Is Another Challenge to the PTO’s PTE “Product” Interpretation Looming?

By Kurt R. Karst –

Earlier this year, the U.S. Patent and Trademark Office (“PTO”) denied an application for a Patent Term Extension (“PTE”) for U.S. Patent No. 6,869,939 (“the ‘939 patent”).  The ‘939 patent is one of four patents listed in FDA’s Orange Book as covering NEXTERONE (amiodarone HCl) Injection, which FDA approved in December 2008 under New Drug Application (“NDA”) No. 22-325. 

Amiodarone has been around for a while.  It was first approved in December 1985 as CORDARONE under NDA No. 18-972.  So it was no surprise when the PTO, in March 2010, denied a PTE for the ‘939 patent based on an analysis of the “first permitted commercial marketing” criterion in the PTE statute. 

Under 35 U.S.C. § 156(a)(5)(A), 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” (emphasis added).  The term “product” as used in § 156(a)(5)(A) is defined in § 156(f)(1) to mean “drug product,” which is defined in § 156(f)(2) to mean the “active ingredient of (a) new drug, antibiotic drug, or human biological product . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.”  The FDA’s PTE regulation at 21 C.F.R. § 60.3(b)(2) defines the term “active ingredient” to mean:

any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or of animals.  The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

Although the PTO had historically defined the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active moiety” (i.e., the molecule in a drug product responsible for pharmacological action, regardless of whether the active moiety is formulated as a salt, ester, or other non-covalent derivative) rather than “active ingredient” (i.e., the active ingredient physically found in the drug product, which would include any salt, ester, or other non-covalent derivative of the active ingredient physically found in the drug product), in May 2010, a 3-judge panel of the U.S. Court of Appeals for the Federal Circuit ruled in two cases – Photocure ASA v. Kappos and Ortho-McNeil Pharmaceutical, Inc. v. Lupin Pharmaceuticals, Inc. (here and here) – that the “active ingredient” interpretation of the statute is the proper interpretation.  (See our previous post here.)

The PTO’s denial of a PTE for the ‘939 patent is based on a straightforward analysis:

It is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product. . . .  It is also undisputed that amiodarone hydrochloride was approved by the FDA under section 505 of the FFDCA prior to the December 24, 2008 approval of NEXTERONE®. . . .  Accordingly, the later approved NEXTERONE® (amiodarone hydrochloride) does not represent the first permitted commercial marketing or use of the “product” under the provision of law under which such regulatory review occurred.

The PTO next turns its attention to two curious statements in the PTE application – namely that NEXTERONE “is a sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride intravenous solution,” and that “[t]he sulfobutyl ether -cyclodextrin-amiodarone hydrochloride complex was not previously approved prior to the approval of NEXTERONE®.”  The PTO’s response is that these statements are irrelevant for purposes of § 156(a)(5)(A):

[A]s already stated, it is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product.  The sulfobutyl ether ß-cyclodextrin component is not identified as an active ingredient of NEXTERONE® by the electronic Orange Book.  Indeed, the PTE Application itself does not identify sulfobutyl ether ß-cyclodextrin as an active ingredient of NEXTERONE®.  Accordingly, whether sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex has been previously approved prior to the approval of NEXTERONE® is irrelevant to the determination of whether the requirement of section 156(a)(5)(A) has been fulfilled.

The PTE applicant recently filed a Request for Reconsideration of the PTO’s denial of a PTE for the ‘939 patent “on the grounds that NEXTERONE® represents the first permitted commercial marketing or use of the Nexterone ‘product,’ sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex. . . .”  According to the PTE applicant:

The identification of “amiodarone hydrochloride” . . . was simply to indicate that amiodarone hydrochloride provides the pharmacological activity of the drug product.  It was the intention of Applicants to convey that the “active ingredient” in the drug product NEXTERONE® is the sulfobutyl ether ß-cyclodextrin amiodarone hydrochloride complex.

Because the definition of “active ingredient” at 21 C.F.R. § 60.3(b)(2) includes components that are “present in the drug product in a modified form intended to furnish the specified activity or effect,” and because, according to the PTE applicant, “amiodarone forms an inclusion complex with sulfobutyl ether-ß cyclodextrin,” and the  ‘939 patent “describes the interaction between amiodarone and sulfobutyl ether-ß cyclodextrin resulting in a complex in which the amiodarone is ‘part of a clathrate or inclusion complex,’”  “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex” is the active ingredient in NEXTERONE and the “drug product” under 35 U.S.C. § 156(f)(2).  FDA has not previously approved “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex,” so the approval of NEXTERONE would, according to the PTE applicant, meet the first permitted commercial marketing or use PTE criterion at 35 U.S.C. § 156(a)(5)(A).

The PTO typically holds firm to its PTE denials, so it seems unlikely that the Office will reverse the ‘939 PTE denial in light of the reconsideration request.  If that is the case here, then it is possible that more PTE litigation will be on the way.  Stay tuned!