Pfizer Files IPR Petitions Against Biogen’s Rituximab Patents

On April 21, 2017, Pfizer filed two IPR petitions against Biogen’s patents directed to methods of treating non-Hodgkin’s Lymphoma with rituximab:

Patent Number/IPR	Claim 1
8,557,244 IPR2017-01166	1. A method of treating a patient with diffuse large cell lymphoma, comprising administering an unlabeled chimeric anti-CD20 antibody and CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone) chemotherapy to the patient, wherein the patient is >60 years old and has bulky disease (tumor >10 cm in diameter).
8,329,172 IPR2017-01167	1. A method of treating low grade B-cell non-Hodgkin's lymphoma in a human patient comprising administering to the patient chemotherapy consisting of CVP therapy to which the patient responds, followed by rituximab maintenance therapy, wherein the maintenance therapy comprises four weekly administrations of rituximab at a dose of 375 mg/m.2 every 6 months, and wherein the maintenance therapy is provided for 2 years.
9,296,821 IPR2017-01095 Filed by Celltrion but not Pfizer	1. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient a therapeutically effective amount of rituximab during a chemotherapeutic regimen, wherein the chemotherapeutic regimen consists of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the method comprises administering 375 mg/m2 of rituximab, and wherein the method provides a beneficial synergistic effect in the patient.

Celltrion and Boehringer have also filed petitions against these two patents:

AIA Review #		Filing Date	Institution Decision Date	Petitioner			PO/Respondent Patent #	Respondent	Status
IPR2015-00418		12/15/2014	07/13/2015	Boehringer Ingelheim Pharmaceuticals, Inc.			8329172	Biogen Inc.	Terminated
IPR2017-01093		03/15/2017		Celltrion Inc.			8329172	Biogen, Inc.	Pending
IPR2017-01166		04/21/2017		Pfizer, Inc.			8329172		Pending
IPR2017-01094	03/15/2017				Celltrion Inc.	8557244		Biogen, Inc.	Pending
IPR2017-01167	04/27/2017				Pfizer, Inc.	8557244			Pending

The PTAB denied Boehringer’s IPR petition because Boehringer failed to show that the prior art it relied on (clinical trials) were publicly available before the priority date of the patents.  Celltrion subsequently filed petitions against the same patent relying on the same clinical trials as Boehringer.  Celltrion, however, relied on a new declarant who allegedly has personal knowledge of the clinical trials and could verify that the clinical trials were publicly disclosed before the priority dates of the patents. 

In its IPR petitions, Pfizer does not rely on the clinical trials relied on by Boehringer and Celltrion.  Pfizer relies on the following two grounds of invalidity, which include the Coiffier and the McNeil references that were also relied on by Celltrion:

Ground 1

[A] POSA would have been motivated to add rituximab to a regimen of CHOP for patients over 60 with bulky disease, particularly in light of Shipp’s[1] teaching that CHOP treats patients over 60 years old with bulky disease and Link’s[2] teaching that the addition of rituximab adds efficacy but not toxicity. McNeil[3] expressly suggested combining these teachings by suggesting “CHOP plus the monoclonal antibody [rituximab]” as an “alternative” for patients over 60 years old with intermediate-grade NHL.

Ground 2

A POSA would have been motivated to combine rituximab, a “chimeric antiCD20 antibody,” to the regimen disclosed by Shipp in light of Coiffier.[4] Coiffier taught that rituximab—a chimeric anti-CD20 antibody—had activity in intermediate grades of NHL, but without the toxicity of normal CHOP regimens. Coiffier demonstrated that although one of the “dominant features of [its patient] population [was] a relatively old age,” the response rate was “above the minimal desirable threshold that was defined by the protocol and is similar to what would be expected with single-agent therapy in this patient population.” A POSA would have understood from Coiffier that rituximab had anti-cancerous activity in elderly patients with NHL and was a viable treatment option for them.

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[1] J. Clin. Oncol., 13(12):2916-2923 (1995)

[2] American Society of Clinical Oncology, Program/Proceedings, Thirty-Fourth Annual Meeting, (May 1998)

[3] J. Nat’l Cancer Inst., 90(4):266-67

[4] Blood, 92(6):1927-1932 (1998)