IP Law Daily, PATENT—Fed. Cir.: Merck’s diabetes drug patent survives challenge by rival Mylan; not obvious over prior art, (Sep 29, 2022)

By Robert B. Barnett Jr., J.D.

The Federal Circuit agreed with the PTAB that Merck’s proposed drug patent was not obvious because skilled artisans would not “at once envisage” the proposed drug via prior art.

The U.S. Court of Appeals for the Federal Circuit has upheld a decision by the Patent Trial and Appeal Board (PTAB) that Merck’s patent on a diabetes drug was not anticipated and was not obvious over prior art, thus thwarting rival Mylan Pharmaceuticals’ efforts to have the patent invalidated. The court concluded both that no disclosure existed of all of the limitations contained in the prior art and that no skilled artisan could be expected to know what was missing and to fill in the gaps. Thus, the claims made in Merck’s patent application “were neither expressly nor inherently anticipated” by the prior art (Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp., September 29, 2022, Lourie, A.).

Merck Sharp & Dohme Corp. received a patent that describes sitagliptin dihydrogenphosphate (sitagliptin DHP), which is a drug used to treat diabetes. The patent describes a 1:1 sitagliptin DHP salt. Competitor Mylan Pharmaceuticals Inc., petitioned for inter partes review of the patent. Mylan argued that the patent was anticipated by a combination of publication of a Merck-owned paper and another Merck patent (collectively referred to as “Edmondson”). Edmondson disclosed 33 species of a genus of dipeptidyl peptidase-IV enzyme (DP-IV inhibitors), one of which is sitagliptin. Edmonson also revealed that pharmaceutically acceptable salts can be formed using one of eight “particularly preferred” acids, one of which is phosphoric acid.

Mylan also argued that nine of the claims in the patent would have been obvious because of Edmondson and two additional publications, called Brittain and Bastin. Brittain described the pharmaceutical importance of crystalline hydrates of pharmaceutical compounds. Bastin taught salt selection and optimization procedures during the development of pharmaceutical compounds.

The PTAB denied Mylan’s inter partes review, finding that Edmondson made no express disclosure of all of the limitations of the 1:1 sitagliptin DHP salt. Mylan, therefore, “could not fill in the gaps by arguing that a skilled artisan would ‘at once envisage’ what is missing.” The PTAB also ruled that the nine challenged patent claims would not have been obvious from a combination of Edmondson, Brittain, and Bastin, in part because the patent antedated Edmondson. Mylan appealed the decision to the Federal Circuit in D.C.

Grounds for appeal. On appeal, Mylan made three arguments: (1) the PTAB erred when it determined that a 1:1 stoichiometry of sitagliptin DHP was not anticipated, (2) the PTAB erred in determining that the patent antedated Edmondson, and (3) the PTAB erred when it ruled that Mylan failed to prove that two of the claims would have been obvious over a combination of Edmondson, Brittain, and Bastin.

Anticipated. The appellate court agreed that substantial evidence existed to support the PTAB’s determination that a 1:1 sitagliptin DHP salt was not anticipated. Edmondson identified 33 DP-IV inhibitors, one of which was sitagliptin. Nothing in Edmondson singled out sitagliptin. When combined with the eight “pharmaceutically preferred” acids, 957 different salts were possible.

Prior decisions had established that anticipation results if a skilled artisan could “at once envisage each member of a limited class” (In re Petering, 301 F.2d 676, 681 (C.C.P.A. 1962)). The key term, the appellate court said, was “limited class.” How small must a class be in order to be “limited”? Refusing to provide a specific number in defining a “limited class,” the Federal Circuit pointed out that a class of 20 compounds had previously been rejected (Petering at 681). Thus, the court had no problem affirming a decision finding that 957 salts did not constitute a limited class.

Antedated. Moving to the second issue raised on appeal, Mylan took issue with the PTAB’s determination that the patent antedated Edmondson, noting that Merck did not make the salt until two months after Edmondson was published on January 16, 2003. The Federal Circuit, however, agreed with Merck that substantial evidence supported Merck’s contention that it developed the 1:1 sitagliptin DHP salt back in December 2001, with experimental confirmation in early 2002. Such a finding was not usual where a product requires extensive testing prior to be being manufactured. Thus, the PTAB correctly concluded that Merck’s salt antedated Edmonson.

As a result of the antedating, Edmondson could not serve as prior art under 35 U.S.C. §102(a), but rather only as a reference under 35 U.S.C. §102(e). Furthermore, because Merck owned both the patent and Edmondson, Merck qualified for the exception in Section 103(c)(1), which provides that patentability is not precluded where the entity owned both the invention and the alleged prior art. As a result, obviousness for seven of the nine patent claims was eliminated because Mylan’s arguments for obviousness relied solely on Edmondson.

Obvious. The final issue was whether the PTAB erred when it concluded that the two remaining claims of the original nine would not have been obvious to a skilled artisan. Mylan argued that (1) a combination of Edmondson and Bastin would have allowed a skilled artisan to envisage and create 1:1 (S)-sitagliptin DHP and (2) a combination of Edmondson, Brittain, and Bastin would have allowed a skilled artisan to envisage and create a crystalline monohydrate.

The Federal Circuit shot down both theories. Regarding the first theory, the appellate court concluded that a combination of Edmondson and Bastin would not have motivated an artisan to make 1:1 (S)-sitagliptin DHP because the (S)-enantiomer was not disclosed in Edmondson, as Mylan’s expert witness acknowledged. The general disclosure in Edmondson, the appellate court said, “encompasses millions of potential compounds and salts with no motivation to make the (S)-enantiomer with a reasonable expectation of success, particularly in an unpredictable activity like salt formation.”

Moving to the second theory, the Federal Court ruled again that no motivation existed to combine the three sources with a reasonable expectation of success in creating a crystalline monohydrate. Mylan’s own expert witness admitted that a skilled artisan could not predict with any degree of certainty that he or she could create a hydrate formation.

The Federal Circuit, therefore, affirmed the PTAB’s decision to reject the inter partes review of Merck’s patent.

The case is No. 21-2121.

Attorneys: Eric Thomas Werlinger (Katten Muchin Rosenman LLP) for Mylan Pharmaceuticals Inc. Jeffrey A. Lamken (MoloLamken LLP) for Merck Sharp & Dohme Corp.

Companies: Mylan Pharmaceuticals Inc.; Merck Sharp & Dohme Corp.

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