On Wednesday, August 9, 2017 I will be present as a featured speaker during the one-hour webinar, “The BPCIA Patent Dance: Recent Trends, Developments and Court Decisions,” hosted by the Knowledge Group.
Event Title: The BPCIA Patent Dance: Recent Trends, Developments and Court Decisions LIVE Webcast
Event Date: Wednesday, August 9, 2017 @ 3:00 PM to 4:00 PM (ET)
Homepage link: https://www.theknowledgegroup.org/webcasts/legal/intellectual-property-law/the-biosimilar-patent-dance
I have several complimentary passes available to those interested in registering for the event. Please contact me directly if you are interested in registering.
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.
On July 6, 2017, the U.S. Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB) struck down a key patent on Abbvie’s blockbuster rheumatoid arthritis drug, Humira® (adalimumab). This was the second time in as many months that the PTAB struck down U.S. Patent No. 8,889,135 (“the ‘135 patent) finding it obvious over the prior art. The Final Written Decisions by the PTAB were issued in IPR2016-00408 and IPR2016-00409, both IPRs filed by Boehringer Ingelheim. The ‘135 patent was previously struck down on May 16, 2017 as obvious in IPR2016-00172, an IPR filed by Coherus.
The ‘135 patent is directed to methods of treating rheumatoid arthritis with a human anti-tumor necrosis factor α (TNF) antibody known as Humira®. 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….”
The ‘135 patent is important because it covers the dosing and treatment regimen of the drug, which is necessary for any biosimilar drug looking for gain FDA approval.
In each of its Final Written Decisions, the PTAB relied on different combinations of prior art as the basis for finding obviousness. In particular, the PTAB rejected Abbvie’s argument that the commercial success of Humira® supported the nonobviousness of the claimed invention, stating, in part, that Abbvie failed to establish a nexus between the commercial success and the claimed dosing regimen.
On a positive note, Abbvie successfully petitioned the USPTO to extend the term of the ‘135 patent by about 300 days, which means that Humira® could gain nearly one additional year of market exclusivity. To gain this additional time, however, AbbVie would need to successfully appeal the IPR decisions against it.
Other patents covering Humira® have also been under attack. On June 9, 2017, the PTAB has issued Final Written Decisions in IPRs filed by Coherus against two other Humira® patents, U.S. Patent No. 9,017,680 (the ‘680 patent) and U.S. Patent No. 9.073,987 (the ‘987 patent), finding the patent claims obvious over the prior art in IPR2016-00188 and IPR2016-00189, respectfully. The ’680 patent, like the ’135 patent, is directed to methods of treating rheumatoid arthritis with human anti-TNFα antibody, while the ’987 patent is directed to methods of treating rheumatoid arthritis by subcutaneously administering a 40 mg dose of human anti-TNFα antibody once every 13–15 days.
One other Humira® patent, U.S. Patent No. 9,085,619 (the ‘619 patent), which covers the formulation of Abbvie’s antibody, is also under challenge at the PTAB.
The PTAB’s decisions here show the vulnerability that biotech and pharma patents face from IPR challenges. Humira® has been the leading drug on the market since about 2011. It costs approximately $3,100USD a month and generates Abbvie billions of dollars a year in revenue, $16 billion in global sales in 2016 alone. If patents protecting blockbuster drugs like Humira® are susceptible to IPR attack, companies that invest millions into developing these biopharmaceutical products should conduct regular reviews of their high value patent properties and develop strategies for better protecting such properties a post grant challenge.
BioPharma Law Blog posts updates and analyses on IP topics, FDA regulatory issues, emerging legal developments, and other news in the constantly evolving world of biotech, pharma, and medical devices.