U.S. Pat. No. 6,436,989B1
July 9, 2015
Brief Summary: Petition to institute IPR ordered for claims 1, 4-8 and 9 of Vertex’s US 6,436,989B1 encompassing fosamprenavir calcium (marketed as Lexiva). The petition was denied as to claims 2, 3 and 10-12 based on secondary considerations and unpredictability.
Summary: Lupin filed a petition to institute IPR of Vertex’s US 6,436,989B1 encompassing prodrugs of HIV aspartyl protease inhibitors (claims 1-3) (including phosphate prodrugs of amprenavir / VX-478, including fosamprenavir calcium (marketed as Lexiva)), pharmaceutical compositions thereof (claims 4-8), and methods of treating mammals therewith (claims 9-12). The petition argued obviousness in view of a combination of two or three references disclosing an anti-HIV effective oral pharmaceutical composition of VX-478, difficulties in formulating the same, and the addition of a “solubilising group” (“a sodium or potassium salt of a phosphate or phosphite residue) to the hydroxyl group of another known HIV protease inhibitor having some structural similarities to fosamprenavir. Vertex argued “that there was not a reasonable expectation of success that a phosphate ester salt derivative of VX-478 would have been successful as a bioavailable alternative to VX-478” in view of deficiencies in the prior art and unpredictability in the field. Vertex also argued objective indicia of non-obviousness including unexpected results, long-felt need, copying of others, failure of others, commercial success, and a nexus between those and the claimed invention. The Board “agree[d] with the Petitioner that Grobelny provides an exemplary roadmap for using a phosphate ester salt derivative at the free hydroxyl of VX-478 for solving the solubility problem of VX-478 that was missing in the teaching of Roy.” However, it also found the secondary evidence persuasive and commensurate with claims 2 and 3 “directed only to the common salts” but not claim 1 which includes “compounds that are not phosphate esters.” It therefore found a reasonable likelihood that Lupin would prevail in demonstrating the unpatentability of claims 1, 4-8 (due to their dependency from claim 1), and claim 9. Claims 10-12 escaped this conclusion because the same require treatment of HIV infection, which is unpredictable. Thus, the Board ordered IPR of claims 1 and 4-9.