Otsuka Pharm. Co v. Sandoz Inc
| Decision Date | 15 November 2010 |
| Docket Number | Consolidated Civil Action No. 3:07-cv-01000 (MLC) |
| Parties | OTSUKA PHARMACEUTICAL CO., LTD., Plaintiff, v. SANDOZ, INC., TEVA PHARMACEUTICALS USA, INC., TEVA PHARMACEUTICAL INDUSTRIES LTD., BARR LABORATORIES, INC., BARR PHARMACEUTICALS, INC., APOTEX INC., APOTEX CORP., SUN PHARMACEUTICAL INDUSTRIES, LTD., SYNTHON HOLDING BV, SYNTHON BV, SYNTHON PHARMACEUTICALS, INC., and SYNTHON LABORATORIES, INC., Defendants. |
| Court | U.S. District Court — District of New Jersey |
NOT FOR PUBLICATION
Otsuka Pharmaceutical Co., Ltd. ("Plaintiff" or "Otsuka") brought this action and a number of now-consolidated actions against generic drug manufacturers, Sandoz, Inc. ("Sandoz"); Teva Pharmaceuticals USA, Inc., Teva Pharmaceutical Industries Ltd. ("Teva"); Barr Laboratories, Inc., Barr Pharmaceuticals, Inc. ("Barr"); Apotex Corp., Apotex Inc. ("Apotex"); Sun Pharmaceutical Industries, Ltd. ("Sun"); Synthon Holding BV, Synthon BV, Synthon Pharmaceuticals, Inc., and Synthon Laboratories, Inc. ("Synthon") (collectively, "Defendants").1 Otsuka alleges infringement of U.S. Patent No. 5, 000, 528 (the '''528 Patent"), which claims, inter alia, the chemical compound aripiprazole, based on Defendants' submissions of an Abbreviated New Drug Application ("ANDA") to the United States Food and Drug Administration ("FDA") for approval to engage in the commercial manufacture, use, or sale in the United States of generic aripiprazole products. Infringement is not contested in this action, as Defendants concede that their ANDA filings constitute literal acts of infringement "to the extent [the asserted] claims are valid and enforceable." (See Pl.'s Post-Trial Br. at 9.) 35 U.S.C. § 271(e)(2)(A); see also Glaxo, Inc. v. Novopharm Ltd., 110 F.3d 1562, 1569 (Fed. Cir. 1997) (). Defendants contend that the '528 Patent is invalid as obvious under 35 U.S.C. § 103; invalid due to obviousness-type double patenting over Otsuka's prior art U.S. Patent No. 4, 734, 416 (the "'416 Patent"); and unenforceable due to inequitable conduct arising from Otsuka's failure to disclose certain information to the United States Patent and Trademark Office ("USPTO"). Because this civil action arises under the United States patent laws, Title 35, United States Code, the Court exercises subject matter jurisdiction pursuant to 28 U.S.C. §§ 1331 and 1338(a).
The parties tried the case before the Court from August 5, 2010 through August 26, 2010. The parties thereafter submitted proposed findings of fact and conclusions of law. The Court heard closing arguments and received additional documentary evidence on October 21, 2010.2This Memorandum Opinion constitutes the Court's findings of fact and conclusions of law on the issues of invalidity and unenforceability, pursuant to Fed.R.Civ.P. 52(a). For the reasons set forth herein, the Court concludes that Defendants did not show by clear and convincing evidence that '528 Patent is invalid as obvious under either 35 U.S.C. § 103 or the judicially-created doctrine of obviousness-type double patenting, or that the '528 Patent is unenforceable due to inequitable conduct. Accordingly, the Court will enter judgment in favor of Otsuka on its claims that Defendants have infringed the '528 Patent.
Otsuka markets aripiprazole under the trade name Abilify®. Abilify® is approved by the FDA for the treatment of, inter alia, schizophrenia, bipolar disorder, irritability associated with autistic disorder in pediatric patients, and as an add-on treatment for depression. (Pl's Post-Trial Br. at 52.) The listing for Abilify® in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") contains references to both the '416 Patent and the '528 Patent as covering aripiprazole. (Defs.' Post-Trial Br. at 1, 11; Pl.'s Post-Trial Br. at 4.) Abilify® was first marketed in the United States in 2002 and was the result of several decades of drug development by Otsuka. (See Defs.' Post-Trial Br. at 144 ().) It has been commercially successful. By the end of 2009, sales of Abilify® were $3.3 billion annually, and from 2005 onward, sales of Abilify® have exceeded a billion dollars each year, qualifying it as a "blockbuster drug." (Pl.'s Post-Trial Br. at 124-25.)
