The PTAB (Patent Trial and Appeal Board) denied a petition to institute an Inter Partes Review (IPR2016-01608) against Genentech’s U.S. Patent No. 6,716,602, which claims a method for increasing the product yield of a properly folded polypeptide of interest produced by recombinant host cells:
1. A method for increasing the product yield of a properly folded polypeptide of interest produced by recombinant host cells, wherein expression of the polypeptide by the recombinant host cells is regulated by an inducible system, which method comprises
(a) culturing the recombinant host cells under conditions of high metabolic growth rate; and
(b) reducing the metabolic rate of the cultured recombinant host cells at the time of induction of polypeptide expression, wherein reducing the metabolic rate comprises reducing the feed rate of a carbon/energy source, or reducing the amount of available oxygen, or both, and wherein the reduction in metabolic rate result in increase yield of properly folded polypeptide.
The Petitioner (bioeq IP AG) relied on Seeger (17 Enzyme & Microbial Tech. 947–53 (1995)), in which cells were grown at 30°C in a fed-batch procedure, with a predetermined exponential feeding rate to ensure constant specific growth rates. Seeger explains that product formation was induced by shifting either the temperature from 30°C to 42°C, or by adding isopropyl-ß-D-thiogalacto-pyranoside (IPTG). Seeger observes acetic acid accumulation in response to temperature-induced product expression. To prevent that accumulation, the exponential feeding rate was reduced after the temperature shift to 42°C. Seeger determined that the temperature-induced production of bFGF (basic fibroblast growth factor) “generated more total and more soluble bFGF compared to IPTG-induced cultures.”
The PTAB disagreed that Seeger anticipated claim 1 since it did not teach reduction of metabolic rate. In particular, “Petitioner relies upon the disclosure of the ’602 patent describing reducing metabolic rate in cells already in a reduced growth state by reducing the rates of oxygen uptake and the corresponding rates of uptake of a carbon/energy source. However, Petitioner has not addressed adequately how Seeger’s method of inducing expression by increasing temperature from 30 to 42°C may have affected the metabolic rate.”
Petitioner relied only on Seeger for anticipation of claim 1, and did not have a back-up obviousness position.