A biosimilar is a biologic product similar to another already approved biological medicine (known as ‘reference medicine’). The biosimilar (complex molecules) is not a generic product of a biological medicine in comparison to pharmaceutical generic medicines (small molecules) because the biosimilar exhibits natural variability and complex manufacturing that do not allow an exact replication of the molecular micro-heterogeneity. Institutions, such as European Medicines Agency (EMA), US Food and Drug Administration (FDA), and Health Products and Food Branch of Health Canada have released guidelines on requirements similar nature of two biological products. In 2009, World Health Organization (WHO) has also provided guidelines for examining similar bio-therapeutic products (SBPs).
Biosimilar can be approved when the ‘reference medicine’ patent expires, wherein the biosimilar approval is purely based upon same standards of quality, safety and efficacy of ‘reference medicine’. Biologics Price Competition and Innovation Act, 2009 (BPCIA) allows to provide an abbreviated approval pathway for biosimilar to be a FDA-licensed biological product. In detail, the BPCIA is related to the Drug Price Competition and Patent Term Restoration Act, 1984 (known as “Hatch-Waxman Act”), which established abbreviated pathways for the approval of biosimilar under the Federal Food, Drug, and Cosmetic Act (FD&C Act). The BPCIA includes two main statutory provisions: 42 U.S.C. § 262(k) encompasses regulatory aspects of the Act, and 42 U.S.C. § 262(l) covers a framework for the applicant and innovator of ‘reference medicine’ to resolve patent issue. The biosimilar receives FDA approval through submission of an abbreviated Biologics License Application (aBLA). The applicant uncovers confidential information disclosed in the aBLA to innovator of ‘reference medicine’.
Patent dance is a descriptive information sharing between an applicant and a ‘reference medicine’ innovator to resolve potential patent disputes before further processing of biosimilar approval, wherein the information includes mainly aBLA details and manufacturing processes of biosimilar. The patent dance can be performed in two focused steps: first, the innovator can allege infringement of his patents identified during the patent dance; and second, the innovator’s patent proceedings after receiving notice of commercial marketing from the applicant. The patent dance is mandatory if anyone wants to develop a biosimilar, particularly, in US, FDA’s Purple Book and BPCIA are necessities that need to be tracked before moving onto the patent dance, wherein the Purple Book provides a compiled list of biological products which have received FDA approval in the form of a license and associated Biologics License Application (BLA). Here, the article will be focusing on how it intends to resolve the patent war in an orderly and expeditious fashion, and impact on the timing and scope of litigation.
The biosimilar applicant initiates patent dance by disclosing complete information of biosimilar to the ‘reference medicine’ innovator, within 20 days of FDA’s approval of the aBLA. The BPCIA ensures that the applicant has provided access of all confidential information to ‘reference medicine’ innovator in aBLA. Additionally, the applicant has to specify the fact that there is no intention to start the commercial marketing before patent expiration. Within 60 days after information exchange, the ‘reference medicine’ innovator provides a list of live patents to the applicant for which a claim of infringement could reasonably be formulated. In the next step, detailed invalidity, unenforceability, and/or non-infringement contentions for each of the noticed patents have to be handed over by the applicant to ‘reference medicine’ innovator within 60 days. Furthermore, a series of responses is taken care during next 8 months, wherein the ‘reference medicine’ innovator can file a lawsuit after final findings in a US federal court. If there is no ground for building a lawsuit by the ‘reference medicine’ innovator, the patent dance gives the green signal to the biosimilar product launch within 180 days after the final discussion.
For instance, Amgen vs. Sandoz was the first case since the act was enforced in US. In July-2014, FDA’s approved aBLA for Sandoz’s Zarxio (filgrastim), further, Sandoz had informed Amgen about a biosimilar to their product. In the same letter, Sandoz gave the commercial marketing notice. Further, Amgen had filed a lawsuit and patent infringement on in the Northern District of California on the basis of BPCIA, wherein two patents were examined claiming ‘methods of peripheral stem cell transplantation required in treating a disease’, and ‘method of antibody purification’. In September-2015, Sandoz brought Zarxio in the US market. In 2017, the court dismissed infringement case of Amgen’s method-of-treatment patent and antibody-purification patent. Thereafter, the court wrote a decision in favor of Sandoz.
In general, biosimilar manufacturers don’t provide the patent information for new drug applications with their biologic license. Also, the Purple Book or Orange Book don’t give a comprehensive information about patents for their reference product. On the contradictory point of view, ‘reference medicine’ innovator piles up an extensive patent portfolio. Although, patent landscape is a prime option to monitor the patent portfolio in the domain, however, it might be a daunting task to search and look into hundreds of patents at once.
To conclude, the patent dance provides a holistic view to the biosimilar applicant and the depth of the ‘reference medicine’ innovator’s consideration for a relevant patent portfolio, resulting in the applicant tightening the control over the timing and scope of the litigation at the first phase. The number of patents to be litigated can be decided by the biosimilar applicant in the initial phase. As a result, the biosimilar applicant can have more control over the timing and scope of the litigation than in the normal infringement procedure. IP attorneys and professionals can assist their clients with the litigation, wherein a thorough review of Purple Book, patent search, patent watch of competitors, and proofreading of aBLA can be helpful to reduce the time usually spent in information exchange, patent review and building invalidation or non-infringement case. On the other hand, the ‘reference medicine’ innovator can also perform validity check of his patents, infringement study, market analysis in timely manner.