In Re: Copaxone Consolidated Cases / Teva Pharm. USA, Inc. et al. v. Sandoz Inc. et al.

Docket No. 2017-1575

October 12, 2018

Brief summary: DC decision finding Teva/Yeda’s patents relating to COPAXONE® invalid for obviousness affirmed.

Summary: Teva (Yeda) appealed DC decision (regarding five consolidated cases) invalidating US 8,232,250; 8,399,413; 8,969,302; and 9,155,776 relating to COPAXONE® 40 mg/mL for multiple sclerosis (glatiramer acetate (GA), “a mixture of polypeptides”; 40 mg/ml for relapsing-remitting multiple sclerosis (RRMS); all sharing a common specification and priority) unpatentable for obviousness. A separate Oct. 12 FC opinion affirmed PTAB IPR final written decisions (FWDs) finding the ‘250, ‘413, and ‘302 patents obvious. This opinion explains that prior to FDA approval of COPAXONE® 40 mg/mL, the 20 mg/ml formulation was approved for daily injection which was known to cause negative side effects (injection-site reactions (ISRs) and immediate post-injection reactions (IPIRs)). Except for claim 1 of the ‘302 patent (see FN2 regarding its dependent claim 10 which does require the separation), the asserted claims are explained to require at least one day between doses and the ‘776 patent also requires the treatment to have “reduced severity of injection site reactions relative to administration of 20 mg…daily.” The DC construed the terms “sufficiency” (‘250 and ‘413 patents), “reduced frequency of relapses” and “effectiveness” (‘776 patent) “as non-limiting statements of intended effect” (Bristol-Myers, FC 2001 (terms “non-limiting” as “merely express[ed] a purpose” and “only state[d] an intended result”)), and the FC panel agreed (“e.g., therapeutically effective [regimen…being sufficient] is superfluous, does not change the claimed method or require any additional required structure or condition”). The DC also found that the 40 mg GA dose was explicitly disclosed and that daily injections were known to be difficult to tolerate from the prior art, that there would have been a motivation “to pursue less frequent dosing with a reasonable probability of success”, and rejected Teva’s teaching away arguments that the POSITA “would have thought that 20 mg was the optimal dose.” It therefore found “that a 40 mg GA 3x/week dosage would be obvious to try” and enough here because “there were a finite number of predictable solutions that a person of ordinary skill in the art would have good reason to pursue” and that “none of” the “objective indicia of nonobviousness…warranted a finding of nonobviousness”. The FC panel reviewed the DC’s conclusions of law (obviousness) de novo and its findings of fact for clear error (Senju, FC 2015). Teva argued the DC’s obvious to try conclusions were “at odds with…In re Cyclobenzaprine” (FC 2012) but the FC panel disagreed, explaining that this reasoning is improper “where the prior art gave no indication of critical parameters and no direction as to which of the many possibilities is likely to be successful” or “gave only general guidance as to the particular form or method” (In re Kubin, FC 2009) and finding neither of these apply in this case (e.g., “the prior art focused on two critical variables, dose size and frequency”, “less frequent doses should be explored” (e.g., the non-prior art Khan 2009 reference), the DC “had ample evidence besides hindsight”). The FC panel also explained that it “has previously employed the same frequency-and-dosage-amount approach to obviousness used by the [DC] here” (Hoffman-La Roche, FC 2014) and that “In re Cyclobenzaprine…does not warrant a different outcome” since, in that case, “there were no prior art clinical studies to suggest what would be a therapeutically effective formulation” (not “read” to “establish[] a rigid rule categorically precluding obviousness without pk/pd data”). The FC panel also agreed with the DC that improved tolerability as well as reduced frequency and severity of side effects were reasonably expected from the prior art and common sense (e.g., “reducing the number of injections they receive would reduce the number of times they have a reaction”). The DC decision was therefore affirmed.

This entry was posted in Claim Construction, Generics / ANDA, Obviousness, Obviousness-Teaching Away. Bookmark the permalink.

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