In a law review article entitled "The Death of the Genus Claim,"1 which published in the aftermath of the Federal Circuit decision in Idenix v. Gilead, 941 F.3d 1149 (Fed. Cir. 2019), the authors stated that, "in the past thirty years, there are virtually no significant examples of genus claims in the life science fields upheld on appeal as compliant with § 112(a) outside the unique context of . . . 'interference" proceedings.'" The authors accused the Federal Circuit of "abandon[ing] a practical focus on whether others could make use of the claimed invention in favor of a fruitless search for the exact boundaries of that invention" and characterized the court's "'full scope possession' theory [as] invalidat[ing] a genus claim unless the patent can show exactly which species within the genus will work as intended."
This full scope possession theory is front and center in the ongoing dispute between Amgen and Sanofi in a case now on appeal to the Federal Circuit related to claims that cover Amgen's REPATHA® product. The dispute between the parties concerns Amgen's claims in US Pat. Nos. 8,829,165 (the '165 patent) and 8,859,741 (the '741 patent) to a genus of therapeutic antibodies that bind a specific site of PCSK9 and block binding of PCSK9 to LDL receptors. Amgen alleges that Sanofi's PRAULENT® product infringes these claims.
In 2014, Amgen asserted its patents directed to cholesterol-lowering antibodies against Sanofi and Regeneron, which sold cholesterol-lowering antibody drugs under the tradename PRAULENT®. After the parties stipulated to infringement, a jury in the District of Delaware found in favor of Amgen and held that Amgen's claims were valid. The court subsequently issued a permanent injunction. Sanofi and Regeneron appealed to the Federal Circuit, which stayed the permanent injunction and remanded the case for a new trial on written description and enablement. Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). Amgen sought en banc rehearing and Supreme Court review of the decision; however, both were declined.
On remand, the jury rendered a verdict finding claims 19 and 29 of the '165 patent and claim 7 of the '741patent satisfied the written description and enablement requirements and, as a result, were valid. Sanofi moved for Judgment as a Matter of Law that those claims were invalid for lack of enablement and written description. On August 28, 2019, the Court issued a Memorandum (Amgen, Inc. v. Sanofi, Case 1:14-cv-01317-RGA (D. Del.)) reversing the jury verdict on enablement and holding the claims invalid as a matter of law. Amgen appealed the decision.
Amgen argued in its appeal brief that two separate juries properly rejected Sanofi's enablement challenge and that, in granting judgment as a matter of law for Sanofi, the judge ignored evidence and departed from Supreme Court and Federal Circuit precedent on enablement. Amgen contended that the jury was reasonably justified in finding that Sanofi failed to clearly and convincingly prove lack of enablement and that the judge improperly failed to defer to the jury's underlying factual determinations. Specifically, Amgen argued that the asserted patents teach how to make variants with conservative amino acid substitutions and further argued that conservative substitutions do not require validation. Amgen noted that Sanofi showed no examples of antibodies with conservative substitutions that do not work. Additionally, Amgen argued that analysis under In re Wands, 858 F.3d 731 (Fed. Cir. 1988), which also related to antibody claims, showed that screening antibodies was not undue.
In response, Sanofi argued that numerous Federal Circuit cases have found genus claims lack enablement and that, in granting judgment as a matter of law for Sanofi, the district court judge properly applied this precedent. In particular, Sanofi argued that conservative amino acid substitutions could yield millions of antibodies to be tested (including variations on non-CDR regions) – requiring undue trial and error. Sanofi cited Idenix as showing a person of skill in the art must be able to practice the full scope of the claimed invention. Additionally, Sanofi distinguished the facts of the case from those of Wands because, unlike Wands, the claim scope required proof of binding to a specific site on PCSK9, not merely binding PCSK9.
Pfizer and Eli Lilly each filed amicus briefs in support of Sanofi's position that the claims are invalid. Eli Lilly went so far as to argue that the court should make clear that purely functional claims should be per se invalid until such time as the unpredictability is resolved. But, Bristol-Myers Squibb Company and Merck Sharp & Dohme jointly filed an amicus brief in support of Amgen's position in the case. The joint amici argue that the district court's decision
essentially set forth a legal rule that would prevent a patentee from claiming a genus of antibodies unless the patentee has identified with certainty each and every possible antibody within the claims. This rule, if followed in cases going forward, would make it effectively impossible for innovator companies to obtain sufficiently broad patent protection,
and would "hinder innovation to the detriment of patients and physicians."
The Federal Circuit panel hearing the oral argument on December 9th, 2020 consisted of Chief Judge Prost, Judge Hughes, and Judge Lourie. Judge Lourie immediately made clear to Amgen's counsel that the claims are directed to antibodies having two functions (binding to a specific region of PCSK9 and blocking binding of PCSK9 to LDL receptors), thereby creating a double enablement requirement and a significant uphill battle in establishing enablement. Amgen insisted that binding to a specific binding site requires a specific antibody structure and the patent provides a roadmap for testing antibodies that bond the requiring binding site using standard techniques. Amgen pointed out that 40 years ago Wands found no undue experimentation in routine screening for antibody binding. Chief Judge Prost, however, questioned whether the roadmap provided predictability of the full scope of antibodies that bind 2-9 residues within the PCSK binding site. Amgen replied that the patent provided only 10 examples, although Amgen identified 300-400 antibodies.
Sanofi argued it was impossible to predict the number of candidate antibodies that would need to be screened, finding no support in the record for the limit of 300-400 proffered by Amgen. When Judge Lourie noted that enablement should be easier than written description, which the district court said was satisfied, Sanofi's counsel argued that the written description decision should have been decided differently and again pointed to the enormous number of potential candidate antibodies to be tested for purposes of enablement. Chief Judge Prost further questioned enablement by noting that the three dimensional structure provided in the specification was limited to about half of the binding site.
Judge Hughes stated that he finds it difficult to distinguish the facts of Wands but also difficult to reconcile Wands with other enablement decisions. He questioned why repeating routine screening steps many times would be undue and whether a genus claim with functional limitations would ever be possible. Sanofi responded that genus claims must be directed to structure, not function, but was unwilling to say a genus claim based on function would never be enabled.
It will be interesting to see if the Federal Circuit panel in Amgen v. Sanofi attempts to address Judge Hughes' concerns with reconciling various precedential enablement cases. However, given Federal Circuit decisions over the last thirty years focusing on enablement to the full scope of the claims in biotechnology inventions, any such reconciliation is likely to affirm the district court's judgment as a matter of law and to hold the Amgen genus claims invalid. Given the challenges in stating a genus claims without function and the number of therapeutic antibody already on the market or in clinical trials, the upcoming decision could have far reaching consequences.
1. Karshtedt, Dmitry and Lemley, Mark A. and Seymore, Sean B., The Death of the Genus Claim (August 5, 2020). Harvard Journal of Law & Technology (available at https://ssrn.com/abstract=3668014).
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.