Derivation not demonstrated by conception of an idea different from claimed invention, even where the idea would make the claimed invention obvious

Ryan Chirnomas | April 5, 2017

Cumberland Pharmaceuticals v. Mylan Institutional LLC

January 26, 2017

Before Moore, Reyna and Taranto.  Opinion by Taranto.

Summary

In an unusual argument, Mylan posited that Cumberland’s employee was not the inventor of a patent, but rather that the inventor was “someone at the FDA”.  Mylan based this assertion on the FDA’s seeking justification for an ingredient in an earlier formation which was excluded—without a direct substitute—in the claimed later formulation.

Details

Background

In 2002, Cumberland was applying to the FDA for permission to market Acetadote ®, a drug which acts as an antidote to acetaminophen overdoses.   The drug under review included EDTA, which acts as a chelating agent, surrounding and binding metal ions to prevent the metal ions from acting as catalysts that oxidize acetylcysteine (the active ingredient).  Although EDTA was regarded as safe, it had potential side effects.

In December 2002, the FDA contacted Cumberland to request justification for the inclusion of EDTA, and the pharmaceutical properties thereof.  In a telephone conversation six days later, the FDA indicated that data should be provided regarding EDTA, since a non-trivial amount was included.  Four days later, Cumberland provided a written reply explaining that EDTA was provided to stabilize the formulation, and lower concentrations of EDTA would raise questions of safety and efficacy.

After this letter, the inventor, Leo Pavliv, stated that he had the idea of testing an acetylcysteine without EDTA.   In March 2003, Cumberland contacted the FDA to schedule a call to discuss the justification for EDTA.  In the call, Pavliv suggested the idea of a study of a formulation without EDTA.  At least one FDA official approved this, and requested the proposal be put in writing.

Cumberland did so, and agreed to initiate studies of an EDTA-free formulation upon approval of the EDTA-containing formulation.  The FDA approved the EDTA-containing formulation in January 2004, with a reminder for Cumberland to study an EDTA-free formulation.  Cumberland then contracted with Mylan’s predecessor company to study a formulation without EDTA or any other chelating agent.  The data was encouraging, and Cumberland filed a patent application.  Cumberland ultimately obtained U.S. Patent Nos. 8,148,356 and 8,399,445, the latter of which is at issue in this case.  The FDA ultimately approved the EDTA-free version of Acetadote ® in January 2011.  In December 2011, Mylan filed an ANDA application, indicating that the patent for the new formulation was invalid.

Cumberland then sued Mylan.  Mylan stipulated to infringement, but argued that the patent was invalid for two reasons:  First, the inventor was not Mr. Pavliv, but rather, “someone at the FDA”.  Second, the invention would have been obvious in view of prior art communications from the FDA and other art.  The district court disagreed with both arguments, and held the patent valid and infringed.

CAFC’s Analysis

The CAFC first addressed the issue of pre-AIA 102(f) derivation.   As a matter of law, the inventor named on the patent is presumed to be correct, absent clear and convincing evidence to the contrary.  The CAFC focused on the technical point of not only removing all EDTA, but also not replacing EDTA with a different chelating agent.  The CAFC agreed with the district court finding that there was no direct evidence of an FDA person conceiving the invention prior to Mr. Pavliv.

First, the CAFC stated that the FDA’s request for data justifying EDTA is not the same as a suggestion to remove it, and certainly not the same as a suggestion not to replace EDTA with another chelating agent.  Mylan argued that the FDA’s request would have inevitably led Cumberland to the invention.  However, the CAFC stated that this was insufficient, since derivation is not demonstrated by showing conception of an idea different from the claimed invention, even where the idea would make the claimed invention obvious.   A general suggestion, even if relevant to an obviousness analysis, is not relevant to a derivation analysis.

Additionally, even where the FDA documents suggested removing EDTA, they did not also explicitly suggest the absence of another chelating agent.  The FDA documents also provide no comment as to a person besides Mr. Pavliv being the inventor.  Regardless, these documents all postdate the call that gave Mr. Pavliv the idea for the invention.

Several Cumberland documents stated that the FDA “requested” the study on the EDTA-free formulation, but the CAFC interpreted this as relating to the FDA requesting data implementing an idea previously proposed by Mr. Pavliv at Cumberland.

Additionally, the fact that the FDA relied upon Cumberland’s commitment to study an EDTA-free formulation to approve the EDTA-containing formulation does not demonstrate conception by the FDA.  Cumberland could have satisfied this requirement by adding another chelating agent, for example.  Furthermore, it was Mr. Pavliv who designed the protocol which reduced the invention to practice.

Finally, Mylan argued that the FDA communications stated that Cumberland should remove EDTA from “the” formulation, therefore requiring the specific EDTA-containing formulation.  According to Mylan, this necessarily would result in a formulation free of EDTA and any other chelating agents.  However, the CAFC replied that Cumberland’s letters, to which the FDA was replying, were written by Pavliv and formalized by Cumberland Dept. of Regulatory Affairs.  As such, if such weight is placed on “the”, this would only further demonstrate that Mr. Pavliv was the inventor.  Thus, there is no clear and convincing evidence of derivation.

Next, the CAFC turned to the obviousness argument.  Mylan pointed to packaging of the EDTA-containing version of Acetadote, in combination with publically-available FDA communications regarding EDTA, and U.S. Patent Application Publication No. 2004/0022873, which describes intravenous acetylcysteine formulations.

The CAFC agreed with the district court determination that one skilled in the art would have thought EDTA (or another cheating agent) was required for stabilization of an acetylcysteine formulation.  This was supported by expert evidence, as well as Mylan’s concern in 2011 that removal of EDTA would result in increased oxidation.

Mylan provided evidence that it might be unnecessary to provide a chelating agent, for instance because oxidation can be avoided in other ways (using inert gas atmosphere).  However, this was not shown as of 2005.  Finally, as to U.S. Patent Application Publication No. 2004/0022873, this disclosed a lack of a chelating agent, but provided no data regarding stability.  Thus, there could be no expectation that acetylcysteine could be stable without a chelating agent.  As such, the CAFC concluded that the claimed embodiments are not obvious in view of the cited art.

Takeaways

Pre-AIA derivation remains very difficult to prove, since it requires clear and convincing evidence.  Furthermore, derivation is not demonstrated by showing conception of an idea different from the claimed invention, even where the idea would make the claimed invention obvious.

Full Opinion

 

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