India – How To Deal With The Patent Dance.

Basics of Biologics and Biosimilars

An important factor when looking to market a biosimilar in the US is the patent dance. In this context, it is important to touch upon the topics of Purple Book and BPCIA before moving onto the patent dance. The FDA’s Purple Book provides an electronic compilation of names of biological products which have received FDA approval in the form of a license viz. Biologics License Application (BLA). A BLA contains particulars such as an FDA Form 356h, applicant information, product/ manufacturing information and safety, efficacy and use of the new biological product. The Purple Book also provides details regarding the date on which the biological product was licensed and whether any product was determined to be a biosimilar to or interchangeable with an already licensed reference product. Since the approved biological product is termed as Reference product, ergo the BLA holder is called as the Reference Product Sponsor (RPS). Accordingly, it can be said that a BLA is a request for permission to market a new biological product (reference product) and an aBLA (Abbreviated Biologics License Application) allows a manufacturer to market a biosimilar version of the approved biological product. In the US, the Biologics Price Competition and Innovation Act (BPCIA), 2009 provides an abbreviated 351k pathway for biosimilar applicants to submit an aBLA and obtain FDA approval for the biosimilar. To obtain biosimilar approval, it is necessary to demonstrate that the proposed product is biosimilar to or interchangeable with an FDA approved reference product. The BPCIA is also responsible for creating the patent dance scheme. The BPCIA awards a 12 year exclusivity period for approved BLAs from the date of first authorization of the reference product, during which period, approval cannot be granted to a biosimilar by the FDA. An aBLA application can be submitted only after four years from the date of first licensure of the reference product.

Need for patent dance

Unlike biosimilar applicants, generic drug applicants wishing to enter the US market are required to certify against the NDA (New Drug Application) holder’s patents by taking help of the FDA’s Orange Book patent listing which provides information of not only the approved drugs but also the patents covering the drug/active ingredient, formulation comprising the drug and method of use. Surprisingly, the Purple Book does not furnish such aforementioned patent information relating to the reference product and this makes it difficult for the 351(k)/aBLA applicant to identify how many and which of the BLA holder’s patents can be asserted against the aBLA applicant when entering the market. This is where the patent dance comes in and regulates situations in which the aBLA applicant intends to market the biosimilar prior to the expiry of a patented biologic. It is equivalent to the process of certification and subsequent infringement proceedings between the NDA and ANDA party.

Patent dance

An aBLA applicant has to keep in mind the patent dance process. The patent dance is an elaborate back and forth exchange of information between a biosimilar applicant (BA) and a reference product sponsor (RPS) to resolve potential patent disputes prior to approval of the biosimilar. This information includes the aBLA, related manufacturing processes, notice of patents that could be subject to an initial pre-launch litigation and exchange of contentions on all patents that could possibly be in a suit. To sum it up, the process allows for several rounds of exchange of information and two rounds of litigation.

In view of the above, let’s have a brief look at the patent dance timeline as provided in 42 U.S.C. § 262 (l):

Sharing the list of biosimilar patents

However, there may be situations in which the two parties do not concur on the final list of patents to be litigated within the period of 15 days. Here, the BA must notify the RPS of the number of patents it will include in the final list and each party is given the opportunity to identify and exchange their respective patent lists they wish to assert within an additional period of five days. Subsequently, the RPS takes the process forward by filing the complaint. This is followed by the first phase of litigation in which the critical and pertinent patents are litigated immediately, while the FDA simultaneously reviews the aBLA. The next step involves the BA giving a notice of commercial marketing (NCM) to the RPS 180 days prior to marketing the biosimilar product. The second phase of litigation commences when the RPS is notified of the NCM and involves litigation (preliminary injunction) of patents which were left out from the first phase or newly issued patents.

Amgen v Sandoz

In Amgen v. Sandoz, there were two issues which needed adjudication i.e. consequences of failure to follow the patent dance and when the notice of commercial marketing needs to be given by the biosimilar applicant to the RPS. It was held by the Federal Circuit and affirmed by the Supreme Court that the BPCIA urges the biosimilar applicant to provide its product information to the RPS, albeit there is no mandatory obligation to do so. Failure to participate in the patent dance is not a violation of the BPCIA and no injunctive relief is available to the RPS for compelling compliance in this regards.

Furthermore, it was held that a biosimilar applicant may provide notice of commercial marketing either before or after receiving FDA approval which permits faster entry of the biosimilar products into the U.S market. Naturally, this decision came a ray of hope for biosimilar applicants.

