Biovail Corp. Intern. v. Andrx Pharmaceuticals, Inc.

• Decision Date: 06 March 2000
• Docket Number: No. 98-7096-CIV.,98-7096-CIV.
• Citation: 158 F.Supp.2d 1318
• Parties: BIOVAIL CORPORATION INTERNATIONAL, et al., Plaintiffs, v. ANDRX PHARMACEUTICALS, INC., Defendant.
• Court: U.S. District Court — Southern District of Florida

158 F.Supp.2d 1318

BIOVAIL CORPORATION INTERNATIONAL, et al., Plaintiffs, v. ANDRX PHARMACEUTICALS, INC., Defendant.

No. 98-7096-CIV.

United States District Court, S.D. Florida.

March 6, 2000.

Alan M. Grimaldi, Richard H. Kjeldgaard, Mark R. Buscher, Elaine T.L. Wu, Howrey Simon Arnold & White, Washington, DC, Benedict Paul Kuehne, Sidney Katz, Eric C. Cohen, Kathleen A. Rheintgen, Charles Krikorian, Sale & Kuehne, Miami, FL, for Biovail Corporation International, plaintiff.

Alan M. Grimaldi, Richard H. Kjeldgaard, Eric C. Cohen, Kathleen A. Rheintgen, Charles Krikorian, Sale & Kuehne, Miami, FL, for Biovail Laboratories, Inc., plaintiff.

Benedict Paul Kuehne, Sidney Katz, Eric C. Cohen, Kathleen A. Rheintgen Charles Krikorian, Sale & Kuehne, Miami, FL, for Galephar P.R., Inc., Ltd., plaintiff.

FINDINGS OF FACT AND CONCLUSIONS OF LAW

DIMITROULEAS, District Judge.

THIS CAUSE came on for non-jury trial on January 24, January 31, February 14, February 15 and February 16, all in the year 2000. The Court has carefully considered the arguments of counsel, the evidence presented, and the testimony of the witnesses. The Court has also determined the credibility of witnesses and is otherwise fully advised in the premises.

Pursuant to Rule 52(a) of the Federal Rules of Civil Procedure, the Court makes the following Findings of Fact and Conclusions of Law.

1. Plaintiff, Biovail Corporation International, is an Ontario Canada corporation with its principal place of business at 2488 Dunwin Dr., Mississauga, Ontario, Canada L5L IJ9.

2. Plaintiff, Biovail Laboratories, Inc., is a Barbados corporation with its principal place of business at Chelston Park, Building 2, Collymore Rock, St. Michael, BH1, Barbados, West Indies.

3. Plaintiff, Galephar P.R., Inc., is a Puerto Rico corporation with its principal place of business at Carolina, Puerto Rico 00984-33468.

4. Defendant, Andrx Pharmaceuticals, Inc., is a Florida corporation with its principal place of business at 4001 S.W. 47th Avenue, Fort Lauderdale, Florida 33314.

5. Galephar P.R., Inc. is the owner of United States Patent No. 5,529,791 ("the '791 patent").

6. Biovail Corporation International is the exclusive licensee of Galephar P.R. Inc. under the '791 patent.

7. Biovail Laboratories, Inc. is a wholly owned subsidiary of Biovail Corporation Inc.

8. The alleged act of infringement constituted the filing by Defendant (hereinafter "Andrx") of an Abbreviated New Drug Application (hereinafter "ANDA") with the Food and Drug Administration (hereinafter "FDA") for permission to sell a bioequivalent formulation to the brand name drug Tiazac®.

9. Shortly after filing the ANDA on June 22, 1998, Andrx served Biovail with its paragraph IV certification stating that the formulation described in the ANDA did not infringe the '791 patent which Biovail had listed in the FDA Orange Book as covering the Tiazac® product and that the claims of the '791 were invalid.

10. On October 7, 1998, Biovail filed the present action against Andrx alleging infringement of the '791 patent under 35 U.S.C. 271(e)(2)(a).

CLAIM INTERPRETATION

11. The invention claimed by the '791 patent provides for an extended-release composition for the drug diltiazem.

12. Diltiazem is a well known drug compound which itself is no longer the subject of an extant patent.

13. Diltiazem is generally prescribed for its calcium channel blocking properties, and, therefore, is useful in the treatment of angina and/or hypertension; either alone or in combination with other medications.

14. The '791 patent contains four claims. Col. 8, line 59 to col. 10, line 11 of '791 patent (Defendant's Exhibit 1).¹

15. Claim 1 of the '791 patent states:

1. An extended-release galenical composition of one or more pharmaceutically-acceptable salts of Diltiazem which comprises beads containing an effective amount of one or more of said Diltiazem salts as the active ingredient, each bead containing one or more of the Diltiazem salts and an effective amount of wetting agent in admixture with the one or more Diltiazem salts to maintain the solubility of the Diltiazem in each bead, ensuring that the solubility of the Diltiazem is unaffected by the pH of the gastrointestinal tract or other adverse conditions which the composition will meet therein, said beads being coated with a microporous membrane comprising at least a water-soluble or water-dispersible polymer or copolymer, and a water-, acidand base-insoluble polymer and a pharmaceutically acceptable adjuvant, and wherein the wetting agent is selected from the group consisting of sugars, C₁₂ -C₂₀ fatty acid esters of sucrose, or xylose, glycerides of sucrose, fatty acid esters of polyoxyethylene, ethers of fatty alcohols and polyoxyethylene, esters of sorbitan, esters of polyoxyethylene sorbitan, alcohol-polyglycide esters, glyceride-polyglycides, lecithins and a combination thereof.

