In our blog post of November 18, 2013 (“No Avoiding BPCIA For Biosimilars: No Patent Declaratory Judgment Before Biosimilars Application is Filed”), we discussed the decision of the U.S. District Court for the Northern District of California holding that a biosimilars applicant could not avoid the Biologics Price Competition and Innovation Act (“BPCIA”) patent exchange process by filing a patent declaratory judgment prior to filing its 351(k) biosimilar application.  That case – Sandoz, Inc. v. Amgen Inc. – is on appeal to U.S. Court of Appeals for the Federal Circuit.  (Appeal docketed as No. 14-1693, Fed. Cir., December 13, 2013).  While that case, involving Amgen’s ENBREL® product, will decide the issue of whether BCPIA patent process can be avoided by filing a declaratory judgment prior to filing of the 351(k) application, another dispute has arisen between Sandoz and Amgen as to whether the patent and application certification and exchange process in Section 351(l)(2) of the Public Health Service Act is mandatory or permissive.

Amgen also owns a Biologics License Application (BLA) for NEUPOGEN® (filgrastim), a product used to treat side effects of cancer therapy.  Sandoz has filed a 351(k) application for a biosimilar of filgrastim.

On October 29, 2014, Amgen filed a Citizen Petition requesting that the U.S. Food and Drug Administration (“FDA”) require biosimilar applicants to participate in the exchange of information (colloquially known as the “patent dance”) under the BPCIA.  (See Docket No. FDA-2014-P-1771, dated October 29, 2014, on www.regulations.gov.)  Amgen’s Citizen Petition requests that FDA require biosimilar applicants to file, at the time of filing of a 351(k) application, a certification that the applicant will comply with the requirements of Section 351(l)(2)(A) by providing the Reference Product sponsor a copy of the 351(k) application within 20 days of being informed by FDA that its application has been accepted for review.  Amgen argues-in-brief-that the statutory language provides that the applicant “shall” do so, and, hence, it is not an option that a biosimilars applicant  can avoid.  It suggests that the certification could be added to the 356h form filed with each BLA.

Amgen’s petition followed the October 24, 2014, filing of its complaint in the U.S. District Court for the Northern District of California, asserting claims of patent infringement, conversion and unfair competition under Cal. [Bus. & Prof.] Code § 17200 based on Sandoz’s failure to participate in this exchange of application and patent information.

Amgen asserted that Sandoz’s refusal to comply with 351(l)(2)(A) deprives it of the benefits of Reference Product holder, including the ability to seek a preliminary injunction against approval of Sandoz’s application, resulting in irreparable harm to it.  It has requested that the Court enjoin Sandoz from marketing the biosimilar of NEUPOGEN ® until Amgen is restored to the position it would have been absent Sandoz’s refusal to follow the statutory framework in the BPCIA, and Amgen receives notice of Sandoz’s commercial marketing after FDA licenses Sandoz’s biosimilar product.  Amgen is also requesting the Court enjoin Sandoz from continuing with FDA review of Sandoz’s biosimilar application until Sandoz complies with the BPCIA’s statutory framework, as opposed to is proposed alternative.  Last, Amgen seeks a judgment that Sandoz has infringed Amgen’s asserted patent by submitting its biosimilar application without providing the application and manufacturing information to Amgen.

The “patent dance” begins with a biosimilar applicant’s filing of a BLA, under Section 351(k) of the Public Health Service Act which includes product and manufacturing information, clinical studies and labeling information relating to the biosimilar product.  Once the FDA notifies the biosimilar applicant that its BLA has been accepted for review, the biosimilar applicant and the innovator (Reference Product sponsor) are to engage in a series of timed exchanges of information, starting with the biosimilar applicant providing a copy of its BLA and its manufacturing processes.  This disclosure is to be provided to the innovator within 20 days after the biosimilar applicant is notified that the FDA has accepted its BLA for review.  Specifically, relevant portions of the BPCIA provides that the biosimilar applicant “shall provide” this information to the innovator.  42 U.S.C. 262(l)(2)(A).  The biosimilar applicant “may provide” additional information as requested by the innovator.  42 U.S.C. 262(l)(2)(B).

The recent dispute between Amgen and Sandoz arises from Sandoz’s failure to provide a copy of its BLA and information relating to its manufacturing processes of its NEUPOGEN® biosimilar.  Amgen contends that the disclosure of this information is mandatory.  Sandoz, on the other hand, appears to have taken on the position that it is optional.  In its complaint, Amgen asserts:

Defendants are attempting to obtain the benefits of the BPCIA by filing their BLA under the § 262(k) pathway without complying with the requirements that Congress also imposed through the BPCIA on biosimilar applicants.  For example, Defendants made a deliberate decision not to provide Amgen with a copy of its BLA, together with other information necessary to describe the process(es) for manufacturing the biosimilar product, within 20 days of receiving notification of FDA acceptance of their application.

According to Amgen, Sandoz proposed that it would provide only its BLA and not its manufacturing information and further on the condition that Amgen forfeit its right to use the BLA as a basis to allege infringement under 35 U.S.C. § 271(g), which provides for infringement of a patented process based on importation of a product into the U.S. that is made from the patented process.  When Amgen refused to agree with Sandoz’s proposal as improperly limiting the scope of disclosures mandated by the BPCIA, Sandoz responded that it “opted not to provide Amgen” the information and suggested that Amgen could initiate a declaratory judgment action.

This is not the first time that a federal district court has been asked to construe the “patent dance” provisions of the BPCIA.

In addition to the prior Sandoz/Amgen dispute discussed in our prior blog post, on March 31, 2014, Celltrion filed two declaratory judgment actions – one in the U.S. District Court for the District of Massachusetts seeking a declaration of invalidity and unenforceability of patents to Janssen Biotech, Inc. and the other filed in the U.S. District Court for the Southern District of New York seeking a declaration of invalidity of patents to Kennedy Trust for Rheumatology Research.  Janssen holds patents cover Remicade®, an antibody biologic drug that is approved in the United States for treating rheumatoid arthritis and other medical conditions.  Kennedy holds patents that cover methods of treating rheumatoid arthritis by co-administering a combination an antibody (such as Remicade®) and a known arthritis drug methotrexate.  It its complaints, Celltrion alleges that it developed Remsima®, a biosimilar of Janssen’s antibody product, which it claims “will become the first biosimilar of an antibody drug ever approved in the United States.”

As with the Sandoz case, Celltrion filed its declaratory judgment actions before it had even filed a 351(k) application.  As expected, both Janssen and Kennedy filed motions to dismiss for lack of subject matter jurisdiction, arguing that Celltrion had not yet engaged in meaningful preparation to conduct potentially infringing activity and that Celltrion should not be permitted to bypass the BPCIA framework.

On October 23, 2014, Celltrion voluntarily dismissed its action against Janssen after fully briefing the issue and informing the court that it had submitted its BLA in August 2014.  Celltrion’s action against Kennedy, however, is still pending a resolution of Kennedy’s motion to dismiss.

How the courts address these two issues – Can a declaratory judgment of patent non-infringement be filed prior to filing a 351(k) biosimilars application? And is the application and patent exchange process in 351(l) mandatory or not? – will go a long way in clarifying the resolution of patent disputes between Reference Product sponsors and biosimilar applicants going forward.