Amgen Inc. v. Sandoz Inc. et al.
Docket No. 2020-1147, 1149-51 (https://cafc.uscourts.gov/opinions-orders/22-1147.OPINION.4-19-2023_2113208.pdf)
LOURIE, CUNNINGHAM, STARK
April 19, 2023
Brief Summary: DC finding that two of Amgen’s Otezla® composition patents not invalid for obviousness affirmed. DC finding that another of Amgen’s Otezla® method of treatment patents invalid for obviousness affirmed.
Summary: Sandoz appealed DC holding claims 3 and 6 of Amgen’s US 7,427,638 and claims 1 and 15 of its US 7,893,101 not invalid for obviousness. Amgen cross-appealed DC finding that claims 2, 19 and 21 of its US 10,092,541 invalid as obvious. These Orange Book patents (three of 11 listed) relate to Amgen’s apremilast product for inhibiting phosphodiesterase-4 (PDE-4) for treating psoriasis and related conditions (stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2- methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione; Otezla®; NDA 205437). Celgene assigned the patents to Amgen, and initially filed this Hatch-Waxman suit against Sandoz.
Sandoz alleged ‘638 claims 3 and 6 were invalid as obvious over US 6,020,358 and a PCT application WO 01/034606 as the ‘358 patent as it describes “a racemic mixture containing apremilast” (a mixture including 50% of the (+) enantiomer) and “a genus of phosphodiesterase inhibitors, including a racemic mixture containing apremilast” with “seventeen example compounds that fall within the scope of the claimed genus”. Both references were argued to teach “that racemates can be separated into individual enantiomers.” The DC concluded Sandoz did not show a “reason or motivation to resolve the Example 12 racemic mixture into its enantiomers”, “that the desirable properties of Example 12 derived in whole or in part from the apremilast enantiomer”, “a reasonable expectation of success in resolving Example 12 into its individual enantiomeric components”, and a nexus between the claims and unexpected “substantial improvement over previously known” PDE inhibitors, “a long-felt need for a psoriasis treatment that was suitable for oral administration to a patient, without the risks and barriers to adherence that were common with other psoriasis treatments”, failure of others in development, skepticism in the industry, and “the commercial success of Otezla since it achieved FDA approval”. The FC panel found no clear error with the DC’s conclusion (distinguishing it from PharmaStem, FC 2007 (“not unfair to hold the inventors to the consequences of their admissions because their characterization of the prior art references was not unreasonable”); and citing, e.g., Ortho-McNeil, FC 2008 and Ruiz, FC 2000 (objective indicia); stating there is no “line between a difference in degree insufficient to rebut a showing of obviousness and a difference in kind that may be sufficient to do so; each inquiry need be fact-specific” (Bristol-Myers, FC 2014).
Sandoz alleged the forms and compositions of the ‘101 claims, “directed to solid forms (e.g., crystalline polymorphic forms) of apremilast” (“Form B”), were not “explicitly nor inherently disclosed” in the priority provisional application (Yeda, FC 2016; Bettcher, FC 2011; In re Cruciferous, FC 2002; In re Olerich, CCPA 1981) and that Celgene “represented to the [EPO] that following Example 2 could result in crystalline Form C of apremilast as well as Form B.” The DC disagreed based in part on Amgen’s expert testimony that Celgene’s representation was a mistake. The FC panel agreed with the DC that ‘101 claims 1 and 15 are entitled to the priority date and did not address inherency as the evidence supported Form B was “actually disclosed”. The FC panel also found no error with the DC’s finding the Celgene made a mistake in its statements to the EPO. Sandoz alleged the asserted claims of the ’541 patent, directed to dose titration methods of treatment, were obvious over three clinical trial-related prior art references, and the DC agreed as to claims 2, 19, and 21 (“a routine aspect of treating psoriasis with a drug like apremilast”, “obvious to try” (In re Cyclonezaprine, FC 2012 (“obvious-to-try theory must show that the possible options skilled artisans would have encountered were finite, small, or easily traversed”)). The FC panel found no error with the DC’s conclusion of obviousness (e.g., “routine aspect of treating psoriasis”; Genentech, FC 2022 (“well-established, hence obvious, practice”)).