FDA Rejects “Extraordinary” Position in Battle Over BUTRANS Patent Term Extension

By Kurt R. Karst –   

A recent letter decision from FDA to the Patent and Trademark Office (“PTO”) concerning the availability of a Patent Term Extension (“PTE”) for U.S. Patent No. RE 41,571 (“the ‘571 patent), a method-of-use patent listed in the Orange Book covering Purdue Pharma L.P.’s (“Purdue’s”) BUTRANS (buprenorphine) Transdermal System (NDA 021306; approved on June 30, 2010) might mean that we are one step closer to another PTE court battle.  In a March 28, 2016 letter, FDA rejects Purdue’s characterization of the active ingredient in BUTRANS as buprenorphine levulinate, instead of buprenorphine base, as explained in Purdue’s February 28, 2014 supplemental PTE submission. 

As we previously reported, Purdue submitted a PTE application in August 2010 (Docket No. FDA-2012-E-0152) requesting a PTE for the ‘571 patent.  The PTE application was submitted only a few months after the U.S. Court of Appeals for the Federal Circuit ruled on May 10, 2010 in PhotoCure v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010) and Ortho-McNeil Pharm., Inc. v. Lupin Pharms., Inc., 603 F.3d 1377 (Fed. Cir. 2010).  Those decisions concern the proper interpretation of 35 U.S.C. § 156(a)(5)(A), which states that the term of a patent claiming a drug shall be extended from the original expiration date of the patent if, among other things, “the permission for the commercial marketing or use of the product . . . is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred.”  The Federal Circuit ruled that that an “active ingredient” interpretation instead of an “active moiety” interpretation of the PTE statute – and the term “product” in particular – should be applied for PTE purposes (see our previous post here).  In dicta in the PhotoCure decision, however, the Federal Circuit suggested that the PTO might look at additional factors in considering whether or not a patent covering a product is eligible for a PTE. 

Although buprenorphine is not new – FDA has approved several applications for drug products containing buprenorphine, including BUPRENEX (NDA 018401), SUBUTEX (NDA 020732) – Purdue latched on to the PhotoCure dicta and made its case for a PTE for the ‘571 patent:

In contrast to [previous FDA approvals], the active ingredient for Butrans™ is buprenorphine base, which has never before been approved by the FDA. Moreover, buprenorphine base was required to undergo full FDA review, and has pharmacological properties that set it apart from buprenorphine hydrochloride.  Accordingly, the ‘571 patent that covers Butrans™ remains eligible for a patent term extension under 35 U.S.C. § 156.  See Photocure ASA v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010) (allowing a § 156 extension even where similar active ingredient was previously approved by the FDA, since later approved active ingredient covered by extension application had different biological properties and underwent separate regulatory approval); Ortho-McNeil Pharm. v. Lupin Pharm., 603 F.3d 1377 (Fed. Cir. 2010) (allowing § 156 extension for enantiomer even though the racemate had already been approved by the FDA).

In other words, notwithstanding FDA’s previous buprenorphine NDA approvals, Purdue took the position that the ‘571 patent covering BUTRANS is eligible for a PTE because the drug product contains a different active ingredient (i.e., buprenorphine base) and has different properties that warranted separate patenting and separate FDA NDA approval (i.e., a different regulatory review period).

In June 2012, FDA sent a letter to the PTO stating that the Agency’s records “indicate that BUTRANS does not represent the first permitted commercial marketing or use of the product, as defined under 35 U.S.C. § 156(f)(1).”  And in a separate PTE matter, the PTO rejected arguments similar to those raised by Purdue with respect to dicta in the PhotoCure decision (see our previous post here).

Given these events, Purdue took a different tack.  In a February 28, 2014 supplemental PTE submission, the company argued that BUTRANS does not contain buprenorphine base, but rather buprenorphine levulinate.  If that were the case, then the ‘571 patent would be eligible for a PTE, because FDA has not previously approved an application under FDC Act § 505 for a drug product containing buprenorphine levulinate, or a salt or ester of buprenorphine levulinate.  However, FDA’s March 28, 2016 letter to the PTO rejects this approach: 

Purdue’s position is extraordinary.  Essentially it argues that the submissions that it made to obtain approval of this NDA, which asserted and presented evidence that the active ingredient of the drug was buprenorphine, were false.  Moreover, Purdue’s position would mean that the drug product that it has been marketing is misbranded because its labeling fails to bear the proportion and quantity of what Purdue now claims to be the active ingredient, buprenorphine levulinate. . . . 

Purdue has not submitted sufficient evidence to demonstrate that buprenorphine levulinate, a salt form of buprenorphine, is formed in the adhesive matrix of the Butrans Transdermal Delivery System (TDS). . . .  [Purdue’s nuclear magnetic resonance] experiments show, at best, that there is an interaction between buprenorphine and levulinic acid in chloroform, which is likely to occur for any given organic acid and organic base if present in a solvent environment like chloroform under soluble conditions.  For example, any combination of the ingredients in Butrans could hypothetically produce interactions leading to other undefined substances in the matrix.  While theoretically salts can be formed in situ, there is no evidence of this actually occurring in the TDS adhesive matrix.

With FDA’s position in hand, we expect that the PTO will, in due course, issue a determination that the ‘571 patent is ineligible for a PTE.  Once that decision becomes final, Purdue could abandon further efforts to obtain a PTE, or fight on in court.