526 F.2d 1399 | C.C.P.A. | 1975
This is an appeal from the decision of the Patent and Trademark Office Board
The Invention
Appellants claim certain derivatives of bis-imidazolyl-bisphenylmethane which are disclosed as being non-toxic and pharmaceutically acceptable antimycotics especially useful against dermatomycosis and also against yeast infections of the skin and internal organs. The claims on appeal are as follows:
2. A compound of the formula:
wherein
R1 is hydrogen, alkyl of 1 to 4 carbon atoms or phenyl,
R2 and R3 are the same or different and are hydrogen, alkyl of 1 to 4 carbon atoms or phenyl,
X and Y are the same or different and are halogen, N02, CN, alkyl of 1 to 12 carbon atoms,
S-alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, and
m is 0, 1 or 2, and
n is 1 or 2 or m is 1 or 2 and n is 0, 1 or 2.
6. A compound according to claim 2 wherein R1 is hydrogen or alkyl of 1 to 4 carbon atoms, R2 and R3 are hydrogen, X and Y are the same or different and are halogen, CN, NO 2, methoxy or methyl and n is 0 or 1.
References
Fournari et al., Bull. Soc. Chim. France, No. 356 (1968), pages 2438-46 (hereafter Fournari).
Mussell et al. 3,321,366, May 23, 1967 (filed Nov. 15, 1965) (hereafter Mussell).
Tolkmith et al., Science, Vol. 158 (1967), pages 1462-63 (hereafter Tolkmith).
Fournari discloses various methods of preparing N-substituted imidazole derivatives. Once prepared, the spectra of the various imidazoles were analyzed to determine the exact chemical structures of the compounds. Of the numerous materials studied, three were found of particular interest by the Patent and Trademark Office in formulating its rejection (which will be discussed in detail):
It is an advantage of the present invention that compositions containing these compounds can be applied to growing vegetation in amounts required for effective control without significant injury to the plants. It is a further advantage that the compounds of the present invention are of very low toxicity to mammals.
Last, the Tolkmith article presents the results of a study of certain substituted imidazoles and concludes that:
[Ijmidazoles substituted on the imine nitrogen atom are likely to be active if the substituent is electron-attracting, and if the atom connecting it to the imidazolyl moiety has tetrahedral geometry. Fungitoxicity is high with phosphinamidothionate and triarylmethyl groups as substituents. The presence of an asymmetric phosphorus atom in the substituent has no effect 1 on fungitoxicity, but affects mammalian toxicity.
Tolkmith began by studying the properties of N,N-diethyl imidazol-l-yl phenylphosphinamidothionate
The tritylimidazole was found to be nearly as active as the reference compound, while demonstrating “moderate mammalian toxicity.”
The Rejection
The board affirmed the examiner’s rejection of claims 2 and 6 as being unpatentable (35 U.S.C. § 103) over (1) Fournari, (2) Fournari in view of Mussell, and (3) Fournari in view of Mussell and Tolkmith. Noting that Fournari does not disclose any utility for the compounds recited therein, the board stated:
At the outset we point out that appellants’ invention (i. e., that which is claimed) is a chemical compound or group of compounds; it is not the method of using the compound or of treating humans or animals infected with pathogenic fungi.
*1402 Our consideration of the references convinces us that not only would the claimed alkyl or methyl analogue have been obvious, its usefulness as a fungicide also would have been equally obvious. For example, Tolkmith et al. indicate that the fungicidal activity is primarily due to the imidazole moiety of the compound and that the remainder of said compound (a triphenylmethyl group in the case of compound II) “is not in fact critical for high fungicidal activity.” Mussell et al. additionally indicate that in imidazole-substituted phenylmethane fungicides both the methyl-substituted phenyl and unsubstituted phenyl derivatives possess fungicidal activity. Consequently anyone skilled in the art would expect not only the Fournari et al. bis-imadazolylbisphenylmethane to possess fungicidal activity but would also expect similar activity for the corresponding methyl-substituted analogue.
