Application of Pantzer

• Decision Date: 05 May 1965
• Docket Number: Patent Appeal No. 7176.
• Citation: 52 CCPA 1135,341 F.2d 121
• Parties: Application of Myron PANTZER and Milton Feier.
• Court: U.S. Court of Customs and Patent Appeals (CCPA)

52 CCPA 1135, 341 F.2d 121 (1965)

Application of Myron PANTZER and Milton Feier.

Patent Appeal No. 7176.

United States Court of Customs and Patent Appeals.

February 11, 1965.

Rehearing Denied May 5, 1965.

A. A. Orlinger, New York City, for appellants.

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

Before RICH, Acting Chief Judge, and MARTIN, SMITH, and ALMOND, Judges, and Judge WILLIAM H. KIRKPATRICK.^*

KIRKPATRICK, Judge.

The appellants have appealed the decision of the Patent Office Board of Appeals affirming the examiner's rejection of claims 9 and 11 to 17 in their application Serial No. 579,137, filed April 19, 1956, entitled "Therapeutic Solutions," as unpatentable over the prior art. No claim is allowed.

Claim 9 is illustrative and reads as follows:

"9. A solution of methetharimide in excess of one-half of one percent and up to its maximum solubility in a member of the class consisting of propylene glycol, a liquid polyethylene glycol, a solution of any of these glycols with one another, and a solution of at least one of these individual glycols with an amount of water up to about ten percent of the total solution; said solution being physiologically innocuous on internal administration as well as by injection, and the methetharimide dissolved therein being stable against hydrolysis, said solution being in therapy a barbiturate antagonist."

Claims 11 and 12 call for a solution of methetharimide in propylene glycol in various concentrations. Claims 13 to 15 call for a solution of methetharimide in various liquid polyethylene glycols. Claim 16 is limited to a solution of methetharimide in propylene glycol and liquid polyethylene glycol. Claim 17 calls for a solution of methetharimide in propylene glycol and water, the amount of water present being up to ten per cent of the weight of solution.

According to the specification, methetharimide has been used as a barbiturate antagonist¹ and is administered in about the same quantity as the barbiturate to be overcome. For this use, methetharimide has been prepared as a saturated solution in water or physiological saline but its solubility therein is limited to 0.5%. Administration of methetharimide by intramuscular or intravenous injection thus required an excessive amount of liquid. Moreover, it was found that the aqueous solution lost effectiveness due to hydrolysis of the methetharimide. Appellants state that they have found that methetharimide is more soluble in the glycols than in water and that the glycols protect the antagonist against hydrolysis.

The references relied on by the examiner and the board are:

I. G. Farben (Br.) 384,176 Dec. 1, 1932.

Jour. Am. Phar. Assoc. (1) July 1939, Vol. 28, No. 7, pgs. 416-421 (i. e. Dumez article).

Jour. Am. Phar. Assoc. (2) May 1955, Vol. 44, No. 5, pgs. 296-301 (i. e. Bodin & Taub article).

Jour. Am. Phar. Assoc. (3) Jan. 1952, Vol. XLI, No. 1, pgs. 27-29 (i. e. Carpenter et al. article).

The Lancet, Jan. 22, 1955, Vol. 268, page 181.

Koppanyi, "Antioxidant and Stabilizing Action of Propylene Glycol," Federation Proceedings, Vol. 9, Mar. 1950, pgs. 291 and 292.

U. S. Dispensatory, 24th Ed., J. B. Lippincott Co., Philadelphia, 1947, page 940.

The Lancet article shows methetharimide as a barbiturate antagonist administered intravenously. Although the article does not indicate what solvent was utilized, appellants and the board have proceeded on the assumption that the solvent was a physiological saline solution.² We shall do likewise.

Bodin et al. disclose polyethylene glycol as a solvent for barbiturate salts. The instability of the salts, due to hydrolysis in aqueous solutions, is alleviated by the use of that glycol as a stabilizing solvent.

Koppanyi, Dumez, U. S. Dispensatory, and the British patent disclose propylene glycol as a solvent for various medical preparations, vitamins and drugs, including barbiturates and barbiturate salts. Dumez and the British patent place the barbiturate or barbiturate salt, respectively, in anhydrous propylene glycol to form solutions which have sufficient stability to permit of sterilization and which protect the barbiturate material against hydrolysis previously encountered with aqueous solutions.

The examiner and the board regarded Carpenter et al. as cumulative and discussion of that reference here, beyond what appears below, is unnecessary.

The examiner rejected claims 9 and 13-16 as unpatentable over Lancet in view of Bodin et al., and claims 9, 11, 12, 16 and 17 as unpatentable over Lancet in view of any one of Dumez, Koppanyi, U. S. Dispensatory, or the British specification. The examiner's position is that, since the secondary references teach the use of polyethylene glycol or propylene glycol as a solvent for medicinals in general and barbiturates or barbiturate salts in particular to alleviate problems encountered with hydrolysis of the barbiturate materials in aqueous solution, it would "not involve invention" to use the glycols as a solvent for the methetharimide of Lancet. The examiner states that, since "it is well known in the pharmaceutical art that methetharimide is structurally very similar to the barbiturates which are shown to be stabilized by the glycols in the art of record * * * it would be obvious to one skilled in the art to try the glycols (in the place of water) as solvents for the methetharimide * * *."

The board affirmed, seeing nothing unreasonable in the examiner's conclusion that methetharimide would be expected to be soluble in glycols in view of art showing solubility of barbiturates in glycols. The board added, "Chemists are well aware that chemical structure has a bearing on solubility and that compounds of similar structure are, in general, soluble in the same solvents."³

Appellants contend that the examiner's position that "* * * it would be obvious to one skilled in the art to try the glycols (in the place of water) as solvents for the methetharimide * * *" is contrary to 35 U.S.C. § 103 as well as our decision in In re Huellmantel, 324 F.2d 998, 51 CCPA 845, wherein we said:

"We feel compelled to comment on the Patent Office analysis by which patentability under 35 U.S.C. § 103 is herein determined. The examiner concedes that appellant\'s composition `shows improved results.\' The board accepts this as `fact,\' but concludes it is immaterial since `it is obvious to at least try\' (our emphasis) to substitute one steroid for another in the prior art composition.

"We believe this reasoning, insofar as it negates consideration of properties in determining obviousness under section 103, flys in the face of the plain language of the statute * * *. Section 103 says, inter alia, `The subject matter as a whole would have been obvious * * *." Nothing is said about `obvious to try.\' Consideration of the subject matter `as a whole\' in chemical cases requires comparison of properties, pharmaceutical or otherwise, as well as comparison of chemical structures.

"We do not mean to imply that every variance in property of a new compound or composition will tip the balance for patentability where otherwise closely related compounds or compositions are involved. However, all relevant property differences must be considered in the light of the facts of each case in the determination of statutory obviousness."

We agree with the appellants that the issue of obviousness in this case can be resolved only after considering the differences between the prior art and the claimed compositions in view of their pharmacological and chemical properties. To do so, we consider the cited references and what we believe they teach one of ordinary skill in the art.

Although the phrasing of the rejection by the examiner perhaps leaves something to be desired, our study of the record does not convince us that the examiner or the board failed to give proper consideration to the "subject matter as a whole" in determining obviousness under 35 U.S.C. § 103. In this regard, the appellants have set forth in their claims certain properties of the methetharimide solution which we...