`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`___________________
`
`
`HOPEWELL PHARMA VENTURES, INC.,
`Petitioner
`v.
`MERCK SERONO S.A.,
`Patent Owner
`
`___________________
`
`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`___________________
`
`
`PETITIONER HOPEWELL PHARMA VENTURES, INC.’S
`UPDATED 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 IPR2023-00481
`U.S. Patent No. 8,377,903
`Petitioner Hopewell Pharma Ventures, Inc. (“Petitioner”) files this Updated
`
`
`
`Exhibit List to accompany filing of Exhibit 1092, Petitioner’s Demonstratives for
`
`Oral Argument.
`
`1001
`
`1002
`1003
`1004
`1005
`1006
`
`1007
`
`1008
`
`1009
`
`Exhibit No. Description
`De Luca, G., et al., “Cladribine Regimen for Treating Multiple
`Sclerosis,” U.S. Patent No. 8,377,903 B2 (filed April 23, 2010;
`issued February 19, 2013)
`Declaration of Aaron Miller, M.D.
`Curriculum Vitae for Aaron Miller, M.D.
`File History for U.S. Patent No. 8,377,903
`Intentionally Left Blank
`Noseworthy, J.H., et al., “Multiple Sclerosis,” The New England
`Journal of Medicine, 343(13):938-952 (2000)
`Neuhaus, O., et al., “Immunomodulation in multiple sclerosis:
`from immunosuppression to neuroprotection,” TRENDS in
`Pharmaceutical Sciences, 24(3):131-138 (2003)
`Weiner, H.L., et al., “Immunotherapy of Multiple Sclerosis,”
`Annals of Neurology, 23(3):211-222 (1988)
`Wingerchuk, D.M., et al., “Biology of Disease, Multiple
`Sclerosis: Current Pathophysiological Concepts,” Laboratory
`Investigation, 81(3):263-281 (2001)
`Kurtzke, J.F., “Rating neurologic impairment in multiple
`sclerosis: An expanded disability status scale (EDSS),”
`Neurology, 33:1444-1452 (1983)
`Intentionally Left Blank
`Whitaker, J.N., “Rationale for Immunotherapy in Multiple
`Sclerosis,” Annals of Neurology, 36:S103-S107 (1994)
`Stelmasiak, Z., et al., “A pilot trial of cladribine (2-
`chlorodeoxyadenosine) in remitting-relapsing multiple sclerosis,”
`Medical Science Monitor, 4(1):4-8 (1998)
`Beutler, E., et al., “The treatment of chronic progressive multiple
`sclerosis with cladribine,” Proceedings of the National Academy
`of Sciences, USA 93:1716-1720 (1996)
`Tortorella, C., et al., “Cladribine Ortho Biotech Inc,” Current
`Opinion in Investigational Drugs, 2(12):1751-1756 (2001)
`
`1010
`
`1011
`1012
`
`1013
`
`1014
`
`1015
`
`- 1 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`Exhibit No. Description
`Langtry, H.D., et al., “Cladribine, A Review of its Use in
`1016
`Multiple Sclerosis,” BioDrugs, 9(5):419-433 (1998)
`Rudick, R.A., et al., “Management of Multiple Sclerosis,” The
`New England Journal of Medicine, 337(22):1604-1611 (1997)
`Rice, G.P.A., et al., “Cladribine and progressive MS, Clinical and
`MRI outcomes of a multicenter controlled trial,” Neurology,
`54:1145-1155 (2000)
`Barkhof, R., et al., “Limited duration of the effect of
`methylprednisolone on changes on MRI in multiple sclerosis,”
`Neuroradiology, 36:382-387 (1994)
`Pirko, I. and Rodriguez, M., “Pulsed Intravenous
`Methylprednisolone Therapy in Progressive Multiple Sclerosis:
`Need for a Controlled Trial,” Archives of Neurology, 61:1148-
`1149 (2004)
`Weiner, H.L., et al., “Intermittent cyclophosphamide pulse
`therapy in progressive multiple sclerosis: Final report of the
`Northeast Cooperative Multiple Sclerosis Treatment Group,”
`Neurology, 43:910-918 (1993)
`Bodor, N. and Dandiker, Y., “Oral Formulations of Cladribine,”
`International Publication No. WO 2004/087101 A2 (filed March
`26, 2004; published October 14, 2004)
`Grieb, P., et al., “Effect of Repeated Treatments with Cladribine
`(2-Chlorodeoxyadenosine) on Blood Counts in Multiple Sclerosis
`Patients,” Archivum Immunologiae Experimentalis, 43:323-327
`(1995)
`Schultz, T.W., et al., “Cyclodextrine Cladribine Formulations,”
`U.S. Patent No. 6,194,395 B1 (filed February 25, 1999; issued
`February 27, 2001)
`File History for U.S. Patent No. 7,713,947
`Beutler, E., “Use of Substituted Adenine Derivatives for Treating
`Multiple Sclerosis,” U.S. Patent No. 5,506,214 B2 (filed February
`18, 1993; issued April 9, 1996)
`Docket Report, Merck KGaA et al. v. Hopewell Pharma Ventures,
`Inc., Case No. 1:22-cv-01365-GBW (D.Del.)
