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DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Claims 4, 10-11, 16, 20, 23-24, and 28 are cancelled.
Claims 1-3, 5-9, 12-15, 17-19, 21-22, and 25-27 are pending and are examined on the merits in this prosecution.
Claim Objection / Minor Informalities
In claim 7, third line, “benzene” is misspelled.
In claim 27, second line, “heptanoate” is misspelled.
CLAIM REJECTIONS
Indefiniteness Rejection
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 27 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 27 is recited as dependent on “The composition as claimed in claim 19.” However, claim 19 is a process claim and therefore the dependence of claim 27 is as per MPEP 2173.05(f) since the specified product can be easily or realistically produced by a different, non-referenced method.
Obviousness Rejections
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
1) Claim 1, 6-9, 12, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Bird (US 4,980,493), in view of Luckenbaugh (US 3,349,111), Harpp (“2-Bromohexanoyl Chloride,” Organic Syntheses, Coll. Vol. 6, p. 190 (1988); Vol. 55, p. 27 (1976)), and Zhong (“Rate of Enolate Formation Is Not Very Sensitive to the Hydrogen Bonding Ability of Donors to Carboxyl Oxygen Lone Pair Acceptors; A Ramification of the Principle of Non-Perfect Synchronization for General-Base-Catalyzed Enolate Formation,” J. Am. Chem. Soc. 2004, 126, 3488-3495).
Bird teaches a process for preparing phenyl esters of the following structure:
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where R is alkyl, and X is bromine or iodine (Abstract). Bird teaches the esterification is carried out by reacting a 3,5-di-halo-4-hydroxybenzonitrile in a two phase system, said system comprising an aqueous phase and an organic phase comprising a water immiscible solvent, with an acyl chloride in the presence of a base catalyst.
Bird does not teach the halogenation process recited in claim 1, part 1; the process for the formation of the acyl chloride in claim 1, part 2; or the process for the esterification recited in claim 1, part 3.
Luckenbaugh, Harpp, and Zhong teach the missing elements of Bird.
Luckenbaugh teaches the preparation of 3,5-di-bromo-4-hydroxybenzonitrile (Title). Luckenbaugh teaches Step 1 of claim 1, the debromination of 4-cyanophenyl, is carried out using bromine in water (Example 2).
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This teaching also reads on claims 6 and 7 (solvent = water). With regard to the claim 7 recitation of the amount of
For Step 2 of claim 1, Harpp teaches the conversion of hexanoic acid to hexanoyl chloride using thionyl chloride in CCl4 (1. Procedure).
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For claim 12, Harpp teaches the following procedure:
A 200-ml., round-bottomed flask equipped with a magnetic stirring bar is charged with 11.6 g. (0.100 mole) of hexanoic acid (Note 1) and 10 ml. of carbon tetrachloride. After 46.9 g. (28.8 ml., 0.394 mole) of thionyl chloride (Note 2) is added to the solution, an efficient reflux condenser with an attached drying tube is fitted to the flask. The solution is stirred and heated with an oil bath at 65° for 30 minutes (Note 3). The flask is removed from the oil bath and cooled to room temperature.
Regarding step (b) of claim 12, Harpp teaches purification of the 2-bromohexanoyl chloride final product by distillation. As such, Harpp teaches purification of an acid chloride by distillation and one of ordinary skill would have had a reasonable expectation of success in purifying the hexanoyl chloride by a distillation process. It is noted that a significant excess of thionyl chloride is utilized in the transformation, and one of ordinary skill would be able to separate the acyl chloride product from unreacted thionyl chloride utilizing distillation.
For Step 3 of claim 1, Zhong teaches a general procedure for preparation of phenyl esters comprising reaction of the phenol with sodium hydroxide and the acyl chloride in acetonitrile (pg 3493, right column):
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For Steps (a) and (b) of claim 18, Zhong teaches the phenol and sodium hydroxide base is added to acetonitrile (2nd fluid medium), followed by addition of the acyl chloride. For Step (c), Zhong teaches the time period of 16 hours at room temperature. For Step (d), Zhong teaches purification by flash column chromatography.
The skilled artisan would have expected success in utilizing the method of Luckenbaugh for the preparation of the 3,5-di-bromo-4-hydroxybenzonitrile intermediate of Bird since Luckenbaugh teaches the preparation of 3,5-di-bromo-4-hydroxybenzonitrile from 4-hydroxybenzonitrile from two equivalents of bromine in water.
Likewise, the skilled artisan would have expected success in utilizing the method of Harpp to prepare the acyl chloride required of the Bird process since Harpp teaches the conversion of hexanoic acid to hexanoyl chloride using thionyl chloride in CCl4.
For step 3, the skilled artisan would have expected success in substituting the method of Zhong for the two-phase method of Bird for preparing the compound of Formula 1, where X is Br and R is unbranched C5H11 because Zhong teaches the method of preforming the strongly nucleophilic phenoxide anion prior to add addition of the reactive acyl chloride species is effective in providing the final ester.
2) Claims 2-3, 5, 8-9, 13-15, 17, 19, 21-22, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Bird (cited above), in view of Luckenbaugh (cited above), Harpp cited above), and Zhong (cited above), Podall (“Convenient Syntheses of p-Bromo- and p-Aminophenol,” J. Org. Chem. 1958, 23, 280-2810, Hesk (“Synthesis of Pentamidine Labelled with Tritium And Carbon-14,” Journal of Labelled Compounds and Radiopharmaceuticals Vol. XXVl/1, No. 11, 1309-1320), and Loewenthal (“A Guide for the Perplexed Organic Experimentalist, Second Edition,” Chichester: John Wiley & Sons, 1990).
