Application of Henze

• Decision Date: 03 April 1950
• Docket Number: Patent Appeal No. 5659.
• Citation: 181 F.2d 196
• Parties: Application of HENZE.
• Court: U.S. Court of Customs and Patent Appeals (CCPA)

181 F.2d 196 (1950)

Application of HENZE.

Patent Appeal No. 5659.

United States Court of Customs and Patent Appeals.

Argued January 13, 1950.

Decided April 3, 1950.

Whittemore, Hulbert & Belknap, Washington, D. C. (L. Gaylord Hulbert, Detroit, Mich., and George A. Degnan, Washington, D. C., of counsel) for appellant.

E. L. Reynolds, Washington, D. C. (J. Schimmel, Washington, D. C., of counsel) for the Commissioner of Patents.

Before GARRETT, Chief Judge, and JACKSON, O'CONNELL and JOHNSON, Judges.

JOHNSON, Judge.

On May 15, 1944, the appellant filed an application in the United States Patent Office for a patent covering improvements in "Hydantoins and Methods of Obtaining the Same." The subject matter of the patent application is said to be a new class of chemical compounds valuable in therapeutic use by reason of high anticonvulsant activity combined with low toxicity.

On July 16, 1946, the Primary Examiner in the Patent Office entered a final rejection of all of the claims (1, 2, and 3) in the application as lacking invention over the disclosure appearing in a 1936 scientific publication. When the appellant appealed to the Patent Office Board of Appeals the decision of the examiner was, on December 12, 1947, affirmed. The appellant thereupon filed a Petition and Supplemental Petition for Reconsideration, both of which were denied by the board on February 18, 1948.

The applicant has appealed to this court from those decisions of the board. R.S. 4911, 35 U.S.C. 59a Revised Judicial Code 1948, 28 U.S.C.A. § 1542.

Claim 3 is illustrative of the subject matter. Broader claims 1 and 2 are set out in the margin.¹ No claims were presented covering the method of preparing the compositions of matter claimed.

3. 5-Isopropoxymethyl-5-phenylhydantoin.

The publication upon which the finding of lack of invention was based by the examiner and board is Volume 58, Journal of American Chemical Society, pages 474-477.

Hydantoin is considered a derivative of amino-acetic acid. It is found in molasses. C-homologues, phenyl-ethyl-hydantoin, known as nirvanol, are used as hypnotics. Organic Chemistry, Karrer, 3d Ed., 1947, p. 286-7. It is also identified as glycolyl urea with a formula

Chemical and Technical Dictionary, Bennett, 1947.

Henze's application is directed to compounds derived from hydantoin and having the general structural formula where R

represents an alkyl radical² of from 3 to 12 carbon atoms. M represents hydrogen or a non-toxic salt forming element or group, such as sodium, magnesium, ammonium, and substituted ammonium (e. g., mono and di-alkyl ammonium and corresponding hydroxy alkyl ammonium). The specification not only details methods of preparation of the claimed compounds, but also recites specific dosages applicable generally to adults.

Claim 1 is the generic claim. Claim 2 is somewhat narrower, being drawn to compounds in which R represents a branched chain alkyl. Claim 3 is specific to a compound in which R is isopropyl and M is hydrogen. The compound of claim 3 corresponds to the formula

In the March 1936 edition of the Journal of American Chemical Society (Volume 58 at pages 474 to 477) there was published an article written "by Niel E. Rigler with Henry R. Henze," the latter being the appellant, entitled "Synthesis of Compounds with Hypnotic Properties. I. Alkoxy-methylhydantoins." The authors state that soporifics of definite potency and usefulness had been produced, prior to their investigation, as a result of extensive studies performed among the series of alkyl disubstituted barbituric acids. Because of the structural relationship of hydantoin to barbituric acid, the authors selected for their investigation the inquiry of whether the innocuous substance hydantoin might, by the attachment of alkyl, alkyloxy, aryl, or aryloxyalkyl groups to the nucleus, be converted into soporific derivatives. It was stated by the authors that in their research, "the groups attached to the hydantoin nucleus, either directly or through the methoxy grouping, were those which have been demonstrated to possess a definite narcotic effect." They included in their synthesis a variation wherein one of the alkyls was attached indirectly through the methoxyl group "so that the compounds prepared are 5,5' — alkoxymethyl alkyl (or aryl) hydantoins." A method of preparation was used which yielded an end product conforming to the general formula