Implications of the patent dance

Nonetheless, an applicant faces certain consequences if he opts out of the patent dance. The patent dance is optional and the aBLA applicant can either engage in the patent dance or skip this process. If the applicant does not go ahead with the patent dance, the applicant forgoes the right to file a declaratory judgement action challenging the validity of the patents of the RPS. Basically this means that the RPS may bring an action in good faith for a declaration of infringement, validity or enforceability of any patent that claims the biological product or a use of a biological product. Inevitably, the RPS gets to determine when and which patents to litigate. But, this would also make it complicated for the RPS to determine if the method used by the applicant for manufacturing the biosimilar infringes its own method or not. In such a case, the RPS may not want to take a chance at litigation, since he does not have an idea about potential infringement of the process and it could also increase the probability of his patent being challenged on grounds of invalidation. The aBLA applicant is exposed to a similar burden because it will have to assess and ascertain the relevant patent portfolio on its own and a smaller biosimilar company may find it daunting to litigate the several identified patents. In the alternative, if the biosimilar applicant does go ahead with the patent dance, the control considerably shifts to the applicant and it can decide the timing and scope of the initial phase of litigation because it gets a preview about the RPS’s relevant patent portfolio. An implication of exchanging information as required by the patent dance is disclosure of information such as potential trade secret/sensitive information inherent in the process of preparing the biosimilar, which need not have been shared in the traditional infringement suits. In many instances, the process also culminates with the parties entering into settlement agreements. It would be a better idea to stick with the patent dance component, since the process is systematic and it ensures certainty, transparency and provides a clear picture to the applicant, RPS and the public as well. This enables the BA to foresee the future allocation of resources for legal expenses and take strategic litigation decisions before making use of the patent dance provision and how far to take it. Another advantage is that, if the RPS’s relevant patent portfolio is small or if they are weak, they can be easily invalidated by using non-infringement or invalidity defenses. The process also prevents a product prepared by an infringing process from entering the market, which would not only dilute the protection of the RPS’s patents but also eat into its market share.

Contrasting strategies of patent dance

There are two case laws which involve contrasting strategies with respect to engaging in the patent dance. In Amgen v. Sandoz which was the very first BPCIA case to be litigated, Sandoz opted out of the patent dance with regards to its biosimilar Zarxio (filgrastim) which was a biosimilar of Amgen’s Neupogen. The Federal Circuit rejected Amgen’s claim construction arguments and finally ruled in favor of Sandoz, thereby affirming the District Court’s summary judgement of non-infringement. Sandoz adopted an opposite litigation strategy for entering the market with its proposed biosimilar of Amgen’s Neulasta (pegfilgrastim). This time around, Sandoz chose to follow the patent dance and provided Amgen with a notice of commercial marketing, which resulted in Amgen bringing an infringement action against Sandoz and seeking damages and an injunction. Amgen contended that the biosimilar would infringe Amgen’s patents US 8940878 (“the ‘878 patent”) and US 5824784 (“the ‘784 patent”). Since this case was consolidated with the filgrastim case, the final ruling favored Sandoz by passing a non- infringement judgment.

Shifting biologic from orange book to purple book: Implications

In recent biopharmaceutical news, the USFDA removed certain approved biologics (insulin and insulin analogs, human growth hormone, pancreatic enzymes, reproductive hormones) from the Orange Book on March 23, 2020 and inserted them in the Purple Book. Each already approved application for a biological product under the Food, Drug and Cosmetic Act is now deemed to be a license for the biological product under section 351 of the Public Health Service Act. This basically goes to say that going forward, a marketing application for a proposed biological product can only be submitted as a BLA under the Biologics Price Competition and Innovation Act of 2009 and not as an NDA under the FD&C Act. A corresponding change to the statutory definition of biological product with respect to “protein” has also been made. Accordingly, generic applicants for such biologics will have to win approvals as biosimilar applicants. The above move streamlines the FDA approval process for all biosimilars under the BPCIA.

Conclusion

However, in India, there is no patent dance provision. India has also not yet implemented the patent linkage regulation which refers to the linkage of marketing approval of an innovator product with the status of the patents protecting the innovator’s product. In the past, a proposal put forward by the Drugs Controller General of India (DCGI) for adopting this system was rejected after an intense debate between the different stakeholders. But the patent dance is all about resolving patent disputes, ergo it would be pointless to introduce the patent dance provision in India, unless a patent linkage system is introduced first.