When can a prior art reference that discloses a protein purification step at room temperature render invalid a patent claim with a temperature range from about 10°C to about 18°C? Answer: When that prior art reference defines room temperature to include 18°C (which is about 64.4°F). The Federal Circuit reiterated, in Genentech, Inc. v. Hospira, Inc., that even a small overlap at the extremes of a range can invalidate claims that incorporate that range, absent a showing that the particular range is critical or that the parameter is not a result-effective variable.
The technology in this case involved the use of a protein A column to purify certain antibodies. Such columns had been known to leach small amounts of protein A, which ultimately contaminated the purified antibody solution. Genentech’s patent, US Patent 7,807,799 (the “’799 patent”), claimed a method of performing the chromatography “at a temperature in the range from about 10°C to about 18°C” because its scientists found that reducing the temperature reduced protein A leaching.
This appeal stemmed from IPR2016-01837, which Hospira filed alleging that the claims of the ’799 patent were anticipated and/or rendered obvious by, among other references, International Patent Application Publication WO 95/22389 (“WO ’389”). WO ’389 also taught methods of purifying certain antibodies and included the use of a protein A column. The publication also disclosed that all steps were “carried out at room temperature (18-25°C).” The Board found, among other things, that the challenged claims of the ’799 patent were anticipated by the WO ’389 disclosure and obvious over WO ’389 in view of other references, because the disclosed temperature ranges overlapped.
Anticipation of Claimed Ranges
Judge Chen, writing the opinion of the Court, found that there was sufficient evidence to support the Board’s finding regarding the anticipation by WO ’389 because of the overlapping ranges (about 18°C at the high end of the claimed range, and 18°C at the low end of the range for room temperature in WO ’389). Genentech argued that, even if WO ’389 taught performing the chromatography at room temperature, it did not disclose that the composition being applied to the column was at or below about 18°C. In fact, the experts on both sides testified that the bioreactor used to culture the cells in WO ’389 would have likely been at a temperature closer to 37°C. Nevertheless, because the reference was silent as to how long the material had been held at room temperature before being subjected to the protein A column, there was substantial evidence to support the Board’s finding. Even when a prima facie case of anticipation is established based on overlapping ranges, it can be rebutted by a showing that the claimed range is critical to the operability of the invention. However, the Board found that Genentech has failed to establish the criticality of the claimed range in performing protein A chromatography, and Judge Chen noted that Genentech did not challenge this finding.
Obviousness of Claimed Ranges
Judge Chen also found that the Board did not err in concluding that the challenged claims were obvious over WO ’389, either alone or in combination with other prior art references. Similar to the anticipation finding, the overlap of the ranges created a presumption of obviousness. One way to overcome this presumption is to argue the criticality of the claimed range, but again Genentech did not challenge the Board’s lack-of-criticality finding. The presumption can also be overcome by showing that a parameter is not “result-effective,” or that the art did not recognize that the particular parameter would affect the result. However, the Board had found that protein A leaching was known to be caused by proteolysis (i.e., protein cleavage) of bound protein A, which resulted in its leaching from the column, and that proteolysis was affected by temperature. Genentech did not appear to challenge that temperature was a result-effective variable, but instead that protein A leaching was only a concern for large-scale purification. In addition, it argued that chilling an industrial-scale composition would be inconvenient, costly and impractical. However, the Board noted, and the Federal Circuit agreed, that neither the claims nor WO ’389 were limited to large-scale processes. The Court concluded that substantial evidence supported the Board’s conclusion that it would have been routine experimentation to vary the temperature to avoid protein A leaching.
Judge Newman disagreed in a separately written dissent and accused the Court of using hindsight reasoning to invalidate claims to a simple solution for a difficult problem. Judge Newman believed that the mention of the lower boundary of room temperature in WO ’389 could not anticipate the claims because the anticipating reference must describe the entirety of the claimed subject matter (which she did not think it did). Moreover, Judge Newman pointed out that this was not simply a matter of selecting an optimum temperature range for conducting a known process because the prior art did not teach the cooled range, nor the result that the cooled range could prevent protein A leaching. Judge Newman concluded that the relevant inquiry for a result-effective variable was whether it would have been obvious to cool the material to about 10-18°C, not whether it would have been easy to cool the material.
This case can be viewed as a cautionary tale for drafting claims with ranges, especially ranges involving temperatures. The Genentech patent did not include temperature ranges beyond “about 10°C to about 18°C,” and inclusion of a range that did not include 18°C could have saved this patent. In cases where a range is critical to an invention, it is advisable to include multiple or nested ranges in the claims. After all, it is difficult to predict if someone in the art had included one of the extremes of your range in a comparable method, even if that included a range that seems serendipitous or appears to differ from the norm (such as the use of an abnormally cold room temperature).