While Sandoz has grabbed the biosimilar headlines for being the first company to have a product approved under the Biologics Price Competition and Innovation Act (its product Zarxio™ (filgrastim-sndz) is a biosimilar of Amgen’s Neupogen® (filgrastim) product), another biosimilar patent dispute is brewing between Janssen Biotech, Inc. and Celltrion Healthcare Co., Ltd. over Remicade® (infliximab). On March 6, 2015, Janssen filed a complaint against Celltrion in the Massachusetts district court, alleging violations of the BCPIA, and infringement of six patents. Like the pending litigation between Amgen and Sandoz, the Remicade biosimilar case highlights how the carefully orchestrated patent dispute resolution processes of the BCPIA can fall apart when the parties cannot even agree on what the law requires. 

The Biosimilar Framework

According to Janssen’s complaint, Remicade® (infliximab) has been approved for the treatment of Crohn’s disease (1998), rheumatoid arthritis (1999), ankylosing spondylitis (2004), psoriatic arthritis (2005), and ulcerative colitis (2006). Celltrion has filed an application seeking approval of a biosimilar version of Remicade® under the BPCIA, but its application has not been approved.

The BCPIA includes a complicated process for addressing patent disputes surrounding biosimilar products, laid out in 42 USC § 262(l).

The first step is set forth in 42 USC § 262(l)(2):

(2) Subsection (k) application information

Not later than 20 days after the Secretary notifies the subsection (k) applicant that the application has been accepted for review, the subsection (k) applicant−

(A) shall provide to the reference product sponsor a copy of the application submitted to the Secretary under subsection (k), and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application; and

(B) may provide to the reference product sponsor additional information requested by or on behalf of the reference product sponsor.

The next steps are set forth in 42 USC § 262(l)(3), and require the parties to identify which patents they believe should be litigated. First, the sponsor “shall provide … (i) a list of patents for which the … sponsor believes a claim of patent infringement could reasonably be asserted … and “(ii) an identification of the patents on such list that the … sponsor would be prepared to license to the subsection (k) applicant.” In response, the applicant “may provide” its own list of patents, and “shall provide” a detailed statement describing “the factual and legal basis” for the applicant’s opinion that the patents on the sponsor’s list are “invalid, unenforceable, or will not be infringed.” (The applicant also “shall respond” to any offer to license.) Then, the sponsor “shall provide” its own detailed statement describing “the factual and legal basis” for its opinion that the patents will be infringed, and responding to the applicant’s assertions regarding invalidity and unenforceability.

Once those cards are on the table, 42 USC § 262(l)(4) requires the parties to “engage in good faith negotiations to agree on which, if any, patents ” from the sponsor and applicant lists should be litigated.

If agreement is reached, then 42 USC § 262(l)(6)(a) gives the sponsor “not later than 30 days after such agreement” to “bring an action for patent infringement.”

If agreement is not reached, 42 USC § 262(l)(5) calls for a further round of patent lists to be exchanged, but first the applicant “shall notify the … sponsor of the number of patents” that it will include on its list. This gives the applicant some control, because “the number of patents listed by the … sponsor … may not exceed the number of patents listed by the … applicant,” except that if the applicant does not list any patents, then the sponsor may list one patent. Once that is settled, both parties “shall simultaneously exchange” their second lists of patents. Then, under 42 USC § 262(l)(6)(b), the sponsor has “not later than 30 days after the exchange of [the second] lists” to “bring an action for patent infringement with respect to each patent that is included on such lists.”

If that weren’t complicated enough, 42 USC § 262(l)(8) provides for another round of litigation to permit the sponsor to seek a preliminary injunction before the biosimilar is marketed:

(8) Notice of commercial marketing and preliminary injunction

(A) Notice of commercial marketing

The subsection (k) applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k).

(B) Preliminary injunction

After receiving the notice under subparagraph (A) and before such date of the first commercial marketing of such biological product, the reference product sponsor may seek a preliminary injunction prohibiting the subsection (k) applicant from engaging in the commercial manufacture or sale of such biological product until the court decides the issue of patent validity, enforcement, and infringement with respect to any patent that is [included in either of the first lists but not included on the agreed upon list or the second lists].

Complementing the procedures of 42 USC § 262(l), 35 U.S.C. § 271(e) includes provisions imposing consequences on the sponsor/patent holder for failing to list a patent that should have been listed and/or failing to bring suit within the 30-day time periods.

Janssen’s Complaint

Janssen’s complaint alleges that Celltrion failed to follow the requirements of the BCPIA in at least the following ways:

• Celltrion did not provide information regarding its manufacturing process, as required by § 262(l)(2)

• Celltrion “consented to Janssen’s patent list” and circumvented the negotiation procedures of § 262(l)(4) and (5)

• Celltrion has insisted that Janssen bring suit within 30 days of Celltrion’s detailed statement of factual and legal basis provided under § 262(l)(3) instead of following the remaining procedures of § 262(l)(4) and (5)

• Celltrion prematurely provided “notice of commercial marketing” even though its product is not yet approved

Janssen also asserts infringement of six patents and seeks injunctions relating to the same.

What Does The Biosimilar Statute Require?

Taking Janssen’s complaint at face value, it is easy to see why Janssen is frustrated by Celltrion’s conduct. On the other hand, it is hard to image that a court would penalize Celltrion for “consenting” to Janssen’s patent list, even if that consent meant that Janssen had less time overall to bring suit. Between this case and Amgen’s case against Sandoz pending in the Northern District of California, the courts will have to determine which steps of § 262(l) are mandatory, and which can be avoided and under what circumstances.