As we previously reported, one of three Pfizer IPR petitions filed in April 2017 against Biogen-owned patents claiming methods of treatment with rituximab was instituted. The instituted IPR is IPR2017-01168 regarding U.S. Patent No. 8,821,873 (the “’873 patent”), and the PTAB recently issued its Final Written Decision.

Adhering to its institution decision where it consolidated the two asserted grounds into a single ground consisting of five references, the Board found all claims unpatentable over a combination of: (1) Moreau (Moreau et al., Peripheral blood stem cell transplantation as front-line therapy in patients aged 61 to 65 years: a pilot study, 21 BONE MARROW TRANSPLANTATION 1193–96 (1998)); (2) Link (Link et al., Phase II Pilot Study of the Safety and Efficacy of Rituximab in Combination with CHOP Chemotherapy in Patients with Previously Untreated Intermediate- or High-Grade NHL, Program/Proceedings, 17 AM. SOC. CLIN. ONCOL. 3a (Abstract 7) (1998)); (3) McNeil (McNeil, Non-Hodgkin’s Lymphoma Trials In Elderly Look Beyond CHOP, 90 J. NAT. CANCER INST. 266–67 (1998)); (4) Maloney (Maloney et al., IDEC-C2B8: Results of a Phase I Multiple-Dose Trial in Patients with Relapsed Non-Hodgkin’s Lymphoma, 15 J. Clin. Oncology 3266–3274 (1997)); and (5) Coiffier (Coiffier et al., Rituximab (Anti-CD20 Monoclonal Antibody) for the Treatment of Patients with Relapsing or Refractory Aggressive Lymphoma: A Multicenter Phase II Study, 92 BLOOD 1927–32 (1998)).

The ’873 patent generally relates to a method of treating a patient over the age of 60 who has diffuse large cell lymphoma (“DLCL”) by administering anti-CD20 antibody (e.g., Rituxan®) and CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone) chemotherapy “wherein the anti-CD20 is administered in combination with stem cell transplantation.” ’873 patent claim 1 (emphasis added). Claim 4 further claims that the lymphoma is accompanied by bone marrow involvement.

Importantly, during claim construction the Board found that under the broadest reasonable interpretation standard, administering rituximab “in combination with stem cell transplantation,” would include administering the rituximab during induction, which it found was described as one of the “various stages of transplantation” in the specification. FWD at 8 (finding that “in combination with stem cell transplantation” “means that the rituximab may be administered ‘at induction, in vivo purging, mobilization, conditioning, post-transplant reinfusion and at any other time during bone marrow or stem cell transplant for the purpose of improving the survival rate of transplant recipients”). As a result, the Board agreed with Petitioner that administering rituximab at the induction of CHOP chemotherapy but before collecting and transplanting stem cells would fall within the scope of the ’873 patent claims requiring that the antibody be administered in combination with the stem cell transplantation. Id.

In addition, the Board found that a person of ordinary skill in the art of would have at least an M.D. degree and more than a year of experience treating patients with NHL and would have familiarity with the published research and clinical trials directed to treating NHL patients. Id. at 10. Such a person could be an oncologist or hematologist.

With respect to obviousness, and consistent with its institution decision, the Board concluded that it was undisputed by the parties that the primary reference, Moreau, teaches all of the claim elements of claim 1 except for the use of rituximab. FWD at 16. The focus of the analysis, therefore, was whether “a person of ordinary skill in the art would have been motivated to combine rituximab with the CHOP in Moreau’s treatment method, and whether the person of ordinary skill in the art would have had a reasonable expectation of success in treating Moreau’s patient, i.e., a DLCL patient greater than 60 years old, by doing so.” Id. The Board found that there was sufficient motivation as well as a reasonable expectation of success. Id. at 31.

Petitioner argued that because only half of Moreau’s DLCL patients had complete responses, there was motivation to combine another treatment with Moreau’s treatment that would increase efficacy and/or reduce toxicity. Id. at 16-17. The Board found that Petitioner had sufficiently demonstrated that a person of ordinary skill in the art would have understood from McNeil that an alternative to CHOP in elderly patients is the combination of CHOP and rituximab, that Link taught that CHOP plus rituximab may provide an increased response in DLCL patients, that Coiffier taught that rituximab has “significant anti-lymphoma activity in DLCL,” and that Maloney taught that rituximab does not impair bone marrow reserves. Id. at 30. Further, the Board found that rituximab was shown to be well-tolerated and well-tolerated when combined with CHOP, and therefore, it agreed with the Petitioner that it was reasonable to expect Moreau’s well-tolerated method of treatment to remain well-tolerated in combination with rituximab. Id.

The Board also ruled on the parties’ motions to exclude. It denied Petitioner’s motion to exclude exhibits as moot because it had not relied on the exhibits. Id. at 34. It also denied Patent Owner’s motion to exclude the 1997 Rituxan label. Patent Owner argued that Petitioner had not established that the label existed and was available in 1997. Id. at 34-35. The Board noted that this issue related to the status of the exhibit as prior art and should have been raised in the briefing instead of in a motion to exclude. Id. at 35. It further found that Patent Owner failed to show that Petitioner had not sufficiently authenticated the exhibit and was not persuaded that the exhibit constituted hearsay. Id. The Board was likewise unpersuaded that other exhibits constituted hearsay and denied Patent Owner’s motion to exclude with respect to those exhibits. Id. And, it denied Patent Owner’s motion to exclude that was contingent upon the Board’s ruling on Petitioner’s motion to exclude given that the latter had been denied. Id. The Board also rejected Patent Owner’s arguments related to its motion to exclude the redirect testimony of Petitioner’s Reply declarant, Dr. Soiffer.

Given the foregoing, all claims of the ’873 patent have currently been held unpatentable.