Details for Patent: 9,402,874

Title:	Low frequency glatiramer acetate therapy
Abstract:	A method of alleviating a symptom of relapsing-remitting multiple sclerosis in a human patient suffering from relapsing-remitting multiple sclerosis or a patient who has experienced a first clinical episode and is determined to be at high risk of developing clinically definite multiple sclerosis comprising administering to the human patient three subcutaneous injections of a therapeutically effective dose of glatiramer acetate over a period of seven days with at least one day between every subcutaneous injection so as to thereby alleviate the symptom of the patient.
Inventor(s):	Klinger; Ety (Tel Aviv, IL)
Assignee:	YEDA RESEARCH & DEVELOPMENT CO., LTD. (Rehovot, IL)
Filing Date:	Mar 30, 2015
Application Number:	14/673,257
Claims:	1.sub.--suppl/S1.citation> submitted as Exhibit 1037 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Ford et al., "A Prospective Open-Label Study of Glatiramer Acetate: Over a Decade of Continuous Use in Multiple Sclerosis Patients", 12 Multiple Sclerosis, 309-320 (2006), submitted as Exhibit 1038 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Manso et al., "Life Cycle Management of Ageing Pharmaceutical Assets", 3:7 Pharmaceutical Law Insight, (2006), submitted as Exhibit 1041 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Almeida et al., "Localized Panniculitis Secondary to Subcutaneous Glatiramer Acetate Injections for the Treatment of Multiple Sclerosis: A Clinicopathologic and Immunohistcchemical Study", J. Am. Acad. Dermatol 55:968-74 (2006), submitted as Exhibit 1042 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Klauer and Zettl, "Compliance, Adherence and the Treatment of Multiple Sclerosis", J. Neurol. 255 [Supp1.6]:87-92 (2008), submitted as Exhibit 1043 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Teva Provides Update on Forte Trial, published on Jul. 7, 2008 at Jerusalem, Israel by Teva Pharmaceutical Industries Ltd. submitted as Exhibit 1046 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Interferon Beta 1b (Extavia.RTM.), Abbreviated National Drug Monograph, published Sep. 2010 by VA Pharmacy Benefits Management Services, Medical Advisory Panel and VISN Pharmacist Executives, submitted as Exhibit 1053 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Copaxone.RTM., Food and Drug Administration Approved Labeling, Jan. 2014, submitted as Exhibit 1057 in Inter Partes Review Case No. IPR2015-00643. cited by applicant . Thixia, "Copaxone". In Multiple Sclerosis All about MS [online], Apr. 11, 2008 [retrieved on Feb. 5, 2015]. Retrieved from the Internet: <URL:scamparoo.wordpress.com/2008/04/11/ms-therapies-copaxone/>, submitted as Exhibit 1058 in Inter Partes Review Case No. IPR2015-00643, and Exhibit 1062 in Inter Partes Review Case Nos. IPR2015-00644. cited by applicant . Guidance for Industry Population Pharmacokinetics [online]. Food and Drug Administration, Feb. 1999 [retrieved on Jun. 23, 2015]. Retrieved from the Internet: <URL:www.fds.gov/downloads/Drugs/Guidances/UCM072137.pdf>, submitted at Exhibit 1063 in IPR2015-00643 and Exhibit 1059 in Inter Partes Review Case Nos. IPR2015-00644 and IPR2015-00830. cited by applicant . Mar. 25, 2013 Office Action, issued in connection with Taiwanese Patent Application No. 100103482 together with an English language translation thereof. cited by applicant . Sep. 25, 2013 Communication in Response to Mar. 25, 2013 Office Action, filed in connection with Taiwanese Patent Application No. 100103482 together with an English language translation thereof. cited by applicant . Feb. 25, 2014 Office Action, issued in connection with Mexican Patent Application No. Mx/a/2012/000687 together with an English language summary thereof. cited by applicant . Jun. 25, 2014 Amendment in Response to Feb. 25, 2014 Office Action, filed in connection with Mexican Patent Application No. Mx/a/2012/000687 together with an English language translation thereof. cited by applicant . Oct. 10, 2014 Office Action, issued in connection with Mexican Patent Application No. Mx/a/2012/000687 together with an English language summary thereof. cited by applicant . Dec. 19, 2014 Amendment in Response to Oct. 20, 2014 Office Action, filed in connection with Mexican Patent Application No. Mx/a/2012/000687 together with an English language translation thereof. cited by applicant . Mar. 4, 2015 Office Action, issued in connection with Mexican Patent Application No. Mx/a/2012/000687 together with an English language summary thereof. cited by applicant . Dec. 11, 2014 Amendment in Response to Aug. 11, 2014 Official Action, filed in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Aug. 11, 2014 Office Action, issued in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Mar. 21, 2014 Office Action, issued in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Jul. 21, 2014 Amendment in Response to Mar. 21, 2014 Official Action, filed in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Feb. 14, 2014 Amendment in Response to Oct. 16, 2013 Office Action, filed in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Oct. 16, 2013 Office Action, issued in connection with Eurasian Patent Application No. 201270167 together with an English language translation thereof. cited by applicant . Aug. 19, 2014 Office Action, issued in connection with Japanese Patent Application No. 2012-520598 together with an English language translation thereof. cited by applicant . Dec. 19, 2014 Amendment in Response to Aug. 19, 2014 Office Action, filed in connection with Japanese Patent Application No. 2012-520598 together with an English language translation thereof. cited by applicant . Jul. 18, 2013 Application to Amend a Complete Specification, filed in connection with South African Application No. 2012/00586 (Klinger). cited by applicant . Jan. 15, 2015 Official Action Issued in Connection With Canadian Application No. 2,760,802, filed Aug. 19, 2012 (Klinger). cited by applicant . Sep. 23, 2014 Reply to Oppositions filed against EP2405739B in the name of Yeda Research Development Co Ltd. By Activis Group PTC ehf and others in connection with European Application No. 10810282.3 (Klinger). cited by applicant . Jun. 4, 2015 Amendment in Response to Jan. 7, 2014 Official Action filed in Connection With Japanese Application No. 2012-525530, filed Feb. 20, 2012 (Klinger) together with an English translation thereof. cited by applicant . May 26, 2015 Yeda's Patent Owner Preliminary Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,232,250 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00643). cited by applicant . May 26, 2015 Yeda's Patent Owner Preliminary Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,399,413 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00644). cited by applicant . Jun. 19, 2015 Yeda's Patent Owner Preliminary Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,969,302 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00830). cited by applicant . Teva Provides Update on Forte Trial, published on Jul. 7, 2008 at Jerusalem, Israel by Teva Pharmaceutical Industries Ltd., submitted as Exhibit 2001 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Franscisco J. Quintana et al., "Systems Biology Approaches for the Study of Multiple Sclerosis", 12 J. Cell. Mol. Med. 4, 1087-93 (2008), submitted as Exhibit 2002 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . David J. Virley, "Developing Therapeutics for the treatment of multiple sclerosis", 2 The Journal of the American Society for Experimental NeuroTherapeutics, 638-49 (Oct. 2005), submitted as Exhibit 2003 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Manuel A. Friese et al., "The value of animal models for drug development in multiple sclerosis", 129 Brain, 1940-52 (2006), submitted as Exhibit 2004 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2105-00644 and IPR2015-00830. cited by applicant . Copaxone.RTM., Food and Drug Administration Approved Labeling, Jan. 2014, submitted as Exhibit 2005 in Inter Partes Review Case Nos. 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Oliver Neuhaus et al., "Pharmacokinetics and pharmacodynamics of the interferon-betas, glatiramer acetate, and mitoxantrone in multiple sclerosis", 259 Journal of the Neurological Sciences, 27-37 (2007), submitted as Exhibit 2012 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Oded Abramsky et al., "Effect of a Synthetic Polypeptide (COP 1) on Patients With Multiple Sclerosis and With Acute Disseminated Encephalomyelitis. Preliminary Report", 31 Journal of the Neurological Sciences, 433-38 (1977), submitted as Exhibit 2013 in Inter Partes Review Case Nos. IPR2015-0C643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Murry B. Bornstein et al., "Treatment of Multiple Sclerosis with a Synthetic Polypeptide: Preliminary Results", in Transactions of the American Neurological Association, 1980, vol. 105 (New York, Springer Publishing Company), pp. 348-50, submitted as Exhibit 2014 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Murry B. Bornstein et al., "Treatment Multiple Sclerosis: Trial of a Synthetic Polypeptide", 11 Ann. Neurol., 317-19 (Mar. 1982), submitted as Exhibit 2015 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Murry B. Bornstein et al., "A Pilot Trial of COP 1 in Exacerbating-Remitting Multiple Sclerosis", 13 N. Engl. J. Med., 408-14 (Aug. 13, 1987), submitted as Exhibit 2016 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Table of Contents--Sep. 2008; 14(1 suppl) [online]. Sage Journals [retrieved May 22, 2015]. Retrieved from the Internet: <URL msj.sagepub.com/content/14/1.sub.--suppl.toc>, submitted as Exhibit 2017 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Massimo Filippi et al., "Effects of oral glatiramer acetate on clinical and MRI monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo- controlled study", Lancet Neurol. Jan. 20, 2006 [online], Retrieved from the Internet <URL:neurology.thelancet.com> <DOI:10.1016/S1474-4422(06)70327-1>, submitted as Exhibit 2018 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . Yuval Ramot et al., "Comparative Long-Term Preclinical Safety Evaluation of Two Glatiramoid Compounds (Glatiramer Acetate, Copaxonel, and TV- 5010, Protiramer) in Rats and Monkeys", 40 Toxicol. Path., 40-54 (2012), submitted as Exhibit 2019 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 and IPR2015-00830. cited by applicant . U.S. Patent Application No. 2007/0161566 A1 ("Pinchasi"), submitted as Exhibit 2020 in inter Partes Review Case Nos. 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"News Release, Teva to Present Positive Data for Glatiramer Acetate 40 mg/lml Given Three Times Weekly for Relapsing-Remitting MS" [online] Teva Pharmaceutical Industries Ltd. Oct. 10, 2012 [retrieved on Apr. 2, 2013]. Retrieved from the Internet: <URL://www.tevapharm.com/Media/News/Pages/2012/1743500.aspx?year=2012&- page . . . >, submitted as Exhibit D9 of Opposition filed against EP2405749B. cited by applicant . Kahn et al, "Late Breaking News II: A phase 3 trial to assess the efficacy and Safety of glatiramer acetate injections 40mg administered 3 times a week compared to placebo", abstract presented on Oct. 13, 2012 at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis held at Lyon France on Oct. 10-13, 2012, submitted as Exhibit D10 of Opposition filed against EP2405749B. cited by applicant . "Copaxone 20mg/ml, Solution for Injection, Pre-filled Syringe" [online] Teva Pharmaceutical Ltd., Feb. 3, 2009 [retrieved on Jan. 27, 2013]. Retrieved from the Internet: <URL://www.medicines.org.uk/EMC/printfriendlydocument.aspx?documentid=- 17516>>, submitted as Exhibit D11 of Opposition filed against EP2405749B. cited by applicant . PCT International Application Publication No. WO 2005/00120542, Published Dec. 22, 2005 (Rasmussen at al.), submitted as Exhibit D12 of Opposition filed against EP2405749B. cited by applicant . US Application Publication No. 2005-0014696, published Jan. 20, 2005 (Yong et al.), submitted as Exhibit D13 of Opposition filed against EP2405749B. cited by applicant . US Application Publication No. 2009-0149541, published Jun. 11, 2009 (Stark et al.), submitted as Exhibit D14 of Opposition filed against EP2405749B. cited by applicant . Yong et al. "Immunological response to different doses of GA in MS: Analyses from the FORTE trial" dated Apr. 28 2009, Abstract only, submitted as Exhibit D15 of Opposition filed against EP2405749B. cited by applicant . Jul. 1, 2009 Response to Apr. 2, 2009 Final Office Action filed with the U.S. Patent and Trademark Office in connection with U.S Appl. No. 11/651,212, submitted as Exhibit D16 of Opposition filed against EP2405749B. cited by applicant . International Application Publication No. WO 00/18794, published Apr. 6, 2000 (Gad et al.), submitted as Exhibit D17 of Opposition filed against EP2405749B. cited by applicant . Sep. 13, 2012 Response to Aug. 8, 2015 Communication pursuant to Article 94(3) EPC filed with the European Patent Office in connection with European Patent Application No. 10810282.3, submitted as Exhibit D18 of Opposition filed against EP2405749B. cited by applicant . Comi et al. "Results from a phase II, 1-year, Randomized, Double- blind, Parallel-Group, Dose Comparison Study with Glatiramer Acetate in Relapsing-remitting Multiple Sclerosis", abstract at the World Congress on Treatment and Research in Multiple Sclerosis--Montreal 2008, presented on Sep. 20, 2008, [online] [retrieved on Aug. 21, 2015]. Retrieved from the Internet: <URL://www.multiwebcast.com/wctrims/2008/msmontreal/2448/chair.giancar- lo.comi.r . . . >submitted as Exhibit D19 of Opposition filed against EP2405749B. cited by applicant . Slides of G. Comi, Forte: Results from a phase II, 1-year, Randomized, Double-blind, Parallel-Group, Dose Comparison Study with Glatiramer Acetate in Relapsing-remitting Multiple Sclerosis, Presented at World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American, European, and Latin America Committees on Treatment and Research in Multiple Sclerosis, San Raffaele, Italy (ACTRIMS, ECTRIMS, LACTRIMS) (2008), submitted as Exhibit D19a of Opposition filed against EP2405749B. cited by applicant . Oct. 2, 2015 Expert Report of Dr Simon Day, submitted as Exhibit D20 of Opposition filed against EP2405749B. cited by applicant . "News Release: Teva Initiates Phase III Study to Confirm Increased Efficacy of Higher Dose of Glatiramer Acetate for the Treatment of Relapsing-Remitting Multiple Sclerosis" [online] Teva Pharmaceutical Industries Ltd., Jul. 27, 2006 [retrieved on Apr. 6, 2015]. Retrieved from the Internet: <URL://ir.tevapharm.com/phoenix.zhtml?c=73925&p=irol-newsArticle&ID=15- 57343>, submitted as Exhibit D21 of Opposition filed against EP2405749B. cited by applicant . "News Release: Data Published in Neurology Showed That Higher Dose of Copaxone.RTM. Increased Efficacy in Relapsing-Remitting Multiple Sclerosis (Rrms)" [online] Teva Pharmaceutical Industries Ltd., Apr. 17, 2007 [retrieved on Apr. 6, 2015]. Retrieved from the Internet: <URL://ir.tevapharm.com/phoenix.zhtml?c=73925&p=irol-newsArticle&ID=15- 54611>, submitted as Exhibit D22 of Opposition filed against EP2405749B. cited by applicant . "Medscape Medical News: Doubling the Dose of Glatiramer Acetate Does Not Increase Efficacy" [online] Medscape, Sep. 22, 2008, [retrieved on Jan. 6, 2015]. Retrieved from the Internet: <URL://www.medscape.com/viewartice/580865>, submitted as Exhibit D23 of Opposition filed against EP2405749B. cited by applicant . "Daily News: High-dosage Copaxone trial results are bad news for Teva" [online] PharmaTimes, Jul. 7, 2008, [retrieved on Nov. 6, 2015]. Retrieved from the Internet: <URL://http://www.pharmatimes.com/article/08-07-07/High-dosage.sub.--C- opaxone.sub.--trial.sub.--results . . . >, submitted as Exhibit D24 of Opposition filed against EP2405749B. cited by applicant . Committee for Medicinal Products for Human Use (CHMP) "Guidelines on Clinical Investigation of Medicinal Products for the Treatment of Multiple Sclerosis", European Medicines Agency, Nov. 16, 2006, submitted as Exhibit D25 of Opposition filed against EP2405749B. cited by applicant . Varkoni et al. "The glatiramoid class of immunomodulator Drugs" Expert Opinion on Pharmacotherapy 2009 10(4) 657-668, submitted as Exhibit D26 of Opposition filed against EP2405749B. cited by applicant . Meiner et al. in "Frontiers in Multiple Sclerosis: Clinical research and Therapy" Eds Abramsky & Ovadia (1997) 213-221, submitted as Exhibit D27 of Opposition filed against EP2405749B. cited by applicant . McKeage "Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Review" ADIS Drug Evaluation, Apr. 2015, submitted as Exhibit D28 of Opposition filed against EP2405749B. cited by applicant . Wolinsky "Reduced frequency severity of injection site reactions with glatiramer acetate 40mg/mL three times weekly dosing" ECTRIMS/ECTRIMS Conference, Sep. 10-13, 2014, poster, submitted as Exhibit D29 of Opposition filed against EP2405749B. cited by applicant . Wolinsky et al. "Reduced frequency severity of injection site reactions with glatiramer acetate 40mg/mL three times weekly dosing", poster presented at the Joint Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Meeting, held on Sep. 10-13, 2014 at Boston MA, submitted as Exhibit D30 of Opposition filed against EP2405749B. cited by applicant . Oct. 5, 2015 Expert Report of Professor Wolfgang Bruck, submitted as Exhibit D31 of Opposition filed against EP2405749B. cited by applicant . Multiple Sclerosis Society of Canada "Talking About Clinically Isolated Syndrome or CIS" published by Communications and Services, Multiple Sclerosis Society of Canada, Quebec Division, dated 2009, submitted as Exhibit D32 of Opposition filed against EP2405749B. cited by applicant . Affidavit of Marlene S. Bobka dated Nov. 10, 2014, submitted as Exhibit D35 of Opposition filed against EP2405749B. cited by applicant . Aug. 25, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co., Ltd. for U.S. Pat. No. 9,232,250 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00643). cited by applicant . Aug. 25, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co., Ltd. for U.S. Pat. No. 8,399,413 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00644). cited by applicant . Sep. 1, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co., Ltd. for U.S. Pat. No. 8,969,302 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00830). cited by applicant . Nov. 20, 2015 Yeda's Patent Owner Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,232,250 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00643). cited by applicant . Nov. 20, 2015 Yeda's Patent Owner Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,399,413 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00644). cited by applicant . Nov. 25, 2015 Yeda's Patent Owner Response filed in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,969,302 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00830). cited by applicant . Declaration of Edward J. 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Peroutka, M.D., Ph.D., taken on behalf of the Patent Owner Yeda, at 901 New York Avenue, Washington, D.C., beginning at 9:30 a.m. on Oct. 29, 2015, before Michele E. Eddy, RPR, CRR, CLR, and Notary Public for the District of Columbia, submitted as Exhibit 1066 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830 on Nov. 18, 2015. cited by applicant . Slides of G. Comi, Forte: Results from a phase II, 1-year, Randomized, Double-blind, Parallel-Group, Dose Comparison Study with Glatiramer Acetate in Relapsing-remitting Multiple Sclerosis, Presented at World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American, European, and Latin America Committees on Treatment and Research in Multiple Sclerosis, San Raffaele, Italy (ACTRIMS, ECTRIMS, LACTRIMS) (2008), submitted as Exhibit 2028 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Jerry S. 