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Case 2:10-Cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 1 of 59 Pageid: 14610

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Case 2:10-Cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 1 of 59 Pageid: 14610 Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 1 of 59 PageID: 14610 NOT FOR PUBLICATION UNITED STATES DISTRICT COURT DISTRICT OF NEW JERSEY TEA NEUROSCIENCE, INC., TEVA PHARMACEUTICALS USA INC.. and TEVA PHARI’IACEUTICALS INDUSTRIES, LTD., Civil Action No. 2:lO-cv-05078 Plaintiffs, V. Opinion WATSON LABORATORIES, INC., MYLAN PHARMACEUTICALS, INC., MYLAN INC., ORCHID CHEMICALS & PHARMACEUTICALS LTD., ORCHID HEALTHCARE (a division of Orchid Chemicals & Pharmaceuticals Ltd.) and ORGENUS PHARMA INC. Defendants. TEVA NEUROSCIENCE, INC., TEVA PHARMACEUTICALS USA, INC., and TEVA PHARMACEUTICALS INDUSTRIES, LTD., Civil Action No. 2:1l-cv-3076 Plaintiffs, v. APOTEX CORP. and APOTEX INC. Defendants. Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 2 of 59 PageID: 14611 Claire C. Cecchi, U.S.D.J. This matter comes before the Court by complaint of Teva Neuroscience, Inc., Teva Pharmaceuticals USA, Inc. and Teva Pharmaceuticals Industries, Ltd. (collectively, “Teva”) against Mylan’ and certain other defendants,2 This case concerns the validity of United States Patent No. 5,453,446 (“the ‘446 Patent”), which is directed to a method of treating Parkinson’s disease, This Court conducted a non-jury trial in this matter from May 15-31, 2013. This Opinion constitutes the Court’s findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a). For the reasons stated herein, a finding in favor of Teva will be entered. BACKGROUND I. The Parties Plaintiff Teva Pharmaceutical Industries Ltd. (“Teva Ltd.”) is an Israeli company with its principal place of business at 5 Basel Street, Petach Ti.Kva, 49131, Israel. (Joint Pretrial Order, Stipulation of Facts (“SOF”) ¶ 20.) Teva Ltd. is the sole owner of the ‘446 Patent. (Id.) Plaintiff Teva Neuroscience, Inc. (“Teva Neuroscience”) is a Delaware corporation with its 104th principal place of business at 901 E. Street, Suite 900, Kansas City, Missouri 64131. (Id. ¶ 21.) Teva Neuroscience is a wholly-owned subsidiary of Teva Ltd. () Plaintiff Teva Pharmaceuticals USA, Inc. (“Teva USA”) is a Delaware corporation with its principal place of ‘“Mylan” consists of Mylan Pharmaceuticals, Inc., Mylan Inc. and Mylan LLC. 2 These defendants included “Orchid,” consisting of Orchid Chemicals & Pharmaceuticals Ltd., Orchid Healthcare (a division of Orchid Chemicals & Pharmaceuticals Ltd.). and Orgenus Pharma, Inc., “Watson,” consisting of Watson Pharma and Watson Laboratories, Inc., and “Apotex,” consisting of Apotex Corp. and Apotex Inc. Orchid, Watson and Apotex settled with Teva prior to the start of trial. 2 Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 3 of 59 PageID: 14612 business at 1090 Horsham Road, North Wales, Pennsylvania 19454. (Id. ¶ 22.) Teva USA is a wholly-owned subsidiary of Teva Ltd. () Defendant Mylan Inc. is a Pennsylvania corporation with its principal place of business at 1500 Corporate Drive, Canonsburg, Pennsylvania 15317. (Id. ¶ 29.) Defendant Mylan Pharmaceuticals Inc. is a West Virginia corporation with its principal place of business at 781 Chestnut Ridge Road, Morgantown, West Virginia 26505. (j4. ¶ 30.) Mylan Pharmaceuticals is a wholly-owned subsidiary of Mylan. ( ¶ 31.) II. The ‘446 Patent The ‘446 Patent, entitled “Use of the R-Enantiomers of N-Propargyl 1 -Aminoindan Compounds for Treating Parkinson’s Disease,” was issued by the United States Patent and Trademark Office (the “PTO”) on September 26, 1995. (Id. ¶J 3 8-40.) Moussa B.H. Youdim, John P. M. Finberg, Ruth Levy, Jeffrey Sterling, David Lerner, Tirtsah Berger-Paskin and Haim Yellin are the inventors listed on the face of the ‘446 Patent. (Id. ¶ 42.) The named inventors assigned the ‘446 Patent to Teva Ltd. and the Technion Research and Development Foundation Ltd. (“Technion”). Technion subsequently assigned its rights to the ‘446 Patent to Teva Ltd. ( ¶J 45-46.) The ‘446 Patent issued from Application No. 255,046 (“the ‘046 Application”), filed on June 7, 1994. (Id. ¶ 43.) The ‘046 Application is a continuation of Application No. 63,455 (“the ‘455 Application”), which was filed on May 18, 1993, and which issued as Patent No. 5,387,612 (“the ‘612 Patent”) on February 7, l995. The ‘455 Application is a continuation of Application The ‘612 Patent claims the use of R(+)-PAI as monotherapy to treat Parkinson’s disease. (PTX 332.) 