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 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 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), as 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 argued that the PTO and the FDA incorrectly interpreted the statute, as enantiomer is half of its racemate, and 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 both 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 argued 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 argued 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, as 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.  

 

This case clarifies that separate enantiomers can obtain independent patent protection and be entitled to patent term extension for "first commercial marketing or use" as new drug products. However, the Federal Circuit has said that patents for separated enantiomers can be invalidated on obviousness grounds. So pharmaceutical companies that can show (very?) good reasons that separation of enantiomers was not obvious can look forward to a much longer patent term—for now.  

 

Stephen Albainy-Jenei is a patent attorney at Frost Brown Todd LLC, serving up chat at PatentBaristas.com. Write albainy-Jenei with comments or questions at Stephen@patentbaristas.com.