Case Name: In re Erwin F. Schoenewaldt
Court: United States Court of Customs and Patent Appeals
Jurisdiction: United States
Decision Date: 1965-04-22
Citations: 52 C.C.P.A. 1258
Docket Number: No. 7345
Parties: In re Erwin F. Schoenewaldt
Judges: Before Rich, Acting Chief Judge and Martin, Smith, and Almond, Jr., Associate Judges, and Judge William H. Kirkpatrick.
Reporter: Court of Customs and Patent Appeals Reports
Volume: 52
Pages: 1258–1265

Head Matter:
343 F. 2d 1000; 145 USPQ 289
In re Erwin F. Schoenewaldt
(No. 7345)
United States Court of Customs and Patent Appeals,
April 22, 1965
Frank M. Nolan (Albert W. Rinehart, I. Louis Wolk, of counsel) for appellant.
Clarence W. Moore (Raymond E. Martin, of counsel) for the Commissioner of Patents.
[Oral argument February 5, 1965, by Mr. Nolan and Mr. Martin]
Before Rich, Acting Chief Judge and Martin, Smith, and Almond, Jr., Associate Judges, and Judge William H. Kirkpatrick.
United States Senior District Judge for the Eastern District of Pennsylvania, designated to participate in place of Chief Judge Worley, pursuant to provisions of Section 294(d), Title 28, United States Code.

Opinion:
MartiN, Judge,
delivered the opinion of the court:
This appeal is from the board's affirmance of the rejection of the single claim in an application, serial No. 541,299, titled "Chemical Compound and Process of Preparing the Same," filed by appellant on October 18,1955.
The invention is an ester derivative of hydrocortisone. The claim reads:
1. A^-pregnene-ll/S, 17a, 21-trioI-3, 20-dione 21-hemisuccinate having the following structural formula:
The compundcortisone in a pyridine medium at room temperature for 22 hours. The succinic anhydride "selectively" esterilles the hydroxyl on the #21 carbon.
Since only one carboxyl group of the two available in succinic anhy-dride reacts, the product derivative is called a half- or hemisuccinate, or a 21 hemisuccinate, which name also indicates the position of the ester group in the molecule. We shall refer to the claimed compound simply as hydrocortisone hemisuccinate. Also, it should be noted that in referring to hydrocortisone hemisuccinate, we mean the derivative in which the hydroxyl on the #11 ring carbon is in what is known as the ¡3 steric configuration. We shall also have occasion to refer to that 11-hydroxyl in the a configuration.
The sole disclosure of the utility and properties of this compound is stated by appellant as: "When [hydrocortisone hemisuc-cinate] is administered parenterally, it is characterized by and extremely rapid onset of hydrocortisone action making it a drug of choice in cases of medical emergency."
Both appellant and the solicitor present preliminary questions concerning the two references in the record. They are:
Million, 2,050,366, Issued Oct. 20, 1953. Filed July 27, 1950 and
Murray et al., 2,861,088, Issued Nov. IS, 195S. Filed April 10, 1952.
Comparing the dates of these references with appellant's filing date of October 18, 1955 it is clear that the Murray et al. patent (hereinafter Murray) was copending. Appellant contends that 35 TJSC 102(e), under which the effective date of a domestic patent is its filing date, applies only to references which are fully anticipatory in nature, and not to references used in a section 103 rejection, contrary to this court's holding in In re Harry, 51 CCPA 1541, 333 F. 2d 920, 142 USPQ 164, 167.
In response, the solicitor contends that since appellant did not raise that issue before either the examiner or Board of Appeals, it is not properly before this court, especially in view of In re Panagrossi, 47 CCPA 904, 906, 277 F. 2d 181, 125 USPQ 410, and In re Wohnsiedler, 50 CCPA 1153, 315 F. 2d 934, 137 USPQ 336. Appellant's reply brief in rebuttal argues that since this is solely a question of law, rather than a question of technical facts, the issue may be raised here for the first time.
We do not think the solicitor is correct in his contention. The section 102(e) question may be properly raised here for the first time because we must determine whether the reference is available. The particular question, whether we may consider the Murray reference, must be settled prior to determining the legal effect of the disclosure of that reference.