3 Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 4 of 59 PageID: 14613 No. 632,184 (“the ‘184 Application”), which was filed on December 21, 1990, and which claims priority to Israel Application No. 92952, filed January 3, 1990. (Id. ¶J 43-44.) The applicants submitted a terminal disclaimer for the ‘046 Application over the ‘612 Patent on February 28, 1995. (Id. ¶ 62.) The ‘446 Patent issued from the ‘046 Application on September 26, 1995. (Id. ¶J 62-63.) The ‘446 Patent expires on February 12, 2017. (Id. ¶41.) Teva is asserting Claims 1, 2, 17, 18, and 19 of the ‘446 Patent in this litigation. (Id. ¶ 47.) The asserted claims read as follows: Claim 1 A method of treating a subject for Parkinson’s disease which comprises administering to the subject an amount of R(+)-N-propargyl-1 -aminoindan or a phannaceutically acceptable salt thereof effective to treat the subject. Claim 2 The method of claim 1, wherein the R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof is administered orally. Claim 17 The method of claim 1 which further comprises administering to the subject Levodopa in an amount relative to the amount of R(+)-N-propargyl-1 -aminoindan or a pharmaceutically acceptable salt thereof effective to treat the subject. Claim 18 The method of claim 1 which further comprises administering to the subject a decarboxylase inhibitor in an amount effective to ensure L-dopa uptake. Claim 19 The method of claim 18, wherein the decarboxylase inhibitor is Carbidopa. R(+)-N-propargyl- 1 -arninoindan is referred to herein as “R(+)-PAI.” In 1994, the name rasagiline was adopted for R(+)-PAI. (Id. ¶J 47-49.) R(+)-PAI is the R(+) enantiomer of N-propargyl-1-aminoindan.4 (Tr. 6 1:5-14 (Ruffolo).) R(±)PAI has a chiral center (Tr. 63:25-64:3 (Ruffolo)). meaning that it contains a carbon atom that has four different groups of atoms attached to it, (Tr. 64:6-7 (Ruffolo).) “Molecules that have the same chemical substituents, but different spatial arrangements, are referred to as stereoisomers.” Sanofi-Synthelabo v. Apotex, Inc., 470 F.3d 1368, 1372 (Fed, Cir. 2006). N-propargyl-1-aminoindan is also referred to as racemic PAl or AGN 1135. 4 Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 5 of 59 PageID: 14614 “Enantiomers are a pair of stereoisomers that are non-superimposabie mirror images of each other.” Pfizer, Inc. v. Ranbaxy Labs. Ltd., 457 F.3d 1284, 1286 (Fed. Cir. 2006). This characteristic is “often likened to the relative structures of a person’s right and left hands,” Ortho-McNeil Pharm.. Inc. v. 1ylan Labs., Inc., 348 F. Supp. 2d 713, 720 (N.D.W.Va. 2004). Enantiomers are capable of rotating plane-polarized light. Enantiomers that rotate polarized light to the right are referred to as (+), and enantiomers that rotate polarized light to the left are referred to as (-). Id. at 720-21; Sanofi-Synthelabo, 470 F.3d at 1372. Enantiomers are also sometimes designated d- (dextrorotatory or right rotating) or 1- (levorotatory or left rotating), again referring to the direction of optical rotation. jçj. A racemate, or a racemic compound, is a 50/50 mixture of two mirror image enantiomers. (Tr. 65:17-18 (Ruffolo).) A racemic compound does not rotate light. (Tr. 65:19-25; 65:18-66:1 (Ruffolo).) “Chemists also distinguish between enantiomers by designating an enantiomer as either ‘R’ or ‘S’ based upon the arrangement of certain atoms at the enantiomer’s ‘chiral center.’ Where one enantiomer is an ‘R,’ the other will be an ‘S.” Ortho-McNeil, 348 F. Supp. 2d at 720- 21. In other words, the R and S enantiomer naming system simply allows scientists to distinguish and refer to enantiomers based on the orientation of groups of atoms around the chiral center. (Tr. 67:25-68:3; 68:1-4 (Ruffolo).) In sum, the R(±)-PAI that is the subject of the ‘446 Patent is the enantiomer of the racemic compound PAl that has the R absolute configuration and that rotates light in the clockwise (+) direction. (Tr. 68:4-8 (Ruffolo).) III. FDA Approval Teva developed, applied for and obtained approval to make, sell, promote and/or market 5 Case 2:10-cv-05078-CCC-MF Document 540 Filed 09/20/13 Page 6 of 59 PageID: 14615 Azilect®, a rasagiline mesylate tablet product. (SOF ¶ 64.) Azilect® was approved by the FDA and is indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease as both an initial monotherapy and also as an adjunct therapy to levodopa (“L-DOPA”). (SOF ¶f 64.) Teva Ltd. is listed as the holder of New Drug Application (“NDA”) No. 02-1641, under Section 505(a) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 355(a), for 0.5 and 1,0 mg Azilect® tablets. (Id. ¶J 20, 65-66.) Teva Neuroscience is Teva Ltd.’s authorized U.S. agent ,)5 for NDA No. 02-1641. (Id. ¶ 21 Teva Neuroscience and Teva USA have been selling, promoting, distributing and marketing Azilect® in the U.S. since July 2006. (Id. ¶ 68.) In 2006, the FDA granted New Chemical Entity exclusivity to Azilect®, which expired in May 2011. (Id. ¶J 5 1-52.) Mylan filed an Abbreviated New Drug Application (“ANDA”), under 21 U.S.C.
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