The teachings of Bird, Luckenbaugh, Harpp, and Zhong are discussed above.
The combination of Bird, Luckenbaugh, Harpp, and Zhong do not teach the preparation of p-hydroxybenzonitrile (also known as 4-cyanophenol).
It is noted that: for claim 13, Harpp teaches hexanoic acid; for claim 14, Harpp utilizes thionyl chloride as the chlorinating agent; for claim 17, Harpp teaches hexanoyl chloride; and for claim 19, the process of Zhong teaches sodium hydroxide as the base.
It is further noted that for claim 15, Harpp teaches a 3.9 to 1 ratio of thionyl chloride to hexanoic acid. Harpp also teaches the excess thionyl chloride is useful in drying the hexanoic acid and as a co-solvent for the reaction (Note 2). As set forth in MPEP 2144.05(I),
It is well established that, while a change in the proportions of a combination shown to be old, such as is here involved, may be inventive, such changes must be critical as compared with the proportions used in the prior processes, producing a difference in kind rather than degree."); In re Wells, 56 F.2d 674, 675, 12 USPQ 430 (CCPA 1932) ("Changes in proportions of agents used in combinations . . . in order to be patentable, must be critical as compared with the proportions of the prior processes."); E.I. DuPont de Nemours & Company v. Synvina C.V., 904 F.3d 996, 1006, 128 USPQ2d 1193, 1201 (Fed. Cir. 2018.)("[A] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 693, 2023 USPQ2d 448 (Fed. Cir. 2023) ("A difference of degree is not as persuasive as a difference in kind – i.e., if the range produces ‘a new property dissimilar to the known property,’ rather than producing a predictable result but to an unexpected extent.").
Regarding the time and temperature recited in claim 15, Harpp teaches the reaction is carried out at 65° for 30 minutes, and the reaction is monitored by proton NMR (Note 3). Furthermore, applicant has not demonstrated the criticality of the reaction time, which is, in part, dependent upon the temperature of the reaction.
For claim 21, Zhong (see above) teaches the following: for (a), Zhong teaches a molar ratio of phenol (about 80 mmol) to sodium hydroxide (about 98 mmol) of about 1.2:1, within the claimed range; for (b), Zhong teaches a molar ratio of about 91:80 (about 1.1:1), within the claimed range; for the fourth and fifth temperatures recited in part (c), Zhong teaches room temperature, taken to be about 20°C; for part (d), Zhong teaches a fourth time period of 75 minutes, within the claimed range; and for part (e), Zhong teaches stirring for 16 hours, exceeding the claimed range. However, as explained above, a modification of a known process can only be patentable if it produces a new and unexpected result, and such a result is not disclosed by the applicant.
For claim 22, Zhong teaches the second fluid medium as acetonitrile (see above).
For claim 25, Harpp teaches the conversion of hexanoic acid to hexanoyl chloride using thionyl chloride in CCl4, and hexanoyl chloride may be used to acylate the 3,5-di-bromo-4-hydroxybenzonitrile as discussed above.
Podall, Hesk, and Loewenthal teach the missing element of the combination of Bird, Luckenbaugh, Harpp, and Zhong.
For step (a), Podall teaches the following process (pg 281, right column):
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This process reads on claim 9.
Regarding the claimed impurities of o-bromophenol, dibromophenol, and tribromophenol recited in claims 2 and 3, since the reaction taught by Podall reaches conclusion after 190 minutes of reaction at 0°C, one of ordinary skill would expect the claimed impurities, in substantially the same amounts, in the reaction medium. As set forth in MPEP 2144.05(II)(A),
It is well established that, while a change in the proportions of a combination shown to be old, such as is here involved, may be inventive, such changes must be critical as compared with the proportions used in the prior processes, producing a difference in kind rather than degree."); In re Wells, 56 F.2d 674, 675, 12 USPQ 430 (CCPA 1932) ("Changes in proportions of agents used in combinations . . . in order to be patentable, must be critical as compared with the proportions of the prior processes."); E.I. DuPont de Nemours & Company v. Synvina C.V., 904 F.3d 996, 1006, 128 USPQ2d 1193, 1201 (Fed. Cir. 2018.)("[A] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 693, 2023 USPQ2d 448 (Fed. Cir. 2023) ("A difference of degree is not as persuasive as a difference in kind – i.e., if the range produces ‘a new property dissimilar to the known property,’ rather than producing a predictable result but to an unexpected extent.").
For the workup recited in step 2(b), Podall teaches removal of the dichloroethane solvent by atmospheric evaporation.
For claim 3, Podall teaches the reaction utilizes 1.2 moles of phenol and 1 mole of bromine, within the claimed range. Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists.
For claim 8, Podall teaches a 1.2:1 molar ratio of p-hydroxybenzonitrile to bromine, within the claimed range. With regard to the claimed time and temperature ranges recited in claim 8, in general, differences in reaction conditions do not support patentability unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In the instant case, it does not appear that the applicant has provided factual evidence refuting the prima facie obviousness of the teachings of Podall.
Podall does not teach purification of the 4-bromophenol by crystallization.
Loewenthal teaches compounds of moderate polarity with a melting point of from 50-80°C are commonly recrystallizable from hexane (pg 147). It is noted that Podall teaches the melting point of 4-bromophenol is 63°C (pg 281, Experimental).
For step 2(c), Hesk teaches the synthesis of 4-[14C]-cyanophenol, utilizing the following process (pg 1316):
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While Hