Patent Law

When It Comes to Patent Term Extensions, An Enantiomer is a Different Drug From Racemate

By Stephen Albainy-Jenei

US Pat. No. 5,053,407, exclusively licensed to Ortho-McNeil Pharmaceutical, is directed to an enantiomer of a racemic compound that had previously been approved by the Food and Drug Administration (FDA).

On judgment, the district court agreed with the positions of the Patent and Trademark Office and the FDA, and held that the statutory requirements for term extension were met for the ?407 patent.

The district court then enjoined Lupin Pharmaceuticals from infringement during the extended term of the patent. Needless to say, Lupin was crestfallen and appealed but the US Court of Appeals for the Federal Circuit affirmed the district court?s judgment. Ortho-McNeil Pharma v. Lupin Pharma (09-1362).

The ?407 patent is for an antimicrobial compound having the common name levofloxacin. Levofloxacin is the levorotatory enantiomer (also designated the S(-) enantiomer) of the racemate ofloxacin, which is a known antimicrobial product. A racemate consists of equal amounts of spatial isomers called enantiomers, molecules that are mirror images of each other.

Due to their spatial orientation, enantiomers are optically active and are characterized by whether they rotate plane-polarized light clockwise (dextrorotatory) or counter-clockwise (levorotatory). Although enantiomers and their racemates have the same chemical composition, they may differ in their physical, chemical, or biological properties.

The inventors determined that levofloxacin has properties that are significantly superior to those of ofloxacin. The ?407 patent describes this synthesis, and presents data showing that levofloxacin is more effective as an antimicrobial agent, more rapidly available for biological effectiveness, and has lower acute toxicity and thus may be administered in higher doses than ofloxacin.

The PTO concluded that extension of the patent term was warranted, and the PTO and FDA collaborated in calculation of the applicable extension of 810 days, in accordance with §156(d)(2)(A). Lupin the tried to block the extension under 21 U.S.C. §355(j)(2)(A)(vii)(IV) (Paragraph IV certification).

35 U.S.C. §156(a) states that:

The term of a patent which claims a product, a method of using a product, or a method of manufacturing a product shall be extended in accordance with this section . . . , if– . . . (a)(4) the product has been subject to a regulatory review period before its commercial marketing or use; (a)(5)(A) except as provided in subparagraph (B) or (C) [not here relevant], the permission for the commercial marketing or use of the product after such regulatory review period 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 ?drug product? means the active ingredient of (A) a new drug, antibiotic drug, or human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act), . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.

The issue was whether this was the first permitted commercial marketing or use of levofloxacin, as required by 35 U.S.C. §156(a)(5)(A), for the racemate had previously been marketed. The district court held that the extension was in conformity with the practices of the PTO and the FDA with respect to enantiomers, and that the PTO?s determination that levofloxacin is a different ?product? than the racemate ofloxacin must be afforded ?great deference.?

Lupin that the PTO and the FDA have incorrectly interpreted the statute insofar as enantiomers are concerned. Lupin argued that an enantiomer is half of its racemate, and thus that the enantiomer levofloxacin was an ?active ingredient? or component of the previously marketed racemate ofloxacin. Thus Lupin argued that levofloxacin is the same ?drug product? as ofloxacin meaning that levofloxacin was not ?the first permitted commercial marketing or use of the product? as required by §156(a)(5)(A).

Ortho countered that an enantiomer has consistently been recognized, by the FDA and the PTO, as a different ?drug product? from its racemate. The FDA practices were explained by Dr. David Lin, a former acting Division Director in the FDA?s Division of New Drug Chemistry, declaring that ?in each and every instance in which it has considered the question, the FDA has described a racemate as a single active ingredient, distinct from its enantiomers, and each enantiomer as a single active ingredient distinct from the other and from the racemate,?

Lupin treid arguing that the status of enantiomers with was legislatively changed in 2007, in the statute that changed the FDA policy concerning data exclusivity for new enantiomer products. 21 U.S.C. §355(u)(1) (Supp. II 2008). The new provision authorizes an applicant ?for a non-racemic drug containing as an active ingredient (including any ester or salt of the active ingredient) a single enantiomer that is contained in a racemic drug approved in another application? to, under certain conditions, ?elect to have the single enantiomer not be considered the same active ingredient as that contained in the approved racemic drug.? Lupin argues that by specifically allowing an applicant to ?elect? this separate treatment for enantiomers, Congress expressed its understanding that enantiomers were the same active ingredient as the racemate for all other purposes, including patent term extension.

The Federal Circuit said it couldn?t find any support for this theory in the legislative record, or elsewhere and affirmed the district court?s ruling that the ?407 patent on levofloxacin was properly granted the statutory term extension, for the enantiomer is a different drug product from the racemate ofloxacin, and was subject to regulatory approval before it could be commercially marketed and used.

Related posts:

1. Structurally Similar Drug with Different Biological Properties Meets Criteria for Term Extension After the US Patent and Trademark Office denied a patent...
2. Australian Pharmaceutical Patent Term Extension for Patches and Implants Bill Bennett, of Pizzeys in Australia, sent a note detailing...
3. Australian Patent Office Clarifies Novelty Test For Enantiomers A recent decision of an Australian appeal court concerning a...

Related posts brought to you by Yet Another Related Posts Plugin.

Full post as published by Patent Baristas on May 19, 2010 (boomark / email).