In a recent case, the Court of Appeals for the Federal Circuit affirmed the PTAB’s decision that certain claims of Merck’s U.S. Patent No. 6,011,040, which were challenged by Gnosis, were invalid as anticipated or obvious. The case confirms that the Federal Circuit will apply a relaxed standard for review of the Patent Office’s post grant patent review proceedings and will give a good deal of deference to PTAB “findings of facts.”

The ‘040 patent relates to methods of using folates to reduce the level of homocysteine in the human body. More specifically, the challenged claims 8 and 9 of the ‘040 patent recite a method of “preventing or treating disease associated with increased levels of homocysteine … comprising administering at least one tetrahydrofolate in natural stereoisomeric form,” where the tetrahydrofolate is L-5-MTHF or a salt thereof. In addition, the challenged claims 11 and 12 require that the increased levels of homocysteine be associated with deficiency in a reductase enzyme that helps generate L-5-MTHF.

The Board held that a combination of three references (Serofontein, Marazza and Ubbink) renders a number of the challenged claims obvious. The Board also found certain claims as anticipated by Serofontein, which discloses that elevated levels of homocysteine are linked to a number of clinical defects, such a vascular problems, and that high levels of homocysteine are often associated with folate deficiency. Serofontein also teaches a pharmaceutical preparation for treating high levels of homocysteine that includes “a folate or a suitable active metabolite of folate” along with vitamin B6and B12. Marazza discloses L-5-MTHF as a “natural metabolite” that may be used “as at least one active compound” in a treatment of folate deficiency. Ubbink states that the reasons for high levels of homocysteine include enzymatic deficiency, such as “cystathionine- β -synthase deficiency, or possession of a thermolabile variant of methylenetetrahydrofolate reductase, an enzyme required in the remethylation of homocysteine methionine.”

The Board found that the similarity between Serofontein and Marazza would have motived one of skilled in the art to combine these references to arrive at a method of treating elevated levels of homocysteine with L-5-MTHF. Further, one of skilled in the art would have been motivated to use such a method in the situation disclosed in Ubbink, where an enzyme deficiency is the cause of elevated levels of homocysteine.

Merck had presented objective indicia of non-obviousness in the form of evidence of commercial success, licensing, copying and industry praise. The Board, however, found that Merck had failed to show sufficient nexus between this evidence and the claimed subject matter.

The Federal Circuit held that the “Board’s finding of a motivation to combine Serfontein, Marazza, and Ubbink to arrive at the claimed method was supported by substantial evidence.” The Federal Circuit further held that the “Board’s finding that the proferred evidence of objective indicia of non-obviousness lacked an adequate nexus with the merits of the claimed invention.”

Nor was the Federal Circuit persuaded by Merck’s argument that the prior art taught away from the combination of the asserted art by suggesting: (1) administering 5-MTHF would actually increase levels of homocysteine, (2) 5-MTHF would be too unstable for therapeutic use, and (3) L-5-MTHF is a poor substrate for polyglutamation, a process that facilitates retention and use of L-5-MTHF in the cell. The Federal Circuit held that “[v]iewing as a whole, however, the Board’s finding that the prior art does not teach away from combining Serfontein and Marazza is supported by substantial evidence.”

The Federal Circuit also found that the Board’s factual findings regarding Merck’s objective indicia of non-obviousness were supported by substantial evidence. The Federal Circuit held that “although another factfinder may have reasonably evaluated Merck’s evidence of objective indicia of non-obviousness differently in the first instance, the Board’s conclusion … is supported by substantial evidence.”

Judge Newman dissented from the majority’s decision. Specifically, Judge Newman explained that it is not proper for the Federal Circuit, as the only reviewing tribunal of PTAB’s decisions, to rely on highly differential “substantial evidence” standard in reviewing those decisions. Rather, Judge Newman opined that “[o]n appeal to the Federal Circuit, our assignment is to determine whether PTAB ruling is correct in law and supported by a preponderance of the evidence.” Judge Newman concluded that the panel majority erred in law, in stating that “the PTAB impliedly found a reasonable expectation of success” and that such “implication” resided “only in the backward-looking eye of the beholder.”