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IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . H.T. Katz et al., "Successful desensitization to glatiramer acetate (Copaxone) in two patients with multiple sclerosis" in: Abstract Book of 2003 Annual Meeting, American College of Allergy, Asthma & Immunology, New Orleans, LA (vol. 92, Jan. 2004), submitted as Exhibit 2091 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Maria Zellner et al., "Quantitative validation of different protein precipitation methods in proteome analysis of blood platelets", 26 Electrophoresis 2481 (2005), submitted as Exhibit 2092 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Mariana Castells, "Rapid Desensitization for Hypersensitivity Reactions to Medications", 29 Immunology and Allergy Clinics of North America 585 (2009), submitted as Exhibit 2093 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Robert Zivadinov et al., Poster titled "MRI Indicators of Brain Tissue Loss: 3-Year Results of the Glatiramer Acetate Low-Frequency Administration (GALA) Open-Label Extension Study in Relapsing-Remitting Multiple Sclerosis", Presented at the American Academy of Neurology 2015 Annual Meeting, Washington, DC (Apr. 18-25, 2015), submitted as Exhibit 2094 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . E. Rubinchik et al., "Responsiveness of human skin mast cells to repeated activation: an in vitro study", 53 Allergy 14 (1998), submitted as Exhibit 2095 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Daniel Wynn et.al., Poster titled "Patient Experience with Glatiramer Acetate 40mg/1 ml Three-Times Weekly Treatment for Relapsing-Remitting Multiple Sclerosis: Results from the Glacier Extension Study", Presented at The 8th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis, Seoul, Republic of Korea (Nov. 19-21, 2015), submitted as Exhibit 2096 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Avonex.RTM. (Inferon beta-1a) IM Injection, published 2008 by Biogen Idec Inc., submitted as Exhibit 2097 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Rebif Prescribing Information, published 2009 by Pfizer, submitted as Exhibit 2098 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Extavia Highlights of Prescribing Information, published Aug. 2009 by Novartis, submitted as Exhibit 2099 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Curriculum Vitae of Edward J. Fox. Md., PhD., FAAN, submitted as Exhibit 2100 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Soelberg Sorensen et al., "Clinical Importance of neutralizing antibodies against interferon beta in patients with rerlapsing-remitting multiple sclerosis", 362 The Lancet 1184 (Oct. 11, 2003), submitted as Exhibit 2101 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Jan J.M. de Vijlder, "Primary congenital hypothyroidism: defects in iodine pathway", 149 Eur. J. Endocrinology 247 (2003), submitted as Exhibit 2102 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . C.S. Randall, "5. Approaches to the Analysis of Peptides" in: Vincent H. L. Lee ed. Peptide and Protein Drug Delivery, New York, Marcel Dekker, Inc. 1991, pp. 203-246, submitted as Exhibit 2103 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Curriculum Vitae of Dr. Henry George Grabowski, submitted as Exhibit 2104 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . List of Testimony of Henry G. Grabowski, submitted as Exhibit 2105 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Documents Relied Upon by Grabowski, submitted as Exhibit 2106 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Table: Approval Timeline, Multiple Sclerosis Drugs, submitted as Exhibit 2107 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. 40mg/mL Wholesale Dollar Sales (Ql 2014- Q3 2015), submitted as Exhibit 2108 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. 40mg/mL Extended Units (Q1 2014- Q3 2015), submitted as Exhibit 2109 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. 40mg/mL Total Prescriptions (Q1 2014- Q3 2015), submitted as Exhibit 2110 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. 