IN THE 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.1
`Petitioner,
`v.
`MERCK SHARP & DOHME CORP.
`Patent Owner.
`_________________________
`Case IPR2020-00040
`U.S. Patent 7,326,708 B2
`___________________________
`
`PETITIONER’S DEMONSTRATIVE SLIDES
`
`1 Watson Laboratories, Inc. were joined as a party to this proceeding via Motion for
`Joinder in IPR2020-01045; Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s
`Laboratories, Ltd. were joined as a party 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.
`1
`
`146682996v2
`
`
`___________________
`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.1
`Petitioner,
`v.
`MERCK SHARP & DOHME CORP.
`Patent Owner.
`_________________________
`Case IPR2020-00040
`U.S. Patent 7,326,708 B2
`___________________________
`
`PETITIONER’S DEMONSTRATIVE SLIDES
`
`1 Watson Laboratories, Inc. were joined as a party to this proceeding via Motion for
`Joinder in IPR2020-01045; Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s
`Laboratories, Ltd. were joined as a party 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.
`1
`
`146682996v2
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC, et al.
`
`v.
`
`MERCK SHARP & DOHME CORP.
`
`IPR2020-00040
`
`U.S. Patent No. 7,326,708
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`1
`
`
`
`Summary of IPR Grounds: All Challenged Claims are Invalid
`
`1. Anticipation of Claims 1-3, 17, 19, and 21-23 (Slides 3-20)
`
`2. Obviousness of Claims 1-3, 17, 19, and 21-23 (Slides 21-37)
`
`3. Obviousness of Claim 4 (Slides 38-42)
`
`4. No Unexpected Results (Slides 43-48)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`2
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC, et al.
`
`v.
`
`MERCK SHARP & DOHME CORP.
`
`IPR2020-00040
`
`Anticipation: Claims 1-3, 17, 19, and 21-22
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`3
`
`
`
`The ’708 Patent: Representative Claim 1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4
`
`EX1001, col. 16; Pet. 12
`
`
`
`WO ’498 Claims Sitagliptin and its “Pharmaceutically Acceptable Salts Thereof”
`
`Dr. Matzger:
`
`“so 1:1 salts fall under the claims of the ’498 patent” EX1025, 133:18-134:9
`
`“So by looking at [Example 7’s disclosure of a 1:1 HCl salt], you can imagine that the [1:1 phosphoric acid
`salt] would exist” EX1025,146:13-147:5
`
`Pet. 3, 16-18; Reply 3-4; EX1002, ¶¶72-73
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`5
`
`
`
`WO ’498 and the ’871 Patent Share the Same Specification and the ’871 Patent is Listed in
`the Orange Book For a Product Containing Sitagliptin Phosphate Monohydrate
`
`WO498
`
`’871 Patent
`
`FDA Orange Book
`
`Pet. 5, 20
`
`Institution Order at p. 19
`
`EX1014, p. 10
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`6
`
`
`
`Example 7 of WO ’498
`
`Pet. 3-4, 28-30, 37-38; EX1004, 46:1-26, 38:15-24; EX002, ¶¶67, 76-77, 98-101; Reply 2-3; EX2051, 145:22-147:2, 92:13-18, 93:20-94:12, 149:12-150:9;
`Institution Order at 50-51.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`7
`
`
`
`Under the Same Conditions, WO ’498 Shows Only a 1:1 Sitagliptin HCl Salt Whereas Other
`Compounds Showed 1:2 Salts
`
`Pet. 20, 28; EX1002, ¶¶67, 76-77, 99; Reply 2
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`8
`
`
`
`Under the Conditions of WO ’498, Sitagliptin is Only Capable of Being Monoprotonated
`
`Pet. at 19, 29; Institution Order at 50-53; ExX016, 616–17; EX1002 ¶¶ 76, 99, 99 n.15, 147, n. 19; EX2051, 145:22-147:2,
`92:13-18, 93:20-94:12, 149:12-150:9; EX2283, 73:1-574:1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`9
`
`
`
`Merck’s Position: Under the Non-Prior Art Process of WO ’420, Sitagliptin Can Form
`Something Other than the 1:1 DHP Salt
`
`Merck’s Complete Response:
`
`Dr. Matzger
`
`Reply 8-9; EX1025, 87:21-88:17, 67:6-11, 86:4-19; 232:7-14; Merck POR pp.15-16
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`10
`
`
`
`Merck’s Position: Under the Non-Prior Art Process of WO ’420, Sitagliptin Can Form
`Something Other Than the 1:1 DHP Salt
`
`Dr. Matzger (EX2103, ¶135):
`
`Example 1 of WO420 (EX2220)
`at p.33 (Dec 2012):
`
`Dr. Matzger (EX2103, ¶113):
`
`Reply, 3-4, 8-10
`
`Of particular note, and as I discuss in more detail below with respect to claim 21, the salt
`formation step in Example 7 was conducted in methanol. . . . As such, the 1:1
`stoichiometry in Example 7 does not preclude the possibility of acids protonating
`sitagliptin at multiple sites in other reaction conditions—including in other solvents—
`thus creating non-1:1 salts.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`11
`
`
`
`Merck Position: Under the Non-Prior Art Process of WO ’420, Sitagliptin Can Form
`Something Other Than the 1:1 DHP Salt
`
`WO498 & Chyall (4063-19-01)
`
`Matzger Reproduction of WO420
`
`Methanol
`
`Isopropanol
`
`Ambient temperature
`
`No additional water
`
`Stoichiometric excess of acid to
`sitagliptin
`
`70°C for the first 15 minutes
`
`1.4mL of distilled water added
`
`2:1 stoichiometric excess of
`sitagliptin to acid
`
`Methanol and isopropanol are not equivalent solvents. EX1025,
`82:3-85:10, 96:3-8 (Dr. Matzger); Dr. Chorghade (EX1035, ¶32,
`¶¶49- 53); Atwood EX2221, ¶60 (choice of solvent would impact
`salt formation)
`Temperature matters: EX1035, ¶33, ¶¶54-55 (Dr. Chorghade);
`EX1025: 92:15-21 (Dr. Matzger); EX2221, ¶¶57-59 (Dr. Atwood);
`EX1024, 48:17-49:6 (Dr. Hansen)
`EX1035, ¶¶56-57 EX2221, ¶64
`
`EX1025: 65:15-17
`
`Dr. Matzger: Using methanol and ambient conditions: “I think, operationally, what you're describing is
`not a difficult experiment” (EX1025, 93:12-13).
`
`Q. Do you have any reason to doubt that -- in your experiments that if you had -- rather than used a 2:1
`ratio had used a 1:1 ratio that you wouldn't have gotten the 1:1 sitagliptin DHP salt?
`
`A. (Dr. Matzger): Do I -- I neither have any reasons to doubt it or believe it. I didn't do the experiment.
`
`(EX1025, 66:2-9)
`
`Reply, 8-10
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`12
`
`
`
`Merck’s EX2225: “Bear[s] on an Issue That is Already in This Proceeding”
`
`Stanley Fisher
`(Merck’s Lead Counsel):
`
`EX2041, 15:2-14; Merck’s Opposition to Teva’s Joinder Motion, IPR2020-01045, Paper 9 at 6 (“Dr. Leonard Chyall[]
`generated non-privileged data and analysis relating to the feasibility of sitagliptin accepting a second proton and
`creating non-1:1 dihydrogenphosphate salts of sitagliptin.”); EX1028, ¶¶3, 9 (“true and correct” copy); Reply, 6.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`13
`
`
`
`Merck’s EX2225: Dr. Chyall’s 12 Methanol Experiments “Bear on an Issue That is Already
`in This Proceeding”
`
`Dr. Matzger:
`
`Reply, 5-7
`
`EX2225 contains NMR
`analysis, elemental
`analysis, XRPD, and DSC
`data on these methanol
`experiments
`
`EX2103, ¶126; ¶123 (“I
`reviewed materials
`provided to me from the
`Israeli opposition against
`Patent Application No.
`172563”)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`14
`
`
`
`Merck’s EX2225: The 12 Methanol Experiments Showed That it was Not Possible to Make
`Anything Other Than 1:1 DHP Sitagliptin
`
`Reply, 5-7; EX1035, ¶24-25, ¶26, ¶¶63-67; EX2051, 148:16-19; EX2283, 22:9-21:2, 24:22-26:15
`
`EX2225, ¶¶48, 52, 72
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`15
`
`
`
`Merck’s EX2225: Dr. Chyall Reproduced the Salt Forming Step of Example 7 of WO ’498
`
`Merck’s Perceived Differences
`
`Dr. Chorghade (Representative Citations)
`
`“Starting material”
`
`“Acid base”
`
`EX1035, p.4, n.3, p.14, n.11; EX2283, 93:9-94:15, 56:19-13,
`60:4-19
`EX1035, ¶¶26, 27, 46; EX2283, 92:5-93:7
`
`“Molar ratio of acid to sitagliptin”
`
`EX1035, ¶¶26-28; EX2283, 92:5-93:7; EX1025, 220:6-21
`
`“Dropwise instead of all-at-once addition of the acid”
`
`“Concentration of the reactants”
`
`“Use of an aqueous solvent system”
`
`“Use of slurry crystallization”
`
`“Reaction time”
`
`EX1035, ¶¶36-37; EX2283, 49:9-16, 61:2-13 (“And that is the
`standard lab protocol and procedure for safety reasons, not
`necessarily scientific reasons.”)
`EX1035, ¶¶28, 34-35, 41-42; EX1025, 220:6-21, 75:2-76:16
`
`EX1035, ¶27 (“phosphoric acid always contains water”), ¶56;
`EX2283, 34:12-17, 35:2-8, 59:15-19, 94:19-96:1; EX1025,
`178:20-179:6
`
`EX1035, ¶¶38-39 (“Since the reaction was done in methanol
`and the solvent system was not changed but allowed to
`remain the same without any further intervention, this is
`nothing more than allowing the crystals to grow to a
`sufficient size to allow for analysis. EX2192, ¶85. It would not
`change the nature of salt already formed.”); EX2283, 97:4-16
`EX1035, ¶¶29-31; EX2283, 45:8-46:7. 62:9-13
`
`“Isolation of reaction products”
`
`EX1035, ¶40
`
`Reply, pp 5-7
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`16
`
`
`
`Merck’s EX2225: Dr. Chyall Reproduced the Salt Forming Step of Example 7 of WO ’498
`
`Dr. Chorghade (EX1035,
`p.14, n.11):
`
`Dr. Chyall: EX2225, ¶22:
`
`Dr. Matzger: EX2103, p.95:
`
`Reply, 1, 3, 5-8
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`17
`
`
`
`The ’708 Patent: Claims 21-23
`
`Merck’s POR at 13-
`14
`
`Contact: means an actual physical interaction between molecules:
`1. Dr. Chorghade: EX1002, ¶99 (“This reaction necessarily involves contacting the sitagliptin base molecule with the acid molecule in
`
`order to form the salt.”); ¶116 (“contacting...with” referring to molecular interactions), p.44 n.15, ¶99; EX1024, 72:25-73:12;
`
`2. Dr. Matzger: EX2103, ¶194 (“contacting a compound”), ¶258;
`3. Dr. Hansen: EX1024, 72:25-73:12 (contacting molecules); and
`4. EX1020, p.7 (“[t]he touching of two objects or surfaces”).
`
`Pet. 28-31; Reply 11-15; EX2283, 57:2-13
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`18
`
`
`
`The ’708 Patent: Claims 21-23
`
`Merck POR at 14
`
`Dr. Matzger
`(EX1025, 219:18-
`220:5):
`
`Dr. Chorghade
`(EX2283,60:4-19):
`
`Pet. pp. 28-31; Reply 11-15; EX1035, p.14, n.11, p. 4, n.3
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`19
`
`
`
`The ’708 Patent: Claims 2, 3, 17, and 19
`
`Claim Recitation
`
`Representative Citations
`
`Claim 2: The salt of claim 1 of structural formula II having the (R)-
`configuration
`
`See, e.g., Pet. 24; Reply 10
`WO ’498 depicts the (R)-configuration of sitagliptin in Claim 15 (7th
`compound)/Example 7.
`
`Claim 3: The salt of claim 1 of structural formula II having the (S)-
`configuration
`
`Claims 17/19: “therapeutically effective amount ”
`
`See, e.g., Pet. 25; Reply 10
`“[t]he compounds of the instant invention have one asymmetric center
`at the beta carbon atom” and “[e]ach such asymmetric center will
`independently produce two optical isomers” EX1004, 8:21-22, 24-27;
`9:24-26; 11:11-14; EX1002, ¶¶84-86; EX1025, 22:13-9; EX1031, 28:15-
`31:6; EX1022, 107:19-108:2.
`
`See, e.g., Pet. at 26-28, Reply 10
`“a therapeutically effective amount” as “the amount of the subject
`compound that will elicit the biological or medical response of a tissue,
`system, animal or human that is being sought by the researcher,
`veterinarian, medical doctor or other clinician.” EX1004, 11:32-35,
`Claims 19-33; 11:32-35, 13:21-33; 12:18-13:19, 23:20- 26; EX1025,
`117:22-120:1; EX1002, ¶90; EX2051, 293:16-305:11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`20
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC, et al.
`
`v.
`
`MERCK SHARP & DOHME CORP.
`
`IPR2020-00040
`
`Obviousness: Claims 1-3, 17, 19, and 21-22
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`21
`
`
`
`Merck Has Failed to Antedate WO ’498
`
`Mylan’s Reply at 15-16
`
`Merck’s Sur-Reply at 25
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Reply 15-18
`
`22
`
`
`
`WO ’498 Teaches, Discloses and Claims 1:1 DHP Sitagliptin and Hydrates Thereof
`
`WO ’498 teaches that “[s]alts in the solid form may exist in
`more than one crystal structure, and may also be in the form of
`hydrates.” EX1004: 9:32-34.
`
`Dr. Matzger
`
`EX1025 (Dr. Matzger) 133:19-134:1, 131:6-21; EX2051 (Dr. Chorghade) 306:14-307:1, 315:9-318:13; EX1002, ¶169; EX1031, 67:13-20 (Dr. Myerson); Reply at 15-18
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`23
`
`
`
`WO ’498 Teaches, Discloses and Claims 1:1 DHP Sitagliptin and Hydrates Thereof
`
`Institution Order at p.19
`
`EX1014, p10
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`24
`
`
`
`Merck Has Failed to Antedate WO ’498
`
`Merck’s Actual Reduction to Practice
`
`WO ’498
`
`– Three anhydrous forms of sitagliptin
`
`– WO ’498 Discloses and Claims
`
`DHP (EX2124, ¶9)
`
`– “no hydrates of the 1:1 DHP
`
`salt...had been identified.” EX2124,
`¶9
`
`1:1 DHP Sitagliptin and
`Hydrates Thereof.
`
`The teachings of WO ’498 and antedating claims cover all
`types of 1:1 DHP hydrates (stoichiometric and non-
`stoichiometric). EX1027; EX1026, ¶¶33-34; EX2101, ¶141;
`EX1031, 49:17-55:3, 67:13-20, 73:4-76:2; EX1025, 106:20-
`108:14, 206:5-209:13; EX1005, pp.141-154; EX1002,
`¶¶167, 169
`
`EX1026, ¶34
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Reply 15-18
`
`25
`
`
`
`Merck Has Failed to Satisfy its Burden on Antedation
`
`Reply at 17
`
`Merck’s POR at 22
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`26
`
`
`
`WO ’498 Discloses and Claims 1:1 DHP Sitagliptin and Hydrates Thereof
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`27
`
`
`
`There is No Lead Compound Requirement for a Salt Case: Otsuka Pharmaceutical Co., Ltd.
`v. Sandoz, Inc./Pfizer, Inc. v. Apotex, Inc.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Pet. 48-50; Reply 19-21
`28
`
`
`
`There is No Lead Compound Requirement for a Salt Case: Otsuka Pharmaceutical Co., Ltd.
`v. Sandoz, Inc./Pfizer, Inc. v. Apotex, Inc.
`
`Pet. 48-51; Reply 19-21; EX1004, 55, 10:8-15
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`29
`
`
`
`WO ’498 (and Bastin) Would Have Rendered the 1:1 DHP Sitagliptin Salt Obvious
`
`Pet 46-47, 51-53; Reply 21-22; EX1004, 10:8-15; EX1006 at 428; EX1002,¶150, fn. 20
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`30
`
`
`
`WO ’498’s “Particularly Preferred” List (or Cross Referencing it with Bastin (Ground 4))
`Provides a “Few” Choices, Which Include Phosphoric Acid.
`
`Pet. 46-47, 53; Reply 22
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`31
`
`
`
`Claims 2 and 3 Would Have Been Obvious
`
`Claim 15:
`
`Pet. 40-41, 56; Reply 21-22; EX1004, 8:21-27
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`32
`
`
`
`Claims 17 and 19 Would Have Been Obvious
`
`Pet. 41-43; Reply 21-22
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`33
`
`
`
`Claim 21: Would Have Been Obvious
`
`Inventor Vydra:
`
`Dr. Matzger: “as scientists typically try equimolar…
`ratios.” (EX1006 (Bastin) at 428: “[c]oncentration
`solutions of each potential counterion in equimolar
`proportion.”). EX2103, ¶126
`
`EX1032: 53:2-11
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Pet. 43-44; Reply 21-22
`34
`
`
`
`Claim 21: With Equimolar Amounts, There is No Dispute that Under any Condition, Only
`the 1:1 DHP Salt Forms
`
`Inventor Hansen:
`
`EX1024, 75:11-21
`
`Pet. 43-44; Reply 21-22; EX1024, 54:2-55:2, 71:10-72:8, 74:1-75:21; 78:6-17-80:1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`35
`
`
`
`Claim 21: With Equimolar Amounts, There is No Dispute that Under any Condition, Only
`the 1:1 DHP Salt Forms
`
`Inventor Hansen:
`
`EX1024, 78:9-17
`
`Pet. 43-44; Reply 21-22; EX1024, 54:2-55:2, 71:10-72:8, 74:1-75:21; 78:6-17-80:1
`36
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`
`Claims 22 and 23
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`37
`
`Pet. 38, 45-46; Reply, 21
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC, et al.
`
`v.
`
`MERCK SHARP & DOHME CORP.
`
`IPR2020-00040
`
`Obviousness: Claim 4
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`38
`
`
`
`The ’708 Patent: Claim 4 (Obviousness)
`
`WO ’498 teaches that “[s]alts in the solid form may exist in
`more than one crystal structure, and may also be in the form of
`hydrates.” EX1004, 9:32-34
`
`Pet. 59-63; Reply 23-25
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`39
`
`
`
`WO ’498 Discloses and Claims 1:1 DHP Sitagliptin and Hydrates Thereof
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`40
`
`
`
`The ’708 Patent: Claim 4 (Obviousness)
`
`Monohydrate
`
`Merck’s POR at 44, “[I]f any crystalline hydrate of 1:1 sitagliptin DHP forms, it is more likely to be a monohydrate
`than some other hydrate.”
`
`EX1031, 70:1-72:21. “The most commonly encountered solvates among pharmaceuticals are those of 1:1
`stoichiometry.”
`
`EX1031 (Dr. Myerson), 77:4-8: hydrates are always crystalline.
`
`Pet. 59-63; Reply 23-25
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`41
`
`
`
`The ’708 Patent: Claim 4 (Obviousness)
`
`Pet. 59-63; Reply 23-25
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`42
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC, et al.
`
`v.
`
`MERCK SHARP & DOHME CORP.
`
`IPR2020-00040
`
`No Unexpected Results
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`43
`
`
`
`No Unexpected Results: Claims 1-3, 17, 19, and 21-23
`
`Unexpected results are compared to the closest prior art, and must also be commensurate with
`the scope of the claims. Pfizer, 480 F.3d at 1370-71; In re Huai-Hung Kao, 639 F.3d 1057, 1068
`(Fed. Cir. 2011).
