Last week I wrote about the Patent Trial and Appeal Board’s (the “PTAB”) invalidation of U.S. Patent No. 8,889,135 (“the ‘135 patent) covering Abbvie’s blockbuster rheumatoid arthritis drug, Humira® (adalimumab), for the second time in two months finding it obvious over the prior art. The ‘135 patent is a key patent in the Humira® patent portfolio because it covers the dosing and treatment regimen of the drug, features that any biosimilar drug will need to gain FDA approval. The Final Written Decisions by the PTAB were issued in IPR2016-00408 and IPR2016-00409, both IPRs filed by Boehringer Ingelheim. In this post I delve into a little more detail behind the specific reasoning supporting the PTAB’s invalidation of claim 1 of the ‘135 patent as being obvious in IPR2016-00408 because it reveals potential critical flaws lurking in many method of treatment claims.
The ‘135 patent is directed to methods of treating rheumatoid arthritis with a human anti-tumor necrosis factor α (TNF) antibody known as Humira® (adalimumab). Specifically, Claim 1 is directed to “A method for treating rheumatoid arthritis in a human subject, comprising administering subcutaneously to a human subject having rheumatoid arthritis a total body dose of 40 mg of a human anti-TNFα antibody once every 13-15 days for a time period sufficient to treat the rheumatoid arthritis….” (emphasis added)
The PTAB’s decision not only has significant implications for Abbvie, which now faces several post-grant challenges of its Humira® patent portfolio, but also for other biotech and pharma companies that often obtain and rely on method of treatment claims for protecting their products. In particular, this decision highlights the vulnerability that method of treatment claims not requiring a specific level of efficacy face in light of prior art describing results of clinical trials.
The human anti-TNFα antibody used in the claimed dosing regimen is D2E7, the active agent in Humira®. The PTAB found that the challenged claims of the ‘135 patent were obvious in light of two prior art references, van de Putte 2000 and Rau 2000, both of which described results of clinical trials using the same antibody. In finding the challenged claims of the ‘135 patent obvious, the PTAB construed the phrase “for a time period sufficient to treat rheumatoid arthritis” under the broadest reasonable interpretation standard, when read in light of the specification, as meaning “for a time period sufficient to reduce the signs, symptoms, and/or progression of RA.” The PTAB emphasized that such a construction did not require any particular level of efficacy. In other words, under the PTAB’s interpretation, efficacy could not be used to distinguish the claims from the prior art.
In supporting its construction of the claim language as not requiring efficacy, the PTAB turned to the specification of the ‘135 patent. The PTAB rejected Abbvie’s position that the phrase should mean “for a time period sufficient to reduce significantly the signs and symptoms of rheumatoid arthritis” because the specification only described “administering the antibody for therapeutic purposes to alleviate the symptoms and/or progression of RA” but did not provide a discussion about efficacy levels. Abbvie argued that a person of ordinary skill in the art “would have been motivated to pursue an effective treatment regimen, not one that merely provided baseline functionality”. The PTAB, however, remained unconvinced by Abbvie’s arguments, reiterating the lack of any new intrinsic evidence supporting Abbvie’s proposed construction.
The PTAB’s interpretation as not requiring efficacy is important because it prevented Abbvie from distinguishing the ‘135 claims from the two prior art references based on efficacy. While Abbvie did not challenge the PTAB’s decision that all the claim elements were present in the combination of van de Putte and Rau, Abbvie instead tried to argue that one of skill in the art would not have been motivated to combine the references, in part, because the combination would have resulted in reduced efficacy. According to Abbvie, the prior art actually taught away from combining the two references because Rau’s biweekly dosing regimen using 0.5 mg/kg (equivalent to a fixed dose of 40 mg in the average patient of 80 kg) was ineffective across the entire population. In rejecting Abbvie’s arguments, the PTAB found that Rau did not specifically indicate that the 0.5 mg/kg does was “ineffective” at treating RA. Moreover, the PTAB relied on its construction of the phrase “for a period of time sufficient to treat rheumatoid arthritis” as not requiring any particular level of efficacy. To this end, the PTAB dismissed Abbvie’s arguments about efficacy.
The PTAB’s decision in rendering the method of treatment claims of the ‘135 patent obvious over the prior art because they failed to recite a specific level of efficacy has broad implications for biotech and pharma companies. Companies developing biopharmaceutical products often rely on method of treatment claims as a means of protecting their products. In doing so, claims are often broadly drafted to include terms like “to treat”, “to prevent”, “to reduce”, “to mitigate”, but without reciting specific efficacy levels. To protect such patent claims from IPR challenge, it is now important to include additional language concerning efficacy levels in the claims, or at least, to provide a clear definition of “to treat” in the specification.
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