Application of Jerome G. Kuderna, Jr. And Donald D. Phillips

426 F.2d 385, 57 C.C.P.A. 1078

• Court: Court of Customs and Patent Appeals
• Decided: May 14, 1970
• Docket: Patent Appeal 8222
• Status: Published

Opinion

RICH, Acting Chief Judge.

This appeal is from the decision of the Patent Office Board of Appeals affirming the rejection of claim 1, the only remaining claim, of application serial No. 346,997, filed February 24, 1964, and entitled “Nitrogen-Containing Insecticides.” We reverse.

The Invention

The appealed claim is directed to a single compound, 3, 4-dimethyl-5-ethyl-phenyl methylcarbamate, the structural formula of which is provided hereinafter. This compound is an insecticide and ac cording to appellants’ specification “has been found to effectively control soil-dwelling insects for extended periods of time * *

The Rejection

Claim 1 has been rejected for obviousness, under 35 U.S.C. § 103, in view of the following references:

Lemin 3,131,215 Apr. 28, 1964

(filed Oct. 6,1960)

Kohn et al. 3,062,707 Nov. 6, 1962

Kolbezen et al., Journal of Agricultural and Food Chemistry, Yol. 2, pp. 864-70 (1954)

Lemin, the primary reference, discloses a large class of 2-halo-and 2,4-dihalo-alkylphenyl carbamates represented in the reference by the structural formula:

wherein Z contains a total of not more than 10 carbon atoms and is selected, from the group consisting of monoalkylamino, monoalkenylamino dialkylamino, dialkenylamino, and a saturated heterocyclic amino radical

of from 5 to 9 nuclear atoms, inclusive, wherein Z’ represents a saturated bivalent radical selected from the group consisting of alkylene, oxadialkylene, and thiadialkylene; X is halogen; R is alkyl of from 1 to 4 carbon atoms, inclusive; Rx is selected from the group consisting of hydrogen and alkyl of from 1 to 4 carbon atoms, inclusive; and Y is selected from the group consisting of halogen and alkyl of from 1 to 4 carbon atoms, inclusive.

These compounds are said to be useful “for preventing and arresting infestations of insect pests.” Of the many specific carbamates named in Lemin, the one most similar in structure to appellants’ compound is 2-ehloro-3-ethyl-4, 5-di-methylphenyl ethylcarbamate.

Kohn discloses 3-t-amyl-6-chloro-phenyl methylcarbamate, and compares it with its wowchlorinated analog, m-tamylphenyl methylcarbamate, and with m-t-butylphenyl methylcarbamate, showing the wowchlorinated compounds to be significantly poorer inhibitors of the cholinesterase enzyme system of certain animal parasites.

Kolbezen 1 reports the results of an investigation of a wide variety of phenyl- and substituted-phenyl alkylcarbamates for insecticidal activity and activity as inhibitors of the cholinesterase enzyme system of insects. Several of Kolbezen’s conclusions and generalizations are particularly noteworthy (bracketed numerals are added for subsequent reference to individual paragraphs quoted):

It is apparent that the phenyl esters of N-meiZM/Zcarbamic acid are considerably more toxic than the corresponding N~eZ%Zcarbamates. * * * These results are in good agreement with those of Haworth et al., Gysin, and Stevens and Beutel, who found maximum toxicity to be associated with N-^methyl substitution.

The nature and extent of substitution of the phenyl rings of. the Nmethylcarbamatés exert a remarkable influence on toxicity. The order of effectiveness of single ring substituents upon cholinesterase inhibition was N02 < [is less than] Cl < CH3 < C2H5 < ÍS0-C3H7 * * * and the contact toxicity was roughly in the same order * * *. The order of effectiveness of ring position was p < o > m, both for cholinesterase inhibition and for toxicity. * * *

Where multiple substituents in the ring are concerned, reinforcement of the toxicity of meta- alkylates results from additional alkylation in the ortho- or meta- positions as in the 3, 5-dimethylphenyl, 2, 3, 5-trimethyl-phenyl, 2-methyl-5-isopropylphenyl, and 5-methyl-2-isopropylphenyl Nmethylcarbamates. * * * [Emphasis added.]

