UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S
`LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., and
`SUN PHARMACEUTICALS INDUSTRIES LTD.,
`Petitioners,
`
`v.
`
`MERCK SHARP & DOHME CORP.,
`Patent Owner.
`__________________
`
`IPR2020-000401
`Patent 7,326,708
`__________________
`
`
`
`
`
`
`
`PATENT OWNER’S DEMONSTRATIVES
`
`
`
`
`
`1 Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. were joined as
`parties to this proceeding via a Motion for Joinder in IPR2020-01060; and Sun
`Pharmaceuticals Industries Ltd. was joined as a party to this proceeding via Motion
`for Joinder in IPR2020-01072.
`
`
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S
`LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., and
`SUN PHARMACEUTICALS INDUSTRIES LTD.,
`Petitioners,
`
`v.
`
`MERCK SHARP & DOHME CORP.,
`Patent Owner.
`__________________
`
`IPR2020-000401
`Patent 7,326,708
`__________________
`
`
`
`
`
`
`
`PATENT OWNER’S DEMONSTRATIVES
`
`
`
`
`
`1 Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. were joined as
`parties to this proceeding via a Motion for Joinder in IPR2020-01060; and Sun
`Pharmaceuticals Industries Ltd. was joined as a party to this proceeding via Motion
`for Joinder in IPR2020-01072.
`
`
`
`
`
`Pursuant to the Board’s Order Setting Oral Argument dated January 11,
`
`IPR2020-00040 | Patent 7,326,708
`
`2021 (Paper 80), Patent Owner Merck Sharp & Dohme Corp.’s demonstratives are
`
`appended to this filing.
`
`
`Date: February 9, 2021
`
`
`
`
`
`
`
`
`
`Respectfully submitted,
`
`/Stanley E. Fisher/
`Stanley E. Fisher (Reg. No. 55,820)
`Bruce R. Genderson (Pro Hac Vice)
`David M. Krinsky (Reg. No. 72,339)
`Elise M. Baumgarten (Pro Hac Vice)
`Alexander S. Zolan (Pro Hac Vice)
`Shaun P. Mahaffy (Reg. No. 75,534)
`Anthony H. Sheh (Reg. No. 70,576)
`WILLIAMS & CONNOLLY LLP
`725 Twelfth Street, N.W.
`Washington, DC 20005
`T: (202) 434-5000
`F: (202) 434-5029
`sfisher@wc.com
`bgenderson@wc.com
`dkrinsky@wc.com
`ebaumgarten@wc.com
`azolan@wc.com
`smahaffy@wc.com
`asheh@wc.com
`
`Counsel for Patent Owner
`Merck Sharp & Dohme Corp.
`
`
`
`
`2
`
`
`
`Mylan Pharmaceuticals Inc. v.
`Merck Sharp & Dohme Corp.
`
`Case IPR2020-0040
`U.S. Patent 7,326,708
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`
`Claims 1-3, 17, 19, 21-23:
`“At Once Envisage”
`(Grounds 1, 2)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`2
`
`
`
`Salt Formation Is Unpredictable
`
`“The experts of both parties agreed that whether a pharmaceutically
`suitable crystalline salt will form from a particular acid-base
`combination is unpredictable.”
