Merck & Co., Inc. v. Biocraft Laboratories, Inc.

• Decision Date: 10 May 1989
• Docket Number: No. 88-1513,88-1513
• Citation: 10 USPQ2d 1843,874 F.2d 804
• Parties: MERCK & CO., INC., Plaintiff-Appellee, v. BIOCRAFT LABORATORIES, INC., Defendant-Appellant.
• Court: U.S. Court of Appeals — Federal Circuit

Page 804

874 F.2d 804

10 U.S.P.Q.2d 1843

MERCK & CO., INC., Plaintiff-Appellee, v. BIOCRAFT LABORATORIES, INC., Defendant-Appellant.

No. 88-1513.

United States Court of Appeals Federal Circuit.

May 10, 1989.

Rehearing Denied June 7, 1989.

Suggestion for Rehearing In Banc Denied Declined July 3, 1989.

Joseph M. Fitzpatrick, Fitzpatrick, Cella, Harper & Scinto, New York City, argued, for plaintiff-appellee. With him on the brief, were Nicholas M. Cannella and Lawrence Alaburda. Also on the brief, was John J. Francis, Jr., Shanley & Fisher, P.C., Morristown, N.J., of counsel.

Donald R. Dunner, Finnegan, Henderson, Farabow, Garrett & Dunner, Washington, D.C., argued, for defendant-appellant. With him on the brief, were Robert D. Bajefsky and Carol P. Einaudi. Also on the brief, was Beryl L. Snyder, Biocraft Laboratories, Inc., Elmwood Park, N.J., of counsel.

Before BISSELL and MAYER, Circuit Judges, and BENNETT, Senior Circuit Judge.

OPINION

MAYER, Circuit Judge.

Merck & Co., Inc. sued Biocraft Laboratories, Inc. for infringement of its patent, U.S. Patent No. 3,781,430. The United States District Court for the District of New Jersey held that Biocraft failed to show by clear and convincing evidence that the patent was invalid or unenforceable, and enjoined Biocraft from commercially making, using, and selling the claimed diuretic formulations. Merck & Co., Inc. v. Biocraft Laboratories, Inc., 690 F.Supp. 1376 (D.N.J.1988). Biocraft appeals only the validity aspect of the judgment, arguing that the claimed combinations would have been obvious under 35 U.S.C. Sec. 103. We agree and accordingly reverse the judgment of the district court.

Background

The '430 Patent:

In relevant part, U.S. Patent No. 3,781,430 (the '430 patent), assigned to Merck, claims various "Diuretic Formulations." Inducing diuresis (increased urine excretion) or saluresis (increased electrolyte, particularly sodium, excretion), or both, diuretics are useful in the treatment of cardiovascular and renal diseases. Although the therapeutic effects of diuretics are often lifesaving, many cause hypokalemia, the excessive excretion of potassium ions, a condition manifested by severe muscle weakness and physical exhaustion.

In the formulations claimed in the '430 patent, amiloride hydrochloride (amiloride), a known "potassium conserving" diuretic (induces sodium, but not potassium, excretion), is combined with hydrochlorothiazide, a known "potassium excreting" diuretic (induces both sodium and potassium excretion). As stated in the specification, the objective of co-administration is to reduce the amount of potassium ions eliminated, without reducing the amount of sodium ions eliminated. The inventor also reports that co-administration results in a "medically ... synergistic therapeutic accomplishment" because "more sodium ions are eliminated than would be forecast from a knowledge of the natriuretic [sodium excreting] effects of the individual drugs."

The '430 patent contains six claims. The parties agree, however, that all of the claims stand or fall with claims 2 and 3. Claim 1, on which claim 2 depends, and claims 2 and 3 provide as follows:

1. A composition for oral administration comprising amiloride hydrochloride and hydrochlorothiazide, wherein the ratio of amiloride hydrochloride to hydrochlorothiazide ranges from about 1:1 to 1:10 by weight of the composition.

2. A composition according to claim 1 wherein amiloride hydrochloride and hydrochlorothiazide are combined at a ratio of 1 to 10 by weight.

3. A composition for oral administration which comprises 5 mg. of amiloride hydrochloride and 50 mg. of hydrochlorothiazide.

The Infringement Suit:

Merck's suit against Biocraft was prompted by Biocraft's filing of an abbreviated new drug application (ANDA) with the Food & Drug Administration (FDA) for a generic version of Merck's amiloride/hydrochlorothiazide combination, "Moduretic." The Drug Price Competition and Patent Term Restoration Act of 1984 permits the filing if the generic manufacturer can certify its belief that the patent is invalid or will not be infringed by its proposed manufacture, use or sale of the drug, and notifies the patent owner of the reasons for its belief. 21 U.S.C. Sec. 355(b)(2)(A)(iv) and (3). However, under 35 U.S.C. Sec. 271(e)(2), the filing is a technical act of infringement, so infringement is not an issue in this case. If a patent owner brings an infringement suit, the FDA cannot approve the ANDA unless the patent is declared invalid or not infringed. 21 U.S.C. Sec. 355(c)(3)(C).

