`
`_
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ASTRAZENECA AB,
`Patent Owner.
`
`Case IPR2015-01340
`Patent RE44,186
`
`PATENT OWNER ASTRAZENECA AB’S EXHIBIT LIST
`(as of June 27, 2016)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit
`
`Exhibit 2001
`
`
`Exhibit 2002
`
`
`Exhibit 2003
`
`
`Exhibit 2004
`
`
`Exhibit 2005
`
`
`Exhibit 2006
`
`
`Exhibit 2007
`
`
`Exhibit 2008
`
`Description
`Doreen M. Ashworth et al., 4-Cyanothiazolidides
`as Very Potent, Stable Inhibitors of Dipeptidyl
`Peptidase IV, 6 BIOORG. & MED. CHEM.
`LETT. 2745 (1996)
`David R. Magnin et al., Synthesis of Novel Potent
`Dipeptidyl Peptidase IV Inhibitors with
`Enhanced Chemical Stability: Interplay Between
`the N-Terminal Amino Acid Alkyl Side Chain and
`the Cyclopropyl Group of α-Aminoacyl-L-cis-4,5-
`methanoprolinenitrile-Based Inhibitors, 47 J.
`MED. CHEM. 2587 (2004)
`Jeffrey A. Robl & Lawrence G. Hamann, The
`Discovery of the Dipeptidyl Peptidase-4 (DPP4)
`Inhibitor Onglyza™: From Concept to Market, in
`ACCOUNTS IN DRUG DISCOVERY: CASE
`STUDIES IN MEDICINAL CHEMISTRY 1
`(Joel C. Barrish et al. eds., 2011)
`ASTRAZENECA ANNUAL REPORT AND
`FORM 20-F INFORMATION
`2014, available at
`www.astrazeneca.com/annualreport2014
`Jens J. Holst & Carolyn F. Deacon, Inhibition of
`the Activity of Dipeptidyl-Peptidase IV as a
`Treatment for Type 2 Diabetes, 47 DIABETES
`1663 (1998)
`Kathleen Aertgeerts et al., Crystal Structure of
`Human Dipeptidyl Peptidase IV in Complex with
`a Decapeptide Reveals Details on Substrate
`Specificity and Tetrahedral intermediate
`Formation, 13 PROTEIN SCI. 412 (2004)
`K. Augustyns et al., The Unique Properties of
`Dipeptidyl- Peptidase IV (DPP IV / CD26) and
`the Therapeutic Potential of DPP IV Inhibitors, 6
`CURR. MED. CHEM. 311 (1999)
`George R. Flentke et al., Inhibition of Dipeptidyl
`Aminopeptidase IV (DP-IV) by Xaa-
`boroProdipeptides and Use of These Inhibitors to
`Examine the Role of DP-IV in T-cell Function, 88
`
`Status
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`
`
`
`
`
`
`Exhibit
`
`
`Exhibit 2009
`
`
`Exhibit 2010
`
`Description
`PROC. NAT’L ACAD. SCI. 1556 (1991)
`Robert P. Pauly et al., Improved Glucose
`Tolerance in Rats Treated With the Dipeptidyl
`Peptidase IV (CD26) Inhibitor Ile- Thiazolidide,
`48 METABOLISM 385 (1999)
`Hans-U Demuth et al., Abstract, Single Dose
`Treatment of Diabetic Patients by the DP IV
`Inhibitor P32/98, 49 DIABETES 413-P (2000)
`Exhibit 2011 U.S. Patent No. 5,939,560
`Paul Rothenberg et al., Abstract, Treatment with
`
`a DPP-IV Inhibitor, NVP-DPP728, Increases
`Exhibit 2012
`Prandial Intact GLP-1 Levels and Reduced
`Glucose Exposure in Humans, 49 DIABETES
`160-OR (2000)
`Exhibit 2013 U.S. Patent No. 6,166,063
`Ligaya M. Simpkins et al., Potent Non-Nitrile
`
`Dipeptidic Dipeptidyl Peptidase IV Inhibitors, 17
`Exhibit 2014
`BIOORG. & MED. CHEM. LETT. 6476 (2007)
`Pioneer and Analogue Drugs, in ANALOGUE-
`BASED DRUG DISCOVERY III 3 (János
`Fischer et al. eds., 2013)
`Thomas E. Hughes et al., NVP-DPP728: (1-[[[2-
`[(5- Cyanopyridin-2-yl)amino ]ethyl]amino
`]acetyl]-2-cyano-(S)- pyrrolidine ), a Slow-
`Binding Inhibitor of Dipeptidyl Peptidase IV, 38
`BIOCHEM. 11597 (1999)
`Coralie Nguyen et al., Specific and Irreversible
`Cyclopeptide Inhibitors of Dipeptidyl Peptidase
`IV Activity of the T-Cell Activation Antigen
`CD26, 41 J. MED. CHEM. 2100 (1998)
`Aiying Wang et al., Potency, Selectivity and
`Prolonged Binding of Saxagliptin to DPP4:
`Maintenance of DPP4 Inhibition by Saxagliptin
`In Vitro and Ex Vivo When Compared to a
`Rapidly- Dissociating DPP4 Inhibitor, 12 BMC
`PHARM. 1 (2012)
`Defendants Joint Initial Invalidity Contentions
`Regarding U.S. Patent No. RE44,186
`
`
`Exhibit 2015
`
`
`Exhibit 2016
`
`
`Exhibit 2017
`
`
`Exhibit 2018
`
`
`Exhibit 2019
`
`Status
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`Served and Filed
`
`Served and Filed
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`
`
`
`
`
`
`Exhibit
`
`Exhibit 2020
`
`
`Exhibit 2021
`
`Description
`M.A. Nauck et al., Effects of Subcutaneous
`Glucagon-Like Peptide 1(GLP-1 [7–36 Amide])
`in Patients with NIDDM, 39 DIABETOLOGIA
`1546 (1996)
`Nancy L. Thompson et al., A Fischer Rat
`Substrain Deficient in Dipeptidyl Peptidase IV
`Activity Makes Normal Steady-State RNA Levels
`and an Altered Protein: Use as a Liver-Cell
`Transplantation Model, 273 J. BIOCHEM. 497
`(1991)
`Int’l Pub. No. WO 95/15309
`Exhibit 2022
`Exhibit 2023 U.S. Patent No. 6,011,155
`Von R. Hiltmann et al., 2-Acylaminopyridin-
`
`Derivate mit morphinagonistischer und -
`Exhibit2024
`antagonistischer Wirksamkeit, 24 ARZNEIM.
`FORSCH. 584 (1974)
`Exhibit 2025 U.S. Patent No. 4,591,598
`Exhibit 2026 German Patent Pub. No. 25 21 895 A1
`Exhibit 2027 U.S. Patent No. 3,325,478
`Stephen Hanessian et al., Probing the Importance
`
`of Spacial and Conformational Domains in
`Exhibit 2028
`Captopril Analogs for Angiotensin Converting
`Enzyme Activity, 8 BIOORG. & MED. CHEM.
`LETT. 2123 (1998)
`Koert Gerzon et al., The Adamantyl Group in
`Medicinal Agents I. Hypoglycemic N-
`Arylsulfonyl-N’adamantylureas, 6 J. MED.
`CHEM. 760 (1963)
`F. R. Rubio et al., Urinary Metabolites of
`Rimantadine in Humans, 16 DRUG
`METABOLISM & DISPOSITION 773 (1988)
`Gunter Fischer et al., The Conformation Around
`the Peptide Bond Between the P1- And P2-
`Positions Is Important for Catalytic Activity of
`Some Proline-Specific Proteases, 742 BBA 452
`(1983)
`Exhibit 2032 U.S. Patent No. 4,954,158
`Masahiro Yoshioka et al., Role of Rat Intestinal
`
`
`
`Exhibit 2029
`
`
`Exhibit 2030
`
`
`Exhibit 2031
`
`Status
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`Served and Filed
`Served and Filed
`
`Served and Filed
`Served and Filed
`Served and Filed
`Served and Filed
`
`Served and Filed
`{substitution
`proposed and
`served}
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`Served and Filed
`
`
`
`
`
`
`
`
`Exhibit 2037
`
`
`Exhibit 2038
`
`Description
`Exhibit
`Exhibit 2033 Brush-Border Membrane Angiotensin-Converting
`Enzyme in Dietary Protein Digestion, 253 AM. J.
`PHYSIOL. G781 (1987)
`Exhibit 2034 German Patent Pub. No. 3324263 A1
`Stephen Hanessian et al., The Stereocontrolled
`
`Exhibit 2035
`Synthesis of Enantiopure α-Methano
`Heterocycles and Constrained Amino Acid
`Analogs, 37 TETRAHEDRON LETT. 8967 (1996)
`Exhibit 2036 CAplus Records for German Patent Pub. No.
`3324263 A1
`Roberto Pellicciari et al., Synthesis of All Four
`Diastereoisomers of 4-(Carboxymethyl)proline, a
`Conformationally Constrained Analogue of 2-
`Aminoadipic Acid, 1 J. CHEM. SOC. 1251 (1995)
`Viacheslav V. Tverezovsky et al., Synthesis of
`(2S, 3R, 4S)-3,4- Methanoproline and Analogues
`by Cyclopropylidene Insertion, 53 TETRAHEDRON
`14773 (1997)
`Frank L. Switzer et al., Synthesis of (4)-2,3-
`Methanoproline: A Novel Inhibitor of Ethylene
`Biosynthesis, 45 TETRAHEDRON
`6091 (1989)
`Alain Hercouet et al., First Asymmetric Synthesis
`of (-)-(2S, 3R)-Methanoproline, 7
`TETRAHEDRON: ASYMMETRY 1267 (1996)
`Raymond A. Pederson et al., Improved Glucose
`Tolerance in Zucker Fatty Rats by Oral
`Administration of the Dipeptidyl Peptidase IV
`Inhibitor Isoleucine Thiazolidide, 47 DIABETES
`1253 (1998)
`Jingrong Li et al., Aminoacylpyrrolidine-2-
`nitriles: Potent and Stable Inhibitors of
`Dipeptidyi-Peptidase IV (CD 26), 323 ARCH.
`BIOCHEM. & BIOPHYSICS 148 (1995)
`Stephen Hanessian et al., The Synthesis of 4,5-
`Methano Congeners of α-Kainic and α-allo-
`Kainic Acids as Probes for Glutamate Receptors
`37 TETRAHEDERON LETT. 8971 (1996)
`
`
`Exhibit 2039
`
`
`Exhibit 2040
`
`
`Exhibit 2041
`
`
`Exhibit 2042
`
`
`Exhibit 2043
`
`Status
`
`Served and Filed
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`
`
`
`Exhibit 2046
`
`Exhibit
`
`Exhibit 2044
`
`Exhibit 2045
`
`Description
`Koppel et al., The Metabolism of Tromantadine
`12 BIOMED. MASS. SPECTROM. 497 (1985)
`Su et al., Characterization of the In Vitro and In
`Vivo Metabolism and Disposition and
`Cytochrome P450 Inhibition/Induction Profile of
`Saxagliptin in Human 40 DRUG METABOLISM
`AND DISPOSITION 1345 (2012)
`He et al., Absorption, Metabolism, and Excretion
`of [14C]Vildagliptin, a Novel Dipeptidyl
`Peptidase 4 Inhibitor, in Humans 37 DRUG
`METABOLISM AND DISPOSITION 536
`(2009)
`Exhibit 2047 Onglyza® Prescribing Info., revised May 2013
`Exhibit 2048 Kombiglyze™ XR Prescribing Info., revised May
`2013
`Januvia® Prescribing Info., revised Mar. 2015
`Exhibit 2049
`Exhibit 2050 Galvus® Prescribing Info.
`Exhibit 2051 Evidentiary Declaration of ANN E. WEBER,
`PHD.
`Exhibit 2052 CV for ANN E. WEBER, PHD.
`Exhibit 2053 Declaration of John Kozikowski
`Exhibit 2054 Table of Contents for ANALOGUE-BASED
`DRUG DISCOVERY III 3 (János Fischer et al.
`eds., 2013) (Exhibit 2015)
`Exhibit 2055 Transcript of Telephone Conference Call of June
`17, 2016
`
`
`
`Status
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`
`Served and Filed
`Served and Filed
`
`Served and Filed
`Served and Filed
`Served only
`
`Served only
`Served only
`Served only
`
`Served and Filed
`
`Dated: June 27, 2015
`
`Respectfully submitted,
`
`
`
`By: /Anthony Hartmann/
`Anthony A. Hartmann,
`Reg. No. 43,662
`Finnegan, Henderson, Farabow, Garrett
`& Dunner, L.L.P.
`901 New York Avenue, NW
`Washington DC 20008
`Counsel for Patent Owner
`
`
`
`
`
`
`
`
`
`
`
`
`
`CERTIFICATE OF SERVICE
`The undersigned certifies that a copy of the foregoing PATENT OWNER’S
`
`Exhibit List As of June 27, 2016 and Exhibit 2055 were served electronically via
`
`e-mail on June 27, 2016, in its entirety to counsel for Petitioner Mylan
`
`Pharmaceuticals Inc.:
`
`Steven W. Parmalee (sparmalee@wsgr.com)
`
`Richard Torczon (rtorczon@wsgr.com)
`
`
`
`
`
`
`
`
`
`
`
`/Sheila Y. West/
`
`
`Sheila Y. West
`Litigation Assistant
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`
`
`
`
`
`
`
`
`
`
`
`
`Dated: June 27, 2016