`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`PHIGENIX, INC.
`Petitioner
`v.
`IMMUNOGEN, INC.
`Patent Owner
`
`_____________________
`
`CASE IPR2014-00676
`U.S. Patent No. 8,337,856
`_____________________
`
`IMMUNOGEN, INC.'S EXHIBIT LIST
`
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`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
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`
`
`ImmunoGen
`Exhibit #
`2001
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`2002
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`2003
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`2004
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`2005
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`2006
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`2007
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`2008
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Description
`
`Hamel, E., "Natural Products Which Interact with Tubulin in the
`Vinca Domain: Maytansine, Rhizoxin, Phomopsin A, Dolastatins
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`(1992)
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`with Advanced Lymphomas: An Eastern Cooperative Oncology
`Group Pilot Study," Cancer Treatment Reports 64: 1115-1117
`(1980)
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`153858) in Advanced Cancer," American Journal of Clinical
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`Experimental and Clinical Agents, Chapter 17, pp. 371-394
`(1996)
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`1-9 (2011) available at www.medscape.com at
`http://www.medscape.com/viewarticle/754136_print (last
`accessed July 30, 2014)
`
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`1
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`2009
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`2010
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`2011
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`2012
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`2013
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`2014
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`2015
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`2016
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Wildiers, H., et al., "Late Breaking Abstract: T-DM1 for HER2-
`positive metastatic breast cancer (MBC): Primary result from
`TH3RESA, a phase 3 study of T-DM1 vs treatment of physician's
`choice," European Cancer Congress 2013, pp. 1-2, available at
`http://eccamsterdam2013.ecco-org.eu/Scientific-
`Programme/Abstract-search.aspx?abstractid=8879 (last accessed
`July 28, 2014)
`Tolcher, A., et al., "Randomized Phase II Study of BR96-
`Doxorubicin Conjugate in Patients With Metastatic Breast
`Cancer," Journal of Clinical Oncology 17: 478-484 (1999)
`Elias, D., et al., "Monoclonal Antibody KS1/4-Methotrexate
`Immunoconjugate Studies in Non-Small Cell Lung Carcinoma,"
`American Journal of Respiratory and Critical Care Medicine
`150: 1114-1122 (1994)
`Krop, I., et al., "Trastuzumab emtansine versus treatment of
`physician's choice for pretreated HER2-positive advanced breast
`cancer (TH3RESA): a randomised, open-label, phase 3 trial,"
`Lancet Oncology 15: 689-699 (2014)
`Figueroa-Magalhães, M. and Stearns, V., "T-DM1 adds to the
`Armamentarium for Targeting Advanced HER2-Positive Breast
`Cancer," Community Oncology 10: 69-73 (2013)
`Interview Summary dated September 14, 2009 from the File
`History of U.S. Patent No. 8,337,856, p. 1.
`Cao, Y., et al., "Construction and Characterization of Novel,
`Completely Human Serine Protease Therapeutics Targeting
`Her2/neu," Molecular Cancer Therapeutics 12: 979-991 (2013)
`Cao, Y., and Rosenblum, M.G., "Design, Development, and
`Characterization of Recombinant Immunotoxins Targeting
`HER2/neu," in Antibody-Drug Conjugates and Immunotoxins:
`From Pre-Clinical Development to Therapeutic Applications,
`Chapter 18, pp. 319-348 (2013)
`
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`2
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`2017
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`2018
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`2019
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`2020
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`2021
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`2022
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`2023
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`2024
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Engert, A. et al., "The Emerging Role of Ricin in A-Chain
`Immunotoxins in Leukemia and Lymphoma" in Clinical
`Applications of Immunotoxins by Frankel, A.E., (Ed.), pp. 1-23
`(1998)
`Roth, B., et al., "Clinical Cancer Advances 2012: Annual Report
`on Progress Against Cancer From the American Society of
`Clinical Oncology," Journal of Clinical Oncology 31: 131-161,
`2063 (2013)
`Gochenauer, G., "Roche/Genentech's "Magic Bullet" in HER2+
`Breast Cancer," available at
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`gochenauer/2012/06/03/Roche_Genentech_Magic_Bullet_in_HE
`R2_Breast_Cancer (last accessed July 30, 2014) pp. 1-2 (2012)
`Miller, K., et al., "T-DM1: Golden Age in HER2+ Breast
`Cancer?" pp. 1-6 (2012) available at www.medscape.com at
`http://www.medscape.com/viewarticle/765248 (last accessed July
`30, 2014)
`"FDA Approves New Late-Stage Breast Cancer Drug Kadcyla,"
`pp. 1-4 (2013) available at
`http://www.cbsnews.com/news/fda-approves-new-late-stage-
`breast-cancer-drug-kadcyla/ (last accessed July 28, 2014)
`"Breast Cancer Drug Targets Tumor Cells, Spares Healthy Ones,"
`pp. 1-2 (2013) available at
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`Helwick, C., "Refining Current Treatments and Looking Ahead in
`HER2-positive Breast Cancer," Best of ASCO Supplement 3:1-2
`(2012)
`Herper, M., "A Triumph In Breast Cancer--And Another
`Expensive Drug," pp. 1-3 (2013) available at
`http://www.forbes.com at
`http://www.forbes.com/sites/matthewherper/2013/02/22/a-
`triumph-in-breast-cancer-and-another-expensive-drug/ (last
`accessed July 28, 2014)
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`3
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`2025
`2026
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`2027
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`2028
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`2029
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`2030
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`2031
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`2032
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`2033
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`2034
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
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`
`Kadcyla™ Prescribing Information, pp. 1-21(2013)
`Hurvitz, S., et al., "Phase II Randomized Study of Trastuzumab
`Emtansine Versus Trastuzumab Plus Docetaxel in Patients with
`Human Epidermal Growth Factor Receptor 2-Positive Metastatic
`Breast Cancer," Journal of Clinical Oncology 31: 1157-1163,
`2977 (2013)
`Nandini, D., et al., "T-DM1: A Giant Step Forwards in HER2
`Therapeutics," Cancer Therapy 9: 45-54 (2013)
`September 17, 2010 Office Communication from the File History
`of U.S. Patent No. 8,337,856, pp. 1-2.
`Pai-Scherf, L., et al., "Hepatotoxicity in Cancer Patients
`Receiving erb-38, a Recombinant Immunotoxin That Targets the
`erbB2 Receptor," Clinical Cancer Research 5: 2311-2315 (1999)
`Pai, L., et al., "Clinical Evaluation of Intraperitoneal
`Pseudomonas Exotoxin Immunoconjugate OVB3-PE in Patients
`With Ovarian Cancer," Journal of Clinical Oncology 9: 2095-
`2103 (1991)
`Gould, B., et al., "Phase I Study of an Anti-Breast Cancer
`Immunotoxin by Continuous Infusion: Report of a Targeted Toxic
`Effect Not Predicted by Animal Studies," Journal of the National
`Cancer Institute 81: 775-781 (1989)
`Drebin, J., et al., "Monoclonal Antibodies Specific for the neu
`Oncogene Product Directly Mediate Anti-Tumor Effects in vivo,"
`Oncogene 2:387-394 (1988)
`Stancovski, I., et al., "Mechanistic Aspects of the Opposing
`Effects of Monoclonal Antibodies to the ERBB2 Receptor on
`Tumor Growth," Proc. Natl. Acad. Sci. 88: 8691-8695 (1991)
`Kita, Y., et al., "ErbB Receptor Activation, Cell Morphology
`Changes, and Apoptosis Induced by Anti-Her2 Monoclonal
`Antibodies," Biochemical and Biophysical Research
`Communications 226: 59-69 (1996)
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`4
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`2035
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`2045
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Klapper, L., et al., "A Subclass of Tumor-Inhibitory Monoclonal
`Antibodies to ErbB-2/HER2 Blocks Crosstalk with Growth Factor
`Receptors," Oncogene 14: 2099-2109 (1997)
`Xu, F., et al., "Antibody-Induced Growth Inhibition Is Mediated
`Through Immunochemically and Functionally Distinct Epitopes
`on the Extracellular Domain of the c-erb B-2 (HER-2/neu) Gene
`Product p185," Int. J. Cancer 53: 401-408 (1993)
`Rodriguez, G., et al., "The Effect of Antibodies and
`Immunotoxins Reactive with HER-2/neu on Growth of Ovarian
`and Breast Cancer Cell Lines," Am J of Obstet Gynecol 168: 228-
`232 (1993)
`Boyer, C., et al., "Relative Cytotoxic Activity of Immunotoxins
`Reactive With Different Epitopes on the Extracellular Domain of
`the c-erbB-2 (HER-2/neu) Gene Product p185," Int. J. Cancer 82:
`525-531 (1999)
`Deposition Transcript of Michael G. Rosenblum, Ph.D., Vol. I
`Deposition Transcript of Michael G. Rosenblum, Ph.D., Vol. II
`Zimmerman, H.J., "Hepatotoxic Effects of Oncotherapeutic and
`Immunosuppressive Agents," in Hepatotoxicity The Adverse
`Effects of Drugs and Other Chemicals on the Liver Chapter 23,
`pp. 673-708 (1999)
`Eagan, R.T., et al., "Early Clinical Study of an Intermittent
`Schedule for Maytansine (NSC-153858): Brief Communication,"
`J Natl Cancer Inst 60: 93-96 (1978)
`Issell, B., and Crooke, S., "Maytansine," Cancer Treatment
`Reviews 5: 199-207 (1978)
`Cabanillas, F., et al., "Phase I Study of Maytansine Using a 3-Day
`Schedule," Cancer Treatment Rep 62: 425-428 (1978)
`Rosenblum, M., et al., "A Specific and Potent Immunotoxin
`Composed of Antibody ZME-018 and the Plant Toxin Gelonin,"
`Mol Biother 3: 6-13 (1991)
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`2054
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Reiter, Y., et al., "Improved Binding and Antitumor Activity of a
`Recombinant Anti-erbB2 Immunotoxin by Disulfide Stabilization
`of the Fv Fragment," The Journal of Biological Chemistry 269:
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`Protein: Relationship with Shedding of the Extracellular Domain
`and with Prognostic Factors in Breast Cancer," Cancer Research
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`Mechanism of Action of Trastuzumab (Herceptin)," Seminars in
`Oncology 26: 60-70 (1999)
`Zabrecky, J., et al., "The Extracellular Domain of p185/neu Is
`Released from the Surface of Human Breast Carcinoma Cells,
`SK-BR-3," The Journal of Biological Chemistry 266: 1716-1720
`(1991)
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`With Increased Transformation Activity," Molecular
`Carcinogenesis 23: 62-68 (1998)
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`for Determining HER-2/NEU Expression Using Monoclonal
`Antibodies" (filed April 13, 1995, issued July 21, 1998)
`Sorbera, L.A., and Rabasseda, X."Trastuzumab," Drugs of the
`Future 23: 1078-1082 (1998)
`Rao, P., et al., "Cell Cycle Phase-specific Cytotoxicity of the
`Antitumor Agent Maytansine," Cancer Research 39: 3152-3155
`(1979)
`
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`6
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`FDA News Release entitled "FDA Approves Tykerb for
`Advanced Breast Cancer Patients," pp. 1-2, dated March 13,
`2007, available at
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`142 (1992)
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`of a Humanized anti-HER2 Monoclonal Antibody in Patients with
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`Journal of Cancer 81: 1419-1425 (1999)
`Wilson, L., et al., "Modulation of Microtubule Dynamics by
`Drugs: A Paradigm for the Actions of Cellular Regulators," Cell
`Structure and Function 24: 329-335 (1999)
`Burris, H., "Trastuzumab Emtansine: A Novel Antibody-Drug
`Conjugate for HER2-Positive Breast Cancer," Expert Opin. Biol.
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`Wels, W., et al., "Construction, Bacterial Expression and
`Characterization of a Bifunctional Single-Chain Antibody-
`Phosphatase Fusion Protein Targeted to the Human ERBB-2
`Receptor," Biotechnology 10: 1128-1132 (1992)
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`Solid Tumor Agents
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`122-127 (1993)
`Intentionally Left Blank
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`IPR2014-00676
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`
`Maurer-Gebhard, M., et al., "Systemic Treatment with a
`Recombinant erbB-2 Receptor-specific Tumor Toxin Efficiently
`Reduces Pulmonary Metastases in Mice Injected with Genetically
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`(1998)
`Beerli, R., et al., "Intracellular Expression of Single Chain
`Antibodies Reverts ErbB-2 Transformation," The Journal of
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`Chain Antibody Toxins Differ in Their Cell-Killing Activity on
`Tumor Cells Expressing Both Receptor Proteins," Int. J. Cancer
`60: 137-144 (1995)
`Hancock, M.C., et al., "A Monoclonal Antibody Against the c-
`erbB-2 Protein Enhances the Cytotoxicity of cis-
`Diamminedichloroplatinum Against Human Breast and Ovarian
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`Liu, H., et al., "Construction of a Chimeric Antibody with
`Therapeutic Potential for Cancers Which Overexpress c-erbB-2,"
`Biochemical and Biophysical Research Communication 211: 792-
`803 (1995)
`Drebin, J., et al., "Down-Modulation of an Oncogene Protein
`Product and Reversion of the Transformed Phenotype by
`Monoclonal Antibodies," Cell 41: 695-706 (1985)
`Drebin, J., et al., "Inhibition of Tumor Growth By a Monoclonal
`Antibody Reactive with an Oncogene-Encoded Tumor Antigen,"
`Proc. Natl. Acad. Sci 83: 9129-9133 (1986)
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`news.com/news/news/2013-04/roche-reports-new-t-dm1-
`results.html (last accessed Jan. 21, 2014)
`
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
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`
`"Anti-Cancer Drug T-DM1 Benefits Women With Advanced
`Breast Cancer Who Have Failed Several Previous Treatments:
`Results From TH3RESA Trial," pp. 1-3, The European Cancer
`Congress 2013 available at http://www.ecco-
`org.eu/Amsterdam2013/Global/News/ECC-2013-Press-Releases-
`EN/2013/09/Anticancer-drug-T-DM1-benefits-women-with-
`advanced-breast-cancer (last accessed Jan. 21, 2015)
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`February 12, 2002; issued August 1, 2006)
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`Immunoconjugates Prepared with 5-Methyl-2-iminothiolane,"
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`and Proteins That is Stable in Serum and Reversible by
`Lysosomal Hydrolases, As Required for a Lysosomotropic Drug-
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`the Biochemical and Pharmacokinetic Properties of Mgr6-Clavin
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`Brinkley, M., "A Brief Survey of Methods for Preparing Protein
`Conjugates with Dyes, Haptens, and Cross-Linking Reagents,"
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`Schnell, R., et al., "Clinical Trials With an Anti-CD25 Ricin A-
`Chain Experimental and Immunotoxin (RFT5-SMPT-dgA) in
`Hodgkin's Lymphoma," Leukemia and Lymphoma 30: 525-537
`(1998)
`Delprino, L., et al., "Toxin-Targeted Design for Anticancer
`Therapy. II: Preparation and Biological Comparison of Different
`Chemically Linked Gelonin-Antibody Conjugates," Journal of
`Pharmaceutical Sciences 82: 699-704 (1993)
`9
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Goff, D. A., and Carroll, S.R., "Substituted 2-Iminothiolanes:
`Reagents for the Preparation of Disulfide Cross-Linked
`Conjugates with Increased Stability," Bioconjugate Chem. 1: 381-
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`Campbell, A., "Intellectual Property: Exploitation of Intellectual
`Property, Technology Transfer Through the MRC," pp. 1-2,
`available at
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`ssues/articles/1999_03_19/nodoi.1847832825620804321 (last
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`Altenschmidt, U., et al., "Targeted Therapy of Schwannoma Cells
`in Immunocompetent Rats With an erbB2-Specific Antibody-
`Toxin," Int. J. Cancer 73: 117-124 (1997)
`Horak, E., et al., "Radioimmunotherapy Targeting of HER2/neu
`Oncoprotein on Ovarian Tumor Using Lead-212-DOTA-AEI," J
`Nucl Med. 38: 1994-1950 (1997)
`Greenfield, L., et al., "Thiol-Containing Cross-Linking Agent
`with Enhanced Steric Hindrance," Bioconjugate Chem. 1: 400-
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`Immunotoxins Containing a Hindered Disulfide Bond with
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`Conjugates LY203725 and Related Compounds: Design,
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`32: 548-555 (1989)
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`2090
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`2091
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`2092
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`2093
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`2094
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`2095 - 2096
`2097
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`2098
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`2099
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`2100
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Braslawsky, G., et al., "Adriamycin (hydrazone)-antibody
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`Monoclonal Antibody Conjugates of the Calicheamicins: A Novel
`and Potent Family of Antitumor Antibiotics," Cancer Research
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`Intentionally Left Blank
`Ogata, M., et al., "Processing of Pseudomonas Exotoxin by a
`Cellular Protease Results in the Generation of a 37,000-Da Toxin
`Fragment That is Translocated to the Cytosol," The Journal of
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`Lambert, J., et al., "Purified Immunotoxins That Are Reactive
`with Human Lymphoid Cells," The Journal of Biological
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`Edwards, D.C., et al., "A Comparison of the In Vitro and In Vivo
`Activities of Conjugates of Anti-Mouse Lymphocyte Globulin
`and Abrin," Biochimica et Biophysica Acta 717: 272-277 (1982)
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`Targeting for the Treatment of Human Cancer," Bioconjugate
`Chem. 1: 13-23 (1990)
`
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`2101
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`2102
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`2103
`2104
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`2108
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`2109
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`2110
`2111
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`2112
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`2113
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`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Rosenblum, M., et al., "A Novel Recombinant Fusion Toxin
`Targeting HER-2/NEU-Over-Expressing Cells and Containing
`Human Tumor Necrosis Factor," Int. J. Cancer 88: 267-273
`(2000)
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`J. Cancer 55: 227-231 (1987)
`Declaration of Linda T. Vahdat, M.D.
`Curriculum Vitae of Linda T. Vahdat, M.D.
`Declaration of Joyce O'Shaughnessey, M.D.
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