Of the more than fifty carbamates tested apd mentioned specifically in Kolbezen, the one most closely resembling appellants’ compound is 2, 3, 5-trimethyl-phenyl methylcarbamate.

At one point in the prosecution of appellants’ application there were two other rejections which have since been withdrawn, namely, a rejection of claim 1 over the claims of appellants’ commonly-assigned patent 3,130,122, issued April 21, 1964 (hereinafter “Kuderna”), “on grounds of double patenting” and a rejection as unpatentable over Kolbezen alone, presumably under § 103. Appellants overcame these two rejections by affidavits 2 which established to the examiner’s satisfaction that the compound of claim 1 possesses “unexpected insecticidal superiority” in comparison to the 3, 4, 5-trimethylphenyl methylcarbamate of Kuderna and in comparison with the 2, 3, 5-trimethylphenyl methylcarbamate of Kolbezen. The following are the structural formulae of the claimed compounds of appellants and Kuderna and the compounds of Kolbezen and Lemin most structurally similar to that of appellants (moieties of particular interest are italicized):

Referring to the compound of Lemin, the examiner, in his Answer before the board, stated:

This compound differs from the claimed compound in two respects — it has a chlorine atom in the 2 position of the phenyl moiety and the acid substituent is ethyl, instead of methyl. However, at claim 1 * * * the reference clearly suggests the corresponding methyl compound and Kolbezen et al. disclose that the methyl carbamate is known to have superior toxic properties to the ethyl carbamate * * *. Regarding the chloro substituent, Kohn et al. disclose that a chlorine substituent in the ortho position enhances the insecticidal properties of the phenyl carbamate. Accordingly, one skilled in this art and familiar with the references of record would expect that the 2-chloro-3-ethyl-4, 5-dimethylphenyl N-methyl carbamate would be a superior insecticide. However, the skilled worker would also expect the non-chlorinated compound, that claimed herein, to be a good insecticide, although not as toxic as the cholor analog.

The board was of the opinion that the examiner had made out a prima facie case of obviousness and that it was “incumbent upon appellants to offer evidence directly comparing the claimed compound with that disclosed by Lemin.”

Appellants’ Contentions

Appellants take the position that

* * * having established the claimed compound to be unobvious from the art homolog and isomer/homolog, they have a fortiori established it to be unobvious over all other compounds of lesser structural similarity, and it is not necessary that they also compare the claimed compound to any of the compounds of less structural similarity. 3 [Emphasis added.]

Appellants also urge that even if it were shown that, in comparison to Lemin’s compound, their compound is less effective, the unobviousness of their compound would not have been negated. On this point, appellants contend:

The Lemin disclosure runs directly contrary to appellants’ stated objective, namely the provision of a non-halogenated insecticide. Halogenated insecticides have been used for so many years that many classes of insects have developed a resistance to the halogenated compounds and appellants desired to avoid halogen compounds. The very crux of the present invention was to find an insecticide which was highly effective yet one which did not contain halogen. Thus, even if it were shown that the compound of the present invention when tested against some particular organisms was not as effective as the halogenated Lemin compound, nevertheless appellants have made a very substantial advance in this highly complicated art since they have provided a replacement or supplemental insecticide for use in those cases where the insects have become resistant to the halogenated compounds. Appellants’ advance is not necessarily in providing the best insecticide in the world but rather in providing a highly effective insecticide which does not contain a halogen.

Opinion

We agree with appellants that it was unnecessary for them to compare their compound with that of Lemin. We agree not merely because appellants have shown their compound to be unobvious in view of the structurally more similar compounds of Kolbezen and Kuderna; rather, we agree because the evidence which has been submitted demonstrates that their compound possesses an unexpected degree of effectiveness and would not have been obvious in view of all the cited prior art.

