Daiichi Sankyo Co., Ltd. v. MATRIX LABORATORIES

619 F.3d 1346, 96 U.S.P.Q. 2d (BNA) 1526, 2010 U.S. App. LEXIS 18820, 2010 WL 3504759
CourtCourt of Appeals for the Federal Circuit
DecidedSeptember 9, 2010
Docket2009-1511
StatusPublished
Cited by18 cases

This text of 619 F.3d 1346 (Daiichi Sankyo Co., Ltd. v. MATRIX LABORATORIES) is published on Counsel Stack Legal Research, covering Court of Appeals for the Federal Circuit primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
Daiichi Sankyo Co., Ltd. v. MATRIX LABORATORIES, 619 F.3d 1346, 96 U.S.P.Q. 2d (BNA) 1526, 2010 U.S. App. LEXIS 18820, 2010 WL 3504759 (Fed. Cir. 2010).

Opinion

LOURIE, Circuit Judge.

Matrix Laboratories, Ltd., Mylan Inc., Mylan Laboratories, Inc., and Mylan Pharmaceuticals, Inc. (collectively, “Mylan”) appeal from the final decision of the United States District Court for the District of New Jersey sustaining the validity of U.S. Patent 5,616,599 (“the '599 patent”) under 35 U.S.C. § 103. We affirm.

BACKGROUND

I.

Daiichi Sankyo Company, Ltd. and Daii-chi Sankyo, Inc. (collectively, “Daiichi”) own the '599 patent, which claims 1-biphe-nylmethylimidazole compounds and their use as angiotensin receptor blockers (“ARBs”) for the treatment of high blood pressure. Claim 13 of the '599 patent covers the chemical compound olmesartan medoxomil, an ARB approved by the Food and Drug Administration (“FDA”) and commercialized by Daiichi as the active ingredient in Benicar®, Benicar HCT®, and Azor®.

*1348 The invention of olmesartan medoxomil as an effective ARB built on years of research beginning in the 1970s, when scientists first came to appreciate the role of the angiotensin protein in controlling blood pressure. The first non-protein, small molecule ARBs were developed in the late 1970s and early 1980s by the Japanese pharmaceutical company Takeda Pharmaceutical Co. Ltd. (“Takeda”). These compounds each comprised an imidazole ring — a five-membered ring of the formula C3H4N2 — to which other chemical moieties were bonded at the 1-5-positions of the ring. One Takeda compound, S-8307, possessed a chlorophenyl group bonded through a methylene group at the 1-posi-tion, a butyl group (-C4H9) at the 2-posi-tion, a chlorine atom (-C1) at the 4-posi-tion, and an acetic acid moiety (-CH2 COOH) at the 5-position. The chemical structure of S-8307 is pictured below with the ring’s 1-position nitrogen positioned at the bottom of the ring.

[[Image here]]

The Takeda compounds, however, bound only weakly to the angiotensin receptor and thus were of little therapeutic value. Nevertheless, using Takeda’s compounds as leads, scientists at E.I. du Pont de Nemours and Company (“DuPont”) embarked on their own ARB research program with the aim of developing new compounds with increased receptor-binding activity. DuPont’s research led to the discovery of the first orally active ARB, known as losarían, which exhibited tenfold greater binding affinity than the Takeda compounds. To obtain losarían, DuPont modified Takeda’s S-8307 at the 1- and 5-positions of the imidazole ring: At the 1-position, DuPont added a second phenyl group with a tetrazole group attached, generating a biphenyltetrazole substituent. At the 5-position, DuPont replaced the acetic acid group with a hy-droxymethyl group (-CH2OH), which is metabolized to a carboxylic acid (-COOH) in the body. The chemical structure of losartan is depicted below.

*1349 [[Image here]]

DuPont disclosed losarían in U.S. Patent 5,138,069 (“the '069 patent”) along with more than four hundred structurally related ARBs. The '069 patent also discloses binding affinity data, measured as IC50 values, 1 for over two hundred compounds, including forty-two in losartan’s biphenyl-tetrazole series. Chemists were able to use the data disclosed in the '069 patent to uncover correlations between the compounds’ structures and their binding affinities, called “structural-activity relationships” (“SARs”), which they could then use to guide the development of even more potent ARBs. For example, if the presence of a certain chemical moiety or type of chemical moiety at a given position correlates with an increase in binding affinity, chemists could attempt to use that chemical moiety or type of moiety in the next generation of ARBs, and they did.

Following losartan’s success, over twenty different pharmaceutical companies, in-eluding Daiichi, established research programs to develop the next generation of ARBs. Daiichi’s program resulted in the synthesis of olmesartan, the active metabolite of olmesartan medoxomil. Like lo-sarían, olmesartan consists of an imidazole ring containing a biphenyltetrazole substi-tuent at the 1-position and an alkyl group (propyl rather than butyl) at the 2-posi-tion. At the 4-position, however, olmesar-tan replaced losartan’s lipophilic, or fat-loving, chlorine atom with its opposite, a hydrophilic, or water-loving, hydroxyiso-propyl group (-C(CH3)2OH). 2 Of the compounds disclosed in DuPont’s '069 patent, the vast majority contain a lipophilic group at the ring’s 4-position. One compound with a hydrophilic group is losartan’s re-gioisomer, 3 Example 118, in which the 4- and 5-positions on the imidazole ring are reversed. The transposition results in a compound with a chlorine atom at the 5-position and a hydrophilic hydroxymethyl group (-CH2OH) at the 4-position, as shown below.

*1350 [[Image here]]

Olmesartan medoxomil also differs from losarían at the 5-position. Daiichi replaced losartan’s hydroxymethyl group with a car-boxy group masked by a medoxomil pro-drug substituent to improve oral absorption. Like the hydroxymethyl group, the medoxomil moiety is metabolized to the carboxylic acid in the body. The structures of olmesartan medoxomil and olmes-artan are depicted below.

Other second-generation ARBs, all prior art to olmesartan medoxomil, include DuPont’s DuP 532, in which losartan’s chlorine at the 4-position is replaced with multiple lipophilic fluorine atoms (-C2F5), and six compounds disclosed in DuPont’s U.S. Patent 5,137,902 (“the '902 patent”), each of which has a more lipophilic alkyl group at the 4-position. The ARBs disclosed in DuPont’s '902 patent (“the '902 compounds” or “the '902 ARBs”) are the closest structurally to olmesartan, with Example 6 differing from olmesartan by only a *1351 single oxygen atom at the 4-position, as depicted below

Other second-generation ARBs differ more significantly from losartan by not containing an imidazole ring, including Merck & Co., Inc.’s L-158,809 compound, Ciba-Gei-gy Corp.’s valsarían, and Eisai Inc.’s E-4177 compound.

II.

Mylan filed multiple Abbreviated New Drug Applications (“ANDAs”) with Paragraph IV certifications under the Hateh-Waxman Act, 21 U.S.C. § 355, challenging the '599 patent and seeking FDA approval to manufacture generic olmesartan medox-omil in various dosages and combinations. Daiichi responded by filing suit against Mylan for patent infringement in the United States District Court for the District of New Jersey.

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619 F.3d 1346, 96 U.S.P.Q. 2d (BNA) 1526, 2010 U.S. App. LEXIS 18820, 2010 WL 3504759, Counsel Stack Legal Research, https://law.counselstack.com/opinion/daiichi-sankyo-co-ltd-v-matrix-laboratories-cafc-2010.