Last week, Pfizer, Inc. (“Pfizer”) filed two petitions for inter partes review (“IPR”) of two patents related to Genentech and Biogen’s Rituxan® (rituximab).  One petition challenges all but two claims of U.S. Patent No. 7,682,612 (“the ʼ612 patent”), and has been assigned IPR2017-02126.  The other petition seeks review of all nine claims of U.S. Patent No. 8,206,711 (“the ʼ711 patent”), and has been assigned IPR2017-02127.

The challenged claims of the ’612 patent include methods of treating chronic lymphocytic leukemia (“CLL”) by administering an anti-CD20 antibody to the patient in an amount effective to treat CLL, wherein the method does not include treatment with a radiolabeled anti-CD20 antibody (referred to as “single agent” claims).  In addition, Pfizer has challenged claims directed to methods of treating CLL by administering an anti-CD20 antibody in combination with chemotherapy (referred to as “combination” claims).  The two claims of the ʼ612 patent that are not being challenged require the anti-CD20 antibody to be a “human antibody.”

With respect to the “single agent” claims, Pfizer asserts that a joint press release from Genentech and IDEC (who subsequently merged with Biogen) issued before the priority date of the ʼ612 patent “disclosed that they were ‘planning’ clinical trials with rituximab to treat patients with ‘chronic lymphocytic leukemia’ based on ‘encouraging results’ using the drug for another cancer, low-grade non-Hodgkin’s lymphomas (‘NHL’).”  Pfizer argues it would be reasonably expected for “rituximab to treat CLL patients effectively” because it “had already been shown that rituximab can effectively treat NHL by targeting and destroying [cancerous B-] cells” that express the CD20 antigen.

Pfizer asserts the “combination” claims are also obvious because the prior art “taught that rituximab made cancerous B-cells more vulnerable to the effects of chemotherapy…”  Indeed, Pfizer argues that the prior art “expressly suggested using rituximab in ‘combination with or after standard chemotherapy.’”

The challenged claims of the ’711 patent are directed to methods of treating CLL by administering rituximab to a patient in an amount effective to treat CLL where the dosage is at 500 mg/m2.  The ʼ711 patent also contains a claim directed to administering an effective amount of rituximab to a patient at a dosage of 500 mg/m2 in combination with another chemotherapeutic agent comprising fludarabine and cyclophosphamide. Pfizer has challenged all of the ʼ711 patent claims.

For the ʼ711 patent claims, Pfizer again asserts that the Genentech/IDEC press release would have provided a reasonable expectation that rituximab could be effectively used to treat CLL patients.  Pfizer also argues the claimed dose was obvious because that dosage was within the range disclosed in prior art as effective to achieve a “rapid, and specific depletion of the B cells in all [NHL] patients.” Pfizer’s alternative reasoning is that the prior art taught that “B-cell depletion was ‘dose-dependent’ (meaning the greater the dose, the greater the depletion), and a 375 mg/m2 weekly dose was preferred for NHL patients.”  However, Pfizer contends that a person of ordinary skill would have known that a dose higher than 375 mg/m2 “would likely be necessary to treat CLL because…CLL patients have many more (on average, a 100 times more) cancerous B-cells than NHL patients.” Finally, Pfizer asserts the prior art taught that cyclophosphamide and fludarabine “effectively treated CLL patients, resulting in at least partial clinical responses in most patients.”

These two petitions are the latest that Pfizer has filed seeking review of patents related to Biogen and Genentech’s Rituxan® product.  As we previously reported here and here, Pfizer has filed four other petitions seeking review of certain patents.  Pfizer’s petition seeking review of U.S. Patent No. 7,820,161 was instituted and joined with Celltrion, Inc.’s (“Celltrion”) petition seeking review of the same patent.  The PTAB has not yet reached institution decisions in Pfizer’s other three petitions.

As we previously reported, Celltrion has also challenged the ʼ612 and ʼ711 patents.  The PTAB has not yet reached an institution decision on those petitions, but is expected to do so within the next few weeks.  Pfizer asserts that the grounds for institution advanced in its petitions “are different from the grounds asserted by petition Celltrion,” and “also includes prior art…not relied upon by the petitioner Celltrion.”

Rituximab is an anti-CD20 chimeric murine/human monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma, chronic lyphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangitis, and microscopic polyangitis.

We will keep you updated on future developments.