Coordinating Biosimilar Litigation and Proceedings

Biologics and biosimilars together represent a rapidly growing component of the pharmaceutical marketplace, and the unique legal issues that accompany them demand careful strategic planning to successfully navigate proceedings in the myriad venues where disputes will inevitably arise: from the US Patent and Trademark Office (USPTO) and US courts to patent offices and courts abroad.  Here, we outline the regulatory and intellectual property legal regime for biosimilars in the US, including the avenues that legal disputes may take, and highlight considerations that US counsel representing clients in biosimilar disputes must weigh to coordinate a global litigation strategy.
 
Biosimilars and the Biologics Price Competition and Innovation Act
 
Biologics are manufactured by biological processes typically in living cells and tend to be large, complex molecules.  The nature of the final biologic product is dependent on the conditions in which they were manufactured.  Therefore, manufacture of an identical follow-on version of an approved biologic by a competitor is generally not technically possible and no true chemically identical generic versions of a biologic exist.  Rather, follow-on biologics produced by competitors may demonstrate a high enough degree of similarity to an approved biologic (a “reference product”) to be considered biosimilar. 
 
The US established its abbreviated biosimilar approval process in 2010 with the adoption of the Biologics Price Competition and Innovation Act (BPCIA).  Five years later, in March 2015, the FDA approved the first biosimilar for the US market.  Under the BPCIA, a biosimilar manufacturer may file an abbreviated biologics license application (aBLA) for a product that is “highly similar” to a reference product four years after the date that the FDA approved the reference product.  However, the FDA may not approve the biosimilar aBLA until 12 years after reference product approval, thus providing the reference product 12 years of market exclusivity. 
 
US Litigation and USPTO Proceedings
 
Even at the expiration of the market exclusivity period, a patent or, more likely, multiple patents may bar a biosimilar from the market.  The BPCIA provides a framework to resolve biosimilar patent disputes through litigation.  Under this framework, upon filing its aBLA, the biosimilar applicant discloses the aBLA and information regarding its manufacturing process for the biosimilar to the reference product sponsor.  The reference product sponsor and biosimilar applicant may then exchange lists of patents that each party believes are at issue and negotiate to determine which patents will limit the subject matter of litigation.  If the biosimilar applicant chooses not participate in the patent exchange, the reference product sponsor may file an infringement action for one patent that the reference product sponsor has chosen.  Furthermore, litigation under the BPCIA scheme is not mandatory.  Under the current controlling interpretation of the BPCIA, if a biosimilar applicant fails to disclose the required information to the reference product sponsor, the reference product sponsor can file an action against the biosimilar applicant for infringement in US district court for any patent claims that cover the biologic product or use of the product. 
 
Biosimilar manufacturers may choose to forgo the complex BPCIA litigation framework and, instead, challenge patents covering a reference product before the USPTO in an inter partes review (IPR) proceeding or a post grant review (PGR) proceeding.  An accused infringer may request an IPR before the USPTO at any time before a patent owner files a complaint alleging infringement in court and up to one year after a patent owner files the complaint.  Grounds for attacking a patent in an IPR are limited to anticipation or obviousness of the patent in light of prior patents or printed publications, a much more limited scope than that of courtroom litigation.  PGR is only available to patents with a priority date after 15 March 2013 but, unlike IPR proceedings, PGR allows an attack on all bases of unpatentability.
 
A biosimilar manufacturer who chooses the IPR or PGR route and successfully manages to invalidate all of the patents that protect the reference product may be free to pursue its aBLA and enter the US market upon expiration of the reference product’s 12-year market exclusivity period.  The burden of proving invalidity in an IPR is lower than that in district court, and, to date, IPR challenges of patents based on obviousness arguments generally enjoy a higher success rate than challenges in courts.  However, IPR strategies come with risks.  For example, a biosimilar manufacturer who tries but fails to invalidate all of the patents covering a reference product through IPR proceedings risks creating the impression that the surviving patent claims have been strengthened, and, moreover, would be barred from challenging surviving patent claims on the same grounds in any subsequent litigation in US courts.  On balance, IPR challenges to biologics patents may be better viewed by biosimilar manufacturers as a strategy to streamline subsequent US patent litigation and potentially to encourage early settlement by clearing the field of weaker patent claims.
 
Coordinating Global Biosimilar Litigation and Proceedings
 
Patent disputes concerning biosimilars arise around the world in multiple forums, for example, through litigation in courts or opposition proceedings before patent offices.  The resolution of a patent dispute in one country and the procedures conducted to reach that resolution may influence subsequent patent disputes elsewhere, which makes it important for patent counsel to coordinate their strategies across jurisdictional boundaries. 
 
In terms of outcomes, if multiple tribunals in multiple jurisdictions all reach the same conclusion on related biosimilar patent disputes, at some point, those decisions may begin to have cumulative persuasive influence on subsequent tribunals.  Therefore, early favorable decisions from certain tribunals can potentially confer an indirect benefit beyond the benefit of the single favorable outcome in that jurisdiction.  Of course, differences in the patent laws across different jurisdictions may blunt the impact of any particular decision in any particular jurisdiction.
 
Counsel representing a biologic or biosimilar manufacturer in the US also must consider how admissions or arguments made before a US tribunal, whether a court or the USPTO, will affect subsequent proceedings in jurisdictions abroad, and vice versa.  A party potentially may lose credibility, or even be precluded from making an argument, if the party has made statements in prior proceedings in one venue that are inconsistent or contradictory with statements later made in another. 
 
Careful planning between counsel representing the same client across jurisdictions presents one way to address these challenges before they become problems.  The importance of such planning will continue to increase as exclusivity periods expire for existing biologics over the next few years, and biosimilars attempt to gain market entry in the US and abroad.  

Alicia Russo has experience in complex patent litigation, as well as in oil and gas, biotechnology, bioinformatics, vaccine, therapeutic antibodies, and pharmaceutical patent prosecution. In addition, she has experience in licensing of intellectual property, as well as in due diligence, patentability and non-infringement analysis. Her primary focus is in the area of pharmaceuticals and biotechnology. She has handled major due diligence projects for large acquisitions in the pharmaceutical field. In addition, she has successfully represented clients in reexaminations and interferences before the U.S. Patent and Trademark Office.

Alicia can be contacted on (212) 218-2568 or by email at arusso@fchs.com