Schizophrenia is a serious and debilitating mental disease affecting approximately one percent of the human population. (Pl.'s Post-Trial Br. at 25.) Despite extensive research, the cause, mechanism, and etiology of schizophrenia were unknown in 1988 and remain unknown today. (Id. at 26.) Researchers believe that both genetic and environmental factors may play a role in the cause of the illness. (Id.)
Individuals with schizophrenia suffer from positive symptoms, negative symptoms, and cognitive deficits. (Id.) Positive symptoms include hallucinations and delusions, while negative symptoms include flat affect, poverty of speech, inability to experience pleasure, lack of desire to form relationships, and lack of motivation. (Defs.' Post-Trial Br. at 6.)
The first antipsychotic drug, chlorpromazine, was discovered by accident in the early 1950s. (Pl.'s Post-Trial Br. at 27.) After chlorpromazine was discovered, researchers determined that its antipsychotic properties were due to its antagonism, or blocking, of dopamine receptors in the brain. (Id.; Defs.' Post-Trial Br. at 6.) That key finding led to the development of other "typical" antipsychotics, including haloperidol, thiothixene, trifluoperazine, fluphenazine, thioridazine, mesoridazine, loxapine, molindone, perphenazine, and pentoxide. (Pl.'s Post-Trial Br. at 27.) Typical antipsychotic drugs treat the positive symptoms of schizophrenia, but not the negative symptoms. (Defs.' Post-Trial Br. at 6.) Typical antipsychotic drugs also have problematic side effects, including extrapyramidal symptoms ("EPS"), tardive dyskinesia, prolactin elevation (hyperprolactinemia), and sudden decrease in blood pressure (orthostatic hypotension). (Id.) Despite these various drawbacks, the typical antischizophrenic drugs are still used today. (Id.) Loxapine was the last of the typical antipsychotics to be approved by the FDA, in 1975. (PTX 79, Winston Shen, "A History of Antipsychotic Drug Development," Comprehensive Psychol., Vol. 40, No. 6 (1999), at 409.)
The adverse side effects of the first-generation typical antipsychotics led researchers to seek alternatives with a better side effect profile, particularly with regard to EPS. Clozapine, discovered in the early 1960s, was the first "atypical" antipsychotic drug in that it had diminished propensity to cause EPS. (Id.) Clozapine also differed from typical antipsychotics in that it was useful in treating both positive and negative symptoms of schizophrenia. (Shen at 409-10.) Unfortunately, clozapine has several potential adverse side effects including agranulocytosis, a life-threatening decrease in white blood cells; orthostatic hypotension; and frank hypotension. (Defs.' Post-Trial Br. at 6-7; Pl.'s Post-Trial Br. at 28-30.) Because of its side effect profile, clozapine was withdrawn from clinical trials in the 1970s and not approved by the FDA for treatment of schizophrenia until 1990, and then only for treatment-resistant or treatment-intolerant patients, subject to rigorous blood testing. (Pl.'s Post-Trial Br. at 30; dkt. entry no. 352, Roth Tr. at 1129, 1133, 1137.)
Scientists have been attempting since the early 1970s to discover an atypical antipsychotic treatment for schizophrenia that would be similar to clozapine in efficacy, but without the toxicity and significant side effects. (Pl.'s Post-Trial Br. at 30; see, e.g., PTX 116, Samuel Gershon, "Update on Drug Development," Psychopharmacology Bull., Vol. 16, No. 3 (1980), at 32 ().) These efforts, however, were largely unsuccessful, and the FDA approved no new antipsychotic drugs between 1976 and 1989. (Pl.'s Post-Trial Br. at 31; see also PTX 93, Leo E. Hollister, "Strategies in Clinical Psychopharmacology," Psychopharmacology Bull., Vol. 23, No. 3 (1987), at 389 ().)
Risperidone was the first post-clozapine atypical antipsychotic approved by the FDA, in 1994. (Shen at 410.) While clozapine remains the "gold standard" with respect to efficacy, a total of nine atypical antipsychotics, including aripiprazole, have been approved by the FDA and are considered (Shen at 410, 412-13; Pl.'s Post-Trial Br. at 60.) With the exception of aripiprazole, all FDA-approved atypical antipsychotics are structurally related to either clozapine or risperidone.3
Otsuka is the assignee of the '416 Patent covering "Pharmaceutically Useful Carbostyril Derivatives," which issued on March 29, 1988, and expired on March 29, 2005. It teaches that "[c]arbostyril derivatives having antihistamic action and central nervous controlling action are useful as antihistamic agents or central nervous controlling agents." ('416 Patent, Abstract.) The '416 Patent covers approximately nine trillion compounds. (Defs.' Post-Trial Br. at 132; Pl.'s Post-Trial...
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