In Table VII of the experimental data set forth in the article there appears under the heading "Alkoxymethyl Hydantoins" (adjacent to which appears the general formula

which is the equivalent of the general formula next above) columnar tabulations identifying the specific radicals which were substituted for the R and R' in the synthesis and experimentation. The sixth entry in Table VII identifies R as "Ethyl" and R' as "Phenyl." The ethyl radical is C2H5 (or CH3CH2) and the phenyl radical is the aryl or aromatic monovalent hydrocarbon radical C6H5. There is thus disclosed, when the substitution is made in the end product formula, supra, the compound ethoxymethylphenylhydantoin, conforming to the general formula,

which may be stated as 5-ethoxymethyl-5-phenylhydantoin.

It is at once apparent that the compound of the disclosure differs from the compound of claim 3 merely by CH2. The claimed compound is thus the next higher homologue of the compound disclosed in the publication.

Of the pharmacological utility of ethoxy-methylphenylhydantoin, the authors stated that it "in moderate doses causes convulsions and for it the range between the effective and lethal doses is too narrow."

Parke, Davis & Company are the assignees of the appellant's patent application. An affidavit of record by the Director of Chemical Research of that company states that numerous samples of various hydantoins, including "Dilantin" (sodium diphenyl hydantoinate) and 5-isopropoxy-methyl-5-phenylhydantoin, were supplied by him to Drs. Merritt and Putnam. They then submitted to the Director reports of actual clinical tests which indicated that out of many hundreds of compounds studied by them for anti-convulsant activity and effectiveness, the two mentioned possessed outstanding activity and effectiveness in the clinic, were non-toxic, and, on the basis of results secured in their use in the electrically induced convulsion test for cats, both were safe drugs to use. That and other test data were stated by the affiant definitely to show "that 5-Isopro-poxymethyl-5-phenyl hydantoin is a safe anticonvulsant of high activity and outstanding effectiveness."

The examiner had held, following In re Hass, 141 F.2d 130, 31 C.C.P.A., Patents, 908, that the claims in issue were unpatentable, lacking invention over the disclosure of the publication, because the appellant had failed to show that the compounds claimed had an unexpected beneficial property not possessed by the lower adjacent homologue disclosed in the publication. The examiner held that the affidavit did not aid in conferring patentability upon the rejected claims because there was no showing that the lower homologue would not yield results similar to the claimed compounds under certain dosages.

The board upheld the examiner's position and emphasized that it was necessary that there be proof by the appellant that the compound of the reference does not have the same effect as the claimed compounds under the same conditions of dosage. The disclosure in the publication of the class of compounds, 5,5'-alkoxy-methyl alkyl (or aryl) hydantoins, was also held by the board to be a disclosure of the class of compounds of claims 1 and 2.

Appellant admits that 5-ethoxymethyl-5-phenylhydantoin, disclosed in the reference, is a lower homologue of the compound set out in claim 3. He acknowledges that the publication cited against his claims is silent as to the effects produced by 5-ethoxymethyl-5-phenylhydantoin at less than moderate dosages, but he contends that even if convulsions would not occur, there was no inference that the compound would have anti-convulsion utility at such lower dosages. Appellant's position is that it is sufficient if he shows that his compounds have utility and unexpected beneficial properties not known to be possessed by the prior art homologue. He insists that it was error for the Patent Office tribunals to require him to establish that his claimed compounds possessed unexpected properties in fact not possessed by the prior art homologue.

A homologous series is a family of chemically related compounds, the composition of which varies from member to member by CH2 (one atom of carbon and two atoms of hydrogen). In re Loring Coes, Jr., 173 F.2d 1012, 36 C.C.P.A., Patents, 1067. The court's rule on the patentability of a composition of matter over an adjacent homologue old in the art has been uniformly applied. In the case of In re Lincoln 126 F.2d 477, 480,...