`
`
`
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`ELI LILLY AND COMPANY
`Petitioner,
`
`v.
`
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH
`Patent Owner.
`
`_____________________
`
`Case IPR2018-01423
`U.S. Patent No. 9,266,951
`_____________________
`
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH’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
`
`
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
` Exhibit #
`2001
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`2002
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`2003
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`2004
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`2005
`2006
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`2007
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`2008
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`2009
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`2010
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`2011
`
`2012
`
`Description
`Edvinsson, L., “Calcitonin Gene-Related Peptide (CGRP) in
`Cerebrovascular Disease,” TheScientificWorldJOURNAL, 2: 1484–90
`(2002)
`Hasbak, P., et al., “Investigation of CGRP Receptors and Peptide
`Pharmacology in Human Coronary Arteries. Characterization with a
`Nonpeptide Antagonist,” The Journal Of Pharmacology And
`Experimental Therapeutics, 304:326–33 (2003)
`Brain, S. and Grant, A., “Vascular Actions of Calcitonin Gene-Related
`Peptide and Adrenomedullin,” Physiol Rev., 84: 903-34 (2004)
`Chiba, T., et al., “Calcitonin gene-related peptide receptor antagonist
`human CGRP-(8-37),” Am. J. Physiol.: Endocrin. & Metab.
`256:E331-35 (1989)
`File History for U.S. Patent No. 8,597,649 B2
`Gegg, Jr., C., et al., “CGRP Peptide Antagonists And
`Conjugates,” U.S. Patent No. 8,168,592 B2 (filed October 19, 2006;
`issued May 1, 2012)
`Escott, K. and Brain, S., “Effect of a calcitonin gene-related peptide
`antagonist (CGRP8-37) on skin vasodilatation and oedema induced by
`stimulation of the rat saphenous nerve,” Br. J. Pharmacol. 110: 772-76
`(1993)
`Rist, B., et al., “CGRP 27-37 analogues with high affinity to the CGRP1
`receptor show antagonistic properties in a rat blood flow assay,” Regul.
`Pept. 79:153-58 (1999)
`Edvinsson, L., "Blockade of CGRP Receptors in the Intracranial
`Vasculature: A New Target in the Treatment of Headache,"
`Cephalalgia, 24:611-22 (2004)
`Goadsby, P., “Calcitonin Gene-Related Peptide Antagonists as
`Treatments of Migraine and Other Primary Headaches,” Drugs, 65:
`2557-67 (2005)
`Supowit, S., et al., “Calcitonin Gene-Related Peptide Protects Against
`Hypertension-Induced Heart and Kidney Damage,” Hypertension,
`45:109-14 (2005)
`Aiyar, N., et al., “Pharmacology of SB-273779, a Nonpeptide
`Calcitonin Gene-Related Peptide 1 Receptor Antagonist,” The Journal
`Of Pharmacology And Experimental Therapeutics, 296:768–75 (2001)
`
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`Patent No. 9,266,951
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` Exhibit #
`2013
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`2014
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`2015
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`2016
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`2017
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`2018
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`2019
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`2020
`
`2021
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`2022
`
`2023
`
`2024
`
`Description
`Rudolf, K., et al., “Modified Aminoacids, Pharmaceuticals Containing
`These Compounds and Method For Their Production,” U.S. Patent
`Application Publication No. 2003/0069231 A1 (filed April 10, 2002;
`published April 10, 2003)
`Patchett, A., et al., “Benzimidazolinyl Piperidines As CGRP Ligands,”
`U.S. Patent No. 6,552,043 B1 (filed September 22, 1999; issued April
`22, 2003)
`Zimmer, O., et al., “Substituted Cyclopentene Compounds,” U.S.
`Patent No. 7,109,214 B2 (filed November 19, 2004; issued September
`19, 2006)
`Chaturvedula, P., et al., “Constrained Compounds As CGRP-Receptor
`Antagonists,” U.S. Patent No. 7,384,930 B2 (filed October 11, 2005;
`issued June 10, 2008)
`Rudolf, K., et al., “Modified Aminoacids, Pharmaceuticals Containing
`These Compounds And Method For Their Production,” U.S. Patent No.
`6,344,449 B1 (filed September 8, 1997; issued February 5, 2002)
`Paone, D., et al., “CGRP Receptor Antagonists,” U.S. Patent No.
`7,772,224 B2 (filed April 3, 2009; issued August 10, 2010)
`Petersen, K., et al., “The CGRP-antagonist, BIBN4096BS does not
`affect cerebral or systemic haemodynamics in healthy volunteers,”
`Cephalalgia, 25, 139–47 (2004)
`Leahy, D., et al., “Process For The Preparation Of Cycloheptapyridine
`CGRP Receptor Antagonists,” U.S. Patent No. 8,669,368 B2 (filed
`September 19, 2011; issued March 11, 2014)
`Clinical Trials for BIBN4096BS, downloaded from
`https://clinicaltrials.gov/ct2/results?cond=&term=bibn4096bs&cntry=
`&state=&city=&dist (last accessed November 5, 2018)
`Clinical Trials for MK-0974, downloaded from
`https://clinicaltrials.gov/ct2/results?cond=&term=mk-0974&cntry=&st
`ate=&city=&dist (last accessed on November 15, 2018)
`Clinical Trials for BMS-927711, downloaded from
`https://clinicaltrials.gov/ct2/results?cond=&term=BMS-927711&cntry
`=&state=&city=&dist (last accessed on November 5, 2018)
`Zeller, J., et al., “Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide And Methods Using Same,” U.S. Patent No.
