Rituxan® Patents Resurface at the PTAB

Written by Casey Kraning, Ph.D., Tasha Francis, and Jenny Shmuel

Two patents related to methods of treating rheumatoid arthritis (RA) patients with rituximab have been brought before the PTAB for a third time - with mixed results.

The challenged patents are U.S. Patent Nos. 7,976,838 and 7,820,161. The '838 patent, owned by Genentech, Inc., relates specifically to methods of treating RA patients who demonstrate an inadequate response to a TNFa-inhibitor. The '161 patent, co-owned by Genentech and Biogen, Inc., is directed to methods of treating RA patients with both rituximab and methotrexate. Rituximab is a chimeric murine/human monoclonal antibody which, in addition to treating RA, was also the first FDA-approved monoclonal antibody cancer treatment, targeting cancers of the white blood system. Currently marketed as Rituxan®, it brought in over $7 billion in global sales in 2015.

The two Rituxan patents have an unusual history at the PTAB. The '838 and '161 patents were first challenged in 2014 by Boehringer Ingelheim Pharmaceuticals in IPR2015-00417 and IPR2015-00415, respectively. The PTAB instituted IPR review on all fourteen claims of the '838 patent, and half of the twelve claims of the '161 patent (claims 1-2, 5-6, and 9-10). Shortly after institution, Celltrion filed its own petitions and motions to join both of Boehringer's IPRs. In its motions for joinder, Celltrion represented that it would coordinate its activities with Boehringer and not offer separate argument, expert testimony, or briefing.

According to Celltrion, while the parties were negotiating a stipulation to that effect, Boehringer, without consulting with Celltrion, requested authorization to file a motion to terminate the proceedings. The PTAB construes such an abandonment of the contest as a request for adverse judgment against the party abandoning the contest, and judgment was entered accordingly. Boehringer's request came less than two weeks before the scheduled deposition of its key expert, Dr. Kalden, on whose declaration and testimony Celltrion intended to rely. Further, Boehringer prohibited Celltrion from retaining Dr. Kalden for its own proceedings. Thereafter, Celltrion presented these facts to the PTAB and requested dismissal of its own IPR without prejudice, so that it would be free to re-file with its own expert. The PTAB granted Celltrion's request, and Celltrion subsequently re-filed the current petitions roughly ten months later marking the third challenge for both patents.

On February 24, the PTAB instituted IPR review of claims 1-3, 5-7, and 9-11 of the '161 patent, based on essentially the same obviousness grounds that succeeded in the Boehringer IPR. Notably, patent owners Genentech and Biogen elected not to file a preliminary response to Celltrion's petition.

In an interesting twist, the PTAB then denied institution in Celltrion's second challenge of the '838 patent in IPR2016-01667, after previously granting institution on all of the claims during the Boehringer challenge. The Boehringer petitioners had succeeded in persuading the Board to institute IPR based on its obviousness arguments. The Boehringer petitioners did little more than present the six pieces of asserted prior art, and state in a conclusory fashion that "[a] person of ordinary skill would have reason to combine the teachings of the above references with a reasonable expectation of success." From that list of prior art, the PTAB then selected the two combinations of references which it determined had a reasonable likelihood of success. In Celltrion's recent challenge, rather than assert extraneous pieces of prior art, Celltrion essentially selected the prior art which the PTAB had previously found persuasive, and presented detailed arguments on why those combinations alone were obvious. This time, however after considering Genentech's preliminary patent response the PTAB was not persuaded, finding that while "at first glance," one of the prior art references appeared to address the deficiency in the second prior art reference, on further review it did not result in a reasonable likelihood of success of the combination to treat RA.

Why the different outcomes for the '838 patent? While it's impossible to know for sure, it's worth noting a few key facts. First, two of the judges (Judge Franklin and Judge Snedden) served on both panels evaluating the '838 patent challenges, and thus were experienced with both the subject matter and the arguments, which may have influenced their decision. Second, Genentech's win in the '838 IPR could have been attributable to its ability to strategically prepare its counter-arguments, having access to the PTAB's previous reasoning. It is possible that the lack of such strategic counter-arguments in the record of the '161 IPR resulted in a more straightforward decision for the PTAB. It remains to be seen whether Genentech's counter-arguments regarding the '161 patent, when entered into the record, will be sufficient to prevail at trial.

We will continue to monitor these patents and report on updates as they are available.