Court Opinion

ID: 9450620
Source: CourtListenerOpinion
Date Created: 2023-08-04 16:53:19.820998+00
Date Added: 2024-06-11T17:32:23.681510
License: Public Domain

MARTIN, Judge.
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
“1. A 4-pregnene-l lp, 17a,21-triol-3,20-dione 21-hemisuccinate having the following structural formula:

The compound is produced by reacting succinic anhydride with hydrocortisone in a pyridine medium at room temperature for 22 hours. The succinic anhydride “selectively” esterifies the hydroxyl on the #21 carbon.
Since only one carboxyl group of the two available in succinic anhydride reacts, the product derivative is called a half- or hemisuccinate, or a 21 hemisue-cinate, which name also indicates the *1001position of the ester group in the molecule. We «hall refer to the claimed compound simply as hydrocortisone hemi-succinate. Also, it should be noted that in referring to hydrocortisone hemisuc-cinate, 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.2
The sole disclosure of the utility and properties of this compound is stated by appellant as: “When * * * [hydro-cortisone hemisuccinate] is administered parenterally, it is characterized by an 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:
Minion 2,656,366 Issued Get. 20, 1953
Filed July 27, 1950, and
Murray et al. 2,861,088 Issued Nov. ¡8, 1958
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 copend-ing. Appellant contends that 35 U.S.C. § 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, 333 F.2d 920, 51 CCPA 1541.
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 Pana-grossi, 277 F.2d 181, 47 CCPA 904, 906, and In re Wohnsiedler, 315 F.2d 934, 50 CCPA 1153. 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, 312 F.2d 834, 50 CCPA 928, In re Zenitz, 333 F.2d 924, 52 CCPA 746, or our earlier decision in In re Gregg, 244 F.2d 316, 44 CCPA 904, or go contrary to the Court of Appeals of the District of Columbia circuit, Hazeltine Research, Inc. v. Ladd, 340 F.2d 786, cert. granted 380 U.S. 960, 85 S.Ct. 1108.3 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 proc*1002ess as appellant uses with hydrocortisone. Cortisone differs from hydrocortisone in having a keto group [0=C<] rather than a hydroxyl group [HO<X] 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, sueh 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 intramuscularly.”
Murray discloses, as the examiner correctly stated, “various esters of hydro-cortisone 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 al., 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 - 11a,17a - dihydroxy - 4 - pregnene - 3,20-dione and 11a,21 - dibenzoxy - 17a - hy-droxy - 4-pregnene - 3,20 - dione
“Following the procedure of Example 6, using the equivalent proportion of benzoyl chloride in place of trimethylacetyl chloride produced 21-benzoxy-lla,17a-dihydroxy - 4 - pregnene - 3,20 - dione and 11a,21 - dibenzoxy-17a-hydroxy-4-pregnene - 3.20- dione.
“Other mono-esters and di-esters of 11 a, 17 a 21-trihydroxy-4-pregnene-3.20- dione and mono-esters of 11[3, 17a-21-trihydroxy-4-pregnene-3,20 - dione are prepared according to various acylation procedures such as illustrated in the examples, or by reaction with ketene, ke-tenes of selected acids, selected acids, acid anhydrides, or acid chlorides, in an organic solvent such as pyridine or the like. Representative 21-acyloxy-lla,17a-dihydroxy~3-pregnene-3,20 - diones, 11a,21 - dia-cyloxy - 17a - hydroxy - 4-pregene - 3,20 - diones, and 21 - acyloxy - lift, 17a-dihydroxy - 4 - pregnene - 3,20 - diones thus-prepared include one to eight carbon atom carboxylic acid acyloxy esters of saturated or unsaturated aliphatic, carbocyclic, cyclo-aliphatic, aryl, arylalkyl, alkaryl, mono, di or polycarboxylic acids which form ester groups such as, for example, formyloxy, acetoxy, pro-pionyloxy, dimethylacetoxy, trimeth-ylacetoxy, butyryloxy, valeryloxy, hexanoyloxy, heptanoyloxy, octanoyl-oxy, benzoxy, phenylacetoxy, toluoyl-oxy, napthoyloxy, cyclopentylfbrmy-loxy, fi-cyclopentylpropionyloxy, ae-rylyloxy, 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 *1003like, 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 lip compounds are disclosed therein; the structural formula shown in column 1 of the patent is consistent, showing the 11-hydroxyl in the P 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 es-terification at the 11 or 17 position as well as the 21 position in Murray is not tenable. Example" 8 discloses that “21-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 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 they 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 disclosed. 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,4 the properties of hydrocortisone and esters thereof are known, and one skilled in the art would recognize that the 21-hemisuc-cinate would possess the activity of hy-drocortisone, (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 5 which show the similar medical use of both hydrocortisone and cortisone.
For the above reasons we affirm the board.
Affirmed.

. 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. 706:
“ * * * 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 -position * * * 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, 61 S.Ct. 948, 85 L.Ed. 1319, 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, (2d Cir. 1945); Old Town Ribbon Co. v. Columbia Ribbon Mfg. Co., 159 F.2d 379 (2d Cir. 1947). But see, Robinson Aviation, Inc. v. The Barry Corp., 106 F.Supp. 514 (D.Mass.1952). It is only dictum in In re Gray, 136 F.2d 742, 30 CCPA 1175, 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, 1958 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-fc8misuecinate of hydrocorti-soné.” The board reversed, finding the affidavit sufficient, relying on In re Wilkinson, 304 F.2d 673, 50 COPA 701, which had not been available to the examiner.

. The solicitor requested we take judicial notice of The Merck Index, 6th Ed., 1952 under the listing of “Cortisone” and “17-Hydroxycorticosterone,” and Physicians Desk Reference, 1954 Edition, copyrighted 1953, Medical Economics, Inc., Rutherford, N. J., pp. 483-485, particularly 485, under “Hydroeortone acetate.”