Prospective patentees in the antibody arts in Canada have long faced objections to claims that cover antibodies different from those exemplified in their applications. This typically includes non-exemplified antibodies defined in term of percent identity to a reference sequence, and those having conservative sequence modifications based thereon. Patent examiners at the Canadian Intellectual Property Office (CIPO) usually allege that undue experimental burden would befall a skilled person wishing to make candidate mutants and determine which ones are functional. To sustain such objections, examiners usually point to decisions of the Commissioner of Patents dealing with antibody applications from the late 1980s to early 1990s.
In a decision marking the first time that antibody technology has been extensively scrutinized by a Canadian court, the Federal Court of Canada upheld claims covering uses of a human anti-IL12 antibody for treating psoriasis in its recent decision in AbbVie Corporation v. Janssen Inc., 2014 FC 55.
AbbVie, the patent owner, had unexpectedly discovered that psoriasis resolved in a patient who inadvertently received a human anti-IL12 antibody, termed J695 (briakinumab), made using phage display technology. The "use" claims asserted by Abbvie were not, however, limited by specific epitope, antibody sequence, or method of production, though the claims did specify minimum affinity and potency values.
Janssen makes and markets a human anti-IL12 antibody for treating psoriasis under the name STELARA" (ustekinumab). This antibody was not developed by phage display, but rather in mice having a reconstituted human immune system. In fact, the STELARA" product shares only incidental sequence identity with J695 (about 50%), and also binds to a completely different epitope on IL-12.
The patent claims were counter-attacked by Janssen on the grounds of obviousness, over-broad or "covetous" claiming, and ambiguity. The Court upheld the claims, finding them to be both valid and infringed by Janssen.
In his analysis of obviousness, the trial judge provided a helpful and lengthy list of technologies from expert testimony that he accepted as forming the state of the art as of March 1999. These include methods of CDR recovery, modification, mutagenesis, and grafting, as well as activity testing and methods of making human antibodies by either phage display or using immune-reconstituted mice. These are many of the technologies that have, to date, been deemed "non-routine" by patent examiners in applications filed well after 1999.
The inventive concept of the claims in issue was found to be that psoriasis may be treated by the use of human antibodies that bind to human IL-12, which antibodies have an affinity of at least the claimed amount and a potency of at least the claimed amount. Before this discovery there was only hope that binding IL-12 would treat disease, but this was an example where a patient had successfully been treated. The Court noted the distinction between the approaches to obviousness, where an invention that is "worth a try" may not be "more or less self-evident". In this case, the invention was not self-evident having regard to the prior art, and thus it was not obvious. The Court also found that the claims were not unduly broad.
The attack on ambiguity focused on claim features pertaining to minimum affinity and potency variables. Patent applicants may recognize that such features often fall afoul of CIPO examining practice, with examiners alleging that such features are objectionable for "encompassing antibodies with spectacularly high affinities". The trial judge found nothing ambiguous about these limitations, stating that they simply conveyed minimum standards. The trial judge indicated that the question of whether an antibody with vastly higher affinity or potency would be considered a patentable improvement was one best left for another day.
A decision like Abbvie v. Janssen has been long awaited in the field of biologics. Although now under appeal, the decision should nonetheless encourage applicants to argue against antibody claim objections in which an examiner states that departure from a specific set of CDR sequences would result in a lack of utility, or that putting a claimed invention into practice would require impermissible inventive work.
Previously published in LifeSigns - Life Sciences Legal Trends in Canada
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