`Docket Report, Merck KGaA et al. v. Accord Healthcare, Inc.,
`Case No. 1:22-cv-00974-GBW (D.Del.)
`United States District Courts - National Judicial Caseload Profile,
`June 2022
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`- 2 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`Exhibit No. Description
`Curriculum Vitae for Nancy E. Adams, Ed.D.
`1030
`Romine, J. S., et al., “A Double-Blind, Placebo-Controlled,
`Randomized Trial of Cladribine in Relapsing-Remitting Multiple
`Sclerosis,” Proceedings of the Association of American
`Physicians, 111(1):35-44 (1999)
`Docket Report, Merck KGaA et al. v. Aurobindo Pharma USA,
`Inc., et al., Case No. 1:23-cv-00039-GBW (D.Del.)
`Bloom, P.M., “Treatment of Multiple Sclerosis with
`Lymphocytapheresis and Chemo-Immunosuppression,” U.S.
`Patent No. 4,964,848 (filed June 27, 1988; issued October 23,
`1990)
`Order Regarding Motion to Stay, Merck KGaA et al. v. Accord
`Healthcare, Inc. et al., Case No. 1:22-cv-00974 (D. Del.),
`December 15, 2022
`Stipulation and [Proposed] Order Staying Litigation with Respect
`to Accord Healthcare, Inc., Merck KGaA et al. v. Accord
`Healthcare, Inc. et al., Case No. 1:22-cv-00974 (D. Del.),
`December 14, 2022
`Lassmann, H., et al., “Heterogeneity of multiple sclerosis
`pathogenesis: implications for diagnosis and therapy,” TRENDS
`in Molecular Medicine, 7(3):115-121 (March 2001)
`Lublin, F. D., et al., “Defining the clinical course of multiple
`sclerosis: Results of an international survey,” Neurology, 46:907-
`911 (1996)
`Casanova, B., et al., “High clinical inflammatory activity prior to
`the development of secondary progression: a prospective 5-year
`follow-up study,” Multiple Sclerosis, 8:59-63 (2002)
`Publisher's Record for Stelmasiak (EX1013)
`Declaration of Nancy E. Adams, Ed.D.
`Intentionally Left Blank
`Shurkovich, S., et al., “Randomized study of antibodies to INF-γ
`and TNF-α in secondary progressive multiple sclerosis,” Multiple
`Sclerosis, 7:277-84 (2001)
`Khoury, S. J., “Multiple Sclerosis: What Have We Learned From
`Magnetic Resonance Imaging Studies?,” Archives of Internal
`Medicine, 158:565-73 (1998)
`Roitt, I. M., “Essential Immunology, Sixth Edition,” Blackwell
`Scientific Publications, 1-29 (1988) (Excerpt)
`
`1039
`1040
`1041
`
`1036
`
`1037
`
`1038
`
`1042
`
`1043
`
`1044
`
`- 3 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1045
`
`1046
`
`1047
`
`1048
`1049
`1050
`
`1051
`
`1052
`
`1053
`
`Exhibit No. Description
`Filippi, M., et al., “The effect of cladribine on T1 'black hole'
`changes in progressive MS,” Journal of Neurological Sciences,
`176:42-44 (2000)
`Romine, J. S., et al., “Cladribine: Use in Therapy of Multiple
`Sclerosis,” Biodrugs, 7(5):386-93 (1997)
`Selby, R., et al., “Safety and Tolerability of Subcutaneous
`Cladribine Therapy in Progressive Multiple Sclerosis,” Canadian
`Journal of Neurological Sciences, 25:295-99 (1998)
`Liliemark, J., “The Clinical Pharmacokinetics of Cladribine,”
`Clinical Pharmacokinetics, 32(2):120-31 (1997)
`Intentionally Left Blank
`Intentionally Left Blank
`U.S. Patent and Trademark Office, Memorandum, Interim
`Procedure for Discretionary Denials in AIA Post-Grant
`Proceedings with Parallel District Court Litigation (June 21,
`2022)
`Supplemental Declaration of Aaron Miller, M.D. (served not
`filed)
`Declaration of Christina E. Dashe in Support of Motion for Pro
`Hac Vice Admission
`Declaration of John Christopher Rozendaal in Support of Motion
`for Pro Hac Vice Admission
`IVAX Corporation Form 10-K for Fiscal Year 2003
`IVAX Corporation Form 10-K for Fiscal Year 2004
`File History for U.S. Patent No. 7,888,328 to Bodor et al.
