Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE JULIAN HEICKLEN
Appeal No. 88-0953
December 13, 1989
Application for Patent filed November 20, 1985, Serial No. 800,020. Anti-Aging Agents.
William E. McNulty et al. for appellant
Primary Examiner -- Stanley J. Friedman
Before Winters, Steiner and Rollins
Arthur J. Steiner
This is an appeal from the final rejection of claims 1 through 19, which are all of the claims in the application.
The appealed claims are directed to a therapeutic composition comprising a unit dosage of a compound effective to retard the aging process in certain animals, to a method of treating the animals to retard the aging process, and to a comestible containing a unit dosage amount of the compound effective to increase the biological life span of the animals.
Claims 1 and 7 are illustrative and read as follows:
1. A therapeutic composition comprising, in admixture with a pharmaceutically acceptable carrier, a unit dosage amount effective to retard the aging process in animals selected from the group consisting of mice, dogs, cats, fowl, hogs and cattle of a compound of the formula:
its acid salts, a compound containing its corresponding nitroxide radical, R1R 2NO, or its corresponding nitrone, R1N(O) =CR3R4,
wherein R1, R2, R3 and R4 may be the same or different and are selected from hydrogen, lower alkyl, lower alkenes, lower alkyne, cycloalkyl, unsubstituted arylalkyl, alkyl substituted with a hydroxyl or a halide, alkoxy, cycloalkoxy, aryloxy, aryalkoxy, alkanoyl, carboxy, cycloalkanol, arylalkanoyl, carbalkoxy, amino or alkylamino.
7. A method of treatment for retarding the aging process which comprises administration to a recipient animal selected from the group consisting of mice, dogs, cats, fowl, hogs and cattle of a therapeutic composition comprising, in admixture with a pharmaceutically acceptable carrier, an effective amount for retarding the aging process in the animal of a compound of the formula:
its acid salts, a compound containing its corresponding nitroxide radical, R1R 2NO [sic, R1R2NO], or its corresponding nitrone R1N(O)=CR3R4
Wherein [sic, wherein] R1, R2, R3 and R4 may be the same or different and are selected from hydrogen, lower alkyl, lower alkenes, lower alkyne, cycloalkyl, arylalkyl, alkyl substituted with a hydroxyl or a halide, alkoxy, cycloalkoxy, aryloxy, arylalkoxy, alkanoyl, carboxy, cycloalkanoyl, arylalkanoyl, carbalkoxy, amino or alkylamino.
The reference relied upon by the examiner is: Chemical Abstracts, Vol. 101, 205791j, 1984.
Claims 1 through 6 stand rejected under 35 U.S.C. 103 based upon Chemical Abstracts 205791j. In addition, all of the appealed claims stand rejected under 35 U.S.C. 101 for lack of utility. We affirm both rejections.
The Rejection Under 35 U.S.C. 103.
*2 The rejection under 35 U.S.C. 103 is based upon the examiner's determination that the Abstract discloses unit dosages of diethylhydroxylamine in water for the treatment of cancer in mice, which unit dosages correspond to the unit dosages encompassed by the rejected claims. On page 2 of the Answer, the examiner makes it clear that his determination is based on page 13 of the specification.
The unit dosages revealed in the reference are 3, 30 and 300 milligrams per kilogram of body weight per day. On page 13 of the specification, appellant reports an experiment wherein dosages ranging from 30 to 300 milligrams per kilogram of body weight per day were administered to mice. [FN1] The reference also discloses the use of water which satisfies the requirement of the rejected claims for a pharmaceutically acceptable carrier. It would, therefore, appear that the reference describes the invention defined in claims 1 through 6 within the meaning of 35 U.S.C. 102. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Appellant's reliance upon In re Shetty, 566 F.2d 81, 195 USPQ 753 (CCPA 1977), is misplaced. In Shetty, the rejection of claims directed to a composition was sustained. See, also, In re May, supra, and In re Pearson, 494 F.2d 1399, 181 USPQ 641 (CCPA 1974).
Accordingly, the examiner's rejection under 35 U.S.C. 103 is affirmed.
The Rejection Under 35 U.S.C. 101.
Appellant's asserted utility is not merely the extension of the life of certain animals, but the retardation of the aging process. There appears to be no dispute that the asserted utility of retarding the aging process is so incredible as to require objective proof. In re Eltgroth, 419 F.2d 918, 164 USPQ 221 (CCPA 1970).
Appellant relies upon the data in the specification and the data in a declaration submitted pursuant to the provisions of 37 CFR 1.132 to establish utility. We have reviewed the data; however, we do not consider the evidence sufficient to overcome the presumption of inoperativeness generated by the incredible nature of the asserted utility.
The data reveal that, based upon the protocol employed, mice which received diethylhydroxylamine lived longer than mice that did not receive diethylhydroxylamine. Assuming, arguendo, the increased longevity was due directly or indirectly to the administration of diethylhydroxylamine, there is insufficient evidence upon which to conclude that the increased longevity resulted from a retardation of the aging process caused by diethylhydroxylamine.