`8,007,794 B2 (filed November 2, 2006; issued August 30, 2011)
`
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`Patent No. 9,266,951
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` Exhibit #
`2025
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`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
`2034
`2035
`2036
`2037
`2038
`2039
`2040
`2041
`2042
`2043
`2044
`
`Description
`Zeller, J., et al., “Methods of Using Anti-CGRP Antagonist
`Antibodies,” U.S. Patent No. 8,586,045 B2 (filed July 11, 2011; issued
`November 19, 2013)
`Zeller, J., et al., "Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide and Methods Using Same," U.S. Patent No.
`9,340,614 B2 (filed August 31, 2015; issued May 17, 2016)
`Zeller, J., et al., "Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide and Methods Using Same," U.S. Patent No.
`8,597,649 B2 (filed April 25, 2013; issued December 3, 2013)
`Zeller, J., et al., "Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide and Methods Using Same," U.S. Patent No.
`9,346,881 B2 (filed August 31, 2015; issued May 24, 2016)
`Zeller, J., et al., "Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide," U.S. Patent No. 9,890,210 B2 (filed May 5,
`2017; issued February 13, 2018)
`Zeller, J., et al., "Antagonist Antibodies Directed Against Calcitonin
`Gene-Related Peptide," U.S. Patent No. 9,890,211 B2 (filed May 5,
`2017; issued February 13, 2018)
`Zeller, J., et al., "Methods for Treating Headache Using Antagonist
`Antibodies Directed Against Calcitonin Gene-Related Peptide," U.S.
`Patent No. 9,884,907 B2 (filed May 5, 2017; issued February 6, 2018)
`Zeller, J., et al., "Methods for Treating Headache Using Antagonist
`Antibodies Directed Against Calcitonin Gene-Related Peptide," U.S.
`Patent No. 9,884,908 B2 (filed May 5, 2017; issued February 6, 2018)
`File History for U.S. Patent No. 8,007,794 B2
`File History for U.S. Patent No. 8,586,045 B2
`File History for U.S. Patent No. 8,734,802 B1
`File History for U.S. Patent No. 9,115,194 B2
`File History for U.S. Patent No. 9,328,168 B2
`File History for U.S. Patent No. 9,346,881 B2
`File History for U.S. Patent No. 9,266,951 B2
`File History for U.S. Patent No. 9,340,614 B2
`File History for U.S. Patent No. 9,365,648 B1
`File History for U.S. Patent No. 9,890,211 B2
`File History for U.S. Patent No. 9,890,210 B2
`File History for U.S. Patent No. 9,884,907 B2
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`Case IPR2018-01423
`Patent No. 9,266,951
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` Exhibit #
`2045
`2046
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`2047
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`2048
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`2049
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`2050
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`2051
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`2052
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`2053
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`2054
`2055
`2056
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`2057
`
`Description
`File History for U.S. Patent No. 9,884,908 B2
`Clinical Trials for BHV-3000, downloaded from
`https://clinicaltrials.gov/ct2/results?cond=&term=bhv-3000&cntry=&s
`tate=&city=&dist (last accessed on November 5, 2018)
`Alberts, B., et al., Molecular Biology of the Cell, p. G-34, 4th ed.,
`Garland Science, Taylor & Francis Group, New York (2002)
`John H. Byrne, Essential Medical Physiology, Chapter 6:
`Neuromuscular and Synaptic Transmission, pp. 97-122, (Leonard R.
`Johnson, ed.), 3rd Ed., Elsevier Academic Press, Amsterdam (2003)
`Pisegna, J., et al., “Cloning And Characterization Of
`Calcitonin Gene Related Peptide Receptors,” U.S. Patent Application
`Publication No. 2004/0110170 A1 (filed May 16, 2003; published June
`10, 2004)
`Petition for Inter Partes Review of U.S. Patent No. 8,597,649, filed
`August 8, 2018 (IPR2018-01427)
`Knight, D., et al., “Pharmacodynamic enhancement of the anti-platelet
`antibody Fab abciximab by site-specific pegylation,” Platelets 15:
`409–418 (2004)
`Inman, S., “Anti-CGRP Monoclonal Antibodies Transforming
`Migraine Treatment,” (Oct. 22, 2018), NeurologyLive
`https://www.neurologylive.com/conferences/ana-2018/anticgrp-monoc
`lonal-antibodies-transforming-migraine-treatment, (last visited May
`20, 2019)
`“Pain Like No Other,” UCLA Health David Geffen School of Medicine
`38(2): 18-25 (2018)
`Intentionally left blank
`Curriculum Vitae of Steven M. Foord, Ph.D.
