Application of Nathan

• Citation: 140 USPQ 601,328 F.2d 1005
• Decision Date: 12 March 1964
• Docket Number: Patent Appeal No. 7145.
• Parties: Application of Alan H. NATHAN, John A. Hogg and William P. Schneider.
• Court: United States Court of Customs and Patent Appeals

140 USPQ 601, 328 F.2d 1005 (1964)

Application of Alan H. NATHAN, John A. Hogg and William P. Schneider.

Patent Appeal No. 7145.

United States Court of Customs and Patent Appeals.

March 12, 1964.

Eugene O. Retter, Washington, D. C., A. Blaufarb, The Upjohn Company, for appellant.

Clarence W. Moore, Washington, D. C. (J. E. Armore, Washington, D. C., of counsel), for Commissioner of Patents.

Before WORLEY, Chief Judge, and RICH, MARTIN, SMITH and ALMOND, Judges.

MARTIN, Judge.

This appeal is from a decision of the Patent Office Board of Appeals affirming the examiner's rejection of claims 1 through 16 of appellants' application serial No. 759,400, filed September 8, 1958 for "Steroids." No claim has been allowed.

The appealed claims are directed to certain 2-halo (fluorine or chlorine) steroids, the compound 2-halo (fluoro-or chloro-)-17a, 21-dihydroxy-4-pregnene-3,20-dione being representative of the claimed compounds. All the claims further, as the result of an amendment entered during prosecution of the application before the Patent Office, specify the alpha (a) orientation for the 2-halo substituent.

The relationship of the 2-halo atom to the steroid nucleus of the claimed steroids oids can be represented diagrammatically as:

The 2-position of the molecule of appellants' steroids is represented by saturated carbon atom C2. Saturated carbon atom C2 is bonded to saturated carbon atoms C1 and C3, to the hydrogen substituent and to the fluorine or chlorine substituent.

Appellants point out that because of the relation of the valance bond angles of the saturated carbon atoms of the steroid, one of the two substituents attached to saturated carbon atom C2 will project toward one side of the approximate plane of the steroid nucleus and the other substituent toward the other side of that plane. The substituent which projects toward the opposite side from the angular methyl groups (carbon atoms C18 and C19) is said to have the alpha orientation, whereas the substituent projecting toward the same side from the angular methyl group is said to have the beta orientation.

The record shows that on June 15, 1959 appellants amended their specification and claims to indicate that the 2-halo steroids of their invention had the alpha orientation. This amendment was in response to the examiner's first action on the claims. That action, according to the examiner's answer, "merely rejected the claims as unduly broad and indefinite in failing to give the configuration (alpha or beta) of the 2-halo atoms." On June 2, 1960 appellants submitted an affidavit under Rule 132 in support of the propriety of their amendment, which affidavit reads in part:

"THAT, the synthesis of the steroid compounds accomplished in the course of completing the invention described and claimed in the above-identified application involved, in the case of the 2-fluoro compounds, the introduction of a fluorine atom in the 2-position of a certain ?4-3-keto steroid of the pregnane sic series; namely, an alkali metal enolate of 2-alkoxyoxalyl-11ß, 21-dihydroxy-4,-17(20) - cis - pregnadien - 3 - one (Preparation 6 of the specification) by reaction with perchloryl fluoride to produce 2-fluoro-2-alkoxyoxalyl-11 ß, 21-dihydroxy-4,17(20)- cis-pregnadien-3-one;

"THAT, this latter compound was then converted to a 2-fluorinated-11ß, 21-dihydroxy-4,17(20-cis-pregnadien-3-one (the product of Preparation 6 of the specification);

"THAT, we are aware of the work of others wherein a fluorine substituent has been introduced by the reaction of perchloryl fluoride upon the 2-alkoxyoxalyl substituted ?4-3-keto steroid (Kissman et al., J.A.C.S. 81:1262); * * * and we are moreover aware that in * * * that work the stereoconfiguration of the 2-fluorine substituent is designated as the a-configuration based, * * * upon physical evidence consistent with such a configuration; and moreover we are unaware of any facts inconsistent therewith;

"THAT, we converted the product of Preparation 6 of the specification to 2-fluoro hydrocortisone acetate by the process of Preparation 7 and Example 1 and that we hydrolyzed the product of Example 1 by the process of Example 6 thus producing 2-fluoro hydrocortisone;

"THAT, in the case of the Kissman et al. work, we have made a comparison and found that our 2-fluoro hydrocortisone, prepared by the hydrolysis of the product of Example 1 of the specification and have found physical characteristics consistent with and no physical characteristics inconsistent with the identity thereof;

"THAT, these physical constants are:

"For the 2-fluoro hydrocortisone prepared by hydrolysis of our Example 1 by the process of Example 6 of the specification:

"Conjugated ketone band at 5.97 µ.

?max at 242 mµ, E 14,200 (in ethanol).

a D plus 185 degrees (methanol).

Melting point 212-221 degrees centigrade.

"The physical characteristics reported by Kissman et al. are:

"Conjugated ketone band at 5.87 µ.

?max 241 mµ, E 14,800.

a D plus 190 degrees (methanol).

Melting point 216-220 degrees centigrade.

"THAT the product of our Example 6 is identical with the product designated as 2a-fluoro hydrocortisone of Kissman et al.;

"THAT, the subsequent chemical conversions to which the compounds disclosed and claimed in the above-identified application for patent are subjected do not alter the stereoconfiguration of the 2-fluoro substituent; * * *."

In rejecting the...