40mg/mL New Prescriptions (Q1 2014- Q3 2015), submitted as Exhibit 2111 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Multiple Sclerosis Drugs Share of Wholesale Dollar Sales (Q4 2009- Q3 2015), submitted as Exhibit 2112 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Multiple Sclerosis Drugs Share of Total Prescriptions (Q4 2009- Q3 2015), submitted as Exhibit 2113 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Multiple Sclerosis Drugs Share of New Prescriptions (Q4 2009- Q3 2015), submitted as Exhibit 2114 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Figure: Rationale for Requesting Copaxone, submitted as Exhibit 2115 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Figure: Perception of 3-times-a-week Copaxone 40mg compared to Daily Copaxone 20mg, submitted as Exhibit 2116 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Figure: Rationale for Discussing 20mg and 40mg for First Line Patients, submitted as Exhibit 2117 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Figure: Perceptions of Copaxone.RTM. 40mg compared to Daily Generic GA, submitted as Exhibit 2118 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Figure: Perceptions of Copaxone.RTM. 40mg vs. 20mg, submitted as Exhibit 2119 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. Total Prescriptions (Q4 2009- Q3 2015), submitted as Exhibit 2120 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Redacted Figure: Copaxone.RTM. 20 mg/mL, Copaxone.RTM. 40 mg/mL, and GlatopaTM Net Prescriptions Flow (10/26/12-10/9/15), submitted as Exhibit 2121 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Table: Total Promotional Spending to Sales Ratio, submitted as Exhibit 2122 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . G. Comi et al., "Early Treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI", 374 Lancet 1503 (Oct. 31, 2009), submitted as Exhibit 2123 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . R.M. Valenzuela et al., "Clinical response to glatiramer acetate correlates with modulation of IFN-.gamma. and IL-4 expression in multiple sclerosis", 13 Multiple Sclerosis 754 (2007), submitted as Exhibit 2124 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Y. Blanco et al., "Effect of glatiramer acetate (Copaxone.RTM.) on the immunophenotypic and cytokine profile and BDNF production in multiple sclerosis: a longitudinal study", 406 Neuroscience Letters 270 (2006), submitted as Exhibit 2125 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . M. Chen et al., "Sustained immunological effects of Glatiramer acetate in patients with multiple sclerosis treated for over 6 years", 201 J. of Neurological Sciences 71 (2002), submitted as Exhibit 2126 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Zhao Rong Chen et al., "MU Receptor Binding of Some Commonly Used Opioids and Their Metabolites", 48 Life Sciences 2165 (1991), submitted as Exhibit 2127 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Alison Palkhivala, "Doubling the Dose of Glatiramer Acetate Does Not Increase Efficacy", Medscape Medical News (Sep. 22, 2008), submitted as Exhibit 2128 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830. cited by applicant . Curriculum Vitae of Robert William Gristwood PhD, submitted as Exhibit 2130 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Curriculum Vitae of Tjalf Ziemssen, submitted as Exhibit 2131 in Inter Partes Review Case No. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Ziemssen's MS clinical trials, submitted as Exhibit 2132 in Inter Partes Review Case Nos. IPR2015-00643 and IPR2015-00644 on Nov. 20, 2015 and in IPR2015-00830 on Nov. 25, 2015. cited by applicant . Deposition of Stephen J. Peroutka, taken at Washington, D.C., on Oct. 29, 2015, submitted as Exhibit 1066 in Inter Partes Review Case Nos. IPR2015-00643, IPR2015-00644 and IPR2015-00830 on Nov. 18, 2015. cited by applicant . Aug. 25, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,232,250 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00643). cited by applicant . Aug. 25, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,399,413 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00644). cited by applicant . Sep. 1, 2015 Decision on Institution of Inter Partes Review, entered in connection with Mylan Pharmaceuticals Inc. v. Yeda Research & Development Co. Ltd. for U.S. Pat. No. 8,969,302 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. IPR2015-00830). cited by applicant . Oliver Neuhaus, et al., Pharmacokinetics and pharmacodynamics of the interferon-bets, glatiramer acetate, and mitoxantrone in multiple sclerosis, 259 J. Neurol. Sci., 2007. cited by applicant . O. Khan, et al., Randomized, prospective, rater-blinded, four-year, pilot study to compare the effect of daily versus every-other-day [GA] 20 mg subcutaneous injections in relapsing-remitting multiple sclerosis, S295 Multiple Sclerosis, 902 (2008). cited by applicant . S. Fletcher et al., Copolymer 1 (Glatiramer Acetate) in Relapsing Forms of Multiple Sclerosis: Open Multicenter Study of Alternate-Day Administration, 25(1) Clin. Neuropharmacology, 11-15 (2002). cited by applicant . Teva Provides Upate on FORTE Trial (Jul. 7, 2008). cited by applicant . J.A. Cohen et al., Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing-remitting MS, 68:12 Neurology, 939-44 (2007). cited by applicant . Teva Press Release, Phase III Data Published in Annals of Neurology Show That a Higher Concentration Dose of Glatiramer Acetate Given Three Times a Week Reduced Annualized Relapse Rates in the Treatment of Relapsing-Remitting Multiple Sclerosis dated Jul. 1, 2013. cited by applicant . Omar Khan et al., Three Times Weekly Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis, 73 Ann. Neurol., 705-13 (2013). cited by applicant . Kate McKeage, Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Revies, CNS Drugs (Apr. 24, 2015). cited by applicant . Feb. 16, 2016 Petition for Post Grant Review of U.S. Pat. No. 9,155,776 in the United States Patent and Trademark Office Patent Trial and Appeal Board (Case No. PGR2016-00010). cited by applicant . Expert Declaration of Ari Green, M.D. in Support of Petition for Post-Grant Review of U.S. Pat. No. 9,155,776, dated Feb. 7, 2016, submitted as Exhibit 1003 in Post Grant Review Case No. PGR2016-00010. cited by applicant . A Study in Subjects with Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate (GA) Injection 40 mg Administered Three Times a Week Compared to Placebo (GALA), NCT01067521 [online]. ClinicalTrials.gov [retrieved on Feb. 5, 2016]. Retrieved from the Internet: <URL:clinicaltrials.gov/ct2/show/NCT01067521>, submitted as Exhibit 1004 in Post Grant Review Case No. PGR2016-00010. cited by applicant . Safety and Tolerability of Glatiramer Acetate (GLACIER), NCT01874145 [online]. ClinicalTrials.gov [retrieved on Feb. 5, 2016]. Retrieved from the Internet: <URL:clinicaltrials.gov/ct2/show/NCT01874145, submitted as Exhibit 1005 in Post Grant Review Case No. PGR2016-00010. cited by applicant . Plaintiffs' Supplemental Opening Claim Construction Brief, In re Copaxone 40 mg Consolidated Cases, No. 1:14-cv-01171-GMS (D.Del), dated Dec. 18, 2015, submitted as Exhibit 1006 in Post Grant Review Case No. PGR2016-00010. cited by applicant . Citizen Petition Requesting That FDA Refrain from Approving any Abbreviated New Drug Application Referencing Copaxone.RTM. (glatiramer acetate injection) Until Certain Conditions Are Met, dated Jul. 2, 2014, filed with U.S. Food and Drug Administration, submitted as Exhibit 1009 in Post Grant Review Case No. PGR2016-00010. cited by applicant . Citizen Petition Requesting That FDA Consider New Scientific Information and Refrain from Approving Any Abbreviated New Drug Information and Refrain from Approving Any Abbreviated New Drug Application Referencing Copaxone .RTM. (glatiramer acetate injection) Until Certain Conditions Are Met, dated Mar. 31, 2015, filed with U.S. Food and Drug Administration, submitted as Exhibit 1010 in Po