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
`
`
`
`
`
`
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`_____________________
`
`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
`
`
`
`
`
`
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`ImmunoGen
`Exhibit #
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`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
`10 and 15 and Halichondrin B," Pharmacy Therapy 55:31-51
`(1992)
`Maytansine, Annual Report to the Food and Drug Administration;
`Investigational Drug Branch Cancer Therapy Evaluation
`Program Division of Cancer Treatment National Cancer Institute,
`1-21 (1984)
`Cabanillas, F., et al., "Results of a Phase II Study of Maytansine
`in Patients with Breast Carcinoma and Melanoma," Cancer
`Treatment Reports 63: 507-509 (1979)
`Rosenthal, S., et al., "Phase II Study of Maytansine in Patients
`with Advanced Lymphomas: An Eastern Cooperative Oncology
`Group Pilot Study," Cancer Treatment Reports 64: 1115-1117
`(1980)
`Ravry, M., et al., "Phase II Evaluation of Maytansine (NSC
`153858) in Advanced Cancer," American Journal of Clinical
`Oncology: Cancer Clinical Trials 8: 148-150 (1985)
`Blättler, W., et al., "Immunoconjugates," in Cancer Therapeutics:
`Experimental and Clinical Agents, Chapter 17, pp. 371-394
`(1996)
`Dubowchik, G. and Walker, M.A., "Receptor-Mediated and
`Enzyme-Dependent Targeting of Cytotoxic Anticancer Drugs,"
`Pharmacology & Therapeutics 83: 67-123 (1999)
`Cheson, B., et al., "2011 Top Game Changers in Oncology," pp.
`1-9 (2011) available at www.medscape.com at
`http://www.medscape.com/viewarticle/754136_print (last
`accessed July 30, 2014)
`
`
`
`1
`
`
`
`2009
`
`2010
`
`2011
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`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)
`
`
`
`2
`
`
`
`2017
`
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`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
`http://www.kantarhealth.com/blog/oncology/gordon-
`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
`http://abc7.com/archive/9003043/ (last accessed July 28, 2014)
`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)
`
`
`
`3
`
`
`
`2025
`2026
`
`2027
`
`2028
`
`2029
`
`2030
`
`2031
`
`2032
`
`2033
`
`2034
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`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)
`
`
`
`4
`
`
`
`2035
`
`2036
`
`2037
`
`2038
`
`2039
`2040
`2041
`
`2042
`
`2043
`
`2044
`
`2045
`
`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)
`
`
`
`5
`
`
`
`2046
`
`2047
`
`2048
`
`2049
`
`2050
`
`2051
`
`2052
`
`2053
`
`2054
`
`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:
`18327-18331 (1994)
`Rosenblum et al., U.S. Patent No. 7,754,211, "Immunotoxins
`Directed Against C-ERBB-2(HER-2/NEU) Related Surface
`Antigens" (filed on October 13, 2004 ; issued on July 13, 2010)
`Christianson, T., et al., "NH2 –terminally Truncated HER-2-neu
`Protein: Relationship with Shedding of the Extracellular Domain
`and with Prognostic Factors in Breast Cancer," Cancer Research
`58: 5123-5129 (1998)
`Sliwkowski, M., et al., "Nonclinical Studies Addressing the
`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)
`Kwong, K.Y., and Hung, M., "A Novel Splice Variant HER2
`With Increased Transformation Activity," Molecular
`Carcinogenesis 23: 62-68 (1998)
`Koski, U.S. Patent No. 5,783,404, "Methods and Compositions
`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)
`
`
`
`6
`
`
`
`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
`http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncement/
`2007/ucm108866.thm (last accessed Dec. 18, 2014)
`Mountain, A., and Adair, J.A., "Engineering Antibodies for
`Therapy," Biotechnology and Genetic Engineering Review 10: 1-
`142 (1992)
`Park, J., et al., "Biological Therapy of Breast Cancer," BioDrugs
`14: 221-246 (2000)
`Tokuda, Y., et al., "Dose Escalation and Pharmacokinetic Study
`of a Humanized anti-HER2 Monoclonal Antibody in Patients with
`HER2/neu-Overexpressing Metastatic Breast Cancer," British
`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.
`Ther. 11: 807-819 (2011)
`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)
`Representative Clinical Trials of Immunoconjugates As Anti-
`Solid Tumor Agents
`Tecce, R., et. al., "Characterization of Cytotoxic Activity of
`Saporin Anti-GP185/HER-2 Immunotoxins," Int. J. Cancer 55:
`122-127 (1993)
`Intentionally Left Blank
`
`2055
`
`2056
`
`2057
`
`2058
`
`2059
`
`2060
`
`2061
`
`2062
`
`2063
`
`2064
`
`
`
`7
`
`
`
`2065
`
`2066
`
`2067
`
`2068
`
`2069
`
`2070
`
`2071
`
`2072
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`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
`Modified Carcinoma Cells," Cancer Research 58: 2661-2666
`(1998)
`Beerli, R., et al., "Intracellular Expression of Single Chain
`Antibodies Reverts ErbB-2 Transformation," The Journal of
`Biological Chemistry 269: 23931-23936 (1994)
`Wels, W., et al., "EGF Receptor and p185erbB-2 –Specific Single-
`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
`Tumor Cell Lines," Cancer Research 51: 4575-4580 (1991)
`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)
`"Roche Reports New T-DM1 Results," pp. 1-2, European
`Biotechnology available at http://www.european-biotechnology-
`news.com/news/news/2013-04/roche-reports-new-t-dm1-
`results.html (last accessed Jan. 21, 2014)
`
`
`
`8
`
`
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`"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)
`Sedlacek, H., et al., "Antibodies as Carriers of Cytotoxicity,"
`Contributions to Oncology 43: 102-106 (1992)
`Rosenblum, et al., U.S. Patent No. 7,083,957, "Modified Proteins,
`Designer Toxins, and Methods of Making Thereof" (filed
`February 12, 2002; issued August 1, 2006)
`Carroll, S., et al., Enhanced Stability in Vitro and in Vivo of
`Immunoconjugates Prepared with 5-Methyl-2-iminothiolane,"
`Bioconjugate Chem. 5: 248-256 (1994)
`Trouet, A., et al., "A Covalent Linkage Between Daunorubicin
`and Proteins That is Stable in Serum and Reversible by
`Lysosomal Hydrolases, As Required for a Lysosomotropic Drug-
`Carrier Conjugate: In Vitro and In Vivo Studies," Proc. Natl.
`Acad. Sci. 79: 626-629 (1982)
`Dosio, F., et al., "Role of Cross-Linking Agents in Determining
`the Biochemical and Pharmacokinetic Properties of Mgr6-Clavin
`Immunotoxins," Bioconjugate Chem. 9: 372-381 (1998)
`Brinkley, M., "A Brief Survey of Methods for Preparing Protein
`Conjugates with Dyes, Haptens, and Cross-Linking Reagents,"
`Bioconjugate Chem. 3: 2-13 (1992)
`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
`
`2073
`
`2074
`
`2075
`
`2076
`
`2077
`
`2078
`
`2079
`
`2080
`
`2081
`
`
`
`
`
`2082
`
`2083
`
`2084
`
`2085
`
`2086
`
`2087
`
`2088
`
`2089
`
`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-
`386 (1990)
`"PDL's Humanized Antibody Technology," pp. 1-3, available at
`https://web.archive.org/web/20000303232942/http://www.pdl.co
`m/Guided_Tour/Technology/body_technology.html (last
`accessed December 28, 2014)
`Campbell, A., "Intellectual Property: Exploitation of Intellectual
`Property, Technology Transfer Through the MRC," pp. 1-2,
`available at
`http://sciencecareers.sciencemag.org/career_magazine/previous_i
`ssues/articles/1999_03_19/nodoi.1847832825620804321 (last
`accessed December 28, 2014)
`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-