* * * * * *
Regarding appellants’ argument based on the fact that the art does not suggest the treatment of fungal infections pathogenic to human beings and other animals, it is the Examiner’s position that this fact, under the circumstances herein, is not significant. As we have set forth above, the claimed methyl analogue of the Fournari et al. bis-imidazolyl-bisphenylmethane, as well as its use as a fungicide would have been obvious from the art of record. In other words this means that the claimed methyl analogue, as well as its use as a fungicide, would have already been in the possession of the public at the time appellants made their invention. The fact that appellants may have discovered a new specific use for that which is already in the possession of the public does not entitle them to a patent thereon. In effect appellants seek to exclude the public from the use of a chemical compound for any purpose including the use as a fungicide (e. g., as against Phytophthora infestans, Diplocarpon rosae, Sphaerotheca panossa, Erysiphe cichoracearum) when said compound and its use are already in the public domain; Monsanto Company v. Rohm and Haas Company, supra (164 USPQ at 565, 566 [312 F.Supp. 778]).
On reconsideration, it added:
We remain of the view that appellants have not established in this record any unobvious properties of the claimed class of compounds as a whole nor have they established any unexpected improvement in properties not possessed by the art compounds.
In response to these rejections, appellants submitted to the Patent and Trademark Office two declarations under Rule 132. The first attempted to establish unexpected properties of the methyl analogue of bis-imidazolyl-bisphenylmethane as compared to the corresponding unsubstituted imidazole. The second was submitted by appellants with their reply brief before the board; it was not considered “since it has not been indicated nor seen to be limited to new points of argument in the Examiner’s Answer.” No further discussion of these declarations is deemed necessary as neither is relied upon in rendering our decision.
Opinion
As quoted, supra, the board raised the point that appellants’ invention (i. e., that which is claimed) is a chemical compound or group of compounds, not the method of using them in treating humans or animals infected with pathogenic fungi. However, this court on numerous occasions has held that a compound and its properties are inseparable. In re Albrecht, 514 F.2d 1389 (CCPA 1975); In re Murch, 464 F.2d 1051, 59 CCPA 1277 (1972); In re Stemniski, 444 F.2d 581, 58 CCPA 1410 (1971); In re Papesch, 315 F.2d 381, 50 CCPA 1084 (1963). A finding of unobviousness in consequence depends on comparing the old and new compounds as wholes, inclusive of their properties. In re Albrecht, supra.
Although the board affirmed the rejection of claims 2 and 6 as being obvi
Fournari discloses numerous compounds, one of which happens to be bisimidazolyl-bisphenylmethane. The solicitor characterized this compound as the “parent” of the compounds encompassed by the appealed claims. We read this to imply that when a hindsight selection of possible “R’s”, “X’s”, “Y’s”, “m’s” and “n’s” is made in appellant’s claims 2 and 6, it can be made to appear that Fournari differs from appellants’ claimed compounds by an alkyl group on one of the phenyl radicals. Therefore, we are faced with the question whether the secondary references, i. e., Mussell and Tolkmith, disclose enough to render obvious that which is missing in Fournari— the missing alkyl substitution.
Mussell only discloses tritylimidazole compounds. Although the patentees do teach unsubstituted and lower alkyl substituted phenyl radicals, the imidazoles disclosed are those possessing a single imidazole group and three phenyl groups. Furthermore, notwithstanding the board’s characterization of Mussell’s compounds as possessing “fungicidal activity,” we find that such activity is limited to the control of fungi found on plants. As stated by Mussell:
It has been discovered that the tritylimidazole compounds are particularly adapted to be employed for the control of a wide range of fungi, especially those fungal organisms ordinarily found on the aerial portions of plants, such as, for example, cherry leaf spot, black spot, apple scab, rice blast, powdery mildew, Helminthosporium (leaf spot on grasses, cereals, and corn), and late blight. The compounds can also be applied in dormant applications to the woody surfaces of plants or to orchard floor surfaces for the control of the overwintering spores of many fungi. In addition, the tritylimidazole compounds can be applied to seeds to protect the seeds from the attack of fungal organisms such as rot and mildew. Also, the tritylimidazole compounds can be distributed in soil at fungicidal concentrations to control the organisms which attack seeds and plant roots, particularly the fungal organisms of root rot and mildew.
