Mitsubishi Chemical Corp. v. Barr Labs., No. 2010-1432 (Fed. Cir. 2011)
Mitsubishi Chemical owns U.S. Patent No. 5,214,052, which claims a "method for dissolving an arginineamide, comprising dissolving (argatroban) and/or its salt in a solvent containing ethanol, water and a saccharide"; and a "pharmaceutical composition for injection, comprising (argatroban) and/or its salt together with ethanol, water and a saccharide." Barr filed an ANDA for a generic version of argatroban, alleging that each claim of the '052 patent is invalid due to anticipation and/or obviousness.
(As an aside, process patents may not be listed in the Orange Book. In this case, however, the '052 patent also claims pharmaceutical formulations, which makes the patent eligible for listing. Mitsubishi asserted both the process claims and composition claims in the litigation, and it appears that was just fine with Barr.)
Last year, the U.S. District Court for the Southern District of New York held following a trial that the claims of the '052 patent are not invalid, and enjoined Barr from marketing a generic version of argatroban until the '052 patent expires (in 2014). Earlier this week, the Federal Circuit affirmed that decision.
Barr's primary invalidity argument was that the claims of the '052 patent were anticipated by a Japanese article published in 1986 by a Mitsubishi employee, Toshihiro Yamamoto. The key dispute concerned the English translation of a single sentence in the Yamamoto article describing the preparation of an argatroban solution that was administered to laboratory rats.
The district court agreed with Mitsubishi's translation of that sentence: "In 7.5% D-sorbitol-4% ethanol, an argipidine solution dissoved under hydrochloric acid acidity (pH 1.5 to 1.7) was intraperitoneally administered at a dosage of 1 ml/kg, 15 minutes before common carotid artery occlusion." The court further credited corroborating testimony that Yamamoto teaches dissolution of argatroban in hydrochloric acid, followed by formulation of the dissolved argatroban with D-sorbitol and ethanol. Barr, on the other hand, argued that the Yamamoto reference taught dissolution of argatroban in a solution containing HCl, D-sorbitol and ethanol, thereby anticipating the process claims of the '052 patent.
Addressing the district court's findings regarding the correct translation of Yamamoto, the Federal Circuit stated:
The fact-finder's selection of a particular translation as the best translation of a foreign language reference raises pure questions of fact. The district court's selection of the appropriate translation in this case was based in large part on a credibility determination, and such determinations are "virtually never" overturned for clear error. Although Barr contends that (Mitsubishi's) translation should be disregarded because it was prepared for purposes of litigation, that is not a sufficient reason to conclude that the district court's choice of (that) translation was clearly erroneous.
The Federal Circuit further observed that "the district court took note of the fact that Yamamoto's description of the argatroban solution was quite cryptic because, as both experts agreed, Yamamoto focused on the pharmacological activity of the argatroban molecule, rather than on argatroban's solubility or on treating the rats." According to the Federal Circuit, "In order to anticipate, the teaching of a reference must be clear and unambiguous."
With respect to the formulation claims, the district court found that the solution disclosed in Yamamoto is not a "pharmaceutical composition for injection"--i.e., "a composition that is suitable for treating medical conditions by injection." The court further found that in order to be suitable for injection into human patients, "a pharmaceutical composition must have a pH above 3," and the Yamamoto solution, having a pH between 1.5 and 1.7, is too acidic to be suitable for human administration. The key dispute here concerned the proper construction of "pharmaceutical composition for injection." The Federal Circuit affirmed the district court's construction, and thus affirmed the validity of the formulation claims.