`File History for U.S. Patent No. 8,785,415 to Bodor et al.
`Transcript of the Deposition of Nicholas S. Bodor. Ph.D.
`(CONFIDENTIAL – PROTECTIVE ORDER MATERIAL)
`Transcript of the Deposition of Yogesh Dandiker, Ph.D.
`(CONFIDENTIAL – PROTECTIVE ORDER MATERIAL)
`Transcript of the Deposition of Fred D. Lublin, M.D.
`Transcript of the Deposition of Dr. Bernd Meibohm
`Transcript of the Deposition of Alain Munafo, Ph.D.
`(CONFIDENTIAL – PROTECTIVE ORDER MATERIAL)
`Albertioni, F., et al., “On the bioavailability of 2-chloro-2’-
`deoxyadenosine (CdA),” European Journal of Clinical
`Pharmacology, 44:579-582 (1993)
`
`1054
`1055
`1056
`1057
`1058
`1059
`
`1060
`1061
`1062
`1063
`
`1064
`
`- 4 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1066
`
`1067
`
`1068
`
`Exhibit No. Description
`Kottke, M.K., et al., “Tablet Dosage Forms,” Chapter 10 of
`1065
`Modern Pharmaceutics¸4th Ed., Banker, G.S., et al., eds. (2002)
`“Biopharmaceutical Drug Delivery,” BioPharm International
`(August 1, 2004), accessible at
`https://www.biopharminternational.com/view/biopharmaceutical-
`drug-delivery-0 (last accessed February 26, 2024)
`Brewster, M.E., et al., “Applications of chemically-modified
`cyclodextrins: use of hydroxypropyl-β-cyclodextrin as an
`enabling excipient for brain targeting, redox-based derivatives of
`estradiol, A review of preclinical and clinical findings,” Journal
`of Drug Delivery Science and Technology, 14(1):21-34 (2004)
`Davis, M.E., et al., “Cyclodextrin-Based Pharmaceutics: Past,
`Present, and Future,” Nature Reviews, 3:1023-1035 (December
`2004)
`Hellriegel, E.T., et al., “Interpatient variability in bioavailability is
`related to the extent of absorption: Implications for bioavailability
`and bioequivalence studies,” Clinical Pharmacology &
`Therapeutics, 60(6):601-607 (December 1996)
`Leuner, C., et al., “Improving drug solubility for oral delivery
`using solid dispersions,” European Journal of Pharmaceutics and
`Biopharmaceutics, 50:47-60 (2000)
`Martinez, M.N., et al., “A Mechanistic Approach to
`Understanding the Factors Affecting Drug Absorption: A Review
`of Fundamentals,” Journal of Clinical Pharmacology¸ 42:620-
`643 (2002)
`Munafo, A., Tran, D., Marcus, S., Ammoury, N.,
`“Pharmacokinetics
`of
`oral
`cladribine
`(Mylinax)
`after
`administration
`in patients with multiple sclerosis,” Serono
`International S.A., Geneva, Switzerland, Bourn Hall Clinic,
`Cambridge, UK, Ivax Corp Inc., Miami, USA.
`Rajewski, R.A., et al., “Pharmaceutical Applications of
`Cyclodextrins,” Journal of Pharmaceutical Sciences, 85(11)1142-
`1169 (November 1996)
`Saven, A., et al., “Pharmacokinetic Study of Oral and Bolus
`Intravenous 2-Chlorodeoxyadenosine in Patients With
`Malignancy,” Journal of Clinical Oncology¸ 14(3):978-983
`(March 1996)
`
`1069
`
`1070
`
`1071
`
`1072
`
`1073
`
`1074
`
`- 5 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1075
`
`1076
`
`1077
`
`1078
`
`1080
`1081
`
`Exhibit No. Description
`Schultz, T.W., et al., “Cyclodextrin Cladribine Formulations,”
`U.S. Patent No. 6,194,395 B1 (filed February 25, 1999; issued
`February 27, 2001)
`Chapters 2, 5, 6, 10 from Shargel, L., et al., Applied
`Biopharmaceutics & Pharmacokinetics¸4th Ed. (1999)
`Loftsson, T., et al., “2-Hydroxypropyl-β-cyclodextrin: Properties
`and Usage in Pharmaceutical Formulations,” PZ Wissenschaft,
`136(1):5-10 (January 1991)
`Sietsema, W.K., “The absolute oral bioavailability of selected
`drugs,” International Journal of Clinical Pharmacology, Therapy,
`and Toxicology, 27(4):179-211 (1989)
`Hermann, R., “The Clinical Pharmacology of Cladribine Tablets
`for the Treatment of Relapsing Multiple Sclerosis,” Clinical
`Pharmacokinetics, 58:283-297 (2019)
`Declaration of Rodolfo Pinal, Ph.D. (CONFIDENTIAL –
`PROTECTIVE ORDER MATERIAL)
`Curriculum Vitae of Rodolfo Pinal, Ph.D.