`
`Sanofi-Synethelabo v. Apotex, Inc., 550 F.3d 1075, 1089 (Fed. Cir. 2008)
`
`See also Pfizer Inc. v. Mylan Pharm. Inc., 71 F. Supp. 3d 458, 474 (D. Del. 2014); Valeant Int’l
`(Barbados) SRL v. Watson Pharm., Inc., 2011 WL 6792653, at *7 (S.D. Fla. Nov. 8, 2011)
`
`POR 7-12; Sur-Reply 3-5; EX2103 ¶¶ 31-34, 69, 86-98;
`EX2127 ¶15-22; EX2193, 604; EX2042, 137, 138;
`EX2194, 1; EX2195, 322; EX2196, 2; EX2197, 201
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`3
`
`
`
`Salt Formation Is Unpredictable
`
`Ex. 2193 at 604
`
`Ex. 2042 at 137
`
`POR 7-12; Sur-Reply 3-5; EX2103 ¶¶ 31-34, 69, 86-98;
`EX2127 ¶15-22; EX2042, 138; EX2194, 1; EX2195,
`322; EX2196, 2; EX2197, 201
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4
`
`
`
`Salt Formation Is Unpredictable
`
`Ex. 2051, Mylan Expert
`(Chorghade) Dep. Tr. at 105:5-15
`
`Ex. 2051, Mylan Expert
`(Chorghade) Dep. Tr. at 116:6-20
`
`POR 7-12; Sur-Reply 3-5; EX2103 ¶¶ 31-34, 69, 86-98;
`EX2127 ¶15-22, EX2193, 604; EX2042, 137, 138; EX2194,
`1; EX2195, 322; EX2196, 2; EX2197, 201
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`5
`
`
`
`Salt Formation Is Unpredictable
`
`POR 7-12; Sur-Reply 3-5; EX2103 ¶¶ 31-34, 69, 86-98;
`EX2127 ¶15-22, EX2193, 604; EX2042, 137, 138; EX2194,
`1; EX2195, 322; EX2196, 2; EX2197, 201
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`6
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 63:15-64:3
`
`
`
`No Experimental Data Directs the POSA to the Phosphate Salt
`
`POR 12-14; Sur-Reply 6; EX2103 ¶¶ 74, 77-85
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`7
`
`Ex. 2103 ¶ 81
`
`
`
`Salt Formation Is Unpredictable
`
`Ex. 2103 ¶ 86
`
`POR 7-12; Sur-Reply 3-5; EX2103 ¶¶ 31-34, 69, 86-98;
`EX2127 ¶15-22; EX2193, 604; EX2042, 137, 138; EX2194,
`1; EX2195, 322; EX2196, 2; EX2197, 201
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`8
`
`
`
`No Anticipation Where Unpredictable Chemical Reactions Have to Take Place
`
`“This instant case is not analogous to Wrigley, for several
`reasons. . . . Second, not that this Court has any expertise with
`the production of chewing gum, but lisdexamfetamine does not
`appear to be something that you get by mixing a little L-lysine
`and a little d-amphetamine together. There is no dispute that
`some chemical reactions have to take place . . . .”
`
`Shire LLC v. Amneal Pharm., LLC, 2014 WL 2861430, at *17 (D.N.J. June 23, 2014),
`aff’d in part and overruled on other grounds, 802 F.3d 1301 (Fed. Cir. 2015)
`
`POR 10-11; Sur-Reply 4-5
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`9
`
`
`
`Claims 1-3, 17, 19, 21-23:
`Inherent Anticipation
`(Grounds 1, 2)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`10
`
`
`
`Non-1:1 Sitagliptin Phosphate Salts are Not Merely Hypothetical
`
`Institution Decision at 52
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`11
`
`Institution Decision at 53
`
`
`
`Dr. Matzger Indisputably Made Non-1:1 Salts
`
`POPR 47-48, 50-52; POR 15-18; Sur-Reply 11-12;
`EX2103 ¶¶ 102-118
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`12
`
`Ex. 2103 ¶ 102
`
`
`
`Example 7 Irrelevant to Whether Polyprotic Acid Could Form Non-1:1 Salts
`
`POR 15-17, Sur-Reply 5, 11-12
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`13
`
`Ex. 2103 ¶ 113
`
`Ex. 2103 ¶ 113, n.39
`
`
`
`Mylan Ignores Pathway 2
`
`Patent Owner’s Preliminary Response at 51-52
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`14
`
`
`
`Literature Shows Non-1:1 Sitagliptin Phosphate Salts
`
`2 sitagliptin : 1 phosphoric acid
`
`1 sitagliptin : 2 phosphoric acid
`
`POR 15-17; Sur-Reply 5, 9-12; EX2103 ¶¶ 120-122
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`15
`
`Ex. 2220 at 7-8
`
`Ex. 2220 at 16
`
`
`
`Uncontested that Dr. Matzger Made Non-1:1 Salts
`
`Ex. 2103 ¶ 176
`
`POR 2, 15-17; Sur-Reply 5, 11-12; EX 2103 ¶¶ 123-176
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`16
`
`
`
`Uncontested that Dr. Matzger Used Conventional Methods
`
`Stoichiometry
`
`Solvent
`
`POR 15-17; Sur-Reply 5-11; EX2103 ¶¶ 125-128;
`EX2051, 158:5-159:16
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`17
`
`Ex. 1006 at 2
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 30:12-31:5
`
`
`
`Undisputed No 1:1 Salt in What Dr. Matzger Created
`
`POR 2, 15-17; Sur-Reply 6-9, 11-12; EX 2103 ¶¶ 123-176
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`18