We find no compelling reason to overrule our recent decisions in In re Harry, supra, or In re Kander, 50 CCPA 928, 312 F. 2d 834, 136 USPQ 477, In re Zenitz, 52 CCPA 746, 333 F. 2d 924, 142 USPQ 159, or our earlier decision in In re Gregg, 44 CCPA 904, 244 F. 2d 316, 113 USPQ 526, or go contrary to the Court of Appeals of the District of Columbia circuit, Hazeltine Research, Inc. v. Ladd, 340 F. 2d 786, 143 USPQ 337, cert. granted 380 U.S. 960. Thus Murray being available as prior art for a section 103 rejection, we look next to see whether that section is satisfied.
Minion describes production of cortisone hemisuccinate by the same process as appellant uses with hydrocortisone. Cortisone differs from hydrocortisone in having a keto group [0=CC] rather than a hy-droxyl group [HOC;:] at the 11 position. The hemisuccinate of cortisone is found by Minion to be four times as soluble in water as the esters of the prior art, such as cortisone acetate. Alkali metal salts of Minion's acetate esters are between 50 to 1500 times as soluble. The facility of injection of an aqueous solution of a drug which is water-soluble is contrasted by Minion to the "evident disadvantages" of the prior art drugs. The solubility property of the ester derivatives makes them "useful in the cortisone therapy of arthritis and related diseases, particularly where the drug had to be injected intramus-cularly."
Murray discloses, as the examiner correctly stated, "various esters of hydrocortisone and epihydrocortisone (the 11 a-hydroxy isomer)." The examiner specifically pointed to Example 8 of Murray as disclosing "the half ester of succinic acid (hemisuccinate) as an exemplary 21-ester of hydrocortisone." Despite this statement of the examiner, and a rejection of the claim as "unpatentable over Murray et ah, alone, or in view of Minion," the board considered that the examiner meant the rejection to be based only on the combination of references. Since we consider the latter rejection to be sound, we need not discuss whether there is before us a rejection on Murray alone.
Appellant's contentions are that Murray's Example 8 is a "shotgun" disclosure, since thousands of compounds are suggested therein; that Example 8 is drawn to the inactive 11a epimer; that it is unclear whether a half or di-ester is formed, or whether the ester is formed solely at the 21 position; and that "no utility" for the esters is disclosed in Murray except "as intermediates for cortisone esters."
All but the last contention can be disposed of by considering what Murray discloses in Example 8:
Example 8
21-benzoxy-lla,17a-dihydroxy-4-pregnone-3,20-dione and llct,21-dibenzoxy-17a-hydroxy-4-pregnene-3,20-dione
Following the procedure of Example G, using tbe equivalent proportion of benzoyl chloride in place of trimethylaeetyl chloride produced 21-benzoxy-lla, 17a-dihydroxy-4-pregnene 3,20-dione and lla,21-dibenzoxy-17a-hydroxy-4-preg-nene-3,20-dione.
Other mono-esters and di-esters of 11a, 17a 21-trihydroxy-4-pregnene-3,20-dione and mono-esters of lip, 17a-21-trihydroxy-4-pregnene-8,20-dione are prepared, according to various acylation procedures such as illustrated in the examples, or by reaction with ketene, ketenes of selected acids, selected acids, acid anhydrides, or acid chlorides, in an organic solvent such as pyridine or the Wee. Representative 21-acyloxy-lla!,17<x-dihydroxy-3-pregnene-3,20-diones, lla,21-diacyloxy-17a-hydroxy-4-pregnene-3,20-diones, and 21-ac.yioiZ!!/-74j3,17a-dihydroxy-4-pregnene-3, 20-dimes thus-prepared include one to eight carbon atom carboxylic acid aoyloxy esters of saturated or unsaturated aliphatic, carbocyclic, cycloaliphatic, aryl, arylalkyl, alkaryl, mono, di or polycarboxylic acids which form ester groups such as, for example, formyloxy, acetoxy, jwopionyloxy, dimethylacetoxy, trimethylacetoxy, butyryloxy, valeryloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, benzoxy, phenylacetoxy, toluoyloxy, napthoyloxy, cyelopentylformyloxy, /3-cyelo-pentylpropionyloxy, aerylyloxy, cyclohexylformyloxy, the half and di-esters of malonic, maleic, succinic, glutaric and adipic acids, and the like. The acids may also contain non-interfering substituents, such as mono or poly halo, chloro, bromo, hydroxy, methoxy, and the like, if desired. [Emphasis supplied.]