We must approach the issue of patentability in terms of what would have been obvious to one of ordinary skill in the art at the time the invention was made in view of the sum of all the relevant teachings in the art, not in view of first one and then another of the isolated teachings in the art. Here, for example, if one singles out the Lemin patent and the compound therein found to be most structurally similar to that of appellants, the examiner and board's position seems plausible. But where is the reason for one skilled in the art to so emphasize that one isolated teaching? Kolbezen is the only reference that teaches or suggests anything about the structure-activity relationship of nonhalogenated triaikylphenyl alkylcarbamates. Lemin’s disclosure relates only to 2-halo and 2, 4-dihalo-alkylphenyl carbamates. Lemin makes no mention of any nonchlorinated compounds, no mention of any compound unsubstituted in the 2-posi- tion of the phenyl moiety and no mention of any compound substituted only in the 3, 4, and 5 positions. The 2-ehloro-3-ethyl-4, 5-dimethylphenyl ethylcarbamate, which is singled out of the Lemin disclosure by the Patent Office, is merely mentioned in one of several lists of representative compounds, and the 2-chloro-3, 4, 5-trimethylphenyl, 2-chloro-3-ethyl-4-propyl-5-butylphenyl and 2-chloro-3, 4, 5-tributylphenyl ethylcarbamates are also mentioned in the same list with equal emphasis.

The Kohn patent does not seem to support the general proposition for which the examiner cited it, namely, “that a chlorine substituent in the ortho position enhances the insecticidal properties of the phenyl carbamate.” This reference compares only one halogenated carbamate with two nonhalogenated carbamates, and all three compounds had only one alkyl group (of four or five carbon atoms) on the phenyl ring. The board appreciated the danger inherent in attempting to extrapolate a teaching such as that of Kohn to predict the properties of a significantly dissimilar compound such as that of appellants. The board noted that in the Kolbezen tests (which involved compounds structurally more similar to appellants’ compounds than those of Kohn) chlorine in the 2-position of the phenyl ring did not enhance toxicity.

We agree with the examiner and the board that from Kolbezen, one skilled in the art would expect an N-^methyl carbamate to be superior to the corresponding N-ethyl carbamate (see paragraph [1] of the quotation from Kolbezen, supra). However, we feel that from Kolbezen one skilled in the art would also select a 2, 3, 5-trialkyl configuration rather than the 3, U, 5-structure of appellants’ compound (see paragraphs [2] and [3]). There being nothing in either Lemin or Kohn on which to base a prediction of the comparative insecticidal activities of trialkylphenyl methylcarbamates such as those of Kolbezen, Kuderna and appellants, we find that, by demonstrating their compounds to be unexpectedly superior to that of Kolbezen, appellants have succeeded in demonstrating the unobviousness of their compound over the sum of the teachings in the cited prior art.

The decision of the board is therefore reversed.

Reversed.

1 . This reference was also the subject of extensive discussion in In re Kilsheimer, 349 F.2d 441, 52 COPA 1702 (1965).

2 . Not of record here.

3 . As support for this proposition appellants refer to the following statement from Deutsche Gold-Und Silber-Scheideanstalt Vormals Roessler v. Commissioner of Patents, 251 F.Supp. 624 (D.C.D.C.1966) :

An applicant for patent need not compare the properties of a claimed compound with those of all closely related compounds whose structural formulas and beneficial properties are taught or suggested by the prior art, it being sufficient if the beneficial properties of the claimed compound are compared with the corresponding properties of the most closely related prior art compounds. [Emphasis added.]

Appellants further note that in In re Wetterau, 356 F.2d 556, 53 COPA 916 (1966), this court affirmed the decision of the board saying:

We are unable to find “clear and convincing evidence” * * * that appellant’s compounds possess unexpected activity compared to the closest * * reference compound. [Emphasis quoted.]

From this appellants infer that if such evidence had been at hand, evidence relating to less close compounds would not have been required.