Of particular relevance is appellant's disclosure on page 2 of the specification that an investigator, Harman, [FN2] performed experiments wherein free-radical reaction inhibitors were added to the daily diet of mice to confirm the hypothesis that the degradative changes of the basic aging process are due, in part, to free-radical reactions. In the paragraph bridging pages 2 and 3 of the specification, appellant refers to a technical paper (Comfort) [FN3] questioning
*3 the validity of Harman's conclusion. This paper (Comfort) concluded that mice did live longer periods, but that the data were insufficient to support the conclusion that the increased longevity was due to free radical inhibitors (i.e., 2-mercaptoethylamine or butylated hydroxytoulene).
Comfort reports the results of experiments conducted at the National Institute of Medical Research wherein mice were administered antioxidants and an attendant longevity was observed. In column 2 on page 254, the following statements appear:
"Increased longevity in mice fed antioxidant is compatible with, but does not demonstrate, the hypothesis of free radical ageing....
"None of the published survival curves, including our own, were obtained in a special purpose lifespan colony. The maximum lifespans obtained with anti-oxidants are within the recorded natural performance of the strains, and the increments are smaller than those regularly obtained by calorie restriction."
Appellant makes no mention of any survival data for the particular strain of mice tested or whether the reported increase in longevity is without the recorded natural performance of the strain.
After reporting the work of other researchers, Comfort states:
"In the antioxidant feeding experiments so far reported, alternative explanations are at least equally likely....
"Among alternative explanations, it could be suggested (1) that large amounts of chemicals hinder assimilation or spoil the appetite of mice, in the absence of strict pair-feeding measurements, and the effect may be due to covert calorie restriction; (2) that for mice ... excess antioxidant merely reduces the toxicity of a "normal laboratory diet (footnote omitted); (3) that (according to unpublished studies by R.B. Cumming) many antioxidants, especially BHT, are powerful enzyme inducers ...; (4) that with the doses used a hypothesis of straightforward "chemical stress", with or without suppression of a predominant tumour, is a feasible cause of longer gross survival...."
In our opinion, the Comfort article constitutes compelling objective evidence that those skilled in this particular art would not consider the data relied upon by appellant sufficient to establish that the administered compound actually retarded the aging process of the mice who enjoyed increased longevity.
Furthermore, the Comfort article provides a basis for questioning the protocol employed by appellant in conducting the experiments. In the protocol disclosed by Comfort, it is expressly stated that the mice were "subjected to no other manipulations" (col. 1, page 254). No such statement appears in appellant's protocol. Moreover, appellant neither reveals the diet administered to the mice nor the tumor incidence in treated or untreated mice and whether such incidence is low for the particular strain. These factors were reported by Comfort. It is of interest to note that on page 13 of the specification, appellant reports that certain mice were checked for virus profiles and that all dead animals were autopsied and the tissues of about 30 organs were taken for microscopic examination. The results of the check for virus profiles and autopsies are not revealed.
*4 Lastly, we note that the reported testing is confined to mice and one particular compound; whereas, none of the appealed claims is limited to mice and most of the claims are not limited to the particular compound tested, i.e., diethylhydroxylamine. Appellant has not advanced any cogent reasoning or proffered evidence to support the conclusion that the results obtained with mice can reasonably be extrapolated to the other animals encompassed by the appealed claims, such as cattle, or to the other compounds encompassed by claims 1 through 5, 7, 8, 10 through 17 and 19. In re Langer, 503 F.2d 1380, 183 USPQ 288 (CCPA 1974).
In summary, the nature of the asserted utility is so incredible as to create a strong presumption of inoperativeness. Ergo, very clear evidence is required to overcome the presumption of inoperativeness. In re Chilowski, 229 F.2d 457, 108 USPQ 321 (CCPA 1956). For the reasons expressed above, it is our judgment that the evidence relied upon by appellant is insufficient to overcome the proper challenge to the asserted incredible utility. In re Newman, 782 F.2d 971, 228 USPQ 450 (Fed.Cir.1986). The examiner's rejection of the appealed claims under 35 U.S.C. 101 is, therefore, affirmed.
No time period for taking any subsequent action in connection with this appeal may be extended under 37 CFR 1.136(a). See the final rule notice, 54 F.R. 29548 (July 13, 1989), 1105 O.G. 5 (August 1, 1989).
BOARD OF PATENT APPEALS AND INTERFERENCES
Sherman D. Winters,
Arthur J. Steiner,
FN1. The Examiner's Answer incorrectly states both the dosages recited in the references and on page 13 of appellant's specification as being kg/day instead of mg/kg/day.
FN2. Harman. "Chemical Protection Against Aging," Agents and Action, No. 1, pages 3-8 (1969); Harman, "Free Radical Theory of Aging: Dietary Implications," Amer.J. Clinical Nutrition, 25, pp. 839-943 (1972)
FN3. Comfort et al., "Effect of Ethoxyquine on the Longevity of C3H Mice," Nature, Vol. 229, pp. 254-255, 1971. A copy of his paper, and the papers referred to in footnote 1, were made of record by appellant.