
`NOVARTIS PHARMACEUTICALS CORPORATION
`
`Patent Owner.
`
`Case: IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`
`
`
`PETITIONER'S UPDATED EXHIBIT LIST
`DATED JUNE 20, 2018
`
`IPR2018-00507 has been joined to this proceeding (Paper 29, Apr. 03, 2018)
`
`
`
`
`
`
`
`
`
`
`
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`Exhibit Number
`
`Exhibit Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`U.S. Patent No. 8,410,131 ("the '131 patent")
`
`PCT Published Application No. WO 01/51049 A1, O-
`Methylated Rapamycin Derivatives for Alleviation and
`Inhibition of Lymphoproliferative Disorders, to Wasik
`et al. ("Wasik")
`PCT Published Application No. WO 00/33878 A2,
`Macrolides, to Navarro et al. ("Navarro")
`Crowe et al., Absorption and Intestinal Metabolism of
`SDZ-RAD and Rapamycin in Rats, Drug Metab. Disp.
`(1999), 27(5): 627-632 ("Crowe")
`Luan et al., Sirolimus Prevents Tumor Progression:
`mTOR Targeting for the Inhibition of Neoplastic
`Progression, Am. J. Transplant. (2001) 1 Suppl 1,
`243 (Abstr. No. 428) ("Luan")
`Hidalgo et al., The Rapamycin-sensitive Signal
`Transduction Pathway as a Target for Cancer
`Therapy, Oncogene (2000) 19(56): 6680-6686
`("Hidalgo")
`Alexandre et al., CCI-779, A new Rapamycin
`Analog, Has Antitumor Activity at Doses Including
`Only Mild Cutaneous Effects and Mucositis: Early
`Results of an Ongoing Phase I Study, Clin. Cancer
`Res. Suppl. (1999) 5: 3730s, Abstr. No. 7 (AACR-
`NCI-EORTC International Conference, November
`16-19, 1999 held in Washington, DC) ("Alexandre")
`Schuler et al., SDZ RAD, A New Rapamycin
`Derivative, Transplantation (1997) 64(1): 36-
`42 ("Schuler")
`
`1
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`Neumayer et al., Entry-into-human Study with the
`Novel Immunosuppressant SDZ RAD in Stable
`Renal Transplant Patients, Br. J. Clin. Pharmacol.
`(1999) 48(5): 694-703 ("Neumayer")
`Declaration of Allan J. Pantuck, M.D. in Support of
`Petition for Inter Partes Review of U.S. Patent No.
`8,410,131
`
`RAPAMUNE® (sirolimus) Oral Solution
`RAPAMUNE® Approval Letter and approved
`labeling
`Great Britain patent application (GB 0104072.4,
`"GB '072" or "the '072 priority application")
`
`Great Britain patent application (GB0124957.2,
`"GB '957" or "the '957 priority application")
`
`International Patent Application No.
`PCT/EP02/01714 ("the '714 PCT Application")
`
`IPR Final Rules
`
`Dancey, J. E., Rapamycin-Sensitive Signal-
`Transduction Pathways: Protein Translation Control
`of Cell Proliferation, ASCO Educational Book
`(2000) 68-75 ("Dancey")
`Sorbera et al, SDZ-RAD, Drugs of the Future
`(1999) 24(1): 22-29 ("Sorbera")
`U.S. Patent No. 5,362,718, to Skotnicki et al.
`("Skotnichi '718")
`U.S. Patent No. 5,665,772 to Cottens et al.
`("Cottens '772 patent")
`
`2
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`Sedrani et al., Chemical Modification of
`Rapamycin: The Discovery of SDZ RAD,
`Transplantation Proc.(1998) 30(5): 2192-2194
`("Sedrani")
`PCT Published Application No. WO 97/47317 A1,
`Combination of a Somatostatin Analogue and a
`Rapamycin, to G. Weckbecker ("Weckbecker")
`U.S. Patent No. 6,331,547, Water Soluble SDZ
`RAD Esters, which issued to Zhu et al. on
`December 18, 2001 from U.S. Provisional Patent
`Application No. 60/183,035 filed on August 18,
`1999 to Zhu ("Zhu '547 patent")
`U.S. Patent Application Publication No.
