The Federal Circuit posed difficult questions on the "newly characterized antigen" test (a.k.a., the antibody exception as provided in the USPTO Written Description Guidelines) to Sanofi (the appellant-defendants) during oral argument last week in Amgen v. Sanofi, a first opportunity for the Federal Circuit to squarely address the validity of this test. Amgen, Inc. v. Sanofi, No. 17-1480 (Fed. Cir. 2017). In contrast, the judges did not question Amgen on this point and gave little indication on whether they will rule on this issue. With four other issues before the court, including whether a new trial is required on written description and enablement, the court need not reach this issue to decide the case.
35 U.S.C. §112(a) requires that the specification of a patent provide "a written description of the invention and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention." 35 U.S.C. § 112(a) (2012 Current through P.L. 115-30) . In the biological arts, according to case law, written description of a genus may be met by describing "common structural features" among the members of the claimed genus or a "representative number of species." In addition, the USPTO Manual of Patent Examining Procedure provides a "newly characterized antigen" test, which carves out an exception allowing for written description support for a claim to a genus of antibodies through the disclosure of a newly characterized antigen, if the level of skill and knowledge at the time of filing was such that the production of such antibodies was conventional or routine. At trial, the district court held Amgen's antibody claims not invalid, relying, at least in part, on the "newly characterized antigen test," and issued a permanent injunction against Sanofi. MPEP § 2163 (II)(3)(a) ¶ 5 (9th ed. 2015) (quoting Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011). On appeal before the Federal Circuit last week, Sanofi challenged the test's validity.
Amgen alleges that Sanofi and its partner Regeneron infringed Amgen's patents covering antibodies that help reduce LDL cholesterol levels. Amgen's patent claims disclose an epitope and certain species of a broader antibody genus. The claims cover antibodies that bind to a region of the protein PCSK9 and block PCSK9 from binding to LDL-Receptor protein on liver cells. LDLR sits on liver cell surfaces and captures LDL from the bloodstream. Ordinarily, an LDLR-LDL complex migrates inside liver cells, where LDL is destroyed and LDLR recycles back to the cell surface to capture another LDL molecule. However, when PCSK9 is present, it binds to LDLR along with LDL, and the entire complex is destroyed inside liver cells, including LDLR. Thus, PCSK9 prevents LDLR recycling and contributes to higher levels of cholesterol. Both parties developed antibodies that help reduce LDL cholesterol levels, which they commercialized in Amgen's product Repatha® and Sanofi's Praluent®. Sanofi's Praluent® faces a 12 year injunction if the Federal Circuit upholds the district court's injunction.
In their brief, Sanofi argued that the "newly characterized antigen" test has no basis in statute, science, precedent, or common sense. Sanofi contends that the test is not scientifically supported because the structure and sequence of the antigen tells nothing about the antibodies. They also argue that no binding Federal Circuit precedent supports the test.
Amgen's brief, on the other hand, counters that Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004) is a controlling precedent that confirms the validity of the test. Amgen backstops that argument, arguing that any error by the court below on the application of the "newly characterized antigen" test was harmless because the disclosure of representative species supports Amgen's claims even without applying that test.
At the hearing, Judge Prost pushed back against Sanofi's proposition that Federal Circuit precedents on point were dicta, not binding law, stating she considers this position "a little troubling" when the district court relied on quotes from Federal Circuit opinions, some of which she wrote. Initially dodging the issue, Paul Clement of Kirkland & Ellis LLP argued on behalf of Sanofi that even if the test is valid law, Amgen fails to meet it because the test applies only when the generation of claimed antibodies is routine, but the antibodies that satisfy Amgen's functional claims are anything but routine, and Amgen's discovery of the sequence of the PCSK9 epitope did not make the "intensive," "arduous," "trial-and error process" of generating the claimed antibodies any easier. He went on to argue that the "newly characterized antigen" test is invalid in a post-Myriad world because the test allows something akin to claiming a natural compound. Judge Prost's questioning on this issue did not go further.
Later, the panel allowed Daryl L. Joseffer of King & Spalding LLP, arguing for Amgen, to present arguments on the "newly characterized antigen" test without interruption. Mr. Joseffer argued that Noelle establishes the antigen-antibody test as the rule of law and rejected Sanofi's arguments that Amgen's discovery of the epitope did not help even Amgen generate the claimed antibodies. Rather, he reasoned that discovery of the so-called "sweet spot," 15 amino acids on PCSK9 to which antigens can bind and block PCSK9 from binding with LDLR, facilitated routine techniques like conservative substitutions and CDR shuffling that led to more efficient and effective antibody discovery. This, he argued, is precisely the point of the "newly characterized antigen" test, and the ensuing patent protection makes Amgen's two-billion dollar investment in Repatha research worthwhile.
On rebuttal, Clement minimized Amgen's contribution to the "newly characterized antigen" by pointing out that Novartis had already disclosed twelve of the fifteen amino acids in PCSK9, and that Amgen only disclosed two, not twenty-four, representative species. This minimal contribution, he concluded, shows the antibody exception is "fundamentally misconceived," because such a small contribution should not allow Amgen to "corner the market" on a life-saving drug.
Last week's oral arguments leave it uncertain how or even whether the court will rule on the validity of the "newly characterized antigen" test. The court may agree with Sanofi that Amgen fails to satisfy the test (if such a "newly characterized antigen" test is valid), agree with the Amgen that its claims are not invalid on other grounds, or decide the case on one of the four other issues before the court. If, for example, the court grants Sanofi's appeal for a new trial on a post-priority-date evidentiary question that was also at issue, the court need not reach the issue of the test's validity.
Originally printed in AIPLA Biotech Buzz in June 2017.
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