`410 (1990)
`Thorpe, P., et al., "New Coupling Agents for the Synthesis of
`Immunotoxins Containing a Hindered Disulfide Bond with
`Improved Stability in Vivo," Cancer Research 47: 5924-5931
`(1987)
`Laguzza, B., et al., "New Antitumor Monoclonal Antibody-Vinca
`Conjugates LY203725 and Related Compounds: Design,
`Preparation, and Representative in Vivo Activity 1," J. Med. Chem
`32: 548-555 (1989)
`
`
`
`10
`
`
`
`2090
`
`2091
`
`2092
`
`2093
`
`2094
`
`2095 - 2096
`2097
`
`2098
`
`2099
`
`2100
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Braslawsky, G., et al., "Adriamycin (hydrazone)-antibody
`Conjugates Require Internalization and Intracellular Acid
`Hydrolysis for Antitumor Activity," Cancer Immunol Immunother
`33: 367-374 (1991)
`Masuho, Y., et al., "Importance of the Antigen-Binding Valency
`and the Nature of the Cross-Linking Bond in Ricin A-Chain
`Conjugates with Antibody," J. Biochem 91: 1583-1591 (1982)
`Shen, W., et al., "Disulfide Spacer between Methotrexate and
`Poly(D-lysine)," The Journal of Biological Chemistry 260:
`10905-10908 (1985)
`Trail, P.A., et al., "Cure of Xenografted Human Carcinomas by
`BR96-Doxorubicin Immunoconjugates," Science 261: 212-215
`(1993)
`Hinman, L., et al., "Preparation and Characterization of
`Monoclonal Antibody Conjugates of the Calicheamicins: A Novel
`and Potent Family of Antitumor Antibiotics," Cancer Research
`53: 3336-3342 (1993)
`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
`Biological Chemistry 265: 20678-20685 (1990)
`Lambert, J., et al., "Purified Immunotoxins That Are Reactive
`with Human Lymphoid Cells," The Journal of Biological
`Chemistry," 260: 12035-12041 (1985)
`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)
`Koppel, G., "Recent Advances with Monoclonal Antibody Drug
`Targeting for the Treatment of Human Cancer," Bioconjugate
`Chem. 1: 13-23 (1990)
`
`
`
`11
`
`
`
`2101
`
`2102
`
`2103
`2104
`2105
`2106
`2107
`
`2108
`
`2109
`
`2110
`2111
`
`2112
`
`2113
`
`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)
`Embelton, M., "Drug-Targeting by Monoclonal Antibodies," Br.
`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.
`Curriculum Vitae of Joyce O'Shaughnessey, M.D.
`Priestman, T.J., "Quality of Life After Cytotoxic Chemotherapy:
`Discussion Paper," Journal of the Royal Society of Medicine 77:
`492-495 (1984)
`DeVita, V., and Chu, E., "A History of Cancer Chemotherapy,"
`Cancer Res 68: 8643-8653 (2008)
`Mathé, G., et al., "Experimental Medicine – Effect on Mouse
`Leukemia 1210 of a Combination by Means of Diazotization of
`Amethopterin and of y-Globulins from Hamsters with this
`Leukemia by Means of Heterograft," Academy of Science Reports
`246: 1626-1628 (1958) with English Translation
`Declaration of Joseph Morris
`Cao, Y., et al., "Construction and Characterization of Novel,
`Recombinant Immunotoxins Targeting the Her2/neu Oncogene
`Product: In vitro and In vivo Studies," Cancer Res 69: 8987-8995
`(2009)
`Cao, Y., et al., "Single-Chain Antibody-Based Immunotoxins
`Targeting Her2/neu: Design Optimization and Impact of Affinity
`on Antitumor Efficacy and Off-target Toxicity," Mol Cancer Ther
`11: 143-153 (2011)
`Lyu, M., et al., "Cell-Targeting Fusion Constructs Containing
`Recombinant Gelonin," in Methods in Enzymology Chapter 8, pp.