`2002/0183239 A1, Antineoplastic Combinations,
`which published on December 5, 2002 from an
`application filed on April 6, 2001, to Gibbons
`("Gibbons US '239")
`
`U.S. Patent Application Publication No.
`2003/0008923 A1, Antineoplastic Combinations,
`which published on January 9, 2003 from an
`application filed on June 1, 2001 to Dukart ("Dukart
`US '923")
`Flowcharts for 35 U.S.C. § 102(e) Dates ("102(e)
`Date Flowchart")
`
`Published Application No. WO 94/09010 A1, O-
`Alkylated Rapamycin Derivatives and their use,
`particularly as immunosuppressants, to Cottens et
`al. ("Cottens WO '010")
`Selected portions of Prosecution History
`Documents ("May 10, 2010 Amendment re. Cottens
`WO '010")
`
`3
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`Curriculum Vitae of Allan J. Pantuck, M.D.
`
`2015 Orange Book,"35th Edition (2015) with
`respect to AFINITOR® ("2015 Orange Book ")
`Alexandre, Raymond, et al., La rapamycine et le
`CCI- 779, Bull. Cancer (1999) 86(10): 808-811
`("Alexandre" and Raymond")
`Boni et al., Pharmacokinetics of escalating doses of
`CCI-779 in Combination with 5-Fluorouracil and
`Leucovorin in Patients with Advanced Solid
`Tumors, Eur. J. Cancer (2001) 37(Suppl. 6): S68
`(Abstr. No. 242) (The 11th ECCO October 21-25,
`2001 meeting held in Lisbon, Portugal) ("Boni")
`Dinney et al., Biology of Metastasis: Studies in
`Renal Cancer (17-24), in Principles and Practice of
`Genitourinary Oncology (Raghavan et al. eds., 1997)
`("Dinney")
`Shi et al., Rapamycin enhances Apoptosis and
`Increases Sensitivity to Cisplatin in Vitro,
`Cancer Research (1995) 55(9): 1982-1988
`("Shi")
`Fosså et al., Survival of Patients with Advanced
`Urothelial Cancer treated with Cisplatin-based
`Chemotherapy, Brit. J. Cancer (1996) 74: 1655-
`1659 ("Fosså")
`Motzer et al., Survival and Prognostic Stratification of
`670 Patients with Advanced Renal Cell Carcinoma, J.
`Clin. Oncol. (1999) 17(8): 2530-2540 ("Motzer et al.")
`PCT Published Application No. WO 02/40000 A2, Use
`of CCI-779 as an Antineoplastic Agent, to Dukart et al.
`("Dukart WO '000")
`4
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`PCT Published Application No. WO 02/080975 A1,
`Antineoplastic Combinations such as Rapamycin
`together with Gemcitabine or Fluorouracil, to
`Gibbons et al. ("Gibbons WO '975")
`PCT Published Application No. WO 02/098416 A2,
`Antineoplastic Combinations, to Dukart et al. ("Dukart
`WO '416")
`
`U.S. Patent Application Publication No.
`2002/0091137 A1, Use of CCI-779 as an
`Antineoplastic Agent, which published on July 11,
`2002, to Dukart ("Dukart '137")
`
`U.S. Patent No. 7,781,446, Use of CCI-779 as an
`Antineoplastic Agent, which issued to Dukart et al.
`on August 24, 2010 ("Dukart '446"), and which
`claims priority to U.S. Provisional Patent
`Application No. 60/249,077 ("Dukart")
`Perez-Atayde et al., Spectrum of Tumor
`Angiogenesis in the Bone Marrow of Children with
`Acute Lymphoblastic Leukemia, Am. J. Pathol.