We have underlined the portion of the Murray disclosure relied on by the examiner. It includes relatively few compounds. Contrary to appellant's contention, both the 11a and 11/3 compounds are disclosed therein; the structural formula shown in column 1 of the patent is consistent, showing the 11-hydroxyl in the /3 configuration. Further, there is nothing of record to show the 11a epimer, even were Murray drawn only to that species, to be inactive.
The contention that there may be esterification at the 11 or 17 position as well as the 21 position in Murray is not tenable. Example 8 discloses that "^I-acyloxy diones thus prepared include half esters of succinic acids." [Emphasis supplied.] Further, the procedure used in Example 8 is stated to "Follow the procedure of Example 6," which is disclosed to be the reaction of the components in a pyridine medium at room temperature for 24 hours. Under "Other mono-esters," Example 8 clearly teaches acid anhydrides to be reacted in a pyridine medium. Since the same conditions are said by the appellant to lead to "selective" esterification at the 21 position, such a contention of possible reactions at other positions is not well taken.
Apparently the board felt that the Murray disclosure of compounds "thus prepared" really meant not that the were prepared but could be prepared if so desired. While the board apparently did not consider whether the Murray form of listing the compounds was an enabling disclosure of the claimed compounds, any doubt that one of ordinary skill in the art would consider it probable that the hemisuccinate would be more water-soluble is removed by the Minion disclosure of the increased water solubility arising from the similar esterification of cortisone. In looking to see if the water solubility property could be expected, we give the claimed compound the benefit of an arguendo assumption since its solubility property was not originally diclosed. We do not consider that the lack of disclosure in Murray of an anti-inflammatory activity is persuasive of unobviousness since (1) as appellant argued below in another connection, the properties of hydrocortisone and esters thereof are known, and one skilled in the art would recognize that the 21-hemisuccinate would possess the activity of hydrocortisone, (2) Minion teaches the 11-keto hemisuccinate analog has such activity, and (3) although unnecessary, the solicitor has requested we take judicial notice of two standard reference works which show the similar medical use of both hydrocortisone and cortisone.
For the above reasons we affirm the board.
Certain oxygens and hydrogens have been rearranged for clarity, and the numbers 11, 17 and 21 have been added to identify certain carbon atoms.
Karrer, in his text on Organic Chemistry, Elsevier Pub. Co., N.Y., 3d English Ed. (1947), states at p. TOG :
" It has become customary to give the prefix a to substituents which, in the projection formula of this hydrocarbon [a steroid], lie behind the plane, and /3 to those in front of the plane. "
This is in agreement with appellant who stated in oral argument "in that 11 positions the hydroxyl is in the a position as chemists say, is behind the carbon atom of the molecule."
See Detrola Radio and Television Corp. v. Hazeltine Corp., 313 U.S. 259, 265, 49 USPQ 337, 339, and also Judge Hand's views consistent with that case in The Western States Machine Co. v. S.S. Hepworth Co., 147 F. 2d 345, 64 USPQ 141 (2d Cir. 1945) ; Old Town Ribbon Co. v. Columbia Ribbon Mfg. Co., 159 F. 2d 379, 72 USPQ 57 (2d Cir. 1947). But see, Robinson Aviation, Inc. v. The Barry Corp., 106 F. Supp. 514, 95 USPQ 78 (D. Mass. 1952). It is only dictum in In re Gray, 30 CCPA 1175, 136 F. 2d 742, 58 USPQ 317, 320, with regard to the Gray and Eiger patents, which appears inconsistent with In re Harry, supra.
Appellant filed a Rule 131 affidavit showing completion of the invention in the United States prior to May 28, 1954 in an effort to remove a patent to Pinson et al., 2,786,835, issued March 26, 1957 the parent application to which was filed May 28, 1954, and a patent to Beal, 2,842,542, issued July 8, 195S on an application filed June 20, 1955. Example 1 of Pinson et al., and Example 17 of Beal showed the claimed compound. The examiner found the affidavit insufficient in that "said affidavit does not disclose a utility for the 21-hemisuccinate of hydrocortisone." The board reversed, finding the affidavit sufficient, relying on In re Wilkinson, 50 CCPA 701, 304 F. 2d 673, 134 USPQ 171, which had not been available to the examiner.
The solicitor requested we take judicial notice of The Merck Index, Cth Ed., 1952 under the listing of "Cortisone" and "17-Hydroxycorticosterone," and Physicians Best Reference, 1954 Edition, copyrighted 1953, Medical Economics, Inc., Rutherford, N.J., pp. 483-485, particularly 485, under "Hydrocortone acetate."