In January 2019, the Supreme Court denied certiorari in Amgen Inc., Amgen Manufacturing Ltd., and Amgen USA, Inc. v. Sanofi, Aventisub LLC, Regeneron Pharmaceuticals, Inc., and Sanofi-Avantis U.S., LLC, a case that asked the Court to review the law related to the written description requirement of 35 USC Section 112. We previously discussed the case here. This case arose when Amgen sued Sanofi and Regeneron, alleging that their monoclonal antibody product, Praluent® (alirocumab), infringed Amgen’s patents. In ruling on the case, the Federal Circuit (872 F.3d 1367, Fed. Cir. 2017, “Sanofi”) essentially overturned the “well characterized antigen” test, which allowed an antibody product to be described by the antigen that it binds, and held 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 essence, the Federal Circuit’s decision in Sanofi raised the bar for protecting antibody inventions by requiring more data when disclosing and claiming antibodies. The Supreme Court’s refusal to review the Federal Circuit decision means that the standard for obtaining broad protections for therapeutic monoclonal antibodies will continue to be challenging.
In view of the Federal Circuit’s holding in Sanofi, the question becomes: how can a company build a patent portfolio that can withstand invalidation under Sanofi and withstand other challenges? The answer is: by building a multi-layered portfolio offering many different layers of protection.
A great example of a patent portfolio with many layers, creating a so-called “patent thicket,” is the patent portfolio protecting Humira®, also an antibody. Despite the challenges and invalidations of one of Humira’s core patents (the ‘135 patent) over the summer of 2017, no competitor can market a biosimilar of Humira in the US until at least 2023. This is because Humira® is protected by more than 110 patents, some of which extend its patent term all the way to 2034. Humira’s portfolio is so robust that several biosimilar manufactures have entered into settlement agreements with Abbvie that would delay the U.S. launch of a Humira®-based biosimilar product until 2023 rather than litigate the patents. While 2023 cuts Humira’s patent market exclusivity by more than a decade, Abbvie can still market Humira without competition more than five years beyond the expiration of the ‘135 patent, the patent that was invalidated by the PTAB.
The strength of Humira’s patent portfolio comes from several aspects. First, it is big. There are more than 110 patents protecting various aspects of the drug. Such a large portfolio is designed to continue standing even if a few patents may be invalidated.
Second, Humira’s portfolio is also very diverse. In a presentation in October 2015 entitled “Broad U.S. Humira Patent Estate”, Abbvie outlined its strategy: to cover every aspect of the drug. Abbvie listed 22 patents for various diseases or methods of treatment, 14 on the drug’s formulation, 24 on its manufacturing practices, and 15 “other” patents.
Third, Humira’s portfolio is staggered. By not filing all the patent applications at one time, Abbvie was able to extend Humira’s patent term to 2034, 16 years past the initial expiration of the primary patents in 2018.
Of course, it should be mentioned that a portfolio like Humira’s comes with a very steep price tag and not all companies are in the position to invest that much into patent protection. Nevertheless, creating layers within the portfolio as well as within each patent can greatly enhance the chances that at least some patents and claims will remain valid despite challenges and even changes to the laws.
For antibody patents, this can be done in several ways. First, each patent should claim the subject matter using several different formats yielding differences in scope so that even if some claims are invalidated in a post-grant challenge, other claims within the same patent still remain valid. Let us examine functional claims, for instance. Although functional claims directed solely to antigen binding are likely invalid under Sanofi, claiming by function should not entirely be ignored. Instead such claims can be strengthened by adding backup claims, including a set of narrower claims that include parts of the antibody sequence or other features of the antibody that have a greater chance of withstanding a challenge. Including one or two backup claim sets could thus increase the chances that the entire patent is not invalidated in a challenge. Further, functional elements could be combined with structural elements in the same claim, creating hybrid claims as well.
In addition to including multiple layers of claims within each patent application, the portfolio should also be chronologically staggered to include a range of different patent claims that act to extend the patent term. In the antibody space, there are several different types of claims available to developers of therapeutic antibodies. These include sequence claims, pharmaceutical composition claims, function claims, methods of treatment, and antibody-conjugate claims. To build a strong patent portfolio, each of these patent claims can be utilized at different points in the development process. For instance, the core patent could be a composition patent directed to the complimentarity determining region (CDR) sequences of the actual antibody. Later, claims directed to methods of treatment, compositions, and antibody-conjugates (if applicable) can be included. These later filed patents would serve to extend the patent life of the antibody beyond the expiration of the core composition patent.
Patenting antibodies has become more challenging in the wake of the Federal Circuit’s decision in Sanofi. When patenting antibodies, it is now more important to review each antibody on a case-by-case basis and decide which features to claim, and how best to claim them, based on the amount of data and investment available. By taking advantage of the different types of patents claims that are available for antibodies and by including backup claims in the form of layering, a company can increase the likelihood that at least some of the claims will remain patentable when the patent is subject to invalidation.
BioPharma Law Blog posts updates and analyses on IP topics, FDA regulatory issues, emerging legal developments, and other news in the constantly evolving world of biotech, pharma, and medical devices.