`(1997) 150(3): 815-821 ("Perez-Atayde")
`True et al., Pathology of Renal Cancers (799-811),
`in Principles and Practice of Genitourinary
`Oncology (Raghavan et al. eds., 1997) ("True")
`Jennings et al., Renal, Perirenal and Ureteral
`Neoplasms (643-694), In Adult and Pediatric
`Urology; Third Edition. (Gillenwater et al. eds., 3rd
`ed. 1996, Volume 1), Grayhack, Howards, and
`Duckett Eds. Mosby-Year Book, Inc. 1996
`("Jennings")
`
`5
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`1052
`
`Robert R. Bahnson, Renal and Urinary Tract
`Neoplasia (371-379), In Primer on Kidney Diseases
`(Greenberg, A. et al. eds., 2nd ed. 1998)
`("Bahnson")
`Vézina et al., Rapamycin (AY-22,989), A New
`Antifungal Antibiotic I. Taxonomy of the Producing
`Streptomycete and Isolation of the Active Principle,
`J. Antibiot. (1975) 28 (10): 721-726 ("Vézina")
`Sehgal et al., Rapamycin (AY-22,989), a New
`Antifungal Antibiotic II. Fermentation, Isolation,
`and Characterization, J. Antibiotics (1975) 28(10):
`727-
`Baker et al., Rapamycin (AY-22,989), A New
`Antifungal Antibiotic III. In Vitro and In Vivo
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`545 ("Baker")
`U.S. Patent No. 3,929,992 to Sehgal ("Sehgal
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`
`Martel et al. Inhibition of the Immune Response by
`Rapamycin, a New Antifungal Antibiotic, Can. J.
`Physiol. Pharmacol. (1977) 55(1): 48-51
`("Martel")
`Eng et al., Activity of Rapamycin (AY-22,989)
`against Transplanted Tumors, J. Antibiotics (1984)
`37(10): 1231-1237 ("Eng")
`U.S. Patent No. 5,066,493 to Sehgal et al. ("Sehgal
`'493 patent")
`
`U.S. Patent No. 5,206,018 to Sehgal et al. ("Sehgal
`'018 patent")
`
`6
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`1060
`
`1061
`
`Calne et al., Rapamycin for Immunosuppression
`in Organ Allografting, Lancet (1989) 2(8656):
`227 ("Calne")
`Morris et al., Identification of a New
`Pharmacological Action for an Old Compound, Med.
`Sci. Res. (1989) 17(14): 609-610610 ("Morris 1989")
`Morris, R. N., Rapamycins: Antifungal, Antitumor,
`Antiproliferative, and Immunosuppressive
`Macrolides, Transplantation Reviews (1992) 6(1): 39-
`87 ("Morris 1992")
`Van Duyne et al., Atomic Structure of the
`Rapamycin Human Immunophilin FKBP-12
`Complex, J. Am. Chem. Soc. (1991) 113(19): 7433-
`7434 ("Van Duyne")
`Choi et al., Structure of the FKBP12-Rapamycin
`Complex Interacting with the Binding Domain of
`Human FRAP, Science (1996) 273(5272): 239-
`242 ("Choi")
`Rapamune prescribing information as of August 2000
`
`Garber, K., Rapamycin's Resurrection: A New Way
`to Target the Cancer Cell Cycle, J Natl Cancer Inst.
`(2001) 93(2): 1517-1519 ("Garber")
`Breitenbach et al., Rapamycin Inhibits Tumor
`Growth and Metastasis in Mice by Antiangiogenesis,
`Am. J. Transplant. (2001) 1 Suppl 1, 250 (Abstr. No.
`459) ("Breitenbach")
`Guba et al, Rapamycin inhibits Tumor Growth and
`Metastasis by Antiangiogenesis, Chirugicshes
`Forum 2001 für experimentelle und klinsche
`Forschung (2001) 30: 37-39 ("Guba")
`
`7
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1062
`
`1063
`
`1064
`
`1065
`
`1066
`
`1067
`
`1068
`
`1069
`
`1070
`
`1071
`
`Hosoi et al., Studies on the Mechanism of Resistance
`to Rapamycin in Human Cancer Cells, Mol.
`Pharmacol., (1998) 54 815-824 ("Hosoi")
`Zhang et al., Differences in Phosphorylation of the
`IL- 2R Associated JAK/STAT Proteins between
`HTLV-I (+), IL-2-independent and IL-2-dependent
`Cell Lines and Uncultured Leukemic Cells from
`Patients with Adult T-cell Lymphoma/Leukemia,
`Leukemia Res. (1999) 23(4): 373-384 ("Zhang")
`Monograph 8288 of The Merck Index, 12th Ed. (2006)
`("Merck Index")
`U.S. Patent No. 5,260,300 to Hu ("Hu '300 patent")
`
`U.S. Patent No. 5,221,670 to Caufield ("Caufield '670
`patent")
`U.S. Patent No. 5,434,260 to Skotnicki et al.
