USPTO rethinks patent claim requirements?

My post is prompted by this news: Concert rethinks R&D plans after loss in Incyte patent case.

On Jan. 11, 2018, the Patent Trial & Appeal Board of the U.S. Patent & Trademark Office denied Concert Pharmaceuticals' Petition to institute a post-grant review of claims 1–6 of Incyte’s U.S. Patent 9,662,335. Concert sought to invalidate the Incyte ’335 patent for deuterated Jakafi (ruxolitinib), so that Concert could proceed, unencumbered, with development of its own CTP-543, a specifically deuterated form of ruxolitinib, for treatment of alopecia areata.

As an aside, Concert’s business model is to develop deuterated forms of existing drugs. These forms can bring additional benefits to patients, as exemplified by the first specifically deuterated drug to be approved by the Food & Drug Administration, Teva’s Austedo (deutetrabenazine), for the treatment of chorea associated with Huntington’s disease.

For deutetrabenazine—a deuterated form of tetrabenazine—these benefits come not just in the form of more convenient dosing, due to the (expected) slower metabolism, given the deuterium kinetic isotope effect. More importantly, deutetrabenazine exhibits a better safety profile than tetrabenazine due to more consistent drug blood levels—side effects are apparently driven by Cmax, and deutetrabenazine can be dosed in a way that lowers Cmax.

Back to the issue at hand: Concert asserted that Incyte’s ’335 patent was invalid, because it lacks both written description and enablement of the key claims. Concert’s own patent application (WO 2013/188783) covering CTP-543, by contrast, details the synthesis and purification of several deuterated ruxolitinib analogues.

(Related technical legal issues surrounding the date of ’335 filing, and hence the possibility of Concert even being allowed to petition for a post-grant review, were also raised, but I won’t go into those issues here.)

In ’335, Incyte did not actually describe the synthesis of any deuterated compounds, even though such compounds are claimed. Thus, the Claims appear to be unsupported the Specification. If appearances are reality—as Concert argued—then the ’335 patent is invalid.

What did Incyte actually write in ’335? Claim 3 reads “A compound, which is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile [ruxolitinib], wherein one or more hydrogen atoms are replaced by deuterium; or a pharmaceutically acceptable salt thereof.” This claim is supported by a single, rather generic, paragraph in the Specification: “Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.” No descriptions of the synthesis or isolation of any deuterated compounds appear in the Specification—just the synthesis of ruxolitinib containing hydrogen isotopes at natural-abundance levels.

Accordingly, Concert asserted that undue experimentation would be required to make and/or separate the compounds claimed in ’335. Any requirement for such fiddling—starting materials, reaction conditions, and the like—would indeed invalidate ’335…if a person skilled in the art (a “POSA,” in USPTO parlance) wouldn’t reasonably know how to do it straightaway.

In the final analysis, the USPTO ruled in Incyte’s favor, upholding the validity of ’335.

Their reasoning was that a POSA would know how to make deuterated building blocks, and thus that a POSA would simply use such building blocks in the (well-described in ’335) synthesis. The USPTO thus rejected Concert’s Petition that Icyte’s ’335 patent be invalidated. Concert’s stock price dropped 27% today, as this ruling would appear to put their entire business model in some jeopardy.

To me, however, this USPTO ruling raises several broader questions:

1. Why was Incyte’s ’335 patent ever granted? Claim 2 of Incyte’s original ruxolitinib patent, US 7,598,257, reads in essence identically to Claim 3 in ’335, just omitting the deuteration clause: “A compound which is (3R)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile or a pharmaceutically acceptable salt thereof.” Importantly, the ’257 specification includes the identical statement found in ’335: “Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds…include[ing] tritium and deuterium.” If, as the USPTO has now ruled, any POSA could make the compounds of ’335, where then is the novelty of ’335’s claims? ’335 appears to be anticipated by ’257, and the USPTO itself seems to have laid out the grounds for invalidation of ’335 on this basis.
2. If anyone can claim—but not actually exert any effort to exemplify—not just some (or even, as is usual, the [vast] majority) of the species in a genus, but all of the species in the genus, what does this mean for future patent applications? Disregard that the issue here centered on deuteration. Can any compound not be synthesized, and yet still be claimed, just because a POSA would know how to carry out the synthesis? Where is the dividing line?
3. Finally, what is to prevent anyone (Concert, or you or me) from drafting valid patent applications which claim, for example, deuterated forms of any marketed drug for which existing patents (cf. Orange Book) haven’t yet claimed deuterated (or 13-C, etc.) forms? Maybe Concert will have the last laugh after all?

Thoughts?
David Borhani

Originally posted (on LinkedIn) 2018-01-12; minor edits for clarity, 2018-01-13