Application of Siegfried Gottfried and Lily Baxendale, 343 F.2d 490 (C.C.P.A. 1965)Annotate this Case
John T. Miller, Springfield, Va. (A. Ponack, Washington, D. C., of counsel), for appellants.
Clarence W. Moore, Washington, D. C. (J. F. Nakamura, Washington, D. C., of counsel), for the Commissioner of Patents.
Before WORLEY, Chief Judge, and RICH, MARTIN, and ALMOND, Judges.
This appeal is from a decision of the Board of Appeals affirming the examiner's rejection of process claims 1-5 in appellants' application.1 The invention is a method of converting 18β-glycyrrhetinic acid to 18α-glycyrrhetinic acid.
Claim 1 reproduced below is illustrative:
"A process for the production of 18α-glycyrrhetinic acid, wherein 18β-glycyrrhetinic acid is heated with an alkali metal hydroxide in a medium selected from the group consisting of an alcoholic and an aqueous-alcoholic medium."
The reference relied upon by the examiner is Beaton, J.Chem.Soc. pp. 3126-29 (1955). Beaton contains the following disclosure:2
NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE
Formula I is 18β-glycyrrhetinic acid when both R and R' are hydrogen. Formula II is 18α-glycyrrhetinic acid when both R and R' are hydrogen. It can be seen that the α and β forms of the acid differ from each other only in the position of the hydrogen atom on the 18-carbon atom. Appellants' process is represented by the above equation when both R and R' are H and when the reaction medium contains a metal hydroxide (OH —). Beaton does not specifically disclose the claimed reaction. The following portion of Beaton is the most significant:
"Prolonged treatment of methyl glycyrrhetate with concentrated alkali gives an acid different from, and isomeric with, glycyrrhetic acid [18β-glycyrrhetinic]. The isomeric acid is also obtained by heating a solution of glycyrrhetic acid in acetic acid containing concentrated hydrochloric acid.
* * * * * *
"18α-Glycyrrhetic Acid (II; R = R' = H). — (a) A mixture of methyl glycyrrhetate (I; R = H, R' = Me) (10 g.) and potassium hydroxide (400 g.) in water (200 c.c.) and ethanol (1800 c.c.) was refluxed for 120 hr. The solution was diluted with water (2 1.), then acidified with concentrated hydrochloric acid, and the precipitated solid collected. Repeated crystallisation from chloroform-methanol yielded 18α-glycyrrhetic acid * * *."
The examiner rejected the claims as obvious in view of Beaton, reasoning as follows:
"It is considered that the instantly claimed treatment of glycyrrhetic acid is rendered obvious by the reference treatment of the corresponding methyl ester, since for purposes of isomerization the methyl ester is suggestive of the free acid, the isomerization being around the 18-carbon position."
The above language indicates that the statutory basis of the rejection was 35 U.S.C. § 103. The board affirmed the examiner, stating: "We agree in general with the Examiner's position * * *." However, the board then went on to say that appellants' process was inherent in the Beaton disclosure, stating:
"Although the stated starting material in Beaton et al. is the methyl ester of beta glycyrrhetinic acid it is quite apparent from the disclosure that this ester, in the alkaline medium indicated above, first hydrolyzes to the corresponding beta glycyrrhetinic acid, which latter must then isomerize during prolonged treatment to produce alpha glycyrrhetinic acid fully in accordance with the terms of appellants' claims. * * *"
Appellants claim that the board's language is indicative of a rejection under 35 U.S.C. § 102. The solicitor maintains that the rejection is based only on 35 U.S.C. § 103. We feel that the decision can be affirmed on the basis of obviousness and thus will not consider the question of a "102 rejection."
The solicitor's position is that it would be obvious to substitute the 18β-acid for 18β-ester in the Beaton isomerization of 18β-ester to 18α-acid. He points out that isomerization occurs at the 18-carbon which is removed from the acid or ester group and that it is obvious that isomerization would occur in the presence of a base regardless of the particular R'. A further suggestion would come from the equation in Beaton set forth above. Beaton gives only two possibilities for R', H and CH3. When R' in both formulas is H, and basic reaction medium is used, the claimed invention is depicted by the Beaton equation above. Appellants argue that the equation cannot be considered generic but that it was only meant by Beaton to cover the reactions actually carried out by him. Even if this is true, however, the equation encompasses only a rather limited number of reactions (when R and R' are limited to H and methyl). Therefore, we think that inspection of the equation by one of ordinary skill in the art would readily suggest the isomerization of the 18β-acid in basic medium even though the reaction is not fully disclosed by the equation.
Although we do not necessarily agree with the board that the claimed isomerization inherently occurs during the Beaton conversion of the 18β-methyl ester to the 18α-acid in basic medium, we think that such a reaction mechanism is quite likely. Beaton states that hydrolysis of the 18β-methyl ester in 3% potassium hydroxide gave 5% 18β-acid after two hours, the remainder being "unchanged ester." Since prolonged treatment in a stronger basic solution results in conversion of the 18β-ester to the 18α-acid, one could expect that conversion of the 18β-ester to the 18β-acid occurs first and that isomerization of 18β-acid as claimed is the second step of the reaction. Thus, the claimed reaction would also be suggested by a consideration of the reaction mechanism.
The Beaton disclosure, considered in its entirety, contains a teaching which we think would make it obvious, within the meaning of 35 U.S.C. § 103, to isomerize 18β-acid to 18α-acid in a basic medium.
Appellants point to the fact that in the two examples in their specification the yields of 18α-acid from 18β-acid were 55% and 77% compared with Beaton's yield of 38% in going from the 18β-ester to the 18α-acid. The reaction conditions differed in all three reactions, and of course appellants' starting material is different. We cannot agree that the differences in yield between appellants' examples and the Beaton example are persuasive of unobviousness. The differences might well be due to the different reaction conditions. Clearly the optimum reaction time and base concentration are not appellants' invention. If the improved yields do in fact result from the direct isomerization, we do not feel that when weighed with the evidence of obviousness set forth above, the improvement is so great as to result in a finding of unobviousness.
For the foregoing reasons, we affirm the board's decision.
SMITH, J., concurs in the result.