`("Skotnicki '260 patent")
`Freireich et al., Quantitative Comparison of Toxicity of
`Anticancer Agents in Mouse, Rat, Hamster, Dog,
`Monkey, and Man, Cancer Chemotherapy Reports
`(1966) 50(4): 219-244 ("Freireich")
`PRNewswire, August 30, 2000 press release, Novartis
`Announces Positive Trial Results for Two Novel
`Transplantation Drugs ("Press Release")
`AFINITOR® approval letter and prescribing
`information, as of March 30, 2009 ("AFINITOR® Mar
`30, 2009 approval")
`AFINITOR® prescribing information, as of June 14,
`2016 ("AFINITOR® Jun 14, 2016 prescribing
`information")
`
`8
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1072
`
`1073
`
`1074
`
`1075
`
`1076
`
`1077
`
`1078
`
`1079
`
`ZORTRESS® approval letter and prescribing
`information, as of April 20, 2010 ("ZORTRESS®
`approval")
`U.S. Patent No. 7,297,703 to Navarro et al. ("Navarro
`'703 patent")
`International Nonproprietary Names of Pharmaceutical
`Substances (INN), WHO Drug Information, (2000)
`14(3): 183-209 ("Everolimus INN")
`Majewski et al., The Immunosuppresive Macrolide
`RAD inhibits Growth of Human Epstein-Barr Virus-
`transformed B Lymphocytes in vitro and in vivo: A
`Potential Approach to Prevention and Treatment of
`Postrransplant Lymphoproliferative Disorders, Proc.
`Natl. Acad. Sci. (2000) 97(8): 4285-4290 ("Majewski")
`Huang et al., Mechanisms of Resistance to Rapamycin,
`Drug Resistance Updates, (2001) 4: 378-392
`("Huang")
`Beuvink et al., Antitumor Activity of RAD001, an
`Orally Active Rapamycin Derivative, Proc. Amer.
`Assoc. Cancer Res. (2001) 42, 366, Abstr. No. 1972
`("Beuvink")
`International Nonproprietary Names of
`Pharmaceutical Substances (INN), WHO Drug
`Information, (2005) 19(3): 243-270 ("Temsirolimus
`INN")
`Wall Street Journal, Drug Progress on Hard-to-
`Treat Cancers is Cited, by Robert Langreth and
`Michael Waldholz in the November 17, 1999 edition
`("Langreth")
`
`9
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1080
`
`1081
`
`1082
`
`1083
`
`1084
`
`1085
`
`Hidalgo et al., A Phase I and Pharmacological Study
`of CCI-779, a Rapamycin Ester Cell Cycle Inhibitor,
`Ann. Oncol. (2000) 11 (Suppl. 4) 133, Abstr. No.
`606O (25th ESMO Congress, October 13-17, 2000
`held in Hamburg, DE) ("Hidalgo ESMO Abstract")
`December 1, 2000 issue of The Lancet Oncology,
`CCI- 779: A New Targeted Anticancer Agent, by Ezzie
`Hutchinson ("Hutchinson")
`Hidalgo et al., Phase I and Pharmacological Study
`of CCI-779, a Cell Cycle Inhibitor, Clinical Cancer
`Research (2000), Supplement 6: 4548s-4549s,
`Abstr. No. 413 (11th NCI-EORTC-AACR
`November 7-10, 2000 meeting held in Amsterdam,
`NL) ("Hidalgo NCI Abstract")
`Raymond et al., CCI-779, an ester analogue of
`rapamycin that interacts with PTEN/PI3
`KinasePathways: A Phase I Study utilizing a Weekly
`Intravenous Schedule, Clinical Cancer Res. (2000)
`Supplement 6: 4549s, Abstr. No. 414 (11th NCI-
`EORTC-AACR November 7-10, 2000 meeting held in
`Amsterdam, The Netherlands) ("Raymond NCI
`Abstract")
`DeMario et al., Oral Chemotherapy: Rationale and
`Future Directions, J. Clin. Oncol. (1998) 16(7): 2557-
`2567 ("DeMario")
`
`Gibbons et al., The Effect of CCI-779, a Novel
`Macrolide Anti-Tumor Agent, on the Growth of Human
`Tumor Cells In Vitro and in Nude Mouse Xenographs
`In Vivo, Proc. Amer. Assoc. Cancer Res. (1999) 40:
`301, Abstr. No. 2000 ("Gibbons Abstract")
`
`10
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1086
`
`1087
`
`1088
`
`1089
`
`1090
`
`1091
`
`1092
`
`1093
`
`Geoerger et al., Rapamycin analog CCI 779 inhibits
`growth of Human Medulloblastoma Xenographs, Proc.
`Amer. Assoc. Cancer Res. (1999) 40: 603a, Abstr. No.
`3978 (90th Annual Meeting of the AACR, April 10-14,
`1999 held in Philadelphia, PA) ("Geoerger Abstract")
`Geoerger et al., Antitumor Activity of the Rapamycin
`Analog CCI-779 in Human Primitive Neuroectodermal
`Tumor/Medulloblastoma Models as Single Agent and
`in Combination Chemotherapy, Cancer Res. (2001)
`61(4): 1527-1532 ("Geoerger")
`TORISEL® approval letter and prescribing
`information, as of May 30, 2007 ("TORISEL®
`Approval")
`TORISEL® prescribing information, as of July 27,
`2016
`Cowan et al., Sirolimus: Mammalian Target of
`Rapamycin Inhibitor to Prevent Kidney Rejection,
`Nephrol. Nursing Journal (2000) 27(6): 623-625
`("Cowan")
`Serkova et al., Tissue Distribution and Clinical
`Monitoring of the Novel Macrolide Immunosuppressant
`SDZ-RAD and its Metabolites in Monkey Lung
`Transplant Recipient: Interaction with Cyclosporine, J.
`Pharmacol. Exper. Therap. (2000) 294(1): 323-332
`("Serkova")
`U.S. Patent No. 6,432,973, to Zhu et al. ("Zhu '973
`patent")
`
`Neshat et al., Enhanced Sensitivity of PTEN-deficient
`Tumors to Inhibition of FRAP/mTOR, Proc. Natl.
`Acad. Sci. USA (2001) 98(18) 10314-10319 ("Neshat")
`
`11
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1094
`
`1095
`
`1096
`
`1097
`
`1098
`
`1099
`
`1100
`
`Podsypanina et al., An Inhibitor of mTOR reduces
`Neoplasia and Normalizes p70/S6 Kinase Activity in
`PTEN+/- Mice, Proc. Natl. Acad. Sci. (2001) 98(18):
`10320-10325 ("Podsypanina")
`Yu et al., Deregulated P13k/AKT/TOR Pathway in
`PTEN-Deficient Tumor Cells Correlates with an
`Increased Growth Inhibition Sensitivity to a TOR
`Kinase Inhibitor CCI-779, Proc. Amer. Assoc. Cancer
`Res. (2001) 42: 802 (Abstr. No. 4305) ("Yu")
`
`Wen et al., PTEN controls Tumor-induced
`Angiogenesis, Proc. Natl. Acad. Sci. USA (2001)
`98(8): 4622-4627 (92nd Annual Meeting of the AACR,
`March 24-28, 2001 held in New Orleans, LA) ("Wen")
`Cantley et al., New Insights into Tumor Suppression:
`PTEN suppresses Tumor Formation by restraining the
`Phosphoinositide 3-Kinase / AKT Pathway, Proc. Natl.
`Acad. Sci. USA, (1999) 96 (8): 4240-4245 ("Cantley")
`Kondo et al., PTEN/MMAC1/TEP1 Mutations in
`Human Primary Renal-Cell Carcinomas and Renal
`Carcinoma Cell Lines, Intl. J. Cancer (2001) 91(2):
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`Chromosomes 5q, 6q, and 10q in Renal Cell
`Carcinoma, Cancer Res. (1991) 51(21): 5817-
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`Sokoloff et al., Systemic Immunotherapy for
`Genitourinary Neoplasms (869-883), in Principles
`and Practice of Genitourinary Oncology (Raghavan et
`al. eds., 1997) ("Sokoloff")
`
`12
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1101
`
`1102
`
`1103
`
`1104
`
`1105
`
`1106
`
`1107
`
`1108
`
`Motzer et al., Chemotherapy for Renal Cell
`Carcinoma (885-896) in Principles and Practice of
`Genitourinary Oncology (Raghavan et al. eds., 1997)
`("Motzer")
`NEXAVAR® approval letter and prescribing
`information as of December 1, 2005
`("NEXAVAR® approval letter")
`SUTENT® approval letter and prescribing
`information as of January 26, 2006 ("SUTENT®
`approval letter")
`Quinn et al., Renal-Cell Cancer ― Targeting an
`Immune Checkpoint or Multiple Kinases, New
`England J. Med. (2015) 373(19): 1872-1874 ("Quinn")
`Choueiri et al., Cabozantinib versus Everolimus in
`Advanced Renal-Cell Carcinoma, New England
`Journal Med. (2015) 373(19): 1814-1823
`("Choueiri")
`R. J. Motzer, B. Escudier et al., Nivolumab versus
`Everolimus in Advanced Renal-Cell Carcinoma,
`New England Journal Med. (2015) 373(19): 1803-
`1813 ("Escudier")
`AFINITOR® approval letter and prescribing
`information, as of April 26, 2012 ("AFINITOR®
`Apr 26, 2012 approval")
`Kenerson et al., Activated Mammalian Target of
`Rapamycin Pathway in the Pathogenesis of Tuberous
`Sclerosis Complex Renal Tumors, Cancer Research
`(2002) 62(2): 5645-5650 ("Kenerson")
`
`13
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1109
`
`1110
`
`1111
`
`1112
`
`1113
`
`1114
`
`1115
`
`1116
`
`1117
`
`Bissler et al., Sirolimus for Angiomyolipoma in
`Tuberous Sclerosis Complex or
`Lymphangioleimyomatosis, New Engl. Journal Med.
`(2008) 358(2): 140-151 ("Bissler")
`Henske et al., Tuberous Sclerosis Complex, mTOR,
`and the Kidney: Report of an NIDDK-sponsored
`Workshop, Am J Physiol Renal Physiol. (2014)
`306(3): F279-F283 ("Henske")
`Kingswood et al., Review of the Tuberous Sclerosis
`Renal Guidelines from the 2012 Consensus
`Conference: Current Data and Future Study,
`Nephron. Clin. Pract. (2016) 134(2) ("Kingswood")
`Declaration of Daniel R. Evans dated January 18,
`2018
`
`Morel, Inhibitors of mTOR and FTY 720, Special
`Transcript 2001 ("Morel")
`
`Program Book for Joint American Transplant
`Meeting, May 11-16, 2001 ("Transplant 2001
`Program Book")
`Luan et al., Sirolimus Prevents Tumor Progressions:
`mTOR Targeting for the Inhibition of Neapolastic
`Progression, American Journal of Transplantation,
`Sup. 1, Vol.1, Abstract 428, Chicago, May 11-16,
`2001 ("Luan Abstract")
`ISO 26324, Information and documentation – Digital
`object identifier system, 1st Ed. 2012-05-01 ("ISO
`26324")
`The DOI Foundation and Wiley Online Library
`webpages
`
`14
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1118
`
`1119
`
`1120
`
`1121
`
`1122
`
`1123
`
`1124
`
`1125
`
`1126
`
`Declaration of Terrence L. Stokke dated January 18,
`2018
`
`Declaration of Fu L. Luan, M.D., dated January 19,
`2018
`
`List of exhibits with paragraph citations
`
`Shrinkage table showing results of the Weckbecker
`in vivo assay (page 128 from Ex. 2092 marked as
`Burris Depo Ex. 1121) ("Shrinkage Table")
`O'Donnell et al., Phase I Pharmacokinetic and
`Pharmacodynamic Study of the Oral Mammalian
`Target of Rapamycin Inhibitor Everolimus in
`Patients with Advanced Solid Tumors, Journal of
`Clinical Ongology, 2:6(10)1588-1595, April 1, 2008
`(marked as Burris Depo Ex. 1122) ("O'Donnell")
`O'Reilly et al., In vivo activity of RAD001, an orally
`active rapamycin derivative, in experimental tumor
`models, Proceedings AACR, 93rd Annual Meeting,
`43:71 Abstract #359, March 2002 (marked as Burris
`Depo Ex. 1123) ("O'Reilly")
`Pages from US Patent 6,432,973 Zhu (pages from
`Exhibit 1092 marked as Burris Depo Ex. 1124)
`
`Pages from Zhu '973 patent provisional application
`(pages from Exhibit 1092 marked as Burris Depo Ex.
