Merck v. Gnosis

Merck v. Gnosis S.P.A.
808 F.3d 829 (Fed. Cir. 2015)
Authored by Arjun Amernath

Statement of Facts: Merck owns U.S. Patent No. 6,011,040 (“ ‘040 Patent”). Homocysteine is an amino acid that causes cardiovascular, ocular, neurological and skeletal disorders when present in large quantities. A deficiency in the enzymes required for the body’s normal method of regulating homocysteine levels can cause excessive levels of homocysteine levels, called hyperhomocysteinemia. This process, called the methionine cycle, converts homocysteine to methionine. The ‘040 patent involves the use of folates to lower levels of homocysteine in humans.

One of the folates ‘040 patent uses is 5-methyl-tetrahydrofolic acid (“5-MTHF”), a reeducated folate which occurs naturally during the metabolization of folic acid and is found in foods. The patent recites a method of reducing homocysteine levels by using tetrahydrofolates and identifies a deficiency of methylene tetrahydrofolate reductase as a cause of elevated homocysteine levels. The patent further recommends administering L-5-MTHF, a stereoisomer of 5-MTHF with at least one B-vitamin, the active substance, to reduce homocysteine levels.

Procedural History: Gnosis contested claims 1-3, 5, 6, 8, 9, 11-15, and 19-22 of the ‘040 patent in the United States Patent and Trademark Office Patent Trial and Appeal Board (the “Board”). Merck voluntarily cancelled claims 1-3, 5, 6 and 13, while disputing claims 8, 9, 11, 12, 14, 15 and 19-22. The Board invalidated the remaining claims for obviousness. Merck appealed to the Federal Circuit, under 28 U.S.C. § 1295(a)(4)(A).

Questions Presented: Whether, in light of previous art, the ‘040 patent was obvious.

Holding: The Federal Circuit affirmed the Board, holding that claims are invalid as obvious. The Federal Circuit declined to consider anticipation and claim construction.

Reasoning: Obviousness is a question of law based on findings of facts, including the: (1) scope and content of the prior art; (2) differences between the prior art and the claims at issue; (3) level of ordinary skill in the art at the time the invention was made; and (4) objective evidence of nonobviousness, if any. In appeals of Board decisions, these factual findings are reviewed for substantial evidence. Based on the underlying factual findings, the Federal Circuit reviews the Board’s ultimate conclusion of obviousness de novo.

The Board found the ‘040 patent obvious due to three prior art references: European Patent App. No. 0 595 005 (Serfontein), U.S. Patent No. 5,194,611 (Marazza), and 57 Am. J. Clinical Nutrition (Ubbink). Serfontein teaches that folate deficiencies cause elevated homocysteine levels, and that a folate or a “suitable active metabolite of folate,” combined with vitamin B6 or B12 can be a treatment. Serfontein did not specify what made an active metabolite of folate suitable. Marazza identified the L-5-MTHF used here as a natural metabolite, which can be used in treating a folate deficiency. Marazza also teaches how to separate MTFH into the stereoisomers L-5-MTHF and D-5-MTHF. Ubbink studied folate levels in men with elevated homocysteine, and identified a vitamin supplement containing folic acid (a B vitamin) as having a positive result.

Here, the Federal Circuit found all elements of the claim in a combination of prior art and that a person of ordinary skill in the art would be motivated to combine them with a reasonable chance of success. The court recognized that while KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 481 (2007), states that a factfinder’s analysis of a reason to combine known elements “should be made explicit,” it cautions against using formalistic rules to limit the obviousness analysis. KSR International Co., 550 U.S. at 481. Accordingly, the court holds that “KSR does not require an explicit statement of a reasonable expectation of success in every case.” Merck v. Gnosis S.P.A., 808 F.3d 829, 836 (Fed. Cir. 2015). Merck argued that the prior art taught away from the combination of L-5-MTHF and B vitamin because the prior art suggested that 5-MTHF would increase levels of homocysteine. The court disagreed.

The court considered objective indicia of non-obviousness, finding that, although the commercial success (a factor that cuts against obviousness) of Merck’s product was high, there lacked an adequate nexus between the novel features of the ‘040 patent and evidence of success. The successful products which licensed the ‘040 patent from Merck used additional active ingredients and had material features beyond those in the ‘040 patent. In other instances, the product was used for treatments not disclosed by the patent.

Dissenting Opinion: Judge Newman dissented, holding that the majority applied the wrong standard of review and that the patent was not obvious because prior art did not teach toward the usage of L-5-MTHF. While the Board applied a standard of clear and convincing evidence, Judge Newman found that the burden of proof before the Board was a preponderance of the evidence, to give no deference to the prior examination or to the grant of the patent. When the case appeared before the Federal Circuit, Newman criticized the majority’s decision to use the substantial evidence standard of review. Delving into the America Invents Act, Newman proffered that the duty of the Federal Circuit included reviewing decisions with no deference, and that only the standard of a preponderance of the evidence would satisfy the “legislative purpose of providing optimum determination of patent validity” under the act. Merck v. Gnosis, 808 F.3d 829, 841 (Fed. Cir. 2015).

With regard to the substantive arguments, Judge Newman reiterated that Serfontein did not mention L-5-MTHF nor suggest its use for treatment. He found that Marazza did not link the L-5-MTHF molecule to the treatment of elevated homocysteine or suggest the use of the molecule for treatment. He further stated that Serfontein and Marazza references cannot be combined because “the close similarity of purpose and disclosure” would not have been sufficient for a person of ordinary skill in the art to combine them “with a reasonable expectation of success in treating elevated homocysteine.” Merck v. Gnosis S.P.A., 808 F.3d 829, 843 (Fed. Cir. 2015). The majority held that the prior art would not teach away from Merck’s use, satisfying their standard of substantial evidence. Newman, however, believed that no reference taught Merck’s use, failing to satisfy his preponderance of the evidence standard.

When considering evidence of commercial success, Judge Newman found that although the objective indicia of non-obviousness do not have to control the result, they must be considered. He further found that the Board and majority discounted the evidence due to an insufficient nexus. Newman believed that consumers purchased the product for the L-5-MTHF, not the other ingredients.

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