`Chumlea, W.C., “Total body water data for white adults 18 to 64
`years of age: The Fels Longitudinal Study,” Kidney International,
`56:244-252 (1999)
`Sipe, J.C., et al., “A neurologic rating scale (NRS) for use in
`multiple sclerosis,” Neurology, 34:1368-1372 (October 1984).
`Second Declaration of Aaron Miller, M.D. (CONFIDENTIAL –
`PROTECTIVE ORDER MATERIAL)
`Second Supplemental Declaration of Aaron Miller, M.D. (served
`not filed)
`Supplemental Declaration of Rodolfo Pinal, Ph.D. (served not
`filed)
`Errata and Acknowledgement for the Transcript of the Deposition
`of Nicholas S. Bodor. Ph.D. (CONFIDENTIAL – PROTECTIVE
`ORDER MATERIAL) (served not filed)
`Errata and Acknowledgement for the Transcript of the Deposition
`of Yogesh Dandiker, Ph.D. (CONFIDENTIAL – PROTECTIVE
`ORDER MATERIAL) (served not filed)
`Errata and Acknowledgement for the Transcript of the Deposition
`of Fred D. Lublin, M.D. (served not filed)
`Errata and Acknowledgement for the Transcript of the Deposition
`of Dr. Bernd Meibohm (served not filed)
`
`1079
`
`1082
`
`1083
`
`1084
`
`1085
`
`1086
`
`1087
`
`1088
`
`1089
`
`1090
`
`- 6 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`
`1091
`
`Exhibit No. Description
`Errata and Acknowledgement for the Transcript of the Deposition
`of Alain Munafo, Ph.D. (CONFIDENTIAL – PROTECTIVE
`ORDER MATERIAL) (served not filed)
`Petitioner’s Demonstratives for Oral Argument
`(CONFIDENTIAL – PROTECTIVE ORDER MATERIAL)
`
`1092
`
`
`
`Respectfully submitted,
`
`STERNE, KESSLER, GOLDSTEIN & FOX PLLC
`
`/Eldora L. Ellison/
`Eldora L. Ellison, Ph.D., Esq.
`Registration No. 39,967
`Lead Attorney for Petitioner
`
`Date: June 20, 2024
`1101 K Street, NW, 10th Floor
`Washington, DC 20005
`(202) 371-2600
`
`- 7 -
`
`

`

`Case IPR2023-00481
`U.S. Patent No. 8,377,903
`CERTIFICATE OF SERVICE (37 C.F.R. § 42.6(e))
`I certify that the above-captioned PETITIONER HOPEWELL PHARMA
`
`VENTURES, INC.’S UPDATED EXHIBIT LIST and EXHIBIT 1092 were
`
`served in their entireties on June 20, 2024, upon the following parties via electronic
`
`mail:
`
`Emily R. Whelan (Lead Counsel) Emily.Whelan@wilmerhale.com
`Deric Geng (Back-up Counsel) Deric.Geng@wilmerhale.com
`Cindy Kan (Back-up Counsel) Cindy.Kan@wilmerhale.com
`David B. Bassett (Back-up Counsel) David.Bassett@wilmerhale.com
`Vinita Ferrera (Back-up Counsel) Vinita.Ferrera@wilmerhale.com
`David Mlaver (Back-up Counsel) David.Mlaver@wilmerhale.com
`Mary.Pheng (Back-up Counsel) Mary.Pheng@wilmerhale.com
`Asher McGuffin (Back-up Counsel) Asher.McGuffin@wilmerhale.com
`Scott Bertulli (Back-up Counsel) Scott.Bertulli@wilmerhale.com
`WILMER CUTLER PICKERING HALE AND DORR LLP
`WHMerckMavencladIPRs@wilmerhale.com
`
`Respectfully submitted,
`
`STERNE, KESSLER, GOLDSTEIN & FOX PLLC
`
`/Eldora L. Ellison/
`
`Eldora L. Ellison, Ph.D., Esq.
`Registration No. 39,967
`Lead Attorney for Petitioner
`
`Date: June 20, 2024
`1101 K Street, NW, 10th Floor
`Washington, DC 20005
`(202) 371-2600
`
`22573247.1
`
`