The PTAB held that all of Genentech’s challenged antibody purification claims were unpatentable as being anticipated, obvious, or both, in an IPR filed by Hospira and Pfizer, Hospira, Inc., v. Genentech, Inc., IPR2016-01837, Paper 40 (P.T.A.B. March 6, 2018).

The technology at issue related to a protein purification technique using protein A chromatography for the production of antibodies. Genentech’s patent at issue (Pat. No. 7,807,799, the “’799 patent”) stated that the disclosed methods were beneficial for reducing the “leaching” of protein A from the solid phase into the antibody product pool, which could contaminate the product. The sole independent claim at issue did not recite any particular antibody product:

1. A method of purifying a protein which comprises a CH2/CH3 region, comprising subjecting a composition comprising said protein to protein A affinity chromatography at a temperature in the range from about 10 °C to about 18 °C.

The PTAB construed “about 18 °C” as “18 ± 3 °C,” and did not construe the claims to require reduction in protein A leaching. Some dependent claims recited that the protein of the method is a specified antibody, e.g.,:

9. The method of claim 8 wherein the antibody is Trastuzumab or humanized 2C4.

In view of this dependent claim, some commentators have viewed this IPR as part of a larger challenge by Hospira and Pfizer against Genentech’s trastuzumab portfolio.

Regarding anticipation, Hospira and Pfizer had asserted that two separate references each taught purifying antibodies with protein A chromatography at temperature ranges that overlapped with the claimed range (the prior art ranges were “room temperature (18 - 25 °C)” and “20 – 25°C”).

Genentech argued that the claimed temperature range was critical, and thus could not be anticipated based on overlap alone. Specifically, Genentech argued that undesirable protein A leaching generally increases with temperature, and the claimed range was critical because the increase in leaching is “relatively flat” over that range (See, e.g., Patent Owner’s Resp., Paper 23 at 32, 30–34 citing Ex. 2008 at ¶¶112-21, a portion of which is reproduced below):

The PTAB rejected this argument. The PTAB stated that “criticality has been found where only a narrow range of temperature enabled a process to operate as claimed, and problems occurred in practicing the invention below or above the claimed range” (Paper 40 at 23, citing Atofina v. Great Lakes Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006)). The PTAB found that protein A chromatography was known in the prior art to work at temperatures below the claimed range (for example at about 4°C) and that these lower temperatures would be expected to achieve even lower rates of leaching. Based on this finding, the PTAB concluded that the claimed range was not critical because protein A chromatography would work outside of the claimed range, and would be expected to work better (with respect to leaching) at temperatures below the claimed range. The PTAB held Claims 1, 2, and 5 unpatentable as anticipated.

Regarding obviousness, the PTAB held all of the challenged claims unpatentable on five obviousness grounds that were over the same primary references as the anticipation grounds. The PTAB applied similar reasoning to all five obviousness grounds, concluding that a relationship between leaching and temperature was known in the prior art, and that “exploring the temperature dependence of protein A leaching is not more than routine experimentation.”

Successful invalidation of claims based on anticipation (rather than obviousness) has generally been rare in IPRs involving biologic large molecules, particularly anticipation grounds not based on an underlying priority claim attack