Lead Compound Requirement: Not so rigid after all?

On February 11, 2013, the District Court of Delaware ruled that U.S. Patent No. 5,206,244 patent to entecavir (the active ingredient in Bristol-Myers Squibb’s Baraclude, which treats hepatitis B viral infections) is invalid for obviousness. This case marks the first instance where a court has invalidated a molecule patent based on obviousness. The lead compound and motivation to modify inquiries have been rigidly applied and have made it difficult to challenge claims directed to a new chemical compound. So how did Teva succeed, when so many before have failed?

Judge Burke’s analysis focused heavily on whether Teva’s proposed lead compound, 2′-CDG, was a proper “lead compound.” Teva had built up a solid book of evidence supporting its selection of its lead compound. Numerous companies, including the patentee, had used it as a lead compound, and there was no discouraging experimental data regarding the lead compound (at least that was available in the prior art). Further, Teva elicited damaging testimony from the patentee’s expert that others, including himself, had prepared derivates of 2′-CDG, thereby treating it as a lead compound.

On the issue of motivation to modify the lead compound, Teva’s expert testified that one of ordinary skill in the art would have made subtle substitutions to retain the promising activity of the lead compound, and that the relevant prior art identified two particular locations on the molecule where those of skill were focusing on making modifications. The modification at issue was the addition of a methylene at one of those positions, and Teva offered evidence showing that such a modification had been successful in another class of compounds. For its part, BMS’s expert did a poor job arguing against the proposed modification, and the Court ultimately concluded that his expert report and prior deposition were more credible and demonstrated that a skilled artisan would have been motivated to so modify 2′-CDG.

Regarding “reasonable expectation for success,” the Court credited Teva’s expert’s testimony concerning rational drug design, and how those of skill expect similar compounds to have similar properties. Furthermore, the Court noted that BMS’s opening post-trial brief failed to address this factor in any great detail. The lack of toxicity or other negative data concerning the lead compound certainly helped on this issue.

The Court found the patentee’s evidence of objective considerations of nonobviousness insufficient to overcome Teva’s strong prima facie case of obviousness:

[vision_pullquote style=”3″ align=”center”]The evidence that it put forth at trial in that regard was multi-faceted and compelling. In addition, as to almost every single significant portion of the prima facie case, Teva’s position was not only bolstered by the opinion of its expert, Dr. Heathcock, but also by the testimony of BMS’s expert, Dr. Schneller. On cross-examination, Dr. Schneller was forced to concede the accuracy of many significant points that Teva sought to assert as to the prima facie case. The force of this evidence was clear, and it was convincing. [/vision_pullquote]

While the two-part “lead compound” and “motivation to modify” requirements are still essential element to any obviousness challenge in a new molecule case, this case shows that this threshold can be overcome under the right circumstances. This case also perhaps shows the benefits of trying such a case to a judge, rather than a jury, whom may be better equipped to tackle the complex issues posed by a molecule case and less deferential to determinations of the Patent Office.