United Therapeutics Corp. v. Sandoz, Inc.
| Decision Date | 29 August 2014 |
| Docket Number | Civil Action No. 13-CV-316,Civil Action No. 12-CV-01617 |
| Parties | UNITED THERAPEUTICS CORP., Plaintiff, v. SANDOZ, INC., Defendant. |
| Court | U.S. District Court — District of New Jersey |
Pursuant to the Hatch-Waxman Act, 21 U.S.C. § 355(j), this consolidated patent infringement action is brought by Plaintiff, United Therapeutics Corporation ("Plaintiff" or "UTC"), against Defendant, Sandoz, Inc. ("Defendant" or "Sandoz"), for infringement of United States Patent Nos. 6,765,117 ("the '117 patent") and 7,999,007 ("the '007 patent")(collectively the "patents-in-suit")1—which Plaintiff has listed in the Orange Book in connection with treprostinil sodium injection. On March 14, 2012, UTC filed the first of two lawsuits against Sandoz for patent infringement based upon Sandoz's submission of ANDA No. 203649 to the FDA, seeking approval to market and sell a generic form of UTC's patented treprostinil sodium injection. See United Therapeutics Corporation. v. Sandoz, Inc., et al., Civil No. 12-1617.2 On January 16, 2013, UTC filed a second suit against Sandoz for patent infringement, based upon Sandoz's subsequent amendments to ANDA No. 203649. See United Therapeutics Corporation. v. Sandoz, Inc., et al.,13-316 ("13-316"). By agreement of the parties, this consolidated action followed.3 The Court held a Markman hearing on May 20, 2013, and on June 25, 2013, the Court issued an Order construing disputed terms. (ECF No. 95). The Court conducted a 14-day bench trial from May 2-May 29, 2014. (ECF Nos. 345-358). The parties completed post-trial briefing on June 20, 2014, and in connection with same, the parties submitted proposed findings of fact and conclusions of law. ECF Nos. 343, 360, 341, 342. Presently before the Court are the parties' post-trial proposed findings of fact and conclusions of law concerning the infringement and validity of the patents-in-suit.
Pursuant to Federal Rule of Civil Procedure 52(a), and after careful consideration of the entire record in this case and the applicable law, the Court hereby concludes that: (1) UTC has failed to prove by a preponderance of the evidence that Sandoz's proposed ANDA product will induce infringement of the asserted claims of the '007 patent; (2) Sandoz has failed to prove by clear and convincing evidence that the asserted claims of the '007 are invalid; (3) UTC has proved by a preponderance of the evidence that Sandoz's ANDA product will infringe and induce infringement of the asserted claims of the '117 patent; and (4) Sandoz has failed to prove by clear and convincing evidence that the asserted claims of the '117 patent are invalid.
The Court's findings of fact and conclusions of law are set forth in detail below.
Plaintiff United Therapeutics Corporation ("United Therapeutics" or "UTC") is a corporation organized and existing under the laws of the State of Delaware, and having a place of business at 1040 Spring Street, Silver Spring, Maryland 20910.
Defendant Sandoz Inc. ("Sandoz") is a corporation organized and existing under the lawsof the State of Colorado, having a principal place of business at 506 Carnegie Center, Suite 400, Princeton, New Jersey 08540.
United Therapeutics holds an approved New Drug Application (No. 21-272) ("NDA") for Treprostinil Sodium Injection, marketed and sold under the federally registered trademark REMODULIN®4 for the treatment of pulmonary arterial hypertension. Pulmonary arterial hypertension (or "PAH") is a rare, debilitating, and potentially fatal disease, in which the blood pressure between the heart and lungs rises to dangerously high levels, narrowing the arteries and depriving the body of oxygen. 5
Remodulin is an injectable product indicated for the treatment of pulmonary arterial hypertension. It was first approved in the United States in May 2002, and is presently approved for sale in concentrations including 1 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL.
Stereochemistry is the study of the relative spatial arrangement of atoms that form the structure of molecules. The stereochemistry of any given compound is an integral and highly significant aspect of its physical and functional properties.