Tolkmith represents a rather complex study, clearly directed towards a theoretician. The results of the study, presented in abstract form, are as follows:
Abstract. Study of several new types of fungitoxic derivatives of imidazole reveals that imidazoles substituted on the imine nitrogen atom are likely to be active if the substituent is electron-attracting, and if the atom connecting it to the imidazolyl moiety has tetrahedral geometry. Fungitoxicity is high with phosphinamidothionate and triarylmethyl groups as substituents. The presence of an asymmetric phosphorus atom in the substituent has no effect on fungitoxicity, but affects mammalian toxicity.
Both the solicitor and the board rely on Tolkmith for its alleged conclusion that fungicidal activity is primarily due
[FJungitoxic action seemed more likely to result from the nucleophilicity of 17 , that is, from the power of the azole nitrogen of the imidazolyl group to attack an electrophilic site in the fungus organism by donating electrons to this site.
Our reading of Tolkmith leads us to a different conclusion.
Tolkmith presents four compounds which were studied for fungicidal activity. All four possess imidazole moieties, but only compound II, an unsubstituted tritylimidazole, was “nearly as active” as the reference compound N,N-diethylimidazol-l-yl phenylphosphinamidothionate — two others “were markedly less fungicidal.” The only conclusion presented in the Tolkmith article is that imidazoles substituted on the imine nitrogen atom are likely to be active if the substituent is electron-attracting, and if the atom connecting it to the imidazolyl moiety has tetrahedral geometry.
Last, Tolkmith’s disclosed utility for the active compounds studied is that of “foliage fungicides.” Compound II, relied upon by the board, is taught by Tolkmith to have “show[n] moderate mammalian toxicity.”
When we combine the information gleaned from each reference, we are apprised of the following. First, methanes substituted with one, two or three unsubstituted imidazolyls and one, two or three unsubstituted phenyls are known (Fournari). Second, tritylimidazoles with lower alkyl substitution on the phenyl moieties are known as fungicides for plants (Mussell). Third, imidazoles substituted on the imine nitrogen atom are likely to be active foliage fungicides if the substituent is electron-attracting, and if the atom connecting it to the imidazolyl moiety has tetrahedral geometry (Tolkmith). Fourth, and last, tritylimidazole is an active foliage fungicide that exhibits moderate mammalian toxicity (Tolkmith).
We cannot agree with the board that the information derived from the references, taken as a whole, would render obvious claims 2 and 6 which are directed toward substituted bis-imidazolyl-bisphenylmethanes disclosed as being pharmaceutically acceptable and useful as antimycotics especially against dermatomycosis caused by Trichophyton and Microsporium species and also against yeast infections of the skin and internal organs. Accordingly, the decision of the board is reversed.
Reversed.
. Claim 19 was rejected under 35 U.S.C. § 112, second paragraph. Further discussion of this claim is unnecessary. Appellants have withdrawn their appeal of claim 19 by motion dated June 5, 1975.
. Serial No. 873,098, filed October 31, 1969.
. The chemical structure of the imidazolyl group is:
\
. Mussell’s tritylimidazoles are taught to have the following generic structure:
wherein each R independently represents a member selected from the group consisting of halo and lower alkyl and n represents an integer of from 0 to 2, both inclusive, further limited in that one of the 2 and 6 positions is unsubstituted; and each X independently represents hydrogen, lower alkyl, or phenyl, the total number of carbon atoms in all X substituents being an integer of from 0 to 15, both inclusive.
.
. As we have stated in the past, there must be some logical reason apparent from positive, concrete evidence of record which justifies a combination of primary and secondary references. In re Stemniski, supra. Further, as we stated in In re Bergel, 292 F.2d 955, 956, 48 CCPA 1102, 1105 (1961):
The mere fact that it is possible to find two isolated disclosures which might be combined in such a way to produce a new compound does not necessarily render such production obvious unless the art also contains something to suggest the desirability of the proposed combination.
In the present case, it may reasonably be argued that because Fournari discloses no suggestion of utility for the compounds recited therein, one of ordinary skill in the art would not be prompted to combine this reference with either Mussell or Tolkmith.
. Compound I of Tolkmith is as follows:
