Removal of inorganic salts is critical to obtaining carboxymethyl dextran having the desired thickening and gelling property at acid pH.

We also observe that, after describing carboxymethyl starch ethers "which exhibit phenomenal viscosities in aqueous solutions," Moe I states:

It is believed that the removal of water soluble electrolytes and the presence of some free carboxyl groups are responsible for the phenomenal viscosities observed. [Emphasis ours.]

It is clear from appellants' specification that the "water soluble electrolytes" removed by Moe I are the same as the "inorganic salts" removed by appellants. From this teaching of Moe I, it is therefore not "surprising and remarkable" that appellants' ethers have the same effect on the viscosity of water that the ethers of Moe I have. Although it is true, as appellants appear to urge, that their products are not described in any of the reference patents within the meaning of 35 U.S.C. 102, and although one would not know that the carboxymethyl ethers of dextran would be useful as thickening or gelling agents until he actually had such an ether at hand and added it to an aqueous medium, we think appellants' products would be obvious to one with ordinary skill in this art, aware as that person must be presumed to be and as Gaver et al. were of the equivalence of many polysaccharides including dextran in "etherfication" reactions, and aware as he would be of the teachings of Moe I and II and Filbert as to the properties and utility of several other polysaccharide carboxymethyl ethers. In other words, appellants' discovery that certain carboxymethyl dextran ethers give desirable viscosity characteristics to aqueous media does not, in our opinion, impart patentability to those ethers.

We turn next to process claim 12. We agree with the Examiner and the Board that this claim is unpatentable over the prior art, particularly the Moe I patent. The process recited in claim 12 is but an obvious way of making an obvious product. Although, of course, Moe I used starch rather than dextran in his process, as we have discussed in detail supra, these starting materials are known to be equivalent in "etherfication" processes. With regard to the other process details in claim 12, we note that in Example 1 of Moe I, a mixture of starch, water and sodium hydroxide is combined with an aqueous solution of sodium chloracetate and the resultant mixture heated at 80-85° C. for 90 minutes. After acidification "to phenolphthalein," Moe I precipitates his product with methanol. Moe I also teaches the advantage of dissolving his carboxymethyl starch ethers in water and precipitating thereafter with methanol. Thus it can be seen that, except for the step in claim 12 of adjusting the pH of the reaction mixture to 2.0 to 3.0, each of the claim 12 limita

tions is taught by Moe I. With regard to the pH limitations, we observe that Moe I prefers to adjust the pH of his reaction mixture within the range of 4-7.8 Moe I discovered that "the presence of some free carboxyl groups" is partly "responsible for the phenomenal viscosity observed" for his carboxymethyl starch ethers. However, Moe I also states:

Sufficient of the carboxyl groups must, however, be present in the form of a water soluble derivative such as the alkali metal salts, in order to contribute water solubility to the product.

Thus, Moe I seems to have chosen the particular pH range 4–7 because that range represents a compromise between the desirability of some free carboxyl groups and the need for the presence of some carboxyl groups in the alkali metal salt form. In view of the watersolubility of appellants' carboxymethyl dextran ethers and the clear teachings of Moe I as to the reasons for a particular choice of a pH range for precipitation, we think appellants' pH range of 2.0 to 3.0 was merely a matter of obvious choice which one of ordinary skill in this art could be expected to make. We think that such a skilled chemist would be expected to respond to the suggestion of Moe I as to the importance of free carboxyl groups in a carboxymethyl polysaccharide ether and try using pH values lower (more acid and therefore productive of more free carboxyl groups) than those used by Moe I, especially since appellants' ether is soluble in water. The discovery that a pH precipitation range of 2.0 to 3.0 is superior to a range of 4 to 7 in the production of carboxymethyl dextran ethers therefore does not impart patentability to claim 12.

[2] For the foregoing reasons, the decision of the Board is affirmed. AFFIRMED.

KIRKPATRICK, J., sat but did not participate in decision.

U.S. Court of Customs and Patent Appeals

IN RE LEO J. NOVAK AND WALTER S. HOGUE

No. 6799. Decided July 25, 1962

[49 CCPA 1283; 784 O.G. 1113; 306 F.2d 924; 134 USPQ 335]

1. PATENTABILITY-THERAPEUTIC COMPOSITION-LACK OF PROOF OF UTILITY.

"We agree with the Board that the Eyaminer's rejection for lack of proof of utility should be sustained. We observe that no evidence whatever has been presented to demonstrate that the claimed compounds have the alleged properties or will function as alleged in the specification. *** if the claimed products do not have the properties alleged for them or do not function as

According to Rose and Rose, "The Condensed Chemical Dictionary," 5th Ed. (1956), pH is defined as:

A means of expressing the degree of acidity or basicity of a solution. Thus at normal temperature a neutral solution such as pure distilled water has a pH of about 7, a tenthnormal solution of hydrochloric acid (***) has a pH near 1 and a normal solution of a strong alkali such as sodium hydroxide has a pH of nearly 14. **

alleged, then those products will not be useful for the stated purposes, i.e. as drugs, medicaments, and the like in human therapy."

