DC decision of infringement and no Safe Harbor (§ 271(e)(1)) for Hospira’s EPO affirmed

Amgen Inc. et al. v. Hospira, Inc.

Docket Nos. 2019-1067, -1102
December 16, 2019

Brief Summary: DC denial of JMOL and new trial after jury findings of infringement, no anticipation and no Safe Harbor for certain batches of EPO affirmed.

Summary: Hospira appealed DC denial of its motion for judgment as a matter of law (JMOL) or a new trial and the jury’s verdict that Amgen’s US 5,856,298 relating to erythropoietin (EPO) was infringed and not invalid, Hospira’s products were not covered by the § 271(e)(1) Safe Harbor provision, and Amgen was entitled to $70 million in damages. Claim 27 of the ’298 patent is directed to “[a] method for obtaining an erythropoietin composition having a predetermined in vivo specific activity comprising preparing a mixture of two of more isoforms of claim 1” (i.e., “[a]n isolated biologically active erythropoietin isoform having a single isoelectric point and having” 1-14 “sialic acids per molecule”, and that is “the product of expression of an exogenous DNA in a non-human eukaryotic host cell”). The DC construed “[a]n isolated biologically active” EPO as “a group of molecules” that also “appears as a single band on an isoelectric focusing gel (an example of which is shown in Figure 1 of the ‘298 patent)”, and that the “mixture” is “of two or more of the isolated erythropoietin isoforms of Claim 1.” In addition, the DC disagreed with Hospira and further added that “Claim 27 does not require the individual isoforms of Claim 1 to be separately prepared prior to making the mixture.” Hospira argued “that this construction contradicts the intrinsic evidence and the testimony of the inventor Dr. Strickland, who stated that the purpose of his invention ‘was to separate isoforms and then ‘recombine’ them or ‘mix those fractions back together’”, which Hospira argued it did not do (and did not therefore infringe). The FC panel disagreed with Hospira, writing that “[t]he specification clearly contemplates the preparation of mixtures of isoforms in more than one way” and it was “improper to limit claim 27 to one embodiment based on Dr. Strickland’s testimony” (Phillips, Fed. Cir. 2005). Hospira argued the DC erred since “Amgen’s evidence of infringement only demonstrates that Hospira’s product is biosimilar to Amgen’s Epogen” and “insufficient to establish” it “has a ‘predetermined in vivo specific activity’, as required by claim 27.” The FC panel concluded that “[s]ubstantial evidence supports the jury’s infringement verdict”, including inventor and expert testimony and Hospira’s BLA showing “Hospira’s EPO” meets the claim limitations. The FC panel therefore affirmed the DC’s denial of JMOL.

Hospira also argued “no reasonable jury could find claim 27 not invalid” for anticipation since it “disclosed exactly [the] process in [Amgen’s] Example 2” (i.e., “ion exchange chromatography to separate impurities and less biologically active EPO and more biologically active EPO”). The FC panel agreed with Amgen, however, and found that the prior art “does not refer to a composition with a predetermined in vivo activity” but only that “‘[b]iologically active’ EPO was eluted”, as well as expert testimony “that nothing in” it “would indicate one to think there’s a predetermined in vivo activity” and “the product of [the] method depends on what is present in the starting material.”

Regarding Safe Harbor defense ((§ 271(e)(1)), Hospira also argued “that no reasonable jury could have found that some, but not all, of Hospira’s drug substance batches were protected by the Safe Harbor defense” (the jury found 7/14 batches produced in 2013-2015 were protected). Hospira argued that “it only had to provide that the use of the patented invention was reasonably related to submission of information to the FDA, not the manufacture”, and that the jury instructions improperly focused on manufacture. The FC panel explained that “[h]ere, the patented inventions are Amgen’s claimed methods of manufacture”, “[t]he accused activity is Hospira’s use of Amgen’s claimed methods of manufacture”, and “[t]he relevant inquiry…is…whether each act of manufacture was for uses reasonably related to submitting information to the FDA” (Amgen, FC 2009), and found no error in the jury instructions. The FC panel also found substantial evidence supported the jury’s conclusion that not all the batches were protected since, e.g., expert testimony showed that “Hospira was not required to manufacture additional batches after it made its 2012 batches” (e.g., “stability testing of Hospira’s 2013 batches was not required”, much of it was “[to] serve as commercial inventory” (noting however that “some of the ‘commercial inventory’ batches” were protected) (citing Momenta, Fed. Cir. (2015)).

The FC panel also found no reversible error in the DC damages determination, which Hospira argued “does not reflect a ‘reasonable royalty’” (e.g., “[i]t was not unreasonable for the jury to choose a damages award within the amounts proposed by each expert”).

The FC panel also disagreed with Amgen on its cross-appeal of the DC’s denial of Amgen’s motion for JMOL and new trial regarding the jury’s finding of noninfringement of Amgen’s US 5,756,349 directed to “[v]ertebrate cells…producing [EPO]…in excess of 100 U [EPO]…as determined by radioimmunoassay” (e.g., Hospira’s expert testified that Amgen’s dot blot assay results could not be correlated to the required “radioimmunoassay” test).

This entry was posted in Anticipation (35 USC 102), Claim Construction, Infringement, Safe Harbor, FDA exemptions (271(e)(1)), Uncategorized. Bookmark the permalink.

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