`
`Ex. 2103 ¶ 167; see also Ex. 2103 ¶ 156
`
`
`
`No Prior Art Process Combines Sitagliptin with Phosphoric Acid
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 15:2-12
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 50:18-51:6
`
`Sur-Reply 3, 6-9
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`19
`
`
`
`The POSA Is Not Limited to Following Example 7
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 67:4-11
`
`Sur-Reply 9-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`20
`
`
`
`The POSA Would Run a Screen to Make the Phosphate Salt
`
`Ex. 1025, Merck Expert (Matzger) Dep. Tr. at 219:1-17
`
`Sur-Reply 9-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`21
`
`
`
`The POSA Would Run a Screen to Make the Phosphate Salt
`
`Sur-Reply 5, 7-9
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`22
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 42:15-43:5
`
`
`
`Phosphate Salt Requires Many Modifications to Example 7
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 52:17-22
`
`Sur-Reply 6-9
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`23
`
`
`
`Dr. Chyall Did Not Purport to Replicate Example 7
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 13:12-19
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 23:3-11
`
`Sur-Reply 6-9
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`24
`
`
`
`Phosphate Salt Requires Many Modifications to Example 7
`
`Patent Owner’s Sur-Reply at 7-8
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`25
`
`
`
`Arbitrary to Change Other Parameters of Example 7 But Not Methanol
`
`“[T]he court finds that the defendants have failed to demonstrate that their experts’
`experiments were conducted consistent with Preparation I or that their selection
`of such variables as cooling rate, ethanol grade, and concentration, realized the
`full scope of reasonable experimental possibilities in Preparation I . . . .
`[T]he
`evidence presented at trial demonstrated that several reasonable selections were
`available to one of skill in the art and that even slight differences in procedure
`may lead to differences in the form of armodafinil produced. The defendants’
`experts, however, used a limited set of testing parameters, which, after reading
`the ’570 Patent, they would have understood to favor the formation of Form I.
`This limited testing and selection of variables, where reasonable alternatives were
`available, does not show clearly and convincingly that Form I armodafinil is the
`necessary and inevitable result of Preparation I.”
`
`In re Armodafinil Patent Litigation, 939 F. Supp 2d 456, 486 (D.Del. 2013) (internal citations omitted)
`
`POR 42, 44, 53, 54, 57; Sur-Reply 6-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`26
`
`
`
`Arbitrary to Change Other Parameters of Example 7 But Not Methanol
`
`Patent Owner’s Sur-Reply at 10-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`27
`
`
`
`The POSA Could Use Other Solvents
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 30:20-31:5
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 68:12-21
`
`Sur-Reply 9-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`28
`
`
`
`Dr. Chyall’s Experiments Not Exhaustive:
`Literature Discloses 2:1 Sitagliptin Phosphate Salt in Methanol
`
`Sur-Reply 10; EX2103 ¶¶ 120-122
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`29
`
`Ex. 2220 at 33
`
`
`
`Claims 1-3, 17, 19, 21-23:
`Obviousness
`(Ground 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`30
`
`
`
`No Motivation to Select Sitagliptin as Lead Compound
`
`therefore, never addressed any inquiry as to a lead
`“The district court,
`compound because it presumed that the prima facie obviousness case was
`Id. at 1359. Further, it is unclear from the opinion whether such an
`met.
`argument was ever presented to the district court or the Federal Circuit on
`appeal.
`In other words, the circuit court did not perform a lead compound
`analysis because the parties never disputed that amlodipine was the
`compound to be modified–they merely disputed whether it would have been
`obvious to create a besylate salt form of the compound based on the prior
`art. Id. at 1356–61. Here, however, there is a dispute as to which compound
`a POSA would have sought to modify. The ’889 application, and the ’699
`patent, both claim 601 different morpholine compounds.”
`
`Merck Sharp & Dohme Corp. v. Sandoz Inc., 2015 WL 5089543, at *39 (D.N.J. Aug. 27, 2015)
`
`POR 32-33
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`31
`
`
`
`No Motivation to Select Sitagliptin as Lead Compound
`
`“Even if one were to begin with lisdexamfetamine as a known
`chemical entity, it would still be necessary to explain why the
`skilled artisan would have picked that chemical entity out of
`all the others similarly disclosed in AU ’168. And, then, why
`would the skilled artisan have been motivated to modify
`lisdexamfetamine to make lisdexamfetamine dimesylate?”
`
`Shire LLC v. Amneal Pharm., LLC, 2014 WL 2861430, at *17 (D.N.J. June 23, 2014),
`aff’d in part and overruled on other grounds, 802 F.3d 1301 (Fed. Cir. 2015)
`
`POR 32-33; Sur-Reply 4-5
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`32
`
`
`
`No Motivation to Select Sitagliptin as Lead Compound
`
`Ex. 2113 at 1
`
`Ex. 2114 at 2
`
`Ex. 2115 at 2
`
`POR 30-31; EX2103 ¶¶ 201-209; EX2109 ¶¶ 25-31
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`33
`
`
`
`No Motivation to Select Sitagliptin as Lead Compound
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 62:1-9
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 61:2-19
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 91:8-16
`
`POR 13-14, 33-34; EX2103 ¶¶ 68-69, 77-78, 210-212
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`34
`
`
`
`No Motivation to Select Phosphate Salt
`
`“In Pfizer the asserted patent claims all related to amlodopine besylate, which
`was created to solve the known stability problems with amlodopine maleate.
`Id. at 1353–54. The Federal Circuit found the claims to be obvious in view
`of the ‘particularized facts’ of the case. Id. at 1367–68. Saliently, in Pfizer
`the court found that numerous prior art teachings specifically indicated that
`switching to the besylate salt would result in improved stability over the
`maleate salt. Id. at 1362–64. Here, however, as discussed above, Watson has
`offered no similar
`teachings
`suggesting that
`switching from the
`hydrochloride salt to the hydrobromide salt would result in a more stable
`bupropion formulation. Thus, for this and several other reasons the Court
`need not discuss, Pfizer is distinguishable and does not control here.”
`
`Valeant Int’l (Barbados) SRL v. Watson Pharm., Inc., 2011 WL 6792653, at *12 (S.D. Fla. Nov. 8, 2011)
`
`POR 10; Sur-Reply 24
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`35
`
`
`
`No Motivation to Select Phosphate Salt
`
`Ex. 1004 at 46:1-5
`
`POR 33-34; EX2013 ¶¶ 213-218
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`36
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 192:11-21, 193:21-194:6
`
`
`
`No Reasonable Expectation of Success to Obtain 1:1 Sitagliptin DHP
`
`Ex. 2051, Mylan Expert
`(Chorghade) Dep. Tr. at 105:5-15
`
`Ex. 2051, Mylan Expert
`(Chorghade) Dep. Tr. at 116:6-20
`
`POR 10; Sur-Reply 3-5; POR 37-38;
`EX2103 ¶¶ 23, 69, 230-233; EX2193, 2; EX2042, 137
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`37
`
`
`
`Claim 4:
`Crystalline Monohydrate
`(Grounds 5, 6)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`38
`
`
`
`Crystal Forms Are Unpredictable
`
`Ex. 2047 at 906
`
`Ex. 2046 at 18
`
`POR 41-46; EX2101 ¶¶ 58-64, 88-91;
`EX2170; EX2171, 7:32-37
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`39
`
`Ex. 2048 at 3:3-5
`
`
`
`Crystal Forms Are Unpredictable
`
`Ex. 2045 at 215
`
`Ex. 2045 at 215
`
`POR 41
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`40
`
`
`
`Crystal Forms Are Unpredictable
`
`“We are persuaded by the information presented by Patent
`Owner that it would have been known that preparing hydrates
`generally was unpredictable, and that information advanced by
`Petitioner provides insufficient support to establish that one
`would have had a reasonable expectation of success in
`formulating a hydrate of darunavir in particular.
`
`Lupin Ltd. v. Janssen Sciences Ireland UC, IPR2015-01030, Paper 17 at 20 (P.T.A.B. Oct. 16, 2015)
`
`• See also Argentum Pharmaceuticals LLC v. Merck Patentgesellschaft, IPR2018-00423, Paper 7 (P.T.A.B. July
`23, 2018); Application of Irani, 427 F.2d 806 (C.C.P.A. 1970); Kowa Co., Ltd. v. Amneal Pharm., 2017 WL
`10667089 (S.D.N.Y. Sept. 19, 2017); In re Armodafinil Patent Litig. Inc., 939 F. Supp. 2d 456 (D. Del. 2013);
`Takeda Pharm. Co. v. Handa Pharm., LLC, 2013 WL 9853725 (N.D. Cal. Oct. 17, 2013)
`
`POR 41-46
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`41
`
`
`
`Mylan’s Expert Concedes Existence of Monohydrate Unpredictable
`
`POR 46; Sur-Reply 16; EX2101 ¶¶ 59, 147
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`42
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 245:21-246:6
`
`
`
`Mylan’s Expert Concedes Existence of Monohydrate Unpredictable
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 257:18-258:11
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 238:8-18
`
`POR 41, 46; Sur-Reply 16; EX2101 ¶¶ 59, 149
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`43
`
`
`
`WO498 Does Not Provide Reasonable Expectation Monohydrate Exists
`
`POR 47; Sur-Reply 17; EX2101 ¶¶ 102, 136, 150-154
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`44
`
`Ex. 1004 at 9:27-10:7
`
`
`
`WO498 Does Not Provide Reasonable Expectation Monohydrate Exists
`
`Ex. 2101 ¶ 150
`
`POR 45-47, 58; Sur-Reply 17; EX2101 ¶¶ 136, 147, 150
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`45
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 200:1-6
`
`
`
`WO498 Does Not Provide Reasonable Expectation Monohydrate Exists
`
`Ex. 2283, Mylan Expert (Chorghade) Dep. Tr. at 44:8-14
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 197:22-198:9
`
`POR 47, 58; Sur-Reply 10, 17; EX2101 ¶ 153
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`46
`
`
`
`Brittain Does Not Provide Reasonable Expectation Monohydrate Exists
`
`Ex. 2101 ¶ 157
`
`POR 47-48; Sur-Reply 17-18;
`EX2101 ¶¶ 91, 105-108, 155-157
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`47
`
`
`
`Brittain Does Not Provide Reasonable Expectation Monohydrate Exists
`
`POR 47-48; Sur-Reply 17-18; EX2101 ¶ 156
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`48
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 204:12-205:7
`
`
`
`Brittain Does Not Provide Reasonable Expectation Monohydrate Exists
`
`One-sixth chance is not a reasonable expectation of success
`
`“The district court specifically found that . . . the references did not
`show that there was a reasonable expectation of success.”
`
`“Dr. Wall, a professor at UCLA, testified that it would have been
`‘difficult’ to find the gene in 1983, and that there would have been
`no more than a fifty percent chance of success. . . . We are not
`persuaded that the court erred in its decision.”
`
`Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1207-08 (Fed. Cir. 1991)
`
`POR 48-49; Sur-Reply 17-18; Lupin, IPR2015-01030,
`Paper 17, at 20-21; Grunenthal, 919 F.3d at 1343-44
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`49
`
`
`
`Crystallization Conditions Are Virtually Infinite and Unpredictable
`
`POR 50-51; Sur-Reply 19-20;
`EX2101 ¶¶ 65-90, 163-166; EX2178, 1150
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`50
`
`Ex. 2049, B67
`
`
`
`Mylan’s Expert Concedes Crystallization Is Unpredictable
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 267:7-15
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 269:11-20
`
`POR 50-51; Sur-Reply 18-19; EX2101 ¶¶ 88-89
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`51
`
`
`
`The Invention of the Monohydrate Illustrates Crystallization Unpredictability
`
`POR 5, 51-52; EX2101 ¶¶ 172-175; EX2116 ¶¶ 27, 33-36;
`EX2127 ¶¶ 33-36; EX2124 ¶¶ 9-15; EX2119, 10; EX2131,
`12-18; EX2134; EX2137; EX2138
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`52
`
`Ex. 2116 ¶ 36
`
`
`
`Mylan’s New Argument About IPA/Water Fails
`
`Ex. 2101 ¶ 163
`
`Ex. 2101 ¶ 164
`
`POR 50-51; Sur-Reply 18-21; EX2101 ¶¶ 70-90, 163-164
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`53
`
`
`
`Mylan’s New Argument About IPA/Water Fails
`
`Ex. 2101 ¶ 79
`
`Ex. 2101 ¶ 166
`
`POR 50-51; Sur-Reply 20; EX2101 ¶¶ 79-81, 164-166
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`54
`
`
`
`Mylan’s New Argument About IPA/Water Fails
`
`POR 51-52; Sur-Reply 20-21; EX2101 ¶¶ 174-175, 183-185
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`55
`
`Ex. 2101 ¶ 185
`
`
`
`General Motivation Insufficient
`
`“Here, for the reasons detailed above, Form I would not have
`been obvious because there was no more than a general
`motivation to find new crystal forms of armodafinil with
`nothing directed to the unknown Form I itself. However, for
`a patent challenger to establish obviousness, it is insufficient
`to allege a general motivation to discover an undefined
`solution that could take many possible forms.”
`
`In re Armodafinil Patent Litig. Inc., 939 F. Supp. 2d 456, 500 (D. Del. 2013)
`
`POR 53-54; Argentum, IPR2018-00423, Paper 7, at 22;
`Kowa, 2017 WL 10667089, at *29
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`56
`
`
`
`Mylan Failed to Argue Motivation
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 282:18-283:4
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 283:11-19
`
`POR 56, 59; Sur-Reply 15; EX2101 ¶ 135
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`57
`
`
`
`Mylan Failed to Perform a Lead Compound Analysis
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 189:1-8
`
`“As Dr. Zaworotko agreed, ‘[i]f the person of [ordinary] skill
`wouldn’t have had any motivation to work on darunavir, then they
`certainly wouldn’t have found any new crystal forms of it.’”
`
`Janssen Prods. L.P. v. Lupin Ltd., 109 F. Supp. 3d 650, 688-89 (D.N.J. 2014)
`
`POR 30-31, 33, 54-55; Sur-Reply 16;
`In re Depomed, 2016 WL 7163647, at *52
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`58
`
`
`
`Unexpected Monohydrate Properties:
`
`• Thermal Stability
`
`1 2 3 4
`
`• Form Stability
`
`• Minimal Sticking
`
`• Chemical Stability
`
`POR 60-64; EX2101 ¶¶ 186-214
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`59
`
`
`
`The Monohydrate Is Thermally Stable
`
`Patent Owner’s Response at 61
`
`POR 61; EX2101 ¶¶ 188-196, 200-201; EX2116 ¶ 25
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`60
`
`Ex. 1001, Fig.4
`
`Ex. 2118, Fig. 2
`
`
`
`The Monohydrate Does Not Undergo Form Conversion
`
`POR 63; EX2101 ¶¶ 203-208; EX2116 ¶¶ 39-41; EX2149,
`9-11; EX2120, 1-7; EX2117, 8:1-22; EX2119, 1-14
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`61
`
`Patent Owner’s Response at 63
`
`
`
`The Monohydrate Exhibits Formulation Advantages
`
`Ex. 2101 ¶ 210
`
`POR 64; EX2101 ¶¶ 209-10; EX2116 ¶¶ 43-44; EX2140 ¶¶
`45-48; EX2121, 1-5; EX2123, 25-26; EX2122, 38; EX2120, 1-7
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`62
`
`Ex. 2116, Fig. 18
`
`
`
`The Monohydrate Exhibits Formulation Advantages
`
`Patent Owner’s Response at 64
`
`POR 64; EX2101 ¶¶ 211-13; EX2116 ¶ 42;
`EX2140 ¶¶ 49-52; EX2123, 52-55; EX2122, 39-40
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`63
`
`Ex. 2140 ¶¶ 50-51
`
`
`
`Mylan’s Legal Criticisms Are Meritless
`
`Mylan responds that Merck should have compared the
`monohydrate to a “hydrate” of WO498. Reply at 27.
`
`“Unexpected results are shown in comparison to what was
`known, not what was unknown.”
`Millennium Pharms., Inc. v. Sandoz, Inc., 862 F.3d 1356, 1368 (Fed. Cir. 2017)
`
`Ex. 2101 ¶ 136
`
`POR 47; Sur-Reply 15, 25; EX2101 ¶¶ 102, 136, 150
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`64
`
`
`
`Mylan’s Legal Criticisms Are Meritless
`
`Mylan also criticizes Merck for only providing data for
`a “single crystalline monohydrate form.” Reply at 28.
`
`Sur-Reply 25-26; EX2101 ¶ 205; EX1031, 63:22-64:3
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`65
`
`Ex. 2101 ¶ 205
`
`
`
`WO498 Is Not Prior Art
`for Obviousness for
`Claims 1-2, 17, 19, 21-23
`(Grounds 3, 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`66
`
`
`
`Actual Reduction to Practice
`
`Claim 1 (1:1 DHP Salt)
`
`Claim 2 (R-Configuration)
`
`Claims 17 & 19 (method of treatment)
`
`Claims 21-23 (process for preparing)
`
`POR 24-26; Sur-Reply 21-22; EX2103 ¶¶ 48-53;
`EX2002 ¶¶ 9-20; EX2005 ¶¶ 4-19; EX2109 ¶¶ 12-18;
`EX2110; EX2111; EX2127 ¶¶ 16-22, 29-32; EX2135;
`EX2136; EX2140 ¶¶ 30-31; EX2153, 1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`67
`
`
`
`WO498 Does Not “Show” Hydrates
`
`Mylan argues that Merck was required to show “actual
`reduction of the hydrates taught in WO498.” Reply at 18.
`
`Ex. 1004 at 9:32-35
`
`Ex. 2101 ¶ 150
`
`POR 46-47; Sur-Reply 17
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`68
`
`
`
`WO498 Does Not “Show” Hydrates
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 197:22-198:9
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 257:18-258:11
`
`POR 46-47; Sur-Reply 16-17, 22; EX2101 ¶ 149
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`69
`
`
`
`WO498 Does Not “Show” Hydrates
`
`Ex. 2047 at 906
`
`Ex. 2046 at 18
`
`POR 41-46; EX2101 ¶¶ 58-64, 88-91;
`EX2170; EX2171, 7:32-37
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`70
`
`Ex. 2048 at 3:3-5
`
`
`
`Claim 3:
`(S)-Isomer
`(Grounds 1, 2, 3, 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`71
`
`
`
`WO498 Does Not Disclose the (S)-Isomer of Sitagliptin
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 176:18-20
`
`POR 19; Sur-Reply 12-13
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`72
`
`Ex. 1001, Claim 3
`
`Ex. 1004 at 46:1-5
`
`
`
`(S)-Isomer of 1:1 Sitagliptin DHP Not “At Once” Envisaged
`
`POR 19; Sur-Reply 12-13; EX2101 ¶¶ 42-49;
`EX2103 ¶¶ 177-180
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`73
`
`Ex. 2103 ¶ 180
`
`
`
`No Motivation to Make (S)-Isomer
`
`Ex. 2103 ¶ 255
`
`POR 38; Sur-Reply 12-13, 23
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`74
`
`
`
`Claims 17, 19:
`“Therapeutically Effective Amount”
`(Grounds 1, 2, 3, 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`75
`
`
`
`“Therapeutically Effective Amount” Claims Not Anticipated
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 186:1-11
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 187:8-13
`
`POR 19-20; Sur-Reply 13
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`76
`
`
`
`Claims 21-23:
`“Contacting One Equivalent”
`(Grounds 1, 2, 3, 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`77
`
`
`
`WO498 Does Not Use Sitagliptin Free Base
`
`POR 20-21, 38; Sur-Reply 13-14;
`EX2103 ¶¶ 185-195, 256-258
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`78
`
`Ex. 2103 ¶ 190
`
`
`
`WO498 Does Not Use a 1:1 Acid:Base Ratio
`
`POR 20-21, 38; Sur-Reply 13-14;
`EX2103 ¶¶ 185-195, 256-258
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`79
`
`Ex. 2103 ¶ 193
`
`Ex. 2103 ¶ 193
`
`
`
`WO498 Does Not Use a 1:1 Acid:Base Ratio
`
`Ex. 2051, Mylan Expert (Chorghade) Dep. Tr. at 138:1-7
`
`POR 20-21, 38; Sur-Reply 13-14
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`80
`
`
`
`Mylan’s Construction of “Contacting” as Molecular Interactions Is Improper
`
`Spectrum Int’l, Inc. v. Sterilite Corp., 164 F.3d 1372, 1380
`(Fed. Cir. 1998); In re Power Integrations, Inc., 884 F.3d
`1370, 1375-77 (Fed. Cir. 2018)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`81
`
`Patent Owner’s Sur-Reply at 14
`
`
`
`Substitution Does Not Yield Process of Claims 21-23
`
`Petition for IPR at 58
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`82
`
`
`
`Substitution Does Not Yield Process of Claims 21-23
`
`POR 20-21, 38; EX2103 ¶¶ 256-258
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`83
`
`Ex. 2103 ¶ 258
`
`
`
`Unexpected Properties:
`1:1 Sitagliptin DHP
`(Grounds 3, 4)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`84
`
`
`
`1:1 Sitagliptin DHP Exhibits Superior Combination of Properties
`
`• Particle Morphology
`
`• Low Hygroscopicity
`
`1 2 3 4
`
`• Solution Stability
`
`• Thermal Stability
`
`POR 60-64; EX2103 ¶¶ 234-253; EX2116
`¶¶ 11-26, 39-44; EX2140 ¶¶ 13-52
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`85
`
`
`
`1:1 Sitagliptin DHP Exhibits Superior Combination of Properties
`
`POR 60-64; EX2140 ¶¶ 36-37
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Ex. 2157 at 1
`
`86
`
`
`
`Mylan’s Legal Criticisms Are Meritless
`
`Mylan argues that Merck should have made comparisons to
`“other sitagliptin phosphoric acid salts” in WO498. Reply at 25.
`
`“Unexpected results are shown in comparison to what was
`known, not what was unknown.”
`Millennium Pharms., Inc. v. Sandoz, Inc., 862 F.3d 1356, 1368 (Fed. Cir. 2017)
`
`Ex. 2103 ¶ 24
`
`Sur-Reply 24-26; POR 11-13
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`87
`
`
`
`Mylan’s Legal Criticisms Are Meritless
`
`Mylan argues that anhydrous and amorphous forms of 1:1 sitagliptin
`DHP have disadvantages compared to the monohydrate. Reply at 26.
`
`Patent Owner’s Sur-Reply at 26
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`88
`
`
`
`Mylan’s Legal Criticisms Are Meritless
`
`Mylan argues that properties are not commensurate with claims,
`because Merck didn’t offer evidence on Form IV. Reply at 26.
`
`“Evidence of secondary considerations must be
`reasonably commensurate with the scope of the
`claims. . . . This does not mean that an applicant
`is required to test every embodiment within the
`scope of his or her claims.”
`
`In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (citations omitted)
`
`Sur-Reply 25-26; EX2103 ¶¶ 234-253
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`89
`
`
`
`
`
`IPR2020-00040 | Patent 7,326,708
`
`CERTIFICATION UNDER 37 C.F.R. § 42.24(d)
`
`Pursuant to 37 C.F.R. § 42.6(e), the undersigned hereby certifies that a true
`
`and correct copy of the foregoing was served on February 9, 2021, by delivering a
`
`copy via electronic mail on the following attorneys of record:
`
`Jitendra Malik
`Alissa M. Pacchioli
`Christopher W. West
`Heike S. Radeke
`KATTEN MUCHIN ROSEMAN LLP
`550 South Tryon, Street Suite 2900
`Charlotte, NC 28202-4213
`(704) 444-2000
`jitty.malik@kattenlaw.com
`alissa.pacchioli@kattenlaw.com
`christopher.west@katten.com
`heike.radeke@katten.com
`
`Jovial Wong
`Charles B. Klein
`Claire A. Fundakowski
`Zachary B. Cohen
`WINSTON & STRAWN LLP
`1901 L. Street, N.W.
`Washington, D.C. 20036
`(202) 282-5000
`Sunipr@winston.com
`
`
`
`
`
`
`
`
`
`
`
`Russell W. Faegenburg
`Tedd W. Van Buskirk
`Michael H. Teschner
`LERNER, DAVID, LITTENBERG,
`KRUMHOLZ & MENTLIK, LLP
`20 Commerce Drive
`Cranford, New Jersey 07016
`(908) 518-6367
`Rfaegenburg.ipr@ldlkm.com
`Tvanbuskirk@lernerdavid.com
`litigation@lernerdavid.com
`MTeschner.ipr@ldlkm.com
`
`
`
`/Stanley E. Fisher/
`Stanley E. Fisher
`Reg. No. 55,820
`
`
`
`3
`
`
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