2. SAME-SAME-SAME.

"In our opinion, when an applicant bases utility for a claimed invention on allegations of the sort made by appellants here, unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the Examiner to ask for evidence which substantiates them. Here we find no indication that one skilled in this art would accept without question statements that carboxymethyl dextran has the alleged effects on the functioning of any base, physiologically active or not, and no evidence has been presented to demonstrate that the claimed products do have those effects." APPEAL from the Patent Office. Serial No. 359,426.

AFFIRMED.

Toulmin & Toulmin, Harry A. Toulmin, Jr., and Folsom E. Drummond for appellants.

Clarence W. Moore (Jack E. Armore of counsel) for the Commissioner of Patents.

Before WORLEY, Chief Judge, and RICH, MARTIN and SMITH, A880ciate Judges, and Judge WILLIAM H. KIRKPATRICK, United States Senior District Judge for the Eastern District of Pennsylvania MARTIN, J., delivered the opinion of the court.

This is an appeal from a decision of the Board of Appeals of the United States Patent Office affirming the Examiner's rejection of claims 1, 2, 6, 23, 25, 32, 33 and 35 of appellants' application for a patent on "Carboxymethyl Dextranates of Organic Bases and Method for Making Them." Certain other claims were "withdrawn from further consideration under Rule 142 (b), as not being readable on the elected species" and are not before us. No claims have been allowed. The following claims are illustrative:

1. A carboxymethyl dextranate of an organic base resulting from neutralization of the base by the acid carboxymethyl dextran, in aqueous solution.

2. A carboxymethyl dextranate of a physiologically active organic base resulting from neutralization of the base by the acid carboxymethyl dextran, in aqueous solution.

32. The method of making carboxymethyl dextranates or organic bases which comprises adding an aqueous solution of a carboxymethyl dextran containing some free carboxyl groups to the base at a controlled rate to neutralize the same, and separating the resulting salt from the solution.

Claim 23 differs from claim 2 in reciting the prefatory phrase "A parenteral injection fluid comprising." Claims 6 and 25 are product claims like claims 2 and 23 respectively, but are limited to the use of the particular organic base, meperidine. Method claim 33 is like claim 32 but is limited to the use of a "physiologically active watersoluble organic base" and to a particular type of carboxymethyl dextran. Claim 35 limits the method of claim 33 to meperidine.

As the claims point out, the application relates to products resulting from the interaction of carboxymethyl dextran and organic bases.

Carboxymethyl dextran is a polycarboxylic acid the nature of which is discussed in In re Novak and Tyree, 49 CCPA 1267, 306 F.2d 917, 134 USPQ 314, No. 6789, decided concurrently herewith. According to appellants' specification, any organic base may be used in the practice of their invention but physiologically active bases are preferred. Appellants state:

Included among the organic bases, which are, generally speaking, nitrogenous substances and include certain of the antibiotics and, also, many alkaloids most of which have nitrogen in a cyclic structure, there are a large group of substances which exhibit physiological activity and have found wide use in medicine because of their stimulating, sedative, narcotic or analgesic action. Streptomycin is suggested as a suitable antibiotic. Curare, morphine, belladonna, ergot, cocaine, emetine and physostigmine are suggested as suitable alkaloids. Procaine, meperidine and ephedrine are among suitable synthetic drugs. All of these are bases and all will react by a neutralization process with carboxymethyl dextran to form salts within the scope of the product claims.

