Plerixafor – USA

On Dec 18, 2017, The Federal Circuit affirmed a Delaware judge's decision that ANDA filers Dr Reddy’s & Teva Pharmaceuticals failed prove the obviousness of Mozobil (Plerixafor) patent since there was no reasonable expectation of success.

This consolidated set of appeals arises from a Hatch-Waxman action brought by Genzyme Corporation and Sanofi-Aventis U.S. LLC (collectively, Genzyme) against Dr. Reddy’s Laboratories and Teva Pharmaceuticals (collectively, DRL). After a bench trial, the district court held that DRL failed to prove that claim 19 of U.S. Patent No. 7,897,590 (the ’590 Patent) is invalid for obviousness. The ’590 Patent makes use of a regimen comprising a combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor to increase the number of stem cells in the blood for collection. Claim 19 of the ’590 Patent was the only claim at issue in this set of appeals. It recites a “method to obtain progenitor and/or stem cells” by (1) administering G-CSF to a subject; (2) administering plerixafor or a pharmaceutically acceptable salt thereof to the subject, in an amount effective to mobilize the progenitor and/or stem cells; and (3) harvesting the progenitor and/or stem cells.

As part of its obviousness challenge, DRL presented the following prior art: (1) Hendrix et al., (2) International Patent Application Publication No. WO 00/45814 (WO ’814); and (3) U.S. Patent No. 5,824,304 (the ’304 Patent). Hendrix disclosed “binding of [plerixafor] to CXCR4 may inhibit the chemotactic effects of SDF-1α, causing release of WBCs from the endothelium and/or stem cells from bone marrow.” The ’304 Patent teaches a method for increasing the number of stem cells in the peripheral blood by administering a blocking agent of VLA-4 antigens. DRL argued that the only difference between the claimed invention and the ’304 Patent is that the ’304 Patent does not teach that the blocking agent can be plerixafor. But that would have been obvious, DRL argued, because Hendrix expressly suggested that plerixafor could function as a blocking agent for releasing stem cells from the marrow. The district court, however, found that Hendrix was not analogous art. Whereas Hendrix focused on HIV treatment, the ’590 Patent focused on mobilizing stem cells for subsequent harvest and transplantation. But even if Hendrix were deemed analogous art, the district court found that Hendrix would not have rendered claim 19 obvious. The district court expressly rejected DRL’s position that it was “reasonably predictable in October 2000 that plerixafor would mobilize stem cells in sufficient numbers for harvesting and transplantation.” It also found that the evidence established a “history of failure in the field”.

Federal circuit carefully considered the findings and all of the parties’ arguments, & discussed principally the parties’ dispute over whether a person of skill in the art would have had a “reasonable expectation of success” in achieving the claimed invention. The district court’s finding that stem cell mobilization was highly unpredictable at the time of the invention runs counter to an expectation of success. In particular, there was great uncertainty about the role of SDF-1 or CXCR-4, if any, in the process of stem cell mobilization. CXCR-4 antagonists were only studied in the HIV field, and there was a history of failure resulting from the investigation of more than a dozen candidates in the search for a better stem cell mobilization agent. No one had ever mobilized stem cells with any CXCR-4 antagonist, let alone plerixafor. DRL’s alternative basis for invalidating the ’590 Patent is the combination of the WO ’814 Patent and the ’304 Patent. Like Hendrix, “WO ’814 does not disclose information about using plerixafor to mobilize stem cells, but instead reveals the relationship between plerixafor and white blood cell elevation.” Ultimately, the deficiency regarding the combination of Hendrix and the ’304 Patent also undercuts the combination of WO ’814 and the ’304 Patent. As noted, sufficient evidence supported the district court’s finding of a lack of a reasonable expectation of success.

Federal circuit after reviewing the record surrounding the prior art and analyzing the arguments of the parties, finally held that the district court’s factual conclusions regarding an insufficient reasonable expectation of success were not clearly erroneous. Thus Federal circuit affirmed the district court’s holding that the ’590 Patent is not invalid.