At trial, Biocraft argued that the '430 patent was invalid for obviousness under 35 U.S.C. Sec. 103, and unenforceable because of inequitable conduct. The district court ruled against Biocraft on both counts. Biocraft predicated its section 103 argument on two prior art patents and on prior art relating to spironolactone and triamterene, diuretics that, like amiloride, are potassium conserving. Refreshingly, Biocraft challenges the judgment of the district court only as to obviousness, and restricts its arguments to the teachings of U.S. Patent No. 3,313,813 (the '813 patent), also assigned to Merck.

The '813 patent discloses various (3-amino-5,6-disubstituted-pyrazinoyl) guanidines, one of which is amiloride (claim 11). Per the specification, the claimed compounds are effective diuretic and natriuretic agents. Moreover, the '813 patent teaches that guanidines "selectively enhance the excretion of sodium ions without causing an increase in excretion of potassium ions," and "are useful in combination with other classes of diuretic agents to prevent the loss of potassium which the other diuretics otherwise would cause to be eliminated." Hydrochlorothiazide is identified as an example of a potassium excreting diuretic with which the claimed compounds can be combined.

The '813 patent therefore teaches a genus of which the claims of the '430 patent are a species. The question addressed in the district court was whether the '813 patent taught the specific 1:10/5 mg:50 mg, "medically synergistic," amiloride/hydrochlorothiazide, combination claimed in the '430 patent. Biocraft argued that the claimed combination was taught because both amiloride and hydrochlorothiazide were highlighted in the '813 patent. Moreover, Biocraft pointed out that the Patent and Trademark Office considered the claimed combination prima facie obvious, and allowed the '430 patent only after Merck presented evidence allegedly demonstrating a natriuretic synergism produced by the combination. Asserting that the alleged synergistic effect is not exhibited by the 5 mg:50 mg combination, and that therefore, the effect, even if produced, is not commensurate in scope with the claims, Biocraft argued that neither the purported effect nor the dosage limitations distinguish the claims from the disclosure of the '813 patent. The district court, however, was not persuaded, and held that Biocraft failed to carry its burden of proving the obviousness of the claims. This appeal followed.

Discussion

The district court found that the combination of amiloride and hydrochlorothiazide was disclosed in the '813 patent. 690 F.Supp. at 1383. Further finding that more than 1200 combinations are disclosed and that neither amiloride nor hydrochlorothiazide are highlighted as preferred embodiments in the '813 patent, however, the district court concluded that the combinations claimed in the '430 patent would merely be "obvious to try," and therefore not barred by 35 U.S.C. Sec. 103. We do not quarrel with the factual findings of the district court, but we believe its conclusion that obviousness had not been proven is incorrect as a matter of law.

An invention is "obvious to try" "where the prior art [gives] either no indication of which parameters [are] critical or no direction as to which of many possible choices is likely to be successful." In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed.Cir.1988). This is not the situation here. The '813 patent expressly teaches "that when co-administered with other diuretic agents known to enhance the elimination of potassium ions along with sodium ions, the novel pyrazinoylguanidines of this invention will reduce the excretion of potassium ions and thus overcome this undesirable property of other diuretic agents." As is apparent, "success" is not dependent upon random variation of numerous parameters. On the contrary, the '813 patent instructs the artisan that any of the 1200 disclosed combinations will produce a diuretic formulation with desirable sodium and potassium eliminating properties.

That the '813 patent discloses a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art. See In re Corkill, 771 F.2d 1496, 1500, 226 USPQ 1005, 1008 (Fed.Cir.1985) (obviousness rejection of claims affirmed in light of prior art teaching that "hydrated zeolites will work" in detergent formulations, even though "the inventors selected the zeolites of the claims from among 'thousands' of compounds"); In re Susi, 440 F.2d 442, 445, 169 USPQ 423, 425, 58 CCPA 1074 (1971) (obviousness rejection affirmed where the disclosure of the prior art was "huge, but it undeniably include[d] at least some of the compounds recited in appellant's generic claims and it is of a class of chemicals to be used for the same purpose as appellant's additives").

Merck imputes undue significance to the district court's finding that neither amiloride nor hydrochlorothiazide are highlighted in the '813 patent. The description of "specific preferences in connection with a generic formula" is determinative in an analysis of anticipation under 35 U.S.C. Sec. 102. In re Petering, 301 F.2d 676, 681, 133 USPQ 275, 279, 49 CCPA 993 (1962); see also In re Schaumann, 572 F.2d 312, 315, 316, 197 USPQ 5, 8, 9 (CCPA 1978) (...