It has been one year since the Federal Circuit issued its opinion in Amgen v. Sanofi that raised the hurdle for protecting antibody inventions by requiring more data when disclosing and claiming antibodies. Since the court decision on October 5, 2017, it has become more challenging for pharmaceutical companies to obtain broad protections for therapeutic monoclonal antibodies. While obtaining protection for antibodies is still very much possible in this current climate, certain types of claims are now more susceptible to attack and possible invalidation. Below we analyze the different types of claims protecting antibody inventions and discuss their relative strengths in the wake of Sanofi.
In Amgen v. Sanofi, the Federal Circuit ruled that in order to obtain broad patent coverage for a class of antibodies that bind to a particular antigen and perform a particular function, companies must disclose a sufficient number of representative antibodies across the claimed genus or establish a clear relationship between the function of the antibody and the genus of the antibody in their specification. In Sanofi, the claims were directed to a monoclonal antibody that bound to one or more of 15 different amino acid residues on the sequence of the target antigen and performed a certain function (e.g., blocked the antigen from binding to its target). Claim 1 of U.S. Patent No. 8,829,165 ("'165 patent") is representative. It recites:
“An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDL[-]R.”
To support its claim that antibodies that bound one of the 15 residues or any combination of them were covered by the patent, Amgen disclosed two specific antibodies with binding data and affinity data. These data probably would have been sufficient prior to Sanofi. In Sanofi, however, the Federal Circuit ruled that such disclosure was insufficient. The court noted that patent specifications must disclose a representative number of species of the genus of claimed antibodies in order satisfy the written description requirement. The Federal Circuit did not, however, provide any guidance as to what a “representative number” of species would be. Therefore, it still remains an open question as to what counts as a representative number of species remains today.
Below we review several types of antibody-related claims in search of trends on which types of claims have fared better than others in the last year.
Historically, one of the broadest types of claims a company could get to an antibody was by its function. Functional claims to a genus of antibodies typically recite the functional property of an antibody without reciting any sequence information, for example “an antibody that binds to target Y”. Similarly, functional claims can be in the form of competition claims where “an antibody that competes with antibody X for binding to antigen Y” is covered. While such broad claims can cover nearly any antibody in a group of antibody products that are directed to the same target, such functional claims are becoming increasingly vulnerable in light of Sanofi, as courts will require a “representative number” of examples of the genus, i.e. a representative number of antibody sequences and associated binding data.
Method of Use/Treatment
Method of use or method of treatment claims have also proven to be vulnerable as these types of claims have not fared well when challenged in an Inter Partes Review (IPR) at the PTAB. These types of claims are by far the most popular target of IPR petitioners. In a study of antibody-related IPR petitions, the IPR petition grant rate on method of treatment claims is 65% (24 petitions granted, 13 denied), but, in all 6 of the Final Written Decisions to date, all instituted claims were held unpatentable. Therefore, it appears that if the PTAB institutes an IPR on a method of treatment antibody claim, those claims are likely to be found unpatentable. One potential reason for why these types of claims are easy to invalidate is because if you knew the antigen and what it does, it would be obvious to develop an antibody to treat people against that antigen. As such, method of use and method of treatment claims are probably the weakest types of claims in protecting antibodies.
On the opposite side are sequence claims. These types of claims define an antibody by its structure, which is most commonly claimed by its six complementary determining regions (CDRs), by its two variable regions, or even by its heavy and light chain sequences (both cDNA and peptide sequences). Patent prosecutors keen on obtaining the most protection for clients will attempt to claim sequences by the shortest and fewest number of sequences possible. Often times the amount of sequence data needed to pass examination hurdles will depend on the examiner. These types of claims will likely survive invalidation attempts because they are specific to one particular antibody. However, while antibody sequence claims are a strong type of claim to have, they are also the narrowest option, which makes them easier for a competitor to design around.
Besides claiming the antibody itself, a company can claim a pharmaceutical composition or formulation. While these types of claims are theoretically easier to design around because they include the antibody structure, they appear to be successful in surviving IPR challenges at the PTAB. In fact, the PTAB rarely institutes challenges to composition claims, and when it has, the claims almost always survive. Antibody formulation claims are the second most frequently challenged type of antibody claim behind method of treatment claims, discussed above. However, of the 13 IPRs that have been filed against claims to antibody formulations, three were instituted and 10 were denied. In the three instituted IPRs, all of the claims survived the challenge. Of the IPR petitions that were denied, most were because the petitioner failed to establish “a reasonable likelihood that the petitioner would prevail.” It is likely that these types of claims survive challenges because there is high unpredictability in the art since even small changes in antibody formulations can have unexpected effects on protein aggregation, viscosity, and other factors, making it harder to prove that such formulations are predictable and obvious. As such, pharmaceutical formulation patent are important to include when deciding how to protect antibodies.
A final type of patent for protecting an antibody is to develop antibody conjugates. These types of claims describe an antibody with a particular sequence fused to, or conjugated to, a drug. In an IPR challenge to Kadcyla®, an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab, Herceptin®, linked to the cytotoxic agent emtansine, the PTAB ultimately upheld the claims because a person skilled in the art at the time of the invention would have expected Herceptin®-maytansinoid immunoconjugates to be unacceptably toxic. While claims to antibody conjugates may survive obviousness challenges, it is important to remember that they are also narrower because they describe both the antibody sequence and a drug. They will also likely face challenges as to how much data and support is required to be in the specification to broadly claim the antibody conjugate. Nevertheless, these types of claims may be valuable to an antibody patent portfolio.
The case law in the antibody space has made it more challenging for companies to obtain broad protections for therapeutic monoclonal antibodies, especially in the wake of the Sanofi decision. To maximize the value of your antibody portfolio, it is therefore important to review the antibodies on a case-by-case basis and decide which features to claim based on the amount of data and investment available.
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