Schering Corporation v. Gilbert

• Decision Date: 18 January 1946
• Docket Number: No. 156.,156.
• Parties: SCHERING CORPORATION v. GILBERT et al. (UNITED STATES, Intervener).
• Court: U.S. Court of Appeals — Second Circuit

153 F.2d 428 (1946)

SCHERING CORPORATION v. GILBERT et al. (UNITED STATES, Intervener).

No. 156.

Circuit Court of Appeals, Second Circuit.

January 18, 1946.

Briesen & Schrenk, of New York City (Newton A. Burgess and Fred A. Klein, both of New York City, and Harold T. Stowell, of Washington, D. C., of counsel), for plaintiff-appellee.

A. J. Nydick, of New York City, for defendants-appellants.

John F. X. McGohey, U. S. Atty., of New York City (William L. Lynch, Asst. U. S. Atty., of New York City, C. E. Rhetts, Acting Head, War Division, Harry LeRoy Jones, Chief, Alien Property Litigation Unit and M. S. Isenbergh and David Schwartz, Chief Trial Attys., Alien Property Litigation Unit, War Division, all of Washington, D. C., of counsel), for intervener-appellee.

Before SWAN, CHASE, and FRANK, Circuit Judges.

CHASE, Circuit Judge.

The appellee is a New Jersey corporation and the owner of U. S. Patent No. 2,345,384 which was granted to it on March 28, 1944 as the assignee of the inventors whose application was filed on April 6, 1940. It sued the appellants, Jules R. Gilbert and William Bell, partners in business under the firm name of National Synthetics, in the District Court for the Southern District of New York for infringement of the patent, relying at the trial only on Claim 2. Before trial a motion to dismiss the complaint was overruled and after trial an interlocutory decree for damages to be determined upon a reference for the infringement of Claim 2 and for an injunction was entered for the plaintiff, and the defendants' counterclaim was dismissed. This appeal is from that decree.

As stated in the specifications, the invention relates to "poly iodized derivatives of the hydroxy diphenyl carboxylic acids and a process for preparing the same," but the patent contains only product claims. Claim 2 is a short claim for one definite chemical compound not found in nature and never previously synthesized. It is for the beta-(4-hydroxy-3,5-diiodophenyl)-alpha-phenyl propionic acid which melts at 159°C. The claim is in phraseology readily understood by those conversant with such terminology and is a precise and adequate claim for the product it describes. The defendants have conceded infringement if the claim is valid. Its validity, however, has been vigorously contested as has that of claim 4 which is a broad, generic claim for a group of compounds of which that of Claim 2 is one specific example.

It was shown that compliance with the instructions in Example 4 in the specifications by a skilled organic chemist produced the identical product of Claim 2. To be sure it was not a difficult procedure when the way had been blazed but the ease of accomplishment by one who follows the teachings of a patent is added evidence of the adequacy of the disclosure.

The inventors were trying to improve the art of cholecystography and were using known principles of organic chemistry as their tools. The problem was not the mere construction of a chemical formula followed by experiments to see if what had been formulated could be synthesized. They had so to contrive that a stable compound would be produced with ingredients which would after oral administration so act upon the gall bladder, without much, if any, distressing effect upon the person whose gall bladder was being so treated, that sufficiently revealing X-ray pictures of it could be taken. Those ingredients had to have properties which would provide a dye to give opacity and be so bound to a carrier that the gall bladder would, in the exercise of the natural functions of the organs in the body of the patient, be filled with it, and that to the exclusion of unwanted deposits elsewhere. Consequently the carrier had to have such an affinity for the bile that it would be attracted to the gall bladder. Furthermore, in addition to having the proper coloring matter and being sufficiently lipoid soluble, the compound had to be practically free from toxic effect when properly administered by comparatively small oral dosage. To any suggestion that that was a simple problem whose solution should have been obvious to the skillful the sufficient answer seems to be that it eluded all in that class for many long years while persons with diseased gall bladders waited in vain for relief from the harmful effects of distressing methods of diagnosis.

The appellants rely principally on the two-fold and rather technical contention that Claim 2 is invalid as lacking invention because (1) it is a claim for a product which is nothing but a molecule that has resulted from inevitable chemical reactions governed by the laws of nature, and because (2) there was no novelty in the process used to produce the result.

In order to determine whether such a defense is factually correct as to Claim 2 and legally sound, it is necessary to understand what the inventors did as well as what they sought to accomplish and give recognition to their end result as a novel and useful improvement, not in the art of organic chemistry but in that of cholecystography.

They were two Germans, Max Dohrn and Paul Diedrich, who were skillful scientists both in the field of organic chemistry and in that of contrast media needed for use in taking X-ray pictures of certain organs in the human body. They were employed by Schering A. G. of Berlin, Germany. In the compound of Claim 2, they succeeded in combining all three of the characteristics desired in a contrast agent for use in cholecystography, obtaining the required solubility from the carboxyl component, affinity for the bile from the phenyl component, opacity from the iodine component, and, most important of all, a very high degree of compatibility in almost every instance.

The specifications state that:

"Not only the known tetra iodo phenolphthalein but also iodized derivatives of 2-phenyl cinchonic acid (see U. S. Patent No. 1,846,321) have been employed for rendering visible the gall bladder by X-rays. All these compounds yield a good picture but they are not sufficiently indifferent physiologically on application in the necessary rather large amounts.

Now, the poly iodized derivatives of the hydroxy diphenyl carboxylic acids represent lipoid-soluble compounds, which, contrary to the hitherto known contrast agents for the gall bladder combine a very good contrasting effect with an excellent compatibility. Said derivatives are made by iodizing o- or p- hydroxy diphenyl carboxylic acids by methods known per se."

The specifications go on to say that the inventors have found the most suitable contrast agents to be the iodized compounds of hydroxy diphenyl carboxylic acids of a general formula, which is set forth and followed by explanatory language to the effect that it covers all members of the acetic acid radical group and radicals of homologues of acetic acid combined with specified members of the hydroxyl group and the whole iodized. As general examples of what is meant there are given "hydroxy diiodo diphenyl acetic acid, hydroxy — or dihydroxy diiodo diphenyl propionic or — butric acids and others," and it is said that 3,5-diiodo-4 hydroxy diphenyl acetic acid and beta-(4-hydroxy-3,5-diiodo phenyl)-alpha-phenyl propionic acid are especially suitable. After saying that the salts of these acids are soluble in water with neutral reaction, the inventors give eight specific examples of ways to practice the invention and add that, "Of course, many changes and variations may be made in the reaction conditions, the solvents used, the reagents employed and the like" and make some suggestions in that regard. Then they say: "For using the compounds described and claimed as X-ray contrast agents for rendering visible the gall bladder, they are preferably employed in the form of chocolate-covered granules. 3 grs. of these are usually sufficient in order to give excellent X-ray pictures of the gall bladder 12-14 hours after application. Of course, the contrast agents may also be administered in another form, for example, in the form of tablets or the like. Furthermore salt solutions of the acids may be used likewise." After warning that all changes and variations made by those skilled in the art "must comply with the requirements of the principles set forth herein and in the claims annexed hereto," it is explained that, "By the expression `trivalent hydrocarbon residue of an acid of the acetic acid series' as employed in the claims is to be understood the radical of the acid minus the -COOH group; such residue being trivalent by reason of the fact that it is joined to the two phenyl radicals as well as to the -COOH group." This last explanation, however, has to do only with Claim 4 in which alone the quoted expression is used. Four claims were allowed but numbers 1 and 3 are neither shown to have been infringed nor are they relied on by the plaintiffs or attacked by the defendants now.

The foregoing is a fair summary of the contribution to the art which these inventors made in their specifications as the needed consideration for the grant of the claims which were allowed and the question of invention must be resolved in the light of what the situation was when they made that contribution.

Previously the most notable advance in the art of cholecystography had followed the discovery in 1923 or 1924 by Drs. Graham and Cole that good X-ray visualization of the gall bladder could be obtained by the administration of purified tetraiodophenolphthalein or its related compounds. The least painful method of administration was oral, but that, often if not always, required double dosage and sometimes had to be followed by intravenous injection. The after effect on the patient was usually toxic reaction causing much distress from nausea, vomiting, dizziness, diarrhea, headaches and the like; and, when intravenous injections were necessary, they not only were somewhat painful but had to be made slowly under the immediate supervision of a doctor or skilled attendant and...