Rebel Without a Cause: Sun Sues FDA Over 180-Day Exclusivity for Generic ZOMETA

By Kurt R. Karst –      

Finally!  A Hatch-Waxman lawsuit that is not overly complex and not difficult to unravel.  Late last week, Sun Pharma Global FZE, Caraco Pharmaceutical Laboratories, Ltd., and Sun Pharmaceuticals Industries, Ltd. (collectively “Sun”) filed a Complaint and a Motion for a Temporary Restraining Order and a Preliminary Injunction in the U.S. District Court for the District of Columbia (Case No. 1:13-cv-00277-ABJ) against FDA seeking, among other things, entry of a judgment declaring that the company is entitled to 180-day exclusivity for a generic version of Novartis Corporation’s ZOMETA (zoledronic acid) Injection, 4 mg/5 mL (or 0.8 mg (base)/mL).

ZOMETA is approved under NDA No. 021223 and is listed in the Orange Book with three product entries.  Product 001 is identified as “EQ 4MG BASE/VIAL” and was approved on August 20, 2001.  It is a lyophilized version of the drug that is no longer marketed, and is listed in the discontinued section of the Orange Book.  Product 002 – the product at issue in the lawsuit – is identified as “EQ 4MG BASE/5ML.”  It was approved on March 7, 2003 and is a non-lyophilized version of the drug.  Finally, Product 003 is identified in the Orange Book as “EQ 4MG BASE/100ML.”  It was approved on June 17, 2011, and, like Product 002, is currently marketed.

Product 002 is listed in the Orange Book with two patents: (1) U.S. Patent No. 4,939,130 (“the ‘130 patent”), which expired on September 2, 2012, but is subject to a period of pediatric exclusivity that expired on March 2, 2013; and (2) U.S. Patent No. 8,324,189 (“the ‘189 patent”), which expires on May 29, 2025, and is subject to a period of pediatric exclusivity that expires on November 29, 2025.  The ‘130 patent has been listed in the Orange Book for Product 002 since 2003.  (It was originally scheduled to expire on July 24, 2007, but was granted a patent term extension.)  The ‘189 patent was issued on December 4, 2012, and, according to Sun, was timely listed in the Orange Book on January 2, 2013. 

FDA’s Paragraph IV Certifications List identifies June 11, 2008 as the first date on which an ANDA containing a Paragraph IV certification was submitted to FDA seeking approval of Product 002.  That product is identified on FDA’s list as ZOMETA (zoledronic acid) Injection “0.8 mg (base) /mL,” which corresponds to 4 mg/5 mL.  Because the first ANDA containing a Paragraph IV certification was submitted to FDA years before the ‘189 patent was listed in the Orange Book (or even issued), such ANDA must have included a Paragraph IV certification to the ‘130 patent.  Moreover, because the first ANDA for a generic version of Product 002 was submitted to FDA after December 8, 2003, 180-day exclusivity is governed by the Medicare Modernization Act (“MMA”).  Under the MMA, 180-day exclusivity eligibility can be forfeited under one (or more) of the six forfeiture provisions at FDC Act § 505(j)(5)(D).

Sun reportedly submitted ANDA No. 202746 to FDA on January 10, 2011 containing a Paragraph III certification to the ‘130 patent, and reportedly amended that ANDA on January 3, 2013 with a Paragraph IV certification to the ‘189 patent.  According to Sun, the company “should be awarded First Filer status because when Sun filed its Paragraph IV certification [the ‘189 patent], no other ANDA for Zometa® Product 002 was previously filed that contained a Paragraph IV certification and there is no basis in the law or regulations for FDA to approve any other ANDA’s until FDA determines whether SUN has first to file status.” (Emphasis in original)  FDA has already tentatively approved several ANDAs for generic ZOMETA, and the Agency is likely poised to approve several ANDAs for generic versions of Product 002 on Monday now that the period of pediatric exclusivity on the ‘130 patent has expired.  (ANDA No. 202746 is not on the list of tentatively approved applications.)   

Despite Sun’s allegations, the facts in this case seem to point in another direction.  According to a patent infringement lawsuit Novartis filed in July 2008 against Teva Parenteral Medicines Inc. (“Teva”) in the U.S. District Court of Delaware (Case No. 1:08-cv-00459), Teva submitted two ANDAs – ANDA Nos. 078576 and 078580 – for generic versions of ZOMETA (apparently Product 001 and Product 002) containing Paragraph IV certifications to the ‘130 patent.  Based on ANDA submission dates identified in the court docket, that would make Teva the first applicant eligible for 180-day exclusivity.  But 180-day exclusivity for Product 002 (as well as Product 001) has been forfeited.  Indeed, there appear to be several bases for forfeiture. The most obvious forfeiture is patent expiration (FDC Act § 505(j)(5)(D)(i)(VI)); however, failure to obtain tentative approval (FDC Act § 505(j)(5)(D)(i)(IV)), ANDA withdrawal (FDC Act § 505(j)(5)(D)(i)(II), and amendment of certification (FDC Act § 505(j)(5)(D)(i)(III) may also be possibilities.  In other words, Sun’s lawsuit may be short-lived.  As this case moves forward over the next day, we will post periodic updates.

UPDATE:

• The following Minute Order was entered late on March 1st: “During a telephone conference held on this date at which counsel for plaintiff as well as counsel from FDA and DOJ participated, counsel for defendants represented to the Court that FDA will not approve any ANDAs for the drug product at issue in this case until the Court has had an opportunity to address plaintiff's motion for temporary restraining order and preliminary injunction [Dkt. # 2] during a hearing on March 4, 2013.  Accordingly, consistent with the Court's oral ruling during the telephone conference, it is ORDERED that defendants shall file a response to plaintiff's motion by 10:00 am on Monday March 4, 2013. A hearing is scheduled for March 4, 2013 at 11:00 am in Courtroom # 3 before Judge Amy Berman Jackson.”
• On March 1st, FDA issued a letter decision finding that 180-day exclusivity for generic ZOMETA Product 002 was forfeited.
• On March 1st, Sun submitted a citizen petition to FDA requesting that the Agency not approve any affected ANDAs.
• On March 3rd, Sun supplemented its Motion for a Temporary Restraining Order and a Preliminary Injunction motion.
• The following Minute Order was entered on March 3rd: “It is ORDERED that defendants file with the Court by March 4, 2013 at 10:00 am, any application containing a Paragraph IV certification for the same drug for which plaintiffs claim first filer status that was submitted before plaintiffs' application, as well as any documents that reflect notice provided to Novartis of the application that the FDA has deemed to be the first.”
• The following Minute Order was entered on the morning of March 4th: “In light of the in camera submission made by defendants on this date in response to the Court's Minute Order of March 3, 2013, it is ORDERED that before the hearing scheduled for 11:00 am on this date, defendants provide a redacted copy of the documents included in the submission to counsel for plaintiffs, or be prepared to explain to the Court at the hearing why that is not possible.”
• On the afternoon of March 4th, the court issued a Notice of Dismissal stating: “Pursuant to Rule 41(a)(1)(A)(i) of the Federal Rules of Civil Procedure, Plaintiffs Sun Pharma Global FZE, Caraco Pharmaceutical Laboratories, Ltd., and Sun Pharmaceuticals Industries, Ltd., hereby dismiss the above captioned action.”