`1125)
`
`Transcript (updated) of deposition of Howard A.
`Burris taken May 24, 2018 in this action ("Burris
`Tr.")
`
`15
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1127
`
`1128
`
`1129
`
`1130
`
`1131
`
`1132
`
`1133
`
`1134
`
`1135
`
`Transcript (updated) of deposition of Krishna V.
`Komanduri taken June 5, 2018 in this action
`("Komanduri Tr.")
`Burris Trial Demonstratives ("Burris First Trial
`Demonstratives")
`
`Dr. Burris' First Everolimus Trial Testimony,
`Novartis v. Breckenridge, 14cv1043, Trial
`Transcript, DI No. 166 ("Burris First Trial
`Testimony")
`Dr. Burris Second Trial Testimony, Novartis v.
`West-Ward, 15cv-474, Trial Transcript, DI No. 98
`("Burris Second Trial Testimony")
`Alexandre et al., Phase I Study of CCI-779, a novel
`rapamycin analog: preliminary results, Proc. Am.
`Assoc. Cancer Res. (2000) 41: 613 (Abst. No. 3897).
`("Alexandre AACR Abstract")
`Alley et al., Feasability of Drug Screening with
`Panels of Human Tumor Cell Lines Using a
`Microculture Tetrazolium Assay, Cancer Res. (1988)
`45(3): 589-601 ("Alley")
`WO 93/19752 A1, Inhibition of P70 S6 Kinase, to
`Beirer et al. ("Beirer")
`
`Boyd et al., Some Practical Considerations and
`Applications of the National Cancer Institute In
`Vitro Anticancer Drug Discovery Screen, Drug. Dev.
`Res. (1995) 34(2): 91-109 ("Boyd")
`
`Fairlamb et al., Spontaneous Regression of
`Metastases of Renal Cancer, Cancer (1981) 47(8):
`2102-2106 ("Fairlamb")
`
`16
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1136
`
`1137
`
`1138
`
`1139
`
`1140
`
`1141
`
`1142
`
`1143
`
`Fiebig et al., In vitro and in vivo evaluation of US-
`NCI compounds in human tumor xenografts, Cancer
`Treatment Reviews (1990) 17(2-3): 109-117
`("Fiebig")
`Gonzalez-Angulo, Weekly nab-Rapamycin in
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`Angulo")
`European Patent Application EP 0 525 960 A1, Use
`of rapamycin for the treatment of adult T-cell
`leukemia, which published on February 3, 1993 to
`Miller et al. ("Miller EP '960")
`
`Monks et al., Feasibility of a High-Flux Anticancer
`Drug Screen Using a Diverse Panel of Cultured
`Human Tumor Cell Lines, J. Natl. Cancer Inst.
`(1991) 83(11): 757-766 ("Monks")
`Pantuck et al., Prognostic Relevance of the mTOR
`Pathway in Renal Cell Carcinoma, Cancer (2007)
`109(11): 2257-2267 ("Pantuck 2007")
`Paull et al., Identification of Novel Antimitotic
`Agents Acting at the Tubulin Level by Computer-
`assisted Evaluation of Differential Cytotoxic Data,
`Cancer Res. (1992) 52(14): 3892-3900 ("Paull")
`Price et al., Rapamycin-Induced Inhibition of the 70-
`Kilodalton S6 Protein Kinase, Science (1992)
`257(5072): 973-977 ("Price")
`PTE Request for Cottens '772 Patent ("PTE
`Request")
`
`17
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`1144
`
`1145
`
`1146
`
`1147
`
`1148
`
`1149
`
`1150
`
`1151
`
`1152
`
`Raymond et al., Safety and Pharmacokinetics of
`Escalated Doses of Weekly Intravenous Infusion of
`CCI-779, a Novel mTOR Inhibitor, in Patients With
`Cancer, J. Clin. Oncol. (2004) 22(12): 2336-2347
`("Raymond 2004")
`Raymond et al., CCI-779, a Rapamycin Analog with
`Antitumor Activity: A Phase I Study Utilizing a Weekly
`Schedule, Proc. Amer. Soc. Clin. Oncol. (2000) 19:
`187a (Abst. No. 728) ("Raymond ASCO Abstract")
`Retain, M.J., Phase II Oncology Trials: Let's Be
`Positive, Clin. Cancer Res. (2005) 11(16): 5661-
`5663 ("Retain")
`
`Ribomustin (2001) Product Monograph
`("Ribomustin Label")
`
`Robins, P., Poster Highlights I, Drugs (1999) 2(6):
`534-537 ("Robins")
`
`Sausville, E. A., New Agents – Noncytotoxins,
`Antiangiogenesis, ASCO Educational Book (1998)
`112-117 ("Sausville")
`Rapamycin_Tumor or Cancer (1980-2002)
`("SciFinder Search Results")
`
`Stinson et al., Morphological and
`Immunocytochemical Characteristics of Human
`Tumor Cell Lines for Use in a Disease-Oriented
`Anticancer Drug Screen, Anticancer Res. (1992)
`12(4): 1035-1053 ("Stinson")
`
`U.S. Patent No. 6,362,164, Combination of a
`Somatostatin Analogue and a Rapamycin, to
`Weckbecker ("Weckbecker '164 patent")
`
`18
`
`
`
`Exhibit Number
`
`Exhibit Description
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`U.S. Patent Application No. 09/194,957 file wrapper
`("Weckbecker application")
`
`Wyeth's EP 0 763 039 A1, which is a European
`counterpart of the Skotnicki '718 patent related to
`rapamycin hydroxyesters, i.e., temsirolimus
`("Wyeth's EP '039")
`Wyeth's May 11, 2000 letter filed in the EP '671
`application by Wyeth in European Patent
`Application No. 95915671.2 ("Wyeth's May 11,
`2000 letter filed in the EP '671 application")
`A-498 ATCC® HTB-44 (human kidney cell line)
`("HTB-44-A498")
`
`December 15, 2000, press release by Caprius
`("December 15, 2000 press release")
`
`ACHN ATCC ® CRL-1611 (human kidney cell line)
`("CRL-1611-ACHN")
`
`Second Declaration of Allan J. Pantuck, M.D. in
`support of Inter Partes Review of U.S. Patent
`8,410,131
`File history of U.S. Patent Application No.
`13/546,686 ("13/546,686 file history")
`
`MPEP 2136.003.III ("MPEP 2136.003.III")
`
`1153
`
`1154
`
`1155
`
`1156
`
`1157
`
`1158
`
`1159
`
`1160
`
`1161
`
`
`
`
`
`
`19
`
`
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that the foregoing Petitioner's Updated
`
`
`
`
`
`
`Exhibit List Dated June 20, 2018, and Exhibits 1121-1158 and 1160-1161 were
`
`served on June 20, 2018, upon the following parties via email:
`
`Nicholas N. Kallas
`Fitzpatrick, Cella, Harper & Scinto
`1290 Avenue of the Americas
`New York, NY 10104-2100
`NKallas@fchs.com
`ZortressAfinitorIPR@fchs.com
`
`I further certify that a copy of the foregoing documents were served on June 20,
`
`2018, via email on counsel for Petitioner West-Ward Pharmaceuticals International
`
`Limited in Inter Partes Review No. 2018-00507 at the following email addresses:
`
`
`
`
`
`Respectfully submitted,
`
`Keith A. Zullow (kzullow@goodwinprocter.com)
`Marta E. Delsignore (mdelsignore@goodwinprocter.com)
`
`
`Dated: June 20, 2018
`
`
`
`
`
`
`
`By: /Daniel R. Evans/
`Daniel R. Evans, Reg. No. 55,868
`MERCHANT & GOULD P.C.
`191 Peachtree Street, NE, Suite 3800
`Atlanta, GA 30303
`Main Telephone: 404.954.5100
`Main Facsimile: 612.332.9081
`
`Counsel for Petitioner Breckenridge
`20
`
`
`
`Case No. IPR2017-01592
`U.S. Patent No. 8,410,131
`
`
`Pharmaceutical, Inc.
`
`
`
`21
`
`
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