Federal Circuit Denies Rehearing Petition in LEVAQUIN Patent Term Extension Case

By Kurt R. Karst –   

Last week, the U.S. Court of Appeals for the Federal Circuit denied Lupin Pharmaceuticals, Inc.’s (“Lupin’s”) Petition for Rehearing en banc of a May 10, 2010 panel decision in Ortho-McNeil Pharmaceutical, Inc. v. Lupin Pharmaceuticals, Inc. in which the Court affirmed a May 2009 decision from the U.S. District Court for the District of New Jersey that the Patent Term Extension (“PTE”)  granted by the U.S. Patent and Trademark Office (“PTO”) with respect to U.S. Patent No. 5,053,407 (“the ‘407 patent”) covering Ortho McNeil’s (“Ortho’s”) LEVAQUIN (levofloxacin) is valid.  The Court’s May 2010 panel decision, which was issued on the same day as the Federal Circuit’s decision landmark PTE decision in Photocure ASA v. Kappos, and the Court’s July 2010 denial of Lupin’s rehearing petition leave  standing an interesting dichotomy with respect to the treatment of single enantiomers in previously approved racemates insofar as the availability of PTEs and New Chemical Entity (“NCE”) exclusivity are concerned.

Levofloxacin is an enantiomer in the previously approved Ortho racemate drug product FLOXIN (ofloxacin).  Lupin initially challenged the ‘407 patent PTE in the context of ANDA Paragraph IV Certification patent infringement litigation on the grounds that the PTE is invalid because FDA previously approved the active ingredient levofloxacin when the Agency approved the racemate ofloxacin.  (See our previous post here.)

Under the PTE statute at 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.”  The term “product” is defined at 35 U.S.C. 156(f)(2) to mean, in relevant part, “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” (emphasis added).  (The term “active ingredient” is defined in FDA’s regulations 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 of any function of the body of man or of animals.”) 

For several years, the PTO had interpreted  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 contrast, the Federal Circuit’s 1990 decision in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392, 13 USPQ2d 1628 (Fed. Cir. 1990) (“Glaxo II”), construed the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active ingredient.”  The Federal Circuit’s May 2010 decision in Photocure and Ortho-McNeil, both of which concerned the proper interpretation of 35 U.S.C. § 156(a)(5)(A), ruled that the Glaxo II decision and its “active ingredient” interpretation of the PTE statute should be applied for PTE purposes. 

In contrast, FDA has for decades, treated single enantiomers of previously approved racemates as previously approved drugs not eligible for 5-year NCE exclusivity (but eligible for three-year new clinical investigation exclusivity).  For example, FDA stated in the preamble to its 1989 proposed regulations implementing the Hatch-Waxman Amendments that “FDA will consider whether a drug contains a previously approved active moiety on a case-by-case basis.  FDA notes that a single enantiomer of a previously approved racemate contains a previously approved active moiety and is therefore not considered a new chemical entity.”  FDA still adheres to this policy today, although the FDA Amendments Act of 2007 amended the FDC Act to add § 505(u), which permits the sponsor of an NDA for an enantiomer (that is contained in a previously approved racemic mixture) containing full reports of clinical investigations conducted or sponsored by the applicant to “elect to have the single enantiomer not be considered the same active ingredient as that contained in the approved racemic drug,” and thus be eligible for NCE exclusivity.

The dichotomy between the treatment of enantiomers in previously approved racemates with respect to PTE and NCE exclusivity eligibility was at the heart of Lupin’s Petition for Reconsideration.  Lupin argued that: 

The FDA and PTO abused their discretion when they applied two conflicting interpretations to the same words – “active ingredient” – in the same legislation – the “Hatch-Waxman Act.”  Thus, the district court and the panel erred in failing to consider the important legal issue: what the term “active ingredient” means and how it should be applied to enantiomers.  The Court should grant this petition for rehearing en banc to adopt and apply a consistent definition of “active ingredient” and to reverse the district court’s determination that the [PTE] was properly based on the approval of LEVAQUIN®, which contained the previously approved enantiomer, levofloxacin, as its active ingredient.

Lupin also relied on the Federal Circuit’s 2004 decision in Arnold Partnership v. Dudas to build its case.  In that case, which concerned the availability of a PTE for a combination drug, the Court ruled that “the [PTE] statute places a drug product with two active ingredients, A and B, in the same category as a drug product with a single ingredient . . . .  To extend the term of a patent claiming a composition comprising A and B, either A or B must not have been previously marketed.”  In reaching its decision in Arnold Partnership, the Court relied on FDA’s regulations to construe the term “active ingredient” as used in the PTE statute.  Applying the concept that “[w]hen the same term appears in multiple locations in the same Congressional Act, it is generally considered to have the same meaning each time,” Lupin argued (unsuccessfully) that “the term ‘active ingredient’ should be construed to have the same meaning when it appears in the [PTE] provisions of the Hatch-Waxman Act . . . and in the new product exclusivity provisions of the Hatch-Waxman Act,” such that the PTO should have considered levofloxacin to have been previously approved in ofloxacin and not granted a PTE with respect to the ‘407 patent covering LEVAQUIN.