In further regard to the choice of a base, the specification states: *** It will be apparent, also, that the physiologically active base may be one which is tolerated by and used in the medication of both humans and the lower animals, or it may be one which is used predominantly or exclusively in veterinary practice, such as, for example, nicotine. The base may also be one which is used as an insecticide or the like. * *

Appellants predicate patentability for their claimed products and the process of making them partially on the advantages the products possess as drugs, medicaments and the like as compared with the corresponding free organic bases or their known "inorganic acid salts." In that regard, the specification states, inter alia:

The carboxymethyl dextran containing an average of from less than 1.0 to 3.0 carboxymethyl groups per anhydroglucopyranosidic unit of the dextran, associated with the physiologically active organic base in salt combination, exerts an osmotic effect, exhibits a protective colloidal action, and functions as a largemolecule "diluent" for the base which diluent is digested slowly in the body. By reason of this slow digestion of the carboxymethyl dextran and the osmotic effect which it exerts, it serves to control the rate at which the base is released to the system, thus prolonging the effectiveness of the base for any given dosage thereof administered. Less frequent injections are required to maintain the desired blood level of the base and since the rate of release of the base in the system is retarded, and the full effect thereof is not experienced immediately or abruptly, the amount of those drugs which may be safely administered in a given dosage is somewhat less critical than is normally the case. * * * In addition, the carboxymethyl dextran salts of the bases are less "harsh” than hydrochlorides, sulfates, etc. and are, therefore, more acceptable physiologically.

The carboxymethyl dextran salts have the important advantage that by selection of the dextran and the extent of carboxymethylation thereof up to the permissible limit of an average of about 3.0 carboxymethyl groups per anhydroglucopyranosidic unit of the dextran, it is possible to control the molecular weight and viscosity, osmotic and solubility characteristics of the ether. This, in turn, permits accurate control of the properties of the salt, including the

amount of physiologically active organic base chemically combined with the carboxymethyl dextran so that it is possible to control, accurately, pharmacological properties of the salt particularly with regard to dosage form, physiological response, prolongation of the responses at a predetermined level of intensity, rate of absorption of the base, toxicity of the base, stability of the base, etc.

All of the appealed claims were rejected by the Examiner on two grounds, unpatentability over certain prior art and "lack of utility." Claims 1, 2, 23, 32 and 33 were also rejected as being "too broad." The Board affirmed the Examiner on each ground. Since we are able to dispose of this case on the basis of the "utility" rejection,' it will be unnecessary to discuss either of the other grounds.

In his first action on the merits of the appealed application, the Examiner stated:

All the claims are rejected for lack of utility. The composition is set forth as therapeutic. In the absence of clear, convincing, scientific evidence that the composition is safe and effective for the purposes set forth, no claim is allowable. Rudd v. Kingsland, 88 USPQ 418.

In a later action, the Examiner stated in part as to the same rejection:

Claims 1, 2, 6, 23, 25, 32, 33 and 35 are rejected as lacking utility. Since the dextranates are different entities from their component parts, the amine and carboxymethyl dextran, applicants cannot impute the utility of the component parts to the reaction product.

In partial response, appellants thereafter stated:

Appellants are concerned with salts of physiologically active organic bases and acidic carboxymethyl cellulose [dextran ?] both of which are known to be safe and useful. The physiological effectiveness of the organic bases disclosed by appellants requires no proof. The carboxymethyl dextran does not effect [sic] the action of the base except in the physical sense, i.e., by retarding and controlling its release. Carboxymethyl dextran has been safely injected intravenously for the purpose of mobilizing radioactive cation from storage places in the bones, as shown by Dr. K. W. Walton, Manufacturing Chemist, August 1953 (pp. 330–333).

In his answer, the Examiner stated in part:

The claims stand rejected for the lack of utility since applicants have failed to prove each and every allegation of utility.

Although some degraded dextrans are used in therapy with relatively few adverse effects and many of applicants' bases can be used safely (although page 3 of the specification emphasizes the toxicity of these bases), the applicants cannot rely upon the safety and efficacy of these ingredients, many of which, in reality, are admittedly extremely toxic, to prove the harmlessness and efficacy of their dextranates because the carboxymethyl dextranates are entirely differ

1 The following statement made by this court in In re Lorenz and Wegler, 49 CCPA 1227, 305 F. 2d 875, 134 USPQ 312, No. 6787, is pertinent here: "The Examiner and the Board made no distinction between the product claims and the process claims as to the ground of rejection. While appellants filed reasons of appeal which would justify our separate consideration of both groups of claims, we construe appellants' brief to be an abandonment of any issue as to the legality of such a rejection of the process claims. Our decision is thus necessarily limited to a consideration of the rejection solely on the validity of the rejection of the product claims. In re Le Baron, 42 CCPA 956, 223 F.2d 471; 106 USPQ 176 and cases cited therein; and L. & C. Hardtmuth, Inc. v. Fabrique Suisse de Crayons Caran d'Ache S.A., 48 CCPA 873, 287 F.2d 599, 129 USPQ 103."