`Hay, D.L., et al., “A comparison of the actions of BIBN4096BS and
`CGRP8-37 on CGRP and adrenomedullin receptors expressed on
`SK-N-MC, L6, Col 29 and Rat 2 cells,” British Journal of
`Pharmacology 137(1): 80 - 86 (2002)
`Hay, D.L., et al., “CL/RAMP2 and CL/RAMP3 produce
`pharmacologically distinct adrenomedullin receptors: a comparison of
`effects of adrenomedullin22–52, CGRP8–37 and BIBN4096BS,” British
`Journal of Pharmacology 140(3): 477–486 (2003)
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`Case IPR2018-01423
`Patent No. 9,266,951
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` Exhibit #
`2058
`
`2062
`
`Description
`Uren, N.G., et al., “Effect of intravenous calcitonin gene related peptide
`on ischaemia threshold and coronary stenosis severity in humans,”
`Cardiovascular Research 27: 1477- 1481 (1993)
`Geppetti, P., et al., “CGRP and migraine: neurogenic inflammation
`revisited,” Journal of Headache & Pain 6(2):61–70 (2005)
`Hay, D., et al., “Pharmacological discrimination of calcitonin receptor:
`receptor Activity-modifying protein complexes,” Molecular
`Pharmacology 67(5): 1655–1665 (2005)
`Franco-Cereceda, A. and Liska, J., “Potential of Calcitonin
`Gene-Related Peptide in Coronary Heart Disease,” Pharmacology
`60:1–8 (2000)
`The Biochemical Basis of Neuropharmacology, Chapter 4: Receptors,
`65-84, (Jack R. Cooper et al. eds., 8th ed. 2003)
`Excerpt from Rang, H., et al., Pharmacology, p. 15, 5th ed., Elsevier
`Science Limited, (2003)
`2064 Molecular Cell Biology, Chapter 13: Signaling molecules and
`cell-surface receptors, 537-538, (Harvey Lodish et al. eds., 5th ed.
`2003)
`Sheykhzade, M., et al., “Noncompetitive antagonism of BIBN4096BS
`on CGRP-induced responses in human subcutaneous arteries,” British
`Journal of Pharmacology 143(8): 1066–1073 (2004)
`Gallai, V., et al., “Vasoactive peptide levels in the plasma of young
`migraine patients with and without aura assessed both interictally and
`ictally,” Cephalalgia 15(1):384-390 (1995)
`Sarchielli, P., et al., “Nitric oxide metabolites, prostaglandins and
`trigeminal vasoactive peptides in internal jugular vein blood
`during spontaneous migraine attacks,” Cephalalgia, 20(10):
`907-918 (2000)
`Hay, D.L. and Poyner, D. “The Preclinical Pharmacology
`of BIBN4096BS, a CGRP Antagonist,” Cardiovascular Drug Reviews
`23(1): 31-42 (2005)
`Intentionally left blank
`2069
`2070 Wimalawansa, S.J., “Circadian variation of plasma calcitonin
`gene-related peptide in man,” Journal of Neuroendocrinology 3(3):
`319-322 (1991)
`
`2059
`
`2060
`
`2061
`
`2063
`
`2065
`
`2066
`
`2067
`
`2068
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`2071
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`2072
`2073
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`2074
`2075
`
`2076
`2077
`
`2078
`
`2079
`
`2080
`2081
`2082
`
`2083
`2084
`
`2085
`
`Description
`Burgey, C., et al., “CGRP Receptor Antagonists,” PCT International
`Publication No. WO 2004/092166 (filed April 9, 2004; published
`October 28, 2004)
`Intentionally left blank
`Hendrikse, E.R., et al., “Molecular studies of CGRP and the CGRP
`family of peptides in the central nervous system,” Cephalalgia 39(3):
`403–419 (2019)
`Intentionally left blank
`Concise Dictionary of Biomedicine and Molecular Biology, pp. 40, 80
`(Juo, P-S., ed.)
`Intentionally left blank
`Jain, R., “Physiological barriers to delivery of monoclonal antibodies
`and other macromolecules in tumors,” Cancer Research (Suppl.) 50:
`814s-819s (1990)
`Juul, R., et al., “Calcitonin gene-related peptide-LI in subarachnoid
`haemorrhage in man. Signs of activation of the
`trigemino-cerebrovascular system?,” Br. J. Neurosurgery 4: 171-180
`(1990)
`Gennari, C., et al., “Improved cardiac performance with human
`calcitonin gene related peptide in patients with congestive heart
`failure,” Cardiovascular Research 24: 239-241 (1990)
`Intentionally left blank
`Intentionally left blank
`Humbert, M., et al., “Treatment of pulmonary arterial hypertension,” N.
`Engl. J. Med. 351:1425-1436 (2004)
`Intentionally left blank
`Tjen-A-Looi, S., et al., “CGRP and somatostatin modulate chronic
`hypoxic pulmonary hypertension,” Am. J. Physiol. 263(3): H681-H690
`(1992)
`Sagonowsky, E., “Amgen's quick Aimovig launch boosts blockbuster
`hopes for Lilly, Teva and Alder: analyst,” (Aug. 20, 2018) Fierce
`Pharma,
`https://www.fiercepharma.com/pharma/amgen-s-quick-aimovig-launc
`h-has-implications-for-lilly-teva-and-alder-analyst, (last visited May
`29, 2019)
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`Patent No. 9,266,951
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` Exhibit #
`2086
`
`2087
`2088
`
`Description
`Parnetti, L., et al., “Headache and ischemic stroke,” J. Headache Pain
`3(1):15–20 (2002)
`Intentionally left blank
`Etminan, M., et al., “Risk of ischaemic stroke in people with migraine:
`systematic review and meta-analysis of observational studies,” Brit.
`Med. J. 330: 63-65 (2005)
`2089 Wimalawansa, S.J., “Age-related changes in tissue contents of
`immunoreactive calcitonin gene-related peptide,” Aging Clin . Exp.
`Res. 4(1): 211-217 (1992)
`David J. King, Applications and Engineering of Monoclonal
`Antibodies, Chapter 1 Preparation, Structure and Function of
`Monoclonal Antibodies, 1-26 (1998)
`An, Z., “Monoclonal antibodies – a proven and rapidly
`expanding therapeutic modality for human diseases,” Protein Cell 1(4):
`319–330 (2010)
`Alberts, B., et al., Molecular Biology of the Cell, pp. 1736-1780, 4th ed.,
`Garland Science, Taylor & Francis Group, New York (2002)
`Köhler, G. and Milstein, C., “Continuous cultures of fused cells
`secreting antibody of predefined specificity,” Nature 256(5517):
`495-497 (1975)
`Berger, M., et al., “Therapeutic Applications of Monoclonal
`Antibodies,” Am. J. Med. Sci. 324(1):14–30 (2002)
`Siberil, S. and Teillaud, J., Antibodies Volume 2: Novel Technologies
`and Therapeutic Use, Chapter 12: Future Prospects In Antibody
`Engineering And Therapy, pp. 199-215 (G. Subramanian, ed., Kluwer
`Academic/Plenum Publishers, New York (2004))
`Daugherty, A.L. and Mrsny, R.J., “Formulation and delivery issues for
`monoclonal antibody therapeutics,” Advanced Drug Delivery Reviews
`58(5-6): 686-706 (2006)
`Lonberg, N., “Human antibodies from transgenic animals,” Nature
`Biotechnology 23(9): 1117–1125 (2005)
`Presta, L.G., “Engineering of therapeutic antibodies to minimize
`immunogenicity and optimize function,” Advanced Drug Delivery
`Reviews 58(5-6): 640-656 (2006)
`2099 Winter, G., and Harris, W.J., “Humanized antibodies,” Trends in
`Pharmacological Sciences 14(5): 139-143 (1993)
`
`2090
`
`2091
`
`2092
`
`2093
`
`2094
`
`2095
`
`2096
`
`2097
`
`2098
`
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`2100
`
`2101
`
`2102
`
`2103
`
`2104
`
`2105
`
`2106
`
`2107
`
`2108
`
`2109
`
`2110
`
`2111
`
`Description
`Caldas, C., et al., “Humanization of the anti-CD18 antibody 6.7: an
`unexpected effect of a framework residue in binding to antigen,”
`Molecular Immunology 39(15): 941–952 (2003)
`Vaughan, T.J. , et al., “Human antibodies by design,” Nat. Biotechnol.
`16(6): 535-539 (1998)
`Van Dijk, M.A., and Van de Winkel, J.G.J., “Human antibodies as next
`generation therapeutics,” Current Opinion in Chemical Biology
`5(4):368-374 (2001)
`Jacobovits, A., “The long-awaited magic bullets:
`therapeutic human monoclonal antibodies from transgenic mice,” Exp.
`Opin. Invest. Drugs 7(4):607-614 (1998)
`Conflict of Interest in Medical Research, Education and Practice, Lo,
`B. and Field, M.J., eds., pp.1-414, The National Academies Press,
`Washington, D.C. (2009)
`Bains, W., “Failure rates in drug discovery and development:
`will we ever get any better?,” Drug Discovery World 9-18 (2004)
`Hoogenboom, H., et al., “Production of Chimeric Antibodies - A
`Combinatorial Approach,” U.S. Patent No. 5,565,332 (filed September
`23, 1992; issued October 15, 1996)
`Stockwin, L.H. and Holmes, S., “The role of therapeutic antibodies in
`drug discovery,” Biochemical Society Transactions 31(2): 433-436
`(2003)
`Ravandi, F., et al., “Modulation of Cellular Signaling Pathways:
`Prospects for Targeted Therapy in Hematological Malignancies,”
`Clinical Cancer Research 9(2): 535–550 (2003)
`European Medicines Agency Guideline On Strategies To Identify And
`Mitigate Risks For First-Inhuman Clinical Trials With Investigational
`Medicinal Products July 2017
`Janssens, N., et al., “The Wnt-dependent signaling pathways as target in
`oncology drug discovery,” Investigational New Drugs 24(4): 263–280
`(2006)
`British National Formulary, pp.448-445, Vol. 52, BMJ Publishing
`Group Ltd and RPS Publishing (2006)
`
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`Patent No. 9,266,951
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` Exhibit #
`2112
`
`Description
`Knauf, M.J., et al., “Relationship of Effective Molecular Size to
`Systemic Clearance in Rats of Recombinant Interleukin-2 Chemically
`Modified with Water-soluble Polymers,” J. Biol. Chem. 263(29):
`15064-15070 (1988)
`Chapman, A.P., et al., “Therapeutic antibody fragments with
`prolonged in vivo half-lives,” Nature Biotechnology 17(8): 780 – 783
`(1999)
`2114 Murray, J.L., “Monoclonal Antibody Treatment of Solid Tumors:
`A Coming of Age,” Seminars in Oncology 27(6 suppl. 11): 64-70
`(2000)
`Fujimori, K., et al., “Modeling Analysis of the Global and Microscopic
`Distribution of Immunoglobulin G, F(ab’)2, and Fab in Tumors,”
`Cancer Research 49(20): 5656-5663 (1989)
`Leveque, D., et al., “Pharmacokinetics of Therapeutic Monoclonal
`Antibodies Used in Oncology,” Anticancer Research 25(3C):
`2327-2344 (2005)
`2117 Maraschiello, C., “The Relevance of Immunogenicity in Preclinical
`Development,” J. Bioanal. Biomed. 6:1-4 (2014)
`Hamuro, L., et al., “Perspectives on Subcutaneous Route of
`Administration as an Immunogenicity Risk Factor for Therapeutic
`Proteins,” J. Pharm. Sci., 106: 2946-2954 (2017)
`Schunk, M.K. and Macullum, G.E., “Applications and Optimization of
`Immunization Procedures,” ILAR Journal 46(3): 241-247 (2005)
`Fallowfield, L., et al., “ Patients’ preference for administration of
`endocrine treatments by injection or tablets: results from
`a study of women with breast cancer,” Annals of Oncology 17(2):
`205–210 (2006)
`Chowdhury, P.S. and Wu, H., “Tailor-made antibody therapeutics,”
`Methods 36(1): 11-24 (2005)
`Oh-hashi, Y., et al., “Elevated Sympathetic Nervous Activity in Mice
`Deficient in αCGRP,” Circ Res. 89(11):983-990 (2001)
`Intentionally left blank
`2123
`2124 Wimalawansa, S.J., “Age-Related Increase of Calcitonin Gene-Related
`Peptide in Rat Thyroid and Circulation,” Peptides 12(5): 1143-1147
`(1991)
`
`2121
`
`2113
`
`2115
`
`2116
`
`2118
`
`2119
`
`2120
`
`2122
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` Exhibit #
`2125
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`2126
`
`2127
`
`2128
`
`2129
`
`2130
`
`2131
`
`Description
`Gangula, P.R.R., et al., “Increased Blood Pressure in α-Calcitonin
`Gene–Related Peptide/Calcitonin Gene Knockout Mice,” Hypertension
`35(part 2): 470-475 (2000)
`The Seventh Report of the Joint National Committee on Prevention,
`Detection, Evaluation, and Treatment of High Blood Pressure (August
`2004)
`“Hypertension in America: A National Reading,” Am. J. Manag. Care
`11(suppl. 13): S383-S385 (2005)
`Ferrara, N., “VEGF as a Therapeutic Target in Cancer,” Oncology
`69(suppl. 3):11–16 (2005)
`Yotsumoto, F., et al., “Efficacy of Ligand-based Targeting
`for the EGF System in Cancer,” Anticancer Research 29: 4879-4886
`(2009)
`Zeller, J., et al., “CGRP function-blocking antibodies inhibit
`neurogenic vasodilatation without affecting heart rate or arterial blood
`pressure in the rat,” Brit. J. Pharmacol. 155: 1093-1103 (2008)
`Therapeutic Antibody Engineering, Chapter 12: Antibody fragments,
`265-297 (William Strohl and Lila Strohl, No. 11, 2012)
`2132 Wertheimer, A., et al., “Too Many Drugs? The Clinical And Economic
`Value Of Incremental Innovations,” Investing in Health: The Social and
`Economic Benefits of Health Care Innovation 14: 77-118 (2001)
`Intentionally left blank
`Intentionally left blank
`Intentionally left blank
`Intentionally left blank
`Intentionally left blank
`Curriculum Vitae of Ian M. Tomlinson, M.A., Ph.D.
`Juul, R., et al., “Calcitonin gene-related peptide (human α-CGRP)
`counteracts vasoconstriction in human subarachnoid haemorrhage,”
`Neuroscience Letters 170(1) : 67- 70 (1994)
`Christopoulos, G., et al., “Multiple Amylin Receptors Arise from
`Receptor Activity Modifying Protein Interaction with the Calcitonin
`Receptor Gene Product,” Molecular Pharmacology, 56(1):235-242
`(1999)
`Intentionally left blank
`Curriculum Vitae of Michel D. Ferrari, M.D., Ph.D.
`
`2133
`2134
`2135
`2136
`2137
`2138
`2139
`
`2140
`
`2141
`2142
`
`- 11 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
` Exhibit #
`2143
`
`2145
`
`2146
`
`2147
`
`2148
`
`2149
`
`2150
`
`2152
`
`2144
`
`Description
`Collard, C.D. and Gelman, S., “Pathophysiology, Clinical
`Manifestations, and Prevention of Ischemia–Reperfusion Injury,”
`Anesthesiology 94(6): 1133–1138 (2001)
`Solenski, N.J., “Transient Ischemic Attacks: Part I. Diagnosis and
`Evaluation,” Am Fam Physician 69(7): 1665-74,1679-80 (2004)
`Fox, K., et al., “Guidelines on the management of stable angina
`pectoris,” European Heart Journal 27: 1341-1381 (2006)
`Panza, J.A., “Myocardial Ischemia and the Pains of the Heart,” New
`Engl. J. Med. 346(25): 1934-1935 (2002)
`Parker, J.O., “Angina Pectoris: A Review of Current and Emerging
`Therapies,” Am. J. Manag. Care 10(suppl. 11): S332-338 (2004)
`Sobey, C.G. and Faraci, F.M., “Subarachnoid Haemorrhage: What
`Happens To The Cerebral Arteries?,” Clinical and Experimental
`Pharmacology and Physiology 25(11): 867-876 (1998)
`Preibisz, J.J., “Calcitonin Gene-Related Peptide and Regulation of
`Human Cardiovascular Homeostasis,” Am. J. Hypertens.
`6(5 pt. 1): 434-450 (1993)
`Kallner, G. and Franco-Cereceda, A., “Aggravation of Myocardial
`Infarction in the Porcine Heart by Capsaicin-Induced Depletion of
`Calcitonin Gene-Related Peptide (CGRP),” Journal of Cardiovascular
`Pharmacology 32(3): 500-504 (1998)
`2151 Mair, J., et al., “Plasma CGRP in acute myocardial infarction,” Lancet
`335: 168 (1990)
`Li, Y-J., et al., “Calcitonin gene-related peptide-induced
`preconditioning protects against ischemia-reperfusion injury in isolated
`rat hearts,” Eur. J. Pharmacol. 311(2-3): 163-167 (1996)
`2153 Weintraub, A., “Teva abandons Ajovy's cluster headache ambitions,
`clearing a path for Lilly to forge a new market,” (April 24, 2019),
`Fierce Pharma,
`https://www.fiercepharma.com/pharma/teva-ditches-trial-ajovy-cluster
`-headache-clearing-a-path-for-lilly-to-forge-a-new-market, (last visited
`May 29, 2019)
`Edvinsson, L., et al., “Reduced levels of calcitonin gene-related
`peptide-like immunoreactivity in human brain vessels after
`subarachnoid haemorrhage,” Neuroscience Letters 121: 151-154 (1991)
`
`2154
`
`- 12 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
` Exhibit #
`2155
`
`2156
`
`2157
`
`2158
`
`2159
`
`2160
`2161
`
`2162
`
`2163
`
`2164
`
`2165
`2166
`
`2167
`
`2168
`
`Description
`Edvinsson, L. and Uddmann, R., “Neurobiology in primary headaches,”
`Brain Research Reviews 48: 438– 456 (2005)
`Shawket, S.A. and Brown, M., “Pathogenetic and Therapeutic
`Implications of Calcitonin-Gene-Related Peptide in the
`Cardiovascular System,” Trends Cardiovasc. Med. 1(5): 211-215
`(1991)
`Bousser, M.G. and Welch, K.M.A., “Relation between migraine and
`stroke,” Lancet Neurol. 4(9): 533–42 (2005)
`Carolei, A., et al., “Comorbidities of migraine: a user-friendly
`overview,” J. Headache Pain 4(suppl. 1): S23–S25 (2003)
`Stang, P.E., et al., “Headache, cerebrovascular symptoms, and stroke
`The Atherosclerosis Risk in Communities Study,” Neurology 64(9):
`1573–1577 (2005)
`Curriculum Vitae of Alan M. Rapoport, M.D.
`Dodick, D.W., et al., “Safety and efficacy of LY2951742, a monoclonal
`antibody to calcitonin gene-related peptide, for the prevention of
`migraine: a phase 2, randomised, double-blind, placebo-controlled
`study,” Lancet Neurol. 13: 885–92 (2014)
`Goldberg, S.W., and Silberstein, S., “Targeting CGRP: A New Era for
`Migraine Treatment,” CNS Drugs 29:443–452 (2015)
`Pellesi, L., et al., “Spotlight on Anti-CGRP Monoclonal Antibodies in
`Migraine: The Clinical Evidence to Date,” Clinical Pharmacology in
`Drug Development 6(6) 534–547 (2017)
`Li, Y-J. and Peng, J., “The cardioprotection of calcitonin gene-related
`peptide-mediated preconditioning,” European Journal of
`Pharmacology 442: 173– 177 (2002)
`Intentionally left blank
`Lauritsen, C. and Silberstein, S., “Calcitonin Gene-Related Peptide,
`Monoclonal Antibodies, and Migraine,” Practical Neurol. 21-29
`(2016)
`Underwood, E., “A Shot at Migraine,” Science 351(6269): 116-119
`(2016)
`Ajovy (fremanezumab-vfrm) prescribing information (Jan. 2019) FDA
`Label
`
`- 13 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
`2170
`
`2171
`
`2172
`
`Description
` Exhibit #
`2169 Maasumi, K., et al., “CGRP and Migraine: The Role of Blocking
`Calcitonin Gene- Related Peptide Ligand and Receptor in the
`Management of Migraine,” Drugs 78: 913–928 (2018)
`Court, E., “New migraine drugs have promise — and a $8,500
`price tag,” Market Watch,
`https://www.marketwatch.com/story/new-migraine-drugs-have-promis
`e-and-a-8500-price-tag-2017-06-09/print, (last visited May 16, 2019)
`D’Amico, D. and Tepper, S.J., “Prophylaxis of migraine: general
`principles and patient acceptance,” Neuropsychiatric Disease and
`Treatment 4(6): 1155–1167 (2008)
`Carleton, J., “CGRP Antibodies: A Potential Game Changer in
`Migraine Prevention,” (July 11, 2015), Migraine Disorders,
`https://www.migrainedisorders.org/news-and-updates/blog/cgrp-antibo
`dies-a-potential-game-changer-in-migraine-prevention, (last visited
`March 20, 2019)
`2173 McAllister, P., “Monoclonal Antibodies and Migraine:
`What the Neurologist Needs to Know,” Practical Neurol. 18-22 (2017)
`Elvidge, S., “Anti-CGRP antibodies for migraine turn
`industry heads,” Nature Biotechnology 32(8): 707 (2014)
`Ning, X., et al., “Long-Term Safety Fremanezumab: Results of a
`1-Year Study,” poster no. P1.015 at The American Academy of
`Neurology 71st Annual Meeting (2019)
`2176 McAllister, P., et al., “Long-Term Impact of Fremanezumab on
`Response Rates, Acute Headache Medication Use, and Disability in
`Patients with Chronic Migraine: Results of 1-Year Study,” poster no.
`P2.015 at The American Academy of Neurology 71st Annual Meeting
`(2019)
`Brandes, J.L., et al., “Long-Term Impact of Fremanezumab on
`Response Rates, Acute Headache Medication Use, and Disability in
`Patients with Episodic Migraine: Results of 1-Year Study,” poster no.
`P1.005 at The American Academy of Neurology 71st Annual Meeting
`(2019)
`2178 Maassen van den Brink, A.M., et al., “Is CGRP Receptor Blockade
`Cardiovascularly Safe? Appropriate Studies are Needed,” Headache
`58(8):1257-1258 (2018)
`
`2174
`
`2175
`
`2177
`
`- 14 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
` Exhibit #
`2179
`
`2180
`
`2181
`
`2182
`
`2183
`
`2184
`
`2185
`
`2186
`
`2187
`
`2188
`
`Description
`Dumas, P., “To People With Migraine – What You Need To Know,”
`(June 28, 2017), Migraine Again,
`https://migraineagain.com/cgrp-medications-migraine/, (last visited
`March 20, 2019)
`Tso, A.R. and Goadsby, P.J., “Anti-CGRP Monoclonal Antibodies: the
`Next Era of Migraine Prevention?,” Curr. Treat. Options Neurol. 19:
`27 (2017)
`Silberstein, S.D., et al., “The Effect of Beginning Treatment With
`Fremanezumab on Headache and Associated Symptoms in the
`Randomized Phase 2 Study of High Frequency Episodic Migraine:
`Post-Hoc Analyses on the First 3 Weeks of Treatment,” Headache
`59(3): 1-11 (2018)
`Dolgin, E., “Migraine drug race turns its final corner, FDA decisions in
`sight,” Nature Biotechnol. 36(3): 207-208 (2018)
`Digre, K., “American Headache Society president: ‘Exciting, cautious’
`time for patients with migraine,” (October 11, 2018), www.healio.com,
`https://www.healio.com/family-medicine/neurology/news/online/%7B
`e3e75c0f-21c7-4de1-a78c-5e3a2f0ba8d6%7D/american-headache-soci
`ety-president-exciting-cautious-time-for-patients-with-migraine, (last
`visited March 20, 2019)
`Bigal, M. E., et al., “From LBR‑101 to Fremanezumab for Migraine,”
`CNS Drugs 32:1025–1037 (2018)
`Pietrini, U., et al., “Hypertension in headache patients? A
`clinical study,” Acta Neurol. Scand. 112: 259–264 (2005)
`Cassata, C., “Kristin Chenoweth: Migraine Is More Than a Bad
`Headache,” (April 3, 2019) Healthline,
`https://www.healthline.com/health-news/kristin-chenoweth-on-living-
`with-migraines, (last visited March 30, 2019)
`Poyner, D.R., et al., “International Union of Pharmacology. XXXII.
