Tips for Selecting a ‘Lead Compound’ in Compound Claim Challenges

Patent challenges are an indispensable part of the drug approval process under the provisions of the Hatch-Waxman Act (Hatch-Waxman). To gain early market access, multiple types of invention claims, ranging from compositions to method of use and from combinations to “kits”, are frequently challenged under the Hatch-Waxman provisions by abbreviated new drug application (ANDA) filers. However, challenges to claims for chemical compounds are quite rare compared to claims for other types of inventions.

Understanding the Lead Compound Analysis

Though the overall approach for challenging any patent/claim remains broadly similar, a compound claim challenge involves a relatively different approach compare to other types of invention claims involved in the Hatch-Waxman context. The chief difference is the types of art that may be available for citation. A typical compound claim challenge revolves around the structural similarities and differences between the compound(s) known in the art and the claimed compound(s). Any compound claim challenge involves an approach derived by the federal courts through multiple decisions, known as the “lead compound” analysis. The lead compound analysis is typically a two- stage process: the first stage being the “lead identification” or “lead selection” stage, i.e. selection of compound(s) to begin the analysis, and the second stage being the “lead development” or “lead optimization” stage, i.e. modification of the selected “lead” to arrive at the claimed compound.

Only a handful of compound claim challenges have gone up to the trial stage to be decided on the merits by the courts; many other such challenges are expected to have been settled without trials and/or without a final court decision or order. The public outcome of these cases indicates that the success rate with compound claim challenges is much lower when compared with challenges of other types of claims. And it is notable that almost all of the unsuccessful challenges to compound claims failed at the very first first stage, i.e. the lead selection stage. This indicates how important it is to select an “acceptable” lead compound before crafting any lead development or invalidity theory.

The prerequisite for selection of a lead compound is to know what a lead compound actually is. Based on the decisions of the U.S. Court of Appeals for the Federal Circuit in Takeda, Eisai & Altana, a “lead compound” may be defined as:

a compound/structure known in the art that, for the skilled artisan, would be a ‘most promising starting point’ or ‘a natural choice’ to modify, in order to improve upon its properties to obtain a compound/structure with better properties.

As discussed, the “lead compound analysis” revolves around the structural similarities and differences between the known compound(s) and the claimed compound. However, mere structural similarity between the prior art compound(s) and the claimed compound(s) is not enough to qualify a compound as a lead—there must be “something” more than that. Structurally similar compounds remote from the field of the invention may not make a good lead. The probable lead compound may be the best or one of the better performing compounds known in the art, or it may be suggested as a suitable “target” for further modifications to improve upon its properties. The art should reasonably identify it as a “potent” or “promising” compound that may be viewed as such by the skilled artisan. Though the “potency” of the alleged lead compound may not be dispositive alone, it would surely be one of the determining factors in the lead selection process.

Published Evidence

When no clear guidance can be deduced from the art as of the critical date, whether the proposed lead compound was a “promising compound”, “natural choice” or “suitable target for modification”, post-published evidence showing others have or have not found it promising or selected it as a lead for their development may also support the presumption, to a limited extent, as to whether the skilled artisan would have selected the compound as a lead or not. If any art, “prior” or “post,” criticizes the proposed lead as “not so promising” for further development, or teaches away by directing some other compound(s) as a “promising lead(s)”, such teachings of art would disprove the proposed compound as a “lead”. However, when there is “sufficient guidance” in the art to support selection of a compound as lead, knowledge of tens or hundreds or thousands of other compounds in the art may not be sufficient to teach away from the lead; any art pointing to the proposed one should be enough to qualify it as a lead. Also, when the available knowledge as of the critical date supports the selection of a compound as lead, post-published “adverse” knowledge about the proposed lead may not disprove the proposed compound as a lead as of the critical date.

And finally, the lead compound need not always be a single compound. More than one compound, a group of compounds or a class of compounds may also serve as a lead if and when the arts suggest so. But, again, when the record suggests a group or a class of compounds as possible “lead”, picking up any smaller subset of it without being corroborated by supportive teachings in the art may fail at the very threshold of lead selection.

Know the Criteria for Success

In summary, the information available on the priority date should reasonably present the proposed lead compound on a higher footing compared to the other compounds known in the art and there should not be any disabilities in, or impediments to, the selection of it as a lead. The proposed lead should be relevant to the field of the invention and/or should be reasonably related to it, because mere structural similarity may not be enough.

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