Opinion ID: 4766018
Heading Depth: 2
Heading Rank: 2

Heading: IPR Petitions and Prior Art

Text: Lilly filed petitions for inter partes review of claims 1, 3, 4, 8–17, 19, 20, and 24–31 of the ’045 patent, claims 1– 18 of the ’907 patent, and claims 1–18 of the ’908 patent. Lilly asserted that each of the challenged claims would Case: 20-1876 Document: 50 Page: 6 Filed: 08/16/2021 6 ELI LILLY AND COMPANY v. TEVA PHARMACEUTICALS have been obvious over a combination of prior art references that includes Olesen, 2 Tan, 3 and Queen. 4 Olesen describes a clinical trial proving the efficacy of BIBN4096BS (“BIBN”), a nonpeptide CGRP-receptor antagonist, in the treatment of migraine. In Olesen’s study, patients receiving 2.5 mg of BIBN intravenously over a period of 10 minutes had a 66% response rate, with a painfree rate of 44% after two hours and a recurrence rate of 19%. See Board Decision, 2020 WL 1540364, at  (citing Olesen). In short, Olesen teaches that BIBN was effective and safe in treating acute attacks of migraine. Olesen also discusses past studies and discloses that CGRP may have a role in initiating and mediating migraine attacks. J.A. 3741. Tan is a publication describing an in vivo study in rats using an anti-CGRP monoclonal antibody for immunoblockade. 5 The study investigated the anti-CGRP activity of a full-length monoclonal antibody called “MAb C4.19” as well as its Fab’ fragment. 6 See J.A. 3708–18. Tan describes the results of one experiment demonstrating that both the 2 J. Olesen et al., Calcitonin Gene-Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine, N. ENG. J. MED. 350, 1104–10 (2004). 3 K.K.C. Tan et al., Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab’ fragment, 89 CLINICAL SCI. 6, 565–73 (1995). 4 U.S. Patent 6,180,370. 5 Tan defines “immunoblockade” as “the blockade of the effects of a biological mediator by inhibition of its binding to specific receptors with antibodies directed against the mediator.” J.A. 3711. 6 A “Fab’ fragment” is the portion of an antibody that binds to the target antigen. Case: 20-1876 Document: 50 Page: 7 Filed: 08/16/2021 ELI LILLY AND COMPANY v. TEVA PHARMACEUTICALS 7 full-length antibody and the Fab’ fragment successfully achieved immunoblockade by inhibiting the effects of exogenously administered CGRP. See J.A. 3711–12. Tan also describes the results of a second experiment analyzing whether the antibody and its Fab’ fragment inhibit endogenous CGRP-induced blood flow after a prescribed incubation period. J.A. 3714. The results demonstrated that the Fab’ fragment effectively blocked skin blood flow after a 30minute incubation period. Id. The full-length antibody did not block skin blood flow after a 60-minute incubation, but a 2-hour incubation period and higher dose resulted in a 16% block in skin blood flow. Id. Tan posited that “much larger doses and longer distribution times are required for successful immunoblockade” with the full-length antibody. J.A. 3716. Queen “relates generally to the combination of recombinant DNA and monoclonal antibody technologies for developing novel therapeutic agents.” J.A. 27230 at col. 1 ll. 19–21. Specifically, Queen discloses a method of humanizing antibodies to address traditional problems associated with injecting monoclonal antibodies from donors (e.g., mice) into humans.