In Abbvie v. Centocor, (Fed. Cir, 2014), Abbvie’s representative claim was directed to a neutralizing isolated human antibody, or antigen-binding portion thereof, that binds to human IL-12 and disassociates from the human IL-12 with a Koff rate contant of 1×10^-2s-1 or less, as determeind by surface plasmon resonance. Abbvie had developed its IL-12 antibodies using phage display. In brief, Abbview identified a lead antibody that neutralized IL-12 through screening and called this antibody “Joe-9” which had VH3 type heavy chais and Lambda type light chains. In order to improve IL-12 binding affinity, it introduced mutations to the CDRs of Joe-9 and identified an improved antibody that it named “Y61”. Abbive then used site directed mutagenesis to alter individual amino acids at selected positions in Y61 and generated additional antibodies, among which an antibody that it named “J695” showed a signfiicant increase in IL-12 binding and neutralizing activity. Abbvie’s patent described the aino acid sequence of about 300 antibodies having a range of IL-12 binding affinities. Because the IL-12 antibodies described in Abbvie’s patents were all derived from Joe-9, they all had VH3 type heavy chains and Lambda light chains. The described antibodies shared a 90% or more amino acid sequence similarity in the variable regions. 

Centocor had developed its own human IL-12 neutralizing antibody. Of significance to the decision, its antibody had VH5 type heavy chains and Kappa type light chains, not VH3 and Lambda, as with the antibodies of Abbvie. This fact was significant because in finding lack of written support for the functional claim of Abbvie; the Federal Court dwelled on the fact that no representative species could be found in Abbvie’s specification of this parent antibody type. Whereas Abbvie’s claim was directed to a class of fully human antibodies defined by their high affinity and neutralzing activity to human IL-12, a well known antigen, the patents did not disclose structural features common to the members of the claimed genus. Nor did the patents disclose sufficient representative species encompassing the breadth of the claims because the antibodies disclosed were all devived from Joe-9 and had VH3 type heavy chains and Lambda type lights chains but the patents did not describe any example of human IL-12 antibodies having VH5 type heavy chains and Kappa type light chains (the Court also noting that the variable regions of Centocor’s antibody only shared a 50% sequence similarity with the Joe-9 antibodies. In other words, the asserted claims encompassed both the Joe-9 antibodies and the allegedly infringing antibody of Centocor, but Abbvie’s patents only described species of structurally similar antibodies that were derived form Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and did not qualitatively represent other types of antibodies encopassed by the genus. While it is true that every species in a genus need not be described in order that a genus meet the written description requirement, the patents must at least described some species representative of antibodies that are structurally similar to Centocor’s 

Also of importance was the dismissal of Abbvie’s argument that structural differences of the antibodies are legally irrelevant and that reliance should be placed on the Koff rates to show representativeness. In dissmissing this argument, the Court stated that it is undisputed that the structure of the antibody determines its antigen bidning characteristic. In order to demonstrate that it had invented what is claimed, the patents must adequately describe representative antibodies to reflect the structural diversity of the claied genus. 

The Court ended its decision with a warning that functionally defined genus claims can be inherently vulenrable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. 

The federal Court referred to several important court precedential decision phrases as supporting its rationale.

• the essense of the written description requirement is that a patent applicant, as part of the bargain with the public, must describe his or her invention so that the public will know what it is and that he or she has truly made the claimed invention. Festo Corp. v. Shokesu Kinzoku Kogyo Kabushili Co., 535 U.S. 722, 736 (2002).
• The requirements must be satisfied before issuance of the patent, for exclusive patent rights are given in exchange for disclosing the invention to the public. What is claimed by the patent application must be the same as what is disclosed in the specification. O’Reilly v. Morse, 56 U.S. 62, 120-21 (19853). 
• The purpose of the written description requrement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent  specificaiton. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004). 
• One particular question regarding the written description requirement has been raised when a genus is claimed but the specification only describes a part of that genus that is insufficient to constitue a description of the genus. For generic claims, a number of factors must be evaluated in determining the adequancy of the disclosure, including the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the preditability of the aspect at issue. When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed results and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus. A sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the members of the genus.In Regents of the University of California v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997) (holding that a genus of mammalian insulin DNA was not supported by a description of rat insulin DNA since rats are different from other mammals, including humans, and a descripton of one does not describe or show that one has invented the whole genus of mammals. 
• It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is estalbished, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc., v. Gen-Probe inc., 323 F.3d 956, 964 9Fed. Cir. 2002). However, in the Abbvie case, the patents did not describe any common structural features of the claimed antibodies. The asserted claims attempted to claim every fully human Il-12 antibody that would acheive a desired results, i.e., high binding affinity and neutralizing activity and to cover an antibody as different as the one inventoed by Centocor. 

NOVOZYMES v. DUPONT

Facts: Novozymes ‘723 patent (US Patent No. 7,713,723) claimed modified ezymes that exhibit improved function and stability. In particular its specification disclosed 33 separate amino acid positions along an alpha-amylase chain as promising mutation targets using rational protein design or random mutagenesis. The variants were disclosed as having improved stability at high temperatures and/or extreme pH. The specification exemplified two mutants having the properties.

Novozyme sued DuPont for introduction of new alpha-amylase product based on a S239Q variant.

The specification of Novozyme actually included the S239Q variant. The problem with the disclosure, however, is that it also included a group of 33 other positions that could be mutated to produce variant alpha-amylase. In addition, the disclosure focused on a different parent alpha-amylase (the “BSG alpha-amylase) are the parent enzyme and disclosed two working examples. This parent only shared 65.4% sequence identity with the claimed “BSG alpha-amylase”.

Holding: The Federal court affirmed the District Court’s holding that the claims at issue were indeed invalid as lacking written support. The Court stated that one searches the disclosure in vain for the disclosure of even a single species that falls within the claims or for any “blaze marks” that would lead an ordinarily skilled investigator toward such a species among a slew of competing possibilities. The Court stated that Novozymes seeks to derive written support from an amalgam of dislcousres plucked slectively form the disclosure.

The classic Genus-Species scenario: The case was based on the classic Genus-Species situation where patent applicants often go wrong in meeting the written description requirement. The facts, according to the Court, were similar to past cases such as Boston Scientific which required drug eluting stents incorporating a particular drug or a “macrocylic triene analog” of that drug but the specification disclosed a broad genus of “analogs” and made passing reference to the term “macrocylic triene” but failed to describe or identify any member of the claimed suyb-genus of macrocyclic triene analogs as well as University of Rochester where the claims recited administering a drug having a certain selective activity (inhibiting PGHS-2 activity in a human host) but the specificaiton did not disclose any suitable durgs and none were known in the art at the time of filing for carrying out such activity (at most the specification provided screening assays for identifying suitable drug candidates).

The court recited several past famous phrases from other cases regarding the writen description requirement:

“a mere wish or plan for obtaining the claimed invention does not satisfy the written description requirement. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir. 1997).

A patent “is not a reward for the search, but compensation for its successful conclusion” Unviersity of Rochester, 358 F.3d at 930.

Given the holdings of Novozymes, what might satisfy the written description requirement with respect to applicants who want broader coverage or perhaps simply do not have the data necessary to support their claims?

Well, the answer is difficult but the Corut did point to cases where broad or generic disclosures could describe a particular constituent species.

Union Oil Case: In Union Oil, the Court found that claims to gasoline compositions capable of reducing tailpipe emissions had adequate written description support because the claims defined the gasoline compositions in terms of various chemical and physical properties and the record demonstrated that ordinarily skilled petroleum refiners would immediately appreciate that the claimed properties recited in the claims translated to specific, manifest compositions that would yield those properties. This is the classic Function-Structure correlation example. Here, the spcification described relationships linking certain chemical and physical properties of gasoline compositions to the compositions’ emissions profiled. In doding so, the patentee relied on the knowledge of those skill in the relevant art to extrapolate the undisclosed, but claimed, compositions form their recited proeprties.

Given Union Oil, applicants may want to tie in some disclosed property with the claimed structure. If the property holds true for other structures, then one can make the argument that those of skill in the art would recognize those structures. To apply this to Novozyme, the applicant may have tried when written the disclosure to point to how specific mutants would be recognized by a person of skill in the art through guidance provided in the specification based on a set of properties. This of course is easier than said in the biological field where there simply may not be any correlation between one amino acid substitution and functional activity with another amino acid substitution and functional activity.