`167-214 (2012)
`
`
`
`12
`
`
`
`2114
`
`2115
`
`2116
`
`2117
`
`2118
`2119
`
`2120
`
`2121
`
`2122
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Lau, A., et al., "Novel Doxorubicin-Monoclonal Anti-
`carcinoembryonic Antigen Antibody Immunoconjugate Activity
`in vitro," Bioorganic & Medical Chemistry 3: 1305-1312 (1995)
`Kuan, C., et al., "Immunotoxins Containing Pseudomonas
`Exotoxin That Target LeY Damage Human Endothelial Cells in an
`Antibody-specific Mode: Relevance to Vascular Leak
`Syndrome," Clinical Cancer Research 1: 1589-1594 (1995)
`Pollack, A., " In Study, Drug Delays Worsening of Breast Cancer,
`With Fewer Side Effects," pp. 1-3, N.Y. TIMES (2012), available at
`http://www.nytimes.com/2012/06/03/health/research/in-study-
`drug-delays-worsening-of-breast-cancer-with-fewer-side-
`effects.html?ref=science&_r=0 (last visited Dec. 1, 2014)
`Slamon, D., et al., "Human Breast Cancer: Correlation of Relapse
`and Survival with Amplification of the HER-2/neu Oncogene,"
`Science 235: 177-182 (1987)
`Herceptin® FDA Approval Letter, mailed September 25, 1998
`Raedler, L., "Kadcyla (Ado-Trastuzumab Emtansine): First
`Antibody-Drug Conjugate Approved for the Treatment of HER2-
`Positive Metastatic Breast Cancer," American Health & Drug
`Benefits, pp. 1-5, available at http://www.ahdbonline.com/select-
`drug-updates/1433-article-1433 (last access Dec. 1, 2014)
`Krop, I., et al., A Phase II Study of Trastuzumab Emtansine in
`Patients with Human Epidermal Growth Factor Receptor 2-
`Positive Metastatic Breast Cancer Who were Previously Treated
`with Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and
`Capecitabine," Journal of Clinical Oncology 30: 3234-3241
`(2012)
`Verma, S., et al., "Trastuzumab Emtansine for HER2-Positive
`Advanced Breast Cancer," N Engl J Med 367: 1783-1791 (2012)
`Barok, M., et al., "Trastuzumab Emtansine: Mechanisms of
`Action and Drug Resistance," Breast Cancer Research 16: 1-12
`(2014)
`
`
`
`13
`
`
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Carlson, R., "Metastatic Breast Cancer: T-DM1 Conjugate
`Superior to Standard Treatment with Capecitabine-Lapatinib,"
`Oncology Times 34: 26 and 28 (2012)
`Ricart, AD., "Immunoconjugates Against Solid Tumors: Mind the
`Gap," Clinical Pharmacology & Therapeutics 89: 513-523 (2011)
`Burris, H., et al., "Phase II Study of the Antibody Drug Conjugate
`Trastuzumab-DM1 for the Treatment of Human Epidermal
`Growth Factor Receptor 2 (HER2) – Positive Breast Cancer After
`Prior HER2-Directed Therapy," J Clin Oncol 29: 398-405 (2011)
`Intentionally Left Blank
`Kadcyla® Marketing Material “EMILIA: A Phase III Trial
`Establishing the Efficacy and Safety of KADCYLA for the
`Treatment of HER2+ Metastatic Breast Cancer in Patients Who
`Have Previously Received Trastuzumab and a Taxane,”
`TDM0001493600
`Ducry, L., and Stump, B., "Antibody-Drug Conjugates: Linking
`Cytotoxic Payloads to Monoclonal Antibodies," Bioconjug Chem
`21: 5-13 (2010)
`Szöllösi, J., et al., "ERBB-2 (HER2/neu) Gene Copy Number,
`p185HER-2 Overexpression, and Intratumor Heterogeneity in
`Human Breast Cancer," Cancer Research 55: 5400-5407 (1995)
`Smyth, M., et al., "Immunochemotherapy of Human Colon
`Carcinoma Xenografts in Nude Mice Using Combinations of
`Idarubicin-Monoclonal Antibody Conjugates," Immunology and
`Cell Biology 71: 167-179 (1993)
`Declaration of John C. Jarosz
`Curriculum Vitae of John C. Jarosz
`Perrone, M., "FDA Approves First-Of-Its-Kind Breast Cancer
`Drug," pp. 1-3, (2014) available at
`http://www.huffingtonpost.com/2013/02/22/fda-approves-new-
`breast-cancer-drug-kadcyla_n_2742241.html
`Declaration of Geoffrey A. Pietersz, Ph.D.
