District Court of Delaware Construes “Following Fermentation” in Genentech v. Amgen Trastuzumab and Bevacizumab Cases

We have previously reported on the BPCIA Genentech v. Amgen cases relating to trastuzumab and bevacizumab. This week, Judge Connolly construed the term “following fermentation” as it relates to U.S. Patent No. 8,574,869 (“the Kao patent”) to mean “after the earlier of harvesting or purification has begun.”

By way of background, the Kao patent claims a method of preventing disulfide bond breakage during the manufacturing of therapeutic antibodies using sparging (blowing air bubbles through a solution) “following fermentation.” Judge Connolly heard argument on the meaning of “following fermentation” and other disputed claim terms at two Markman hearings last April.  After these Markman hearings, Judge Connolly ordered a hearing “to determine if ‘following fermentation’ can be construed by resort to extrinsic evidence or is invalid for indefiniteness” because he was unable to construe the term “based solely on the intrinsic evidence.” At the October 16, 2019 hearing, the parties presented extrinsic evidence “in the form of affidavits, treatises, articles, reports, and competing expert testimony.”

Judge Connolly stated that the “Kao patent neither defines fermentation nor allows for a cogent inference of fermentation’s meaning, let alone when it ends. The patent is plagued by typographical errors and sloppy language; it suggests at times that fermentation is synonymous with ‘production’ and ‘manufacturing’ and at other times that fermentation is distinct from these concepts.”  Judge Connolly further stated that “[n]either side was able to point me to a treatise, dictionary, or other reference that expressly defines when fermentation ends in the antibody manufacturing process.” Judge Connolly held that, for proteins secreted into the cell culture fluid, it “makes sense to define the end of fermentation for proteins secreted into the cell culture fluid in terms of the beginning of harvesting.”

For cells that are not made by secretion into the cell culture but are instead produced “intracellularly,” Judge Connolly concluded that his “overall impression of the evidence taken as a whole is that a [person of ordinary skill in the art] would understand [] that harvesting is part of purification and that antibody manufacturing consists of two steps—fermentation (i.e., cell culturing or antibody production) and purification.”  Accordingly, he concluded that for proteins made intracellularly, “following fermentation” should be construed “in terms of the beginning of purification.” Ultimately, Judge Connolly concluded that “a person of ordinary skill in the art [] would understand ‘following fermentation’ to mean ‘after the earlier of harvesting or purification has begun.’”