What happens if someone invents an analytical process for demonstrating biosimilarity and patents that process, particularly in a situation where there are no practicable alternative methods available for demonstrating biosimilarity? If the innovator company that brought the original biologic to market owns the patent, it could potentially prevent competitors from bringing a biosimilar to market, because they could not demonstrate biosimilarity required for FDA approval without infringing the patent. Alternatively, if a biosimilar manufacture had such a patent it could exclude other biosimilar manufacturers from bringing their products to market. That is, unless the Hatch-Waxman safe harbor under 35 USC 271(e)(1) applies.
A divided panel of the Federal Circuit actually addressed this issue on August 3, 2012, in Momenta Pharmaceuticals v. Amphastar Pharmaceuticals. The particular drug in question, Lovenox (enoxaparin), it is technically not a biologic, but it is chemically complex and raises the same issues cited above in connection with demonstrating biosimilarity or interchangeability of a biosimilar. Enoxaparin is a low molecular weight version of heparin, a naturally occurring polysaccharide. The chemical structure of heparin is chemically diverse, with molecules ranging in molecular weight between 5000 and 40,000 Da. There are also differences in disaccharide units and in the modifications to individual sugar units that vary from molecule to molecule.
In order to market a generic version of Lovenox, FDA requires the generic manufacturer to demonstrate a sufficient level of chemical similarity in terms of molecular weight and chemical structure between branded Lovenox and the generic enoxaparin. Establishing this similarity was apparently not trivial, and Momenta (a generic manufacturer) obtained a patent claiming a method of performing the analysis, US Patent Number 7,575,886. Momenta received FDA approval to market generic enoxaparin in July 2010, and begin generating sales revenue of $260 million per quarter.
In September 2011, Amphastar received FDA approval to market its own generic version of enoxaparin, and momenta sued Amphastar for infringing its patent. Amphastar defended itself by arguing that its use of the patented method fell under the safe harbor of 35 USC 271(e)(1), which provides:
it shall not be enacted infringement to make, use, offer to sell, or so within the United States * * * a patented invention* * * solely for uses reasonably related to the development and submission of information under a federal law which regulates the manufacture, use, or sale of drugs ** * .
In particular, Amphastar argued that it was required to perform the tests to ensure that the product complies with FDA requirements, and that it retained the data so that it could submit it to FDA as necessary.
In response, Momenta argued that the safe harbor did not apply under the circumstances, since the product had already been approved and because Amphastar did not actually submit the information to FDA.
The District Court sided with Momenta, finding that the safe harbor did not apply under the circumstances, and issued a preliminary injunction. The Federal Circuit's 2011 opinion in Classen Immunotherapies v. BiogenicIDEC would seem to support this decision. In Classen, the panel stated that "[271(e)(1)] does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."
On appeal, a divided panel reversed and remanded, finding that the safe harbor does apply to Amphastar’s activities, essentially because the patented test is being used to confirm that its generic product meets the FDA requirement of similarity to branded Lovenox. The majority opinion is written by Judge Moore, who wrote a dissent in Classen arguing for a more expanded interpretation of the safe harbor that would encompass post-approval submissions to FDA.
In Momenta, Judge Moore found that a plain reading of the statute did not limit the safe harbor to pre-approval FDA submissions, and the legislative intent was to promote the availability of generic drugs. She also felt that the requirement that data be generated for "submission" to FDA was satisfied in this case because FDA regulations required Amphastar to test the drugs for similarity and to maintain the records for one year so they would be available for FDA inspection.
Judge Moore acknowledged that the Classen decision is binding precedent, but she reads Classen as being limited to cases involving "routine submissions" to FDA. In the present case, she found that Amphastar’s actions are not routine, since the company is required to make the data available for FDA in order to maintain FDA approval, in contrast with the optional "routine submissions" at issue in Classen.
Judge Moore also rejected Momenta's argument that the safe harbor did not apply because there were alternate methods available for performing the necessary analysis. She found that the safe harbor applies even if FDA would accept the use of other, non-patented testing methods.
In a strongly worded dissent, Judge Rader (who wrote the majority opinion in Classen) argued that the safe harbor does not apply in this case, and under Classen should not be available for infringing activities relating solely to post-approval FDA submissions. He basically found Judge Moore's decision inconsistent with the majority opinion in Classen, but entirely consistent with her dissent.
Judge Rader adopts a fundamentally different characterization of the Amphastar’s infringing activity than the majority. While the majority finds that the patented test is used to generate data necessary to satisfy FDA regulatory requirements, Judge Rader finds that the method is also being used for the purpose of manufacturing the product. Neither characterization seems implausible to me. Of course the test is being used to analyze the product, but Judge Rader's point is that in order to manufacture FDA-approved generic enoxaparin, it is necessary to conduct the analytical test to ensure that the product meets specifications.
I think the outcome in the case hinges largely upon this distinction between analyzing a product and manufacturing a product. If we accept Judge Rader's view that the patent covers a method used in manufacturing the drug, then the patented invention fails to satisfy the statutory requirement of being used "solely for uses reasonably related to the development and submission of information" to FDA, and the safe harbor should not apply. However, if we characterize the patented method as a method of product analysis, Judge Moore's decision seems reasonable.
In any event, a significant aspect of the decision is that it apparently limits the ability of innovators and biosimilar manufacturers from using patents covering methods of product analysis to keep biosimilar competitors off the market. This could be important as biosimilar manufacturers seek to enter the market in competition with innovators and other biosimilar companies.