Col. 8, line 59 to col. 9, line 13 of '791 patent (DX1).

16. In Claim 1, the core of the '791 patent is claimed as containing two components:

(a) an effective amount of the drug diltiazem or salt thereof as the active ingredient;

in admixture with

(b) an effective amount to maintain the solubility of the diltiazem in each bead and to ensure that the solubility of diltiazem is unaffected by the pH of the gastrointestinal tract or other adverse conditions, of one of a number of specifically listed wetting agents, namely, sugars, C₁₂-C₂₀ fatty acid esters of sucrose or xylose, glycerides of sucrose, fatty acid esters of polyoxyethylene, ethers of fatty alcohols and polyoxyethylene, esters of sorbitan, esters of polyoxyethylene sorbitan, alcohol-polyglycide esters, glyceride-polyglycides, lecithins, and combinations thereof.

Col. 8, line 59 to col. 9, line 13 of '791 patent (Def.Exh.1).

17. All of the four claims of the '791 patent clearly require the two components of the core, i.e., the diltiazem and the wetting agent, to be in admixture. Col. 8, line 67 to col. 10, line 10 of '791 patent (Def.Exh.1).

The '791 Patent Specification

18. The specification of the '791 patent supports the requirement that the wetting agent be in admixture with the diltiazem in the dry state.

19. The '791 patent specification describes two methods for preparing the diltiazem beads.

The patent states as follows:

A first technique consists in mixing the Diltiazem or salt thereof with the wetting agent(s) in a melted or finely divided form, or in solution, in the presence of a solvent, such as water, so as to obtain an extrudable paste or plastic mass. Col. 4, lines 26-30 of the '791 patent (DX1).

20. The patent specification further states that:

Another conventional technique for obtaining beads consists in spraying and/or dusting cores obtained through agglomeration of the Diltiazem or salt thereof, such as the chlorohydrate, contingently mixed to at least a wetting agent, with a dispersions or solution of at least one wetting agent. Col. 4, lines 39-44 the '791 patent (DX1).

21. Additionally, each of the Examples of the '791 patent specification exemplifies the preparation of the beads specifically describing mixing the bead components during the bead manufacturing stage, such as in a planetary mixer for approximately 15 minutes. Col. 5, lines 55-67 and col. 6, lines 4-15 of '791 patent (DX1).

22. The '791 patent issued as a continuation of two prior patent applications, one of which issued as a patent, and the other resulted in an abandonment. Cover of '791 patent (Def.Exh.1); '791 file history (Def.Exh.3); '505 file history (Def.Exh.4)

23. The original application was filed on June 26, 1991 and received Serial No. 721,396 ("the '396 application"). The '396 application eventually issued as United States Patent No. 5,288,505 on February 22, 1994 ("the '505 patent"). '505 file history (DX4).

24. The '505 patent has not been asserted against Andrx in the present lawsuit, and, in fact, is not listed in the FDA Orange Book as covering Tiazac®. Complaint; FDA Orange Book (DX12).

25. Prior to the issuance of the '505 patent, Biovail filed a continuation of the '396 application on May 28, 1993, which continuation application received Serial No. 68,951 ("the '951 application"). '791 patent file history (DX3).

26. The '951 application did not issue as a patent, but instead was abandoned in favor of another continuation application which was filed on September 23, 1994 and which received Serial No. 311,722 ("the '722 application"). 791 patent file history (DX3).

27. The '722 application eventually issued as the '791 patent on June 25, 1996.-'791 file history (DX3).

28. During the prosecution of the '951 application and the '396 application, Biovail consistently referred to the bead as comprising an admixture of the diltiazem and wetting agent during the manufacturing stage in order to avoid the prior art. '505 file history (DX4); '791 file history (DX3).

29. In fact, during the prosecution of the '951 application and the '396 application, Biovail made numerous representations to the USPTO that the claims required the diltiazem and wetting agent needed to be homogeneously admixed during the manufacturing state. '505 file history (DX4); '791 file history (DX3).

30. On pages 8-9 of the May 28, 1993 Preliminary Amendment in the '951 application, Biovail made the following representations regarding the scope of the claims to the USPTO:

Thus, at the outset, it is noted that the present composition is characterized by the use of beads consisting essentially of in admixture together an effective amount of Diltiazem or one or more salts thereof as an active ingredient and the wetting agent as defined in the claims. The beads are also coated with a microporous membrane as defined in the claims.

In essence, in admixture, the wetting agent appears to control, or strongly influence, the solubility of Diltiazem and does not permit this solubility to be affected by pH or other adverse conditions in the...