Multiple IPRs challenging patents covering brand-name biologics have now been filed by biosimilar developers, for reasons we recently discussed, as well as by other entities. Institution decisions in these early IPRs and a small number of final written decisions suggest that broad mechanistic claims as well as follow-on patent claims—such as those covering methods of treating specific patient populations or specific dose regimens—will be vulnerable to obviousness challenges at the PTAB. However, a tougher time should be expected in challenging composition-of-matter patents.
The first such IPRs to reach a final written decision challenged broad method-of-treatment claims reciting mechanistic limitations and dosing limitations used when administering Myozyme® and Lumizyme®, marketed by Genzyme. The PTAB found all challenged claims to be unpatentable based on obviousness, stating that “the claimed subject matter was a product of routine clinical trial processes.” The PTAB was unconvinced by the patent owner’s arguments related to secondary considerations, finding an insufficient nexus between the evidence and the claim features. While BioMarin Pharmaceutical Inc. challenged these patents to clear a path for a competing biologic, rather than a biosimilar, the decisions nevertheless have relevance for potential biosimilar developers since the result could allow earlier market entry for biosimilars.
By contrast, in a proceeding initiated by Phigenix, Inc., challenging a patent covering Genentech’s Kadcyla® (an immunoconjugate comprising a specific antibody and a cytotoxic agent), the PTAB reached the opposite outcome, upholding all of the challenged claims. Notably, the claims in this case were composition-of-matter claims. The PTAB agreed with the patent owner that one of ordinary skill in the art would not have been motivated to combine the cited references, nor have had a reasonable expectation of success. Interestingly, while the PTAB has generally not placed much emphasis on secondary considerations, in the analysis of picture claims covering Kadcyla®, the PTAB found convincing evidence of long-felt need, unexpected results and commercial success, and found a sufficient nexus between the evidence and the claims.
In the first example of a petition filed directly by a biosimilar developer challenging a patent covering a reference product or method of use, the challenged claims were canceled because the patent owner simply conceded. Hospira, which was developing a biosimilar of Erythropoietin (“EPO,” marketed by Janssen as Procrit® and by Amgen as Epogen®), filed an IPR petition challenging claims covering methods of administering EPO. The patent owner chose to disclaim all challenged claims, terminating the proceeding. This favorable result for Hospira provided it with increased certainty at an early stage of its biosimilar development, before even submitting its application to the FDA.
Several biosimilar developers have filed IPR petitions challenging follow-on patents covering Rituxan®, a blockbuster therapeutic monoclonal antibody marketed in the U.S. by Genentech USA, Inc., and Biogen Idec Inc. Out of three initial petitions filed by Boehringer Ingelheim International GmbH and Boehringer Ingelheim Pharmaceuticals, Inc. (BI) challenging claims related to methods of treatment involving specific dose regimens, patient populations, and/or therapeutic combinations, two were instituted, while a third was denied institution. These proceedings were later terminated by BI. While it remains to be seen whether IPR challenges to Rituxan® will continue, the PTAB’s two institution decisions reveal vulnerability in the challenged patents.
Not surprisingly, given that the therapeutic monoclonal antibody Humira® is currently the top-selling drug in the world by sales, multiple parties have also filed IPR petitions challenging follow-on patents covering Humira®. Out of five petitions challenging claims directed to dose regimens, three filed by Coherus BioSciences Inc. have been instituted and an additional two filed by BI await a decision on institution. Out of three petitions filed challenging claims related to formulations, two filed by Amgen Inc. were denied institution, while a third filed by Coherus BioSciences Inc. is awaiting a decision on institution.
Early cases suggest that IPRs will be an effective mechanism for challenging follow-on patents covering biologics, and will likely be incorporated into most, if not all, biosimilar development strategies. However, not all patents may be appropriate for challenge via IPR. Given the significance and complexity surrounding the choices of which patents to challenge, and the timing in light of product development, companies are advised to consult with counsel who have specific experience in post-grant proceedings related to biologics and biosimilars.
Read more in our recent article, Impact of Post-Grant Proceedings on Biologics and Biosimilars, published in Bloomberg BNA’s Life Sciences Law & Industry Report.