Eli Lilly and Company v. Generix Drug Sales, Inc., 69-1241-Civ.

• Decision Date: 05 March 1971
• Docket Number: No. 69-1241-Civ.,69-1241-Civ.
• Citation: 169 USPQ 13,324 F. Supp. 715
• Parties: ELI LILLY AND COMPANY, Inc., an Indiana corporation, et al., Plaintiffs, v. GENERIX DRUG SALES, INC., a Florida corporation, et al., Defendants.
• Court: U.S. District Court — Southern District of Florida

324 F. Supp. 715

169 USPQ 13

ELI LILLY AND COMPANY, Inc., an Indiana corporation, et al., Plaintiffs, v. GENERIX DRUG SALES, INC., a Florida corporation, et al., Defendants.

No. 69-1241-Civ.

United States District Court, S. D. Florida.

March 5, 1971.

Smathers & Thompson, Ralph & Boyd, Miami, Fla., Dewey, Ballantine, Bushby, Palmer & Wood, New York City, David L. Ladd, Chicago, Ill., of counsel, for plaintiffs.

George Wright, Miami, Fla., Robert W. Smiley, Pittsburgh, Pa., John H. Lewis, Miami, Fla., Richard Leben, Hollywood, Fla., Lilling & Siegel, New York City, M. A. Baskin, Miami, Fla., Richard F. Bergner, Houston, Tex., for defendants.

FINDINGS OF FACT AND CONCLUSIONS OF LAW

KING, District Judge.

This cause having come on for hearing upon the motion of Plaintiffs, Eli Lilly and Company, Inc. and Eli Lilly and Company, for a preliminary injunction, enjoining and restraining, pendente lite, the Defendants, Caribe Chemical Company, Inc., Ellencee Pharmaceutical Laboratories, Inc., Houston Biochemical Industries, Inc., and Paolo C. Carlotti from infringing U. S. Patent No. 2,728,779, and the said Defendants having filed a cross-motion seeking an order, pendente lite, from engaging in specified courses of conduct, and the Court having received evidence, including extended testimony of numerous witnesses, taken briefs of the parties, and heard arguments of counsel,

WHEREUPON, the Court makes and enters the following Findings of Fact and Conclusions of Law:

FINDINGS OF FACT

1. The Plaintiffs, Eli Lilly and Company, Inc. (hereinafter referred to as "Lilly Puerto Rico") and Eli Lilly and Company (hereinafter referred to as "Lilly") are corporations organized and existing under the laws of the State of Indiana, the former being a wholly owned subsidiary of the latter.

2. The Defendant, Ellencee Pharmaceutical Laboratories, Inc., (hereinafter referred to as "Ellencee") is a corporation organized and existing under the laws of the State of New York.

3. The Defendant, Caribe Chemical Company, Inc. (hereinafter referred to as "Caribe") is a corporation organized and existing under the laws of the territory of the Virgin Islands.

4. The Defendant, Houston Biochemical Industries, Inc. (hereinafter referred to as "H. B. C.") is a corporation organized and existing under the laws of the State of Delaware.

5. The Defendant, Paolo C. Carlotti, is a citizen of Italy and resides in Houston, Texas.

6. The Plaintiffs have been and are marketing alpha-dextro propoxyphene hydrochloride under the trademark DARVON®, and the Defendants intend to market alpha-dextro propoxyphene hydrochloride, the products being chemically identical and being the alpha dextro form of 1,2-diphenyl-2-propionoxy-3-methyl-4-dimethylaminobutane hydrochloride.

7. On December 3, 1952, United States Patent Application Serial No. 323,947 was filed in the United States Patent Office in the name of Albert Pohland as inventor, and on December 27, 1955, United States Letters Patent No. 2,728,779 was issued thereon by the United States Patent Office to Lilly. Lilly assigned United States Letters Patent No. 2,728,779 to Lilly Puerto Rico by an instrument executed December 5, 1966 and recorded in the United States Patent Office on February 14, 1969, at Reel 2462, Frame 566. At all times material hereto all right, title, and interest in and to said Letters Patent have been in Lilly Puerto Rico.

8. United States Patent No. 2,728,779 relates to a chemical compound, 1,2-diphenyl-2-propionoxy-3-methyl-4-dimethylaminobutane hydrochloride ("propoxyphene hydrochloride" herein) which is useful as a centrally acting analgesic of the morphine class, but which does not have the undesirable toxic side effects commonly associated with analgesics of that class, such as a respiratory depression, which is recognized as an indicator of addiction liability.

9. According to the patent, propoxyphene hydrochloride possesses two centers of asymmetry and, therefore, occurs in two pairs of mirror-image forms. The less-soluble pair is called the "alpha" pair; the more-soluble, the "beta" pair. The individual members, or optical isomers, of each pair are called "dextro" and "levo", respectively. Thus, propoxyphene hydrochloride appears in the forms of the individual alpha-d, alpha-l, beta-d, and beta-l isomers and in mixtures of those isomers, including racemic mixtures (called "alpha-dl" and "beta-dl") having equal parts of the d and l isomers.

10. Plaintiffs have notified the defendants of their election to rely solely upon Claim 2 of the patent. Claim 2 of the patent commences with the expression "-dl," by which is meant a racemic mixture of equal quantities of the less soluble dextro ("d") and levo ("l") isomers, and, as the parties have stipulated, "the d and l optical isomers are both present in the racemic mixture." Propoxyphene hydrochloride is literally presented and discussed in the patent only in its racemic mixture (or "dl") form; the individual optical isomers are not expressly and separately presented or discussed apart from their inherent inclusion in the racemic mixture.

11. The specification of the patent states that "the -dl diastereoisomers are the preferred compounds of the invention since they possess marked analgesic activity in contrast to the ß-dl diastereoisomers, which are substantially inactive." The patent thus states the utility of the compounds to be as analgesics, and the beta (i. e., more-soluble) forms are identified in the patent specification as inactive for this purpose. Thus, the inventor expressed his intent to disclose and claim the analgesic forms of the optically active compounds, including propoxyphene hydrochloride. Claim 2 of the patent is literally drawn, in normal chemical nomenclature, to the alpha-dl form, but interpreted in light of the specification and the inventor's intention, covers the analgesically active forms, both of which are alpha forms— namely, the alpha-dl and the alpha-d. Claim 2 by its literal language excludes the analgesically inactive beta forms— that is, the beta-l, beta-d, and their beta-dl mixture—and interpreted in light of the specification and the inventor's intention, excludes the analgesically inactive alpha-l form as well.

12. The parties have stipulated that it "is common knowledge that optical isomers of a chemical compound frequently differ in their pharmacological action. Specifically, it is known that analgesic compounds related in structure to methadone like propoxyphene occur in optically active forms and that the analgesic activity of such compounds is exclusively or predominantly with one of the isomers, as with methadone itself"; and it is undisputed that this was known prior to the date of Pohland's invention of propoxyphene. Thus, Pohland in his patent specification ruled out the ß forms (beta-l, beta-d, and their mixture beta-dl), and pointed to the analgesic activity as residing in the alpha racemic mixture. In due course, after his patent application was filed, Pohland and his assistant Sullivan, using conventional procedures, resolved the analgesically active alpha-dl racemic mixture into its component isomers, and ascertained the analgesic property to reside in the alpha-d isomer alone. Thus, Pohland explicitly and expressly disclosed in his patent application the alpha-dl form as the best—and only—form of propoxyphene which he had synthesized and tested at the time the application was filed; and in light of the state of the art as acknowledged by the stipulation, Pohland in his patent specification also implicitly and inherently made available the active alpha-d isomer.

13. The Pohland analgesic propoxyphene hydrochloride satisfied a long-felt need for a synthetic analgesic having the pain-relieving properties of morphine but without addiction liability. That search began in the late 1920's and was accelerated in later years by two events. The first of those events was the scarcity of morphine during the second World War. The first fully synthetic analgesic drug to result from this search was a drug known as meperidine, which appeared in the early 1940's. This drug was a landmark development in that it was the first fully synthetic analgesic. Like morphine, however, meperidine proved to be addictive. The second of these two events came at the close of World War II: American scientific intelligence teams investigated German wartime work on synthetic analgesics and published a report (the "Kleiderer Report") summarizing that work for the American scientific community. The Kleiderer Report dealt with a number of synthetic substances, among which was one which subsequently became known as methadone. Methadone proved to be as active an analgesic as morphine, but also proved to be equally high in addiction liability.

14. The publication of the Kleiderer Report caused an intensive research effort to be mounted in the United States and abroad for a nonnarcotic synthetic analgesic of the morphine class. Several major pharmaceutical companies, including Lilly, Ciba, Squibb, Hoffmann-LaRoche, Smith, Kline & French, and Winthrop participated in this effort. To coordinate and foster this research, the Committee on Drug Addiction and Narcotics (later renamed the Committee on Problems of Drug Dependence), a committee of experts formed and sponsored by the National Academy of Science, assumed responsibility for monitoring this work, selecting promising compounds for clinical tests in humans, reviewing publications and research results flowing from this work, and sponsoring annual meetings for exchange of research data among scientists working in the drug companies, universities, and other laboratories, and the U. S. Commissioner on Narcotics.

By 1950, hundreds of compounds evidencing analgesic potency were being submitted for study in human beings for addiction liability—so many that facilities for clinical testing on prisoner volunteers at the Federal Addiction Research Center at...