October 20, 2016
Brief Summary: SP’s petition for IPR of US 8,349,321 directed to a particular formulation of natalizumab (marketed by Biogen IDEC as TYSABRI®) for obviousness denied.
Summary: Swiss Pharma (SP) filed a petition for IPR of US 8,349,321 directed to a particular formulation of natalizumab (marketed by Biogen IDEC as TYSABRI®). US 8,815,236 (method of treatment) and 8,900,577 (20 to 150 mg/ml formulation) were also unsuccessfully challenged in IPR2016-00912 (decided Oct. 17, 2016) and IPR2016-00916 (decided October 17, 2016), respectively. Exemplary ‘321 claim 1 is directed to “[a] stable, aqueous pharmaceutical formulation comprising 20 mg/ml of natalizumab, about 10 mM sodium phosphate buffer, 8.18 mg/ml sodium chloride, and 0.2 mg/ml of polysorbate 80, and wherein the formulation has a pH of 6.1.” The Board determined that none of the claim terms required construction (broadest reasonable construction in light of the specification (Cuozzo, US 2016)). SP’s petition argued ‘321 claims 1-4 would have been obvious over the van Oosten (IV infusion of humanized mouse anti-TNF antibody to treat MS), Zenapax (IV preparation of anti-IL-2 receptor antibody) and Sorbrera (discussing natalizumab for treating IBD), or the Gordon reference (5 mg/ml antibody formulation) with Orthoclone (immunosuppressive anti-CD3 antibody) or Aversano (chimeric anti-CD18 antibody), and relied on two expert declarations. Each of the references were alleged to show formulations similar to that of the ‘321 claims (e.g., van Oosten and Zenapax were alleged to teach a “formulation comprising the identical excipients recited by the claims-sodium phosphate buffer, sodium chloride and polysorbate 80”). While SP acknowledged neither of van Oosten or Zenapax disclosed natalizumab, “the ‘actives [of van Oosten and Zenopax] qualify as simple substitutes under the case law” and modification to the claimed concentration (20 mg/ml) from that of the references (10 and 5 mg/ml) “is nothing more than routine optimization of a result effective variable.” Biogen IDEC argued that “achieving a stable liquid formulation of a [mAb] was an unpredictable and highly antibody-specific challenge” (“high-concentration (e.g., 20 mg/ml) liquid antibody formulations…were particularly difficult to achieve”). The Board concluded that SP did not “demonstrate sufficiently that the adjustment…to 20 mg/ml would have been a matter of routine optimization” (e.g., “Gordon does not suggest the desirability or need for a higher IgG concentration….Xylocaine…and Naropin are both small molecule drugs and Dr. Schoneich does not explain why the ordinary artisan would look to those teaching[s] in formulating the claimed antibody solution.”) Thus, the Board found SP failed to establish a reasonable likelihood of prevailing in showing obviousness.