On May 1, 2012, the United States District Court for the District of Delaware held that two erlotinib patents, RE 41065 and U.S. 6,900,221 listed on the Orange Book against TARCEVA, are valid in litigation involving Mylan.
The ‘065 patent, which was reissued from US patent 5,747,498, contained a narrowed claim (claim eight) that only covered erlotinib. Mylan alleged that the 065 patent was obvious based on a prior patent application (“Barker application”) that disclosed “Compound 51”, a compound with a structure that differed from erlotinib only at position 3’ of the aniline ring (erlotinib: -C≡CH; Compound 51: -CH3)
Mylan had argued that Compound 51 would have been the lead starting compound for a medicinal chemist and that given the similarities between methyl and ethynyl groups, a skilled person looking for new epidermal growth factor receptor (EGFR) inhibitors would start with compound 51 and end up with erlotinib. The skilled person would have been motivated to try ethenyl and ethynyl groups at position 3’ because these substituents were not included in the group of small non polar radicals claimed in the Barker application. The skilled person would have been further motivated to use an ethynyl group at 3’ position based on two abstracts that disclosed that the most potent inhibitors possess relatively small non-polar substituents, including chloro, in the meta-position of the aniline ring.
The Court did not accept that compound 51 would be an obvious choice as a lead compound for a skilled person working on new EGFR inhibitors. The Barker application does not disclose any biological activity of any of its 13 preferred EGFR inhibitors and the Court accepted that the skilled person had several alternatives to consider as a starting point for the development of a new EGFR inhibitor.
Even if the Court was wrong in its lead compound analysis, the Court concluded the absence of ethenyl and ethynyl substituents from the Barker application would not motivate the skilled person to select the ethynyl radical holding:
Moreover, the Barker ‘226 application omits not only alkynes as possible groups for R2, but alkenes as well. Halogens are also not mentioned, such as the chloro- group disclosed at the 3′-position in the Barker Abstracts. While the precise number of alternatives is not clear, on this record, the court does not find persuasive Mylan’s argument that the absence of teaching the ethynyl substituent in the Barker ‘226 application would have suggested to an ordinary artisan to select it.
The Court also held the ‘221 patent, directed to treatment of non-small cell lung cancer (NSCLC) using erlotinib, was neither anticipated nor obvious. While the prior art disclosed thousands of compound for the treatment of various cancers, there was no disclosure or direction the prior art to choose the specific combination of erlotinib and NSCLC. In respect of obviousness, the Court noted that Mylan’s case was not offered “in terms of specific proffered combinations, rather it makes it argument in broad terms and lists collections of references it argues supports each point.”. The Court also found OSI’s evidence on secondary considerations, including the failures of others, as persuasive evidence of non-obviousness.
A copy of the Court’s opinion may be found here.