In re copaxone consolidated cases

Case Name: In re copaxone consolidated cases, No. 14-1171-GMS (consolidated) 2017 U.S. Dist. LEXIS 12168 (D. Del. Jan. 30, 2017) (Sleet, J.) 

Drug Product and Patent(s)-in-Suit: Copaxone® (prefilled syringes of glatiramer acetate, “GA”); U.S. Patents Nos. 8,399,413 (“the ’413 patent”), 8,232,250 (“the ’250 patent”), 8,969,302 (“the ’302 patent”), and 9,155,776 (“the ‘776 patent”)

Nature of the Case and Issue(s) Presented:  Teva owns the NDA for Copaxone® 40mg, which is FDA-approved for treatment of patients with relapsing forms of multiple sclerosis (“MS”) including relapse-remitting multiple sclerosis. Defendants Sandoz, Momenta Pharmaceuticals, Dr. Reddy’s, Mylan, Synthon, Amneal, and Pfizer filed ANDAs to market and sell generic versions of Copaxone. The ’250, ’413, and ’302 patents generally claim the treatment of MS by subcutaneous injections of 40 mg GA, where the frequency of side effects is reduced compared to that observed with daily treatment with 20 mg GA. The ’776 patent additionally claimed limiting the severity of side effects.

Certain of the defendants had also challenged the ’250, ’413, and ’302 patents in IPR proceedings, and by the time of this opinion wherein Judge Sleet invalidating all claims-at-issue as being obvious, the PTAB had also found all claims invalid.

Why Defendants Prevailed: As early as 1996, when it approved the 20 mg daily dosage for Copaxone, the FDA suggested to Teva to explore less frequent dosing of GA. Moreover, various prior-art references disclosed that daily injections may be unnecessary and that a 40 mg dosage strength may present a similar side effect profile as the 20 mg dosage strength. Citing those papers, Plaintiff’s own prior-art patent application discloses 40 mg GA, every other day, dosing regimen to treat MS. Thus, a 40 mg dosage form of GA was explicitly disclosed in references that pre-date the patents-in-suit. Additionally, persons having ordinary skill in the art knew that daily injections were difficult to tolerate. Specifically, they knew that injection-site reactions (“ISRs”) and immediate post-injection reactions (“IPIRs”) were reasons for non-adherence to the 20mg/daily Copaxone treatment regimen.

While a 40 mg dosage form was explicitly mentioned in the prior art, and there was a motivation in the MS community to explore a less frequent dosing regimen to alleviate the well-known adverse side effects associated with daily injections, Plaintiffs argued that no prior art existed explicitly disclosing a three-times-a-week injection regimen. But the court found that evidence adduced at trial rendered a less frequent dosage form obvious to try. The 40 mg dose was obvious to try because it was one of two doses studied extensively. The prior art demonstrated that a number of studies looked at the safety, efficacy, and tolerability of a 20 mg dose and a 40 mg dose, and the 40 mg dose was shown to be as safe, effective, and tolerable as the 20 mg dose. There were also a finite number of days on which to administer injections considering there are only seven days in a week. The prior art disclosed that administering GA every other day was as effective as administering it every day, while decreasing the adverse side effects associated with daily injections.

Next, the court considered secondary considerations of non-obviousness. While there existed a long-felt need in the art for a GA regimen not requiring everyday injections, evidence of a long-felt need is only probative of non-obviousness, however, when both a demand existed for the patented invention, and others tried but failed to satisfy that demand. Here, the court reasoned, those having ordinary skill in the art did not try, but fail to find a solution to the known issues with daily injections. The solutions to the need were in the prior art. Similarly, the court also found that though the claimed invention exhibits an advantage over the 20 mg daily form of Copaxone, that advantage was not surprising or unexpected given the prior art studies. Finally, the court gave little probative weight to the fact that Copaxone 40 mg was commercially successful because there was no evidence adduced at trial supporting a nexus between Copaxone 40 mg three-times-a-week’s success and features not already found in the prior art.