Since 2000, the Federal Circuit has routinely applied the Lead Compound Analysis to assess the patentability of chemical compounds. The Lead Compound Analysis is a two-part test used to evaluate whether a claimed chemical compound would have been obvious. This test considers:
- Whether a person of ordinary skill in the art would have had reason to select a prior art compound as a “lead compound” for further development; and
- Whether a person of ordinary skill would have been motivated to modify the lead compound to make the claimed compound with a reasonable expectation of success.
Where the Lead Compound Analysis is used, both prongs must be satisfied to prove obviousness. This test, especially the first prong, provides a unique tool for challenging and proving obviousness in the chemical arts. This is particularly true at the Federal Circuit, where the test originated, but the test is also gaining traction at the Patent Trial and Appeal Board (PTAB).
So, what is a “lead compound” and how is one selected? A compound can be identified as a lead compound if it is a natural choice for drug development or if it is “most promising” to improve its activity. This is a factual determination based on the compound’s properties, as well as the availability and properties of other known compounds. Relevant properties can include, for example, a compound’s activity, stability and side effects.
However, the above legal framework can be a trap for the unwary since “most promising” does not mean the single most promising drug candidate. Rather, for a given obviousness inquiry, it is possible that many compounds can be properly designated as a lead compound.
Par Pharmaceutical, Inc. et al. v. Novartis AG, IPR2016-00084 (PTAB Jan. 11, 2018) provides a recent example of this point. Here, Par challenged claims 1-3 and 8-10 of U.S. Patent No. 5,665,772 (the ‘772 patent) as being invalid as obvious. As part of its obviousness contention, Par argued that a person of skill in the art would have selected rapamycin as a lead compound in order to arrive at everolimus, a rapamycin derivative recited in claim 10 of the ‘772 patent.
Novartis argued that rapamycin was an immunosuppressant known to be toxic and was therefore not a proper lead compound since other immunosuppressive compounds were reportedly effective and lacked major adverse side effects. In response, Par argued that rapamycin had higher potency than some of these alternative compounds. Additionally, Par argued that, at the time of filing the application that issued into the ‘772 patent, researchers were studying rapamycin as a candidate for further drug development.
Ultimately, the PTAB concluded that the toxicity of rapamycin did not eliminate it as a lead compound since the other immunosuppressants had their own weaknesses. The PTAB held that a skilled researcher, balancing these considerations, would have investigated rapamycin as a starting point in developing improved immunosuppressants. The decision clarified that the selection of rapamycin as a lead compound was not to the exclusion of other compounds, meaning that researchers could very well have selected a different immunosuppressant (i.e., a different lead compound) for further development.
This decision is an important reminder, not only of the nuances involved in the Lead Compound Analysis, but also that this test is alive and well at the PTAB. Thus, in an inter partes review, for example, patent challengers should be prepared to assert and defend their lead compound selection. On the other hand, patent owners should consider defending patentability by, at least in part, attacking an obviousness contention as failing to meet one or both prongs of the Lead Compound Analysis. In this regard, the Lead Compound Analysis serves as yet another tool to evaluate the obviousness of chemical compounds.