When a carbon atom of a molecule is bonded to four different groups, that carbon atom is said to be "chiral" or constituting a "chiral center." A chiral center is also commonly called a "stereogenic center." Each chiral center in a molecule results in two possible stereoisomers. Stereoisomers have the same molecular formula, sequence of atoms, and connectivity of atoms and differ only with respect to the three-dimensional spatial arrangement of their atoms within the molecule.
It "is extremely important to the proper biological function" of a drug to obtain the specific stereoisomer of a compound, because typically, only one stereoisomer behaves in a desirable manner (Tr. 48:8-12 (Williams), May 1, 2014); other stereoisomers may have no biological effect or a deleterious biological effect. (Tr. 48:13-17 (Williams), May 1, 2014.)
Treprostinil sodium is the active pharmaceutical ingredient ("API") of the generic treprostinil injection that is the subject of Sandoz's ANDA. Treprostinil is one of a class of biochemicals that are derived from naturally occurring hormonal substances found in human and animal tissues, called prostacyclin derivatives. The prostacyclin derivative that gives rise to treprostinil is a complex compound containing five chiral centers (Tr. 44:18-25 (Williams), May 1, 2014; Tr. 2052:3-5 (Gorin), May 22, 2014); therefore thirty-two stereoisomers of the molecule are possible. A particular stereoisomer of the prostacyclin derivative is able to mimic the function of the natural hormone prostacyclin by bonding to the same biological receptor to which natural prostacyclin bonds, (Tr. 48:1-8 (Williams), May 1, 2014), because it has the same configuration at the five chiral centers as the natural hormone prostacyclin. (Tr. 48:1-8 (Williams), May 1, 2014.) For that reason, this particular stereoisomer, known as "Treprostinil"6, is the most efficacious and therefore the most desirable of all thirty-two possible stereoisomers. A stereoselective synthesis will make more of this ideal stereoisomer—"Treprostinil"—than any of the other thirty-two possible stereoisomers. (Tr. 2051:17-2052:1 (Gorin), May 22, 2014.)
On a molecular level, there is no sample of Treprostinil that is 100% pure. (Tr. 45:16-17 (Williams), May 1, 2014; Tr. 1734:14-25, 1723:6-10, 1723:16-20 (Aristoff), May 16, 2014.) Each sample of Treprostinil carries with it characteristic impurities including other stereoisomers and impurities related to the synthetic process. (Tr. 1458:9-14 (Buchwald), May 15, 2014.) A person of ordinary skill in the art at the time of the invention would understand that a stereoselectively produced product is a product consisting primarily of one stereoisomer over any other stereoisomers. (Tr. 52:3-8, 52:14-20 (Williams), May 1, 2014.)
The '117 patent, entitled "Process for stereoselective synthesis of prostacyclin derivatives," was issued by the PTO on July 20, 2004. The '117 patent is scheduled to expire on October 24, 2017. The named inventors on the '117 patent are Robert M. Moriarty, Raju Penmasta, Liang Guo, Mungala S. Rao, and James P. Staszewski. The application that matured into the '117 patent was a division of application no. 09/541,521, filed on April 3, 2000, now U.S. Patent No. 6,441,245, which is a continuation-in-part of application no. 09/481,390, filed on January 12, 2000, which is a continuation of application no. 08/957,736, filed on October 24, 1997. The '117 patent priority date is October 24, 1997. The '117 patent is assigned on its face to United Therapeutics Corporation. United Therapeutics is the owner of the '117 patent by assignment. Example 1 in the '117 patent is an embodiment of the claimed invention of the '117 patent.
1. Asserted Claims
UTC asserts that Sandoz's proposed generic product and/or manufacturing process will infringe claims 1-4 of the '117 patent. (ECF No. 218, Exhibit 1 to Pretrial Order, Stipulated Fact No. 30). The asserted claims are reproduced on the pages that follow:
The stereoselectively produced isomeric compound of claim 1, wherein Z is O, n is 1, X is COOH, Y1 is -CH2CH2- M1 is a-OH-ß-R5, wherein R5 is hydrogen, L1 is a-R3:ß-R4, wherein R3and R4 are hydrogen and R7 is butyl.
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