The invention relates to steroid compounds and, according to the application, is "particularly concerned with 6-methyl-16α-hydroxyhydrocortisone, 1-dehydro-6-methyl-16α-hydroxyhydrocortisone, 6-methyl - 9α - fluoro - 16α - hydroxyhydrocortisone, 1-dehydro-6-methyl-9α - fluoro-16α - hydroxyhydrocortisone, the 16, 21-diesters thereof, the 11-keto analogues and the esters thereof and a method for the production thereof. " The application further says:
The new compounds * * * are highly active adrenocortical hormones having greater glucocorticoid activity than hydrocortisone or cortisone. In addition these compounds have diuretic activity and have saltlosing properties which make them especially well suited in the management of chronic congestive heart failure and in the treatment of cirrhosis of the liver, the nephrotic and adrenogenital syndromes and the treatment of eclampsia and preeclampsia.
The claimed invention, however, is narrower than the above broad description, the two claims reading:
3. 1 - dehydro - 6α methyl - 16α - hydroxyhydrocortisone.
5. 1 - dehydro - 6a - methyl - 9α - fluoro - 16α - hydroxyhydrocortisone.
Thus, claim 5 defines the compound of the formula
NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE
and claim 3 defines the compound of the same formula except that the 9α-fluoro atom is replaced by hydrogen.
Bernstein (IV) 2,789,118 Apr. 16, 1957
Bernstein (V) J. Am. Chem. Soc. Nov. 5, 1956
Spero (I) J. Am. Chem. Soc. Dec. 5, 1956
Spero (II) J. Am. Chem. Soc. Mar. 20, 1957
There are four separate rejections: The rejection of claim 3 "as unpatentable over Spero (I) in combination with Bernstein (IV)"; the rejection of claim 5 "as unpatentable over Spero (II) in combination with Bernstein (V)"; and the rejection of claim 5 "as unpatentable over each of the two Bernstein references * * *. "
Spero (I) reports the results of studies on the 6-methylation of various steroids. The reference discloses 1-dehydro-6α-methyl-hydrocortisone which was found to be "sixteen times as active as hydrocortisone" in the "glycogen deposition (glucocorticoid) assay" without showing "salt retaining (mineralocorticoid) activity." This compound differs from the compound of claim 3 in lacking the 16α-hydroxy substituent. The reference says:
* * * demonstration of the absence of mineralocorticoid activity in the presence of high glucocorticoid activity for 6-methylhydrocortisone, the synthesis of which is presently described, was unpredictable and is of considerable interest. Extension of the study to the 1-dehydro series has resulted in the most pronounced selective enhancement of cortical activities reported to date. [Footnotes omitted. ]
Spero (II) refers to Spero (I) as having "reported * * * the preparation of a number of 6-methylated analogs of adrenal hormones which show unusual potentiation of glucocorticoid activity with no sodium-retaining properties" and says that "The group of 9α-fluoro- and 21-fluoro-6-methyl steroids reported herein represents a continuation of this work." 1-Dehydro-6α-methyl-9α-fluoro-hydrocortisone is disclosed and is included among those compounds showing "considerably greater glucocorticoid and anti-inflammatory activity * * * than does hydrocortisone in animal assays." This compound differs from the compound of claim 5 in lacking the 16α-hydroxy substituent.
Jurisdiction: U.S. Supreme Court
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