`The Mammalian Calcitonin Gene-Related Peptides, Adrenomedullin,
`Amylin, and Calcitonin Receptors,” Pharmacol. Rev. 54(2):233-246
`(2002)
`de Turenne, V., “Game Changer,” UCLA Health,
`https://www.uclahealth.org/u-magazine/game-changer-1741, (last
`visited May 20, 2019)
`
`- 15 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
` Exhibit #
`2189
`
`2190
`
`2191
`
`Description
`Bender, K., “Promise and Pitfalls of Preventing
`Migraine With CGRP Inhibitors,” (July 10, 2018), MD Magazine ,
`https://www.mdmag.com/journals/md-magazine-neurology/2018/july-
`neuro-2018/promise-and-pitfalls-of-preventing-migraine-with-cgrp-in
`hibitors, (last visited March 20, 2019)
`Silbertstein, S.D., “Preventative Migraine Treatment,” Continuum
`(Minneap Minn) 21(4):973–989 (2015)
`Transcript from the Deposition of Alain P. Vasserot, Ph.D., Case
`IPR2018-01422, IPR2018-01423, IPR2018-01424, IPR2018-01425,
`IPR2018-01426 and IPR2018-01427 (May 1, 2019)
`Transcript of Andrew C. Charles, M.D., Case IPR2018-01422,
`IPR2018-01423, IPR2018-01424, IPR2018-01425, IPR2018-01426
`and IPR2018-01427 (May 3, 2019)
`Prudenzano, M.P., et al., “The comorbidity of migraine and
`hypertension. A study in a tertiary care headache centre,” J. Headache
`Pain 6(4): 220–222 (2005)
`Scher, A. I., et al., “Comorbidity of migraine,” Curr. Opin. Neurol.
`18(3): 305–310 (2005)
`Chaverneff, F., “Fremanezumab May Help Reduce Medication Overuse
`in Chronic Migraine,” (July 1, 2018), Neurology Advisor,
`https://www.neurologyadvisor.com/conference-highlights/ahs-2018/fr
`emanezumab-may-help-reduce-medication-overuse-in-chronic-migrai
`ne/, (last visited May 21, 2019)
`2196 Mavridis, T., et al., “Anti-Calcitonin Gene-Related Peptide Monoclonal
`Antibodies: Adverse Effects. What Do We Really Know? A Literature
`Review,” EMJ Innov. 3(1): 64-72 (2019)
`Buhlmann, N., et al., “A Receptor Activity Modifying Protein
`(RAMP)2- Dependent Adrenomedullin Receptor Is a Calcitonin
`Gene-Related Peptide Receptor when Coexpressed with
`Human RAMP1,” Endocrinology 140(6): 2883-2890 (1999)
`Fraser, N. J., et al., “The Amino Terminus of Receptor Activity
`Modifying Proteins Is a Critical Determinant of Glycosylation State and
`Ligand Binding of Calcitonin Receptor-Like Receptor,” Molecular
`Pharmacology, 55(6): 1054–1059 (1998)
`
`2192
`
`2193
`
`2194
`
`2195
`
`2197
`
`2198
`
`- 16 -
`
`
`
`Case IPR2018-01423
`Patent No. 9,266,951
`
`2200
`
`2201
`
`2202
`
`2203
`
`Description
` Exhibit #
`2199 Marquez de Prado, B. and Russo, A.F., “CGRP receptor antagonists: A
`new frontier of anti-migraine medications,” Drug Discovery Today
`3(4): 593-597 (2006)
`Allen, D.B., “Limitations of short- term studies in predicting long-term
`adverse effects of inhaled corticosteroids,” Allergy 54: 29-34 (1999)
`International Conference on Harmonisation of Technical Requirements
`for Registration of Pharmaceuticals for Human Use, "ICH Harmonised
`Tripartite Guideline: The extent of population exposure to assess
`clinical safety for drugs intended for long-term treatment of
`non-life-threatening conditions," (October 1994)
`"ADDING MULTIMEDIA Teva Announces U.S. Approval of
`AJOVY (fremanezumab-vfrm) Injection, the First and
`Only Anti-CGRP Treatment with Both Quarterly and
`Monthly Dosing for the Preventive Treatment of Migraine
`in Adults," BusinessWire,
`https://www.businesswire.com/news/home/20180914005613/en/ (last
`visited May 30, 2019)
`Foord, S.M. and Craig, R.K., “Isolation and characterisation of a human
`calcitonin-gene-related-peptide receptor,” Eur. J. Biochem. 170(1-2):
`373 - 379 (1987)
`Intentionally left blank
`Glaser, A., “Emgality approval brings new hope for preventing
`migraines,” Migraine Again,
`https://migraineagain.com/emgality-cluster-migraine/ (last visited May
`23, 2019)
`Limmroth, V., et al., “Features of medica