`
`• Drs. Matzger and Chorghade agree that the “general disclosure” and the claims of WO ’498 cover 1:1
`
`sitagliptin DHP salt and hydrates thereof. EX1025, 131:6-21, 133:19-134:1; EX1002, ¶169. EX2051, 306:14-
`307:1, 315:9-318:13; EX1002, ¶169
`
`• Merck does not provide any comparison to any “phosphoric acid” salt of WO ’498.
`
`Pet. 63-66; Reply 25-27
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`44
`
`
`
`No Unexpected Results: Claims 1-3, 17, 19, and 21-23
`
`• Dr. Matzger admitted that he had not determined the scope of the claims for his analysis. EX1025,
`
`201:21-221:1, 206:5-209:13, 210:9-213:8, 214:11-216:21.
`
`•
`
`Claims 1-3, 17, 19, and 21-23 cover crystalline and amorphous forms, as well as all hydrates thereof.
`EX1025, 203:2-204:2, 206:5-209:13; EX1031, 74:16-78:20.
`
`• Amorphous forms were “completely unsuitable for development”. EX2127, ¶20.
`
`•
`
`Form IV was ignored by Dr. Matzger. EX1025, 212:20-213:8; EX2212, page 33 (Form IV: “DEAD END”)
`
`EX2212, page 33
`
`Pet. 63-66; Reply 25-27
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`45
`
`
`
`No Unexpected Results: Claims 1-3, 17, 19, and 21-23
`
`Issue
`Instability
`
`Record Citations
`EX1022, 29:2-30:18 (Form II as “not a
`thermodynamically stable polymorph”),
`conversion
`78:16-80:21
`posed a “problem”)
`
`(spontaneous
`
`Interconversion
`
`EX1022, 33:18-34:10, 40:1-42:12, 45:2-
`47:5, 51:4-52:15
`
`Lot
`Issues
`
`Variation/Consistency
`
`EX1022, 38:2-14, 47:2-20, 49:4-11
`
`Due to inferior properties the anhydrous forms were eventually abandoned. EX1031, 90:7-
`100:21; EX2101, ¶¶202-206
`
`Pet. 63-66; Reply 25-27
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`46
`
`
`
`No Unexpected Results Claim 4: No Comparison to the Closest Prior Art
`
`Dr. Matzger, Dr. Myerson, Dr. Chorghade: the 1:1 sitagliptin DHP monohydrate and hydrates are within the
`general disclosure and claims of WO ’498. EX1025, 131:6-21, 133:19-134:1; EX2051, 306:14-307:1, 315:9-
`318:13; EX1002, ¶169; EX1031, 67:13-20.
`
`• Merck does not provide any comparison to this teaching of WO ’498.
`
`Pet. 63-66; Reply 27-28
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`47
`
`
`
`No Unexpected Results Claim 4: No Evidence of Unexpected Results Being Reasonably
`Commensurate in Scope
`
`• Merck offers no opinion based on Merck’s single monohydrate whether another monohydrate form
`
`would have the same alleged unexpected properties. EX1031, 64:4-11; EX2101, ¶¶187-214 (not
`opining that any unexpected results would be commensurate in scope with Claim 4).
`
`Pet. 63-66; Reply 27-28
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`48
`
`
`
`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 Petitioner’s Demonstrative Slides were served by February 9,
`
`2021, by delivering a copy via electronic mail on the following attorneys of record.
`
`sfisher@wc.com
`
`jberniker@wc.com
`
`smahaffy@wc.com
`
`asheh@wc.com
`
`bgenderson@wc.com
`
`ebaumgarten@wc.com
`
`azolan@wc.com
`
`jwong@winston.com
`
`ZCohen@winston.com
`
`CKlein@winston.com
`
`Cfundakowski@winston.com
`
`rfaegenburg@lernerdavid.com
`
`tvanbuskirk@lernerdavid.com
`
`mteschner@lernerdavid.com
`
`/s Jitendra Malik/
`Jitendra Malik, Ph.D. (Reg. No. 55,823)
`
`
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