`Curriculum Vitae of Geoffrey A. Pietersz, Ph.D.
`14
`
`2123
`
`2124
`
`2125
`
`2126
`2127
`
`2128
`
`2129
`
`2130
`
`2131
`2132
`2133
`
`2134
`2135
`
`
`
`
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Sharkey, R., et al., "Targeted Therapy of Cancer: New Prospects
`for Antibodies and Immunoconjugates," A Cancer J Clin 56: 226-
`243 (2006)
`Byers, V.S., and Baldwin, R.W., "Therapeutic Strategies With
`Monoclonal Antibodies and Immunoconjugates," Immunology 65:
`329-335 (1988)
`Panowski, S., et al., "Site-specific Antibody Drug Conjugates for
`Cancer Therapy," mAbs 6: 34-45 (2014)
`Antignani, A., et al., "Immunotoxins: The Role of the Toxin,"
`Toxins 5: 1486-1502 (2013)
`Pietersz, G., et al., "Chemoimmunoconjugates for the Treatment
`of Cancer," Advances in Immunology 56: 301-387 (1994)
`"Monoclonal Antibody Production: A Report of the Committee
`on Methods of Producing Monoclonal Antibodies Institute for
`Laboratories Animal Research National Research Council,"
`National Academy Press, pp. 1-47 (1999)
`McGraw, K., et al., "Characterization of Murine and Humanized
`Anti-CD33, Gelonin Immunotoxins Reactive Against Myeloid
`Leukemias," Cancer Immunol Immunother 39: 367-374 (1994)
`Sjogren, H., et al., "Antitumor Activity of Carcinoma-Reactive
`BR96-Doxorubicin Conjugate Against Human Carcinomas in
`Athymic Mice and Rats and Syngeneic Rat Carcinomas in
`Immunocompetent Rats," Cancer Research 57: 4530-4536 (1997)
`Vitetta, E., et al., "Immunotoxins: Magic Bullets or Misguided
`Missiles," Immunology Today 14: 252-259 (1993)
`Kadcyla Product Sheet, pp. 1-2, available at
`http://www.shijiebiaopin.com/upload/product/201411522214319.
`pdf (last accessed Dec. 18, 2014)
`Pastan, I., and FitzGerald, D., "Recombinant Toxins for Cancer
`Treatment," Science 254: 1173-1177 (1991)
`Peaker, B., "Initiation: Kadcyla Fully Prices In, Pipeline Value
`Questionable," in Cowen and Company, pp. 1-30 (2014)
`
`2136
`
`2137
`
`2138
`
`2139
`
`2140
`
`2141
`
`2142
`
`2143
`
`2144
`
`2145
`
`2146
`
`2147
`
`
`
`15
`
`
`
`2148
`
`2149
`
`2150
`
`2151
`
`2152
`
`2153
`
`2154
`
`2155
`
`2156
`
`2157
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Bernstein, ID, "Monoclonal Antibodies to the Myeloid Stem
`Cells: Therapeutic Implications of CMA-676, A Humanized Anti-
`CD33 Antibody Calicheamicin Conjugate," Leukemia 14: 474-
`475 (2000)
`Gutheil, J.C."Novel Immunologic and Biologic Therapies for
`Breast Cancer," Current Oncology Reports 2: 582-586 (2000)
`Dillman, R.O., "Perceptions of Herceptin®: A Monoclonal
`Antibody for the Treatment of Breast Cancer," Cancer Biotherapy
`& Radiopharmaceuticals 14: 5-10 (1999)
`Ewer, M., et al., "Cardiotoxicity in Patients Receiving
`Trastuzumab (Herceptin): Primary Toxicity, Synergistic or
`Sequential Stress, or Surveillance Artifact?," Semin Oncol 26: 96-
`101 (1999)
`Reiter, Y., "Recombinant Immunotoxins in Targeted Cancer Cell
`Therapy," Cancer Research 81: 93-124 (2001)
`Hadden, J.W., "The Immunology and Immunotherapy of Breast
`Cancer: An Update," International Journal of
`Immunopharmacology 21: 79-101 (1999)
`Leland, P., et al., "Human Breast Carcinoma Cells Express Type
`II IL-4 Receptors and Are Sensitive to Antitumor Activity of a
`Chimeric IL-4-Pseudomonas Exotoxin Fusion Protein in vitro and
`in vivo," Molecular Medicine 6: 165-178 (2000)
`Mariano, A., et al., "Analysis of Glycoproteins in Cancers and
`Normal Tissues Reactive with Monoclonal Antibodies B3 and
`B1," International Journal of Oncology 16: 549-553 (2000)
`Gho, Y., and Chae, CB., "Luteinizing Hormone Releasing
`Hormone-RNase A Conjugates Specifically Inhibit the
`Proliferation of LHRH-Receptor-Positive Human Prostate and
`Breast Tumor Cells," Mol. Cells 9: 31-36 (1999)
`Chandler, L., et al., "Targeting Tumor Cells Via EGF Receptors:
`Selectively Toxicity of an HBEGF-Toxin Fusion Protein," Int. J.
`Cancer 78: 106-111 (1998)
`
`
`
`16
`
`
`
`2158
`
`2159
`
`2160
`
`2161
`
`2162
`
`2163
`
`2164
`
`2165
`
`2166
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Yang, D., et al., "Recombinant Heregulin-Pseudomonas Exotoxin
`Fusion Proteins: Interactions with the Heregulin Receptors and
`Antitumor Activity in Vivo," Clinical Cancer Research 4: 993-
`1004 (1998)
`Xu, Y., et al., "Antileukemic Activity of Recombinant
`Humanized M195-Gelonin Immunotoxin in Nude Mice,"
`Leukemia 10: 321-326 (1996)
`Pagliaro, L., et al., "Humanized M195 Monoclonal Antibody
`Conjugated to Recombinant Gelonin: An Anti-CD33
`Immunotoxin with Antileukemic Activity," Clinical Cancer
`Research 4: 1971-1976 (1998)
`Phigenix Website, p. 1, at http://phigenix.com/ (last accessed Dec.
`18, 2014)
`Weiner, L., et al., "Phase I Evaluation of an Anti-Breast
`Carcinoma Monoclonal Antibody 260F9-Recombinant Ricin A
`Chain Immunoconjugate," Cancer Research 49: 4062-4067
`(1989)
`Heppner, G., and Miller, B., "Tumor Heterogeneity: Biological
`Implications and Therapeutic Consequences," Cancer Metastasis
`Reviews 2: 5-23 (1983)
`Ratcliffe, N. et al., "The Combination of In Situ Hybridization
`and Immunohistochemical Analysis: An Evaluation of Her2/neu
`Expression in Paraffin-Embedded Breast Carcinomas and
`Adjacent Normal-Appearing Breast Epithelium," Mod Pathol 10:
`1247-1252 (1997)
`Potts, S., et al., "Evaluating Tumor Heterogeneity in
`Immunohistochemistry-Stained Breast Cancer Tissue,"
`Laboratory Investigation 92: 1342-1357 (2012)
`Rader, C., et al., "A Phage Display Approach for Rapid Antibody
`Humanization: Designed Combinatorial V Gene Libraries," Proc.
`Natl. Acad. Sci. 95: 8910-8915 (1998)
`
`
`
`17
`
`
`
`2167
`
`2168
`
`2169
`
`2170
`
`2171
`
`2172
`
`2173
`
`2174
`
`2175
`
`2176
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Santos, A., and Padlan, E., "Development of More Efficacious
`Antibodies for Medical Therapy and Diagnosis," in Progress in
`Nucleic Acid Research and Molecular Biology 60: 169-194
`(1998)
`Hurle, M., and Gross, M., "Protein Engineering Techniques for
`Antibody Humanization," Current Opinion in Biotechnology 5:
`428-433 (1994)
`Sandhu, J., "A Rapid Procedure for the Humanization of
`Monoclonal Antibodies," Gene 150: 409-410 (1994)
`He, X., et al., "Humanization and Pharmacokinetics of a
`Monoclonal Antibody with Specificity for Both E- and P-
`Selectin," The Journal of Immunology 160: 1029-1035 (1998)
`Rosenblum, M., et al., "An Antimelanoma Immunotoxin
`Containing Recombinant Human Tumor Necrosis Factor: Tissue
`Disposition, Pharmacokinetic, and Therapeutic Studies in
`Xenograft Models," Cancer Immunol Immunother 40: 322-328
`(1995)
`Melton, R., and Sherwood, R., "Antibody-Enzyme Conjugates for
`Cancer Therapy," J Natl Cancer Inst 88: 153-165 (1996)
`Cao, Y., et al., "Design Optimization and Characterization of
`Her2/neu-Targeted Immunotoxins: Comparative in vitro and in
`vivo Efficacy Studies," Oncogene 33: 429-439 (2014)
`Cao, Y., et al., "Single-Chain Antibody-Based Immunotoxins
`Targeting Her2/neu: Design Optimization and Impact of Affinity
`on Antitumor Efficacy and Off-Target Toxicity," Mol Cancer
`Ther 11: 143-153 (2012)
`Erickson, H., et al., "Antibody-Maytansinoid Conjugates Are
`Activated in Targeted Cancer Cells by Lysosomal Degradation
`and Linker-Dependent Intracellular Processing," Cancer Res 66:
`4426-4433 (2006)
`Ramakrishnan, S., et al., "Cytotoxic Conjugates Containing
`Translational Inhibitory Proteins," Annu. Rev. Pharmacol.
`Toxicol. 32: 579-621 (1992)
`
`
`
`18
`
`
`
`2177
`
`2178
`
`2179
`
`2180
`
`2181
`2182
`
`2183
`
`2184
`
`2185
`
`IMMUNOGEN INC.'S EXHIBIT LIST
`IPR2014-00676
`
`
`Chari, R., et al., "Enhancement of the Selectivity and Antitumor
`Efficacy of a CC-1065 Analogue Through Immunoconjugate
`Formation," Cancer Research 55: 4079-4084 (1995)
`FDA Clinical Review of BLA 98-0369, Herceptin®,
`Trastuzumab, approved Sept. 25, 1998, pp. 1-49, available at
`http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDr
`ugsareDevelopedandApproved/ApprovalApplications/Therapeuti
`cBiologicApplications/ucm080591.htm (last visited Dec. 1, 2014)
`LoRusso, P., et al., "Trastuzumab Emtansine: A Unique
`Antibody-Drug Conjugate in Development for Hum
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
