In AbbVie v. Janssen, the Federal Court of Canada recently handed down the first Canadian decision regarding a patent on biologic drugs. Before that decision, there was much debate about the way claims for biologics need to be drafted in order to ensure validity. The case of AbbVie v. Janssen has provided some clarification in this regard and is of great interest for stakeholders in the industry. AbbVie's patent directed to antibodies was found to be valid despite Janssen's arguments of obviousness and claim over breadth.
AbbVie owns patent CA 2,365,281 (the '281 patent) which is directed to human antibodies that bind to human Interleukin 12 (Il-12). Il-12 is a member of a group of proteins known as cytokines (cell-signalling proteins) and one of several interleukin families that are known to be involved in immune reaction pathways and sometimes implicated in autoimmune diseases such as psoriasis.
Although the '281 patent includes 223 claims, only claims 143 and 222 were at issue in this case. These two claims cover the use of an isolated human antibody that binds to human Il-12 at a certain minimal affinity and potency to treat psoriasis.
Neither of these two claims was restricted to a specific method of antibody synthesis. The patent did describe the method of synthesis used, called phage display (an in-vitro method), and made reference to an alternative method based on use of a transgenic mouse (an in-vivo method using mouse genetically modified mouse that bear a human gene for an antibody). However, Abbvie's antibody was not produced through use of the transgenic mouse method.
Janssen launched its STELARA product on the Canadian market: an antibody that binds to Il-12 and approved for the treatment of psoriasis (the "Janssen Antibody"). The Janssen Antibody was produced using the transgenic mouse method. Its amino acid sequence was different than that of AbbVie's antibody product and it bound to a different part of IL-12. Janssen did not file any patent application for the Janssen Antibody, nor for its use to treat psoriasis.
AbbVie filed legal proceedings against Janssen for infringement of claims 143 and 222 of the '281 patent. In its counterclaim, Janssen sought a declaration that these two claims were invalid on the basis of obviousness and claim over-breadth. Janssen claimed to have developed the Janssen Antibody independently, before the priority date of the '281 patent.
The issue of Obviousness
Janssen argued that before the '281 patent's priority date, it was known that (i) Il-12 was involved in inflammatory pathways and had clinical involvement, (ii) Il-12 antibodies could inhibitIl-12 activity, and (iii) antibodies with the affinities claimed on the '281 patent could be made through phage display or transgenic mouse methods.
AbbVie countered with arguments that the role of cytokines in human disease is complicated and that many cytokines have redundant properties (such that multiple antibodies might be needed for effective therapy). AbbVie also presented evidence that many therapeutic antibodies that are implicated in human disease have failed to have any human clinical effect, that more than 22 cytokines had been identified in psoriatic lesions and, importantly, that neither the Il-12 literature nor the psoriasis literature postulated that Il-12 was a cause of psoriasis.
The Court upheld the validity of AbbVie's claim, finding that the inventive concept was that psoriasis may be treated by the use of human antibodies that bind IL-12, which antibodies have an affinity and a potency of at least the value claimed. The Court found that prior to the '281 patent, there was only hope that the Il-12 would treat psoriasis, or any other autoimmune disease where the Il-12 played critical part of the disease, whereas the '281 patent showed an example of a psoriatic patient that was actually successfully treated with antibodies against Il-12. According to the Court, the case is a good example of the difference between the "worth a try" approach (which does not imply obviousness) and the more or less self-evident, or "obvious to try" approach (which does imply obviousness). AbbVie's patent represented the former.
The issue of Over-Breadth
Janssen argued that the claims were over-broad because they did not claim a specific antibody or even an antibody that was made by a specific method (i.e. phage display); rather, the claim captured any antibody that embodies the claimed affinity and potency parameters.
The Court held that the claims did not require a reference to a specific antibody production method. According to the Court, the techniques used to create antibodies were well known in the art before the '281 patent priority date, as were the techniques to measure the affinity and the potency of antibodies. The Court also underlined the fact that there was no evidence that anything that falls within the scope of the claims lacked utility for treating psoriasis. Nor was there evidence that a skilled person was required to use the antibody production methods that had been described in the patent (i.e. other antibody production methods might be possible). Janssen emphasized the differences between the amino-acid sequence and three-dimensional structure of the Janssen Antibody and AbbVie's, and argued that these differences underlie different mechanisms and sites of binding to IL-12. According to Janssen, these differences could yield differences in other properties such as solubility, propensity to aggregate and cross-reactivity to other targets, thereby distinguishing the Janssen Antibody from Abbvie's antibody. The thrust of these arguments appears to have been that Abbvie's antibody should have been claimed with reference to specific biochemical or physical properties (e.g. binding site, specificity). The Court rejected these arguments, finding that the differences between the Janssen Antibody and AbbVie's were not important; rather, what mattered were the functional similarities: both antibodies bind to IL-12 and neutralize its activity with the minimal value that is claimed. Since the differences alleged by Janssen were beyond the parameters set out in the claims and were found not to be essential for the functioning of the antibody to treat psoriasis, the Court concluded that the claims were not overbroad.
The case is important for manufacturers of biologic drugs and their patent counsel because it illustrates that a claim to an antibody without a limitation as to its amino-acid sequence (or even a portion of it, such as the light chain) is not overbroad if defined in terms of antigen binding and minimum affinity. The biotechnology sector should take into consideration the teaching of this decision at the time of drafting or applying for patents on biologics. Under the right circumstances, differences in the method of producing an antibody, or differences in their amino-acid sequences, is not enough to remove an infringing antibody from the scope of s such as those at issue in the AbbVie case. No appeal was filed at the time of drafting this text, we will follow any development on this matter and provide updates as appropriate.