Section 112 of the patent statute, which in earlier years was something of a backwater in patent law, has had a tumultuous quarter century beginning with the Federal Circuit decision in Regents of the University of California v. Eli Lilly & Co., which (in the view of many) heightened the written description requirement for biotechnology inventions. This was particularly true more generally for inventions directed to isolated nucleic acids (those were the days!) and proteins, based on the principle that the complexity of such molecules required disclosure of more than a recitation of the expected product (in Lilly, human cDNA encoding insulin) and methods for making/obtaining it. This decision led to a series of cases from that Court, including Enzo Biochem. v. Gen-Probe, University of Rochester v. G.D. Searle, Carnegie Mellon University v. Hoffman LaRoche, and culminating in the en banc Ariad v. Eli Lilly & Co. decision that imposed the interpretation that written description and enablement in 35 U.S.C. § 112(a) (then, first paragraph) were separate requirements. The enablement requirement in this regime had the steadier interpretation, being a question of law grounded in the factual determinants of the In re Wands factors, so much so that the isolation, discovery, and characterization of a novel antigen was enough for an applicant to be granted a patent for antibodies specific for that antigen without actually disclosing said antibodies, under the Court’s 2004 Noelle v. Ledermann decision. Many recognized that this decision was contrary to the Ariad decision but that apprehension was grounded in the written description rather than enablement requirement.
That situation began to change during the tenure of Chief Judge Prost, who wrote the first Federal Circuit Amgen v. Sanofi opinion harmonizing the Court's precedent by overruling on written description grounds the Ledermann decision. But lurking in the Court's consideration of that case was an inkling that the enablement requirement also contained a limitation, based on the principle of "no undue experimentation" from the Wands decision that bore fruit in several other cases, including Wyeth & Cordis Corp. v. Abbott Laboratories, Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., Pacific Biosciences of California, Inc. v. Oxford Nanopore Technologies, Inc., and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. (the latter being a conventional chemical compound/genus case that, it had been presumed, encompassed molecules of sufficient predictability that did not implicate the complexity issues of biological molecules). This trend reached its apogee (for now) in the Supreme Court's Amgen v. Sanofi decision, where the Court approved the limiting principle that the enablement requirement was satisfied if (but only if) the claims were commensurate in scope with what was disclosed in the specification. The Federal Circuit has applied the Supreme Court's reasoning (and their own) since the Amgen decision, in Baxalta Inc. v. Genentech, Inc.
In the wake of this decision (once one gets beyond the weeping and gnashing of teeth that accompany most Supreme Court forays into patent law) there have been a number of views asserted about how (if at all) biological molecules (and their chemical counterparts) could be protected with claims of sufficient scope not to be easily designed around. An intriguing one has been (independently) promulgated by Bob Armitage and Tom Irving, who have suggested that "means-plus-function" (MPF) claims under 35 U.S.C. § 112(f) would provide a way to expand the scope of claims having great sequence or other complexity while avoiding the conundrum created by (or more accurately, affirmed by) the Amgen decision. As a reminder this provision of the patent statute provides:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
Under this proposal,* exemplified with regard to Amgen's antibody claims, the stratagem would be implemented as follows:
A pharmaceutical composition of an isolated monoclonal antibody preparation comprising a pharmaceutically acceptable excipient and an antibody means that specifically binds to [a particular antigen/epitope/pathogen/etc.].
The specification would then provide (as did Amgen's) expressly disclosed antibodies as exemplars.
Reservations arise regarding this approach because MPF claims are limited to the species expressly disclosed ("the corresponding structure [or] material") and equivalents thereof. For antibodies (as in Amgen) this would have been the about two dozen expressly disclosed antibodies plus "equivalents." But this begs the question because what is an "equivalent" will need to be experimentally determined and thus be subject to the same "undue experimentation" objections that forms the basis for both the Supreme Court's Amgen decision and the several Federal Circuit decisions in recent years limiting their scope even in conventional small molecule/chemical claims. And while the doctrine of equivalents is a thin reed to rely upon to police, at best, "trivial" modifications (like substituting an isoleucine residue with an valine residue, or vice versa, insofar as the difference in these amino acids is one methylene (-CH3-) group) the scope of MPF claims is also more limiting in this regard.
A possibly more fruitful course (which has the benefit of also providing an argument for satisfying the written description requirement) would be the alternative ways of providing a sufficient disclosure first enunciated by Judge Lourie in California v. Eli Lilly & Co. and later in Ariad (v. Eli Lilly & Co.):
• Rely on species and subgenus claims as much as possible, while avoiding broad genus claims, to provide a "representative number" of species
• Focus on structure/function relationships and properties of antibodies (CDRs, for example) not antigens
(or a combination of these). There has been a convergence in the relationship between claim scope and the amount of disclosure supporting claims required for satisfaction of the written description and enablement requirements that can be addressed using Judge Lourie's rubrics.
Another approach would be to align the CDR sequences in expressly disclosed antibodies and provide a sequence alignment that could be used to identify a consensus sequence having three types of alignment. Specifically, there would be 1) invariant amino acids at some positions (which would indicate that these are important for antigenic specificity or structural stability or both); 2) positions having amino acids of related chemical properties (basic, acidic, aliphatic, etc.) that provide more structural variability/scope; and 3) positions having little consistency, except most likely not having proline or glycine which are known to disrupt protein secondary or tertiary structure. The number of variants for such consensus sequence CDRs, while large, would then have a more limited and scientifically rational basis resulting from evolution and would not involve the "trial and error" characteristics that raised judicial disparagement at both the Federal Circuit and Supreme Court.
There is no magic wand that can ensure that a claim will not be found wanting by a court in satisfying the disclosure requirements of Section 112. And of course, sound patent claiming strategies (having claims of varying scope, including genus, subgenus, and species, for example) are useful in reducing the likelihood that a competitor will be able to practice an invention with impunity by clever designing around schemes. The Amgen claims (as well as the claims in Baxalta) were prosecuted under interpretations of the enablement requirement that have now been abrogated by the courts. While it is likely that patents having similar claims will be subject to invalidation if asserted the benefit of decisions like Amgen is that the standard, having been established by the Supreme Court is less likely to change in future, as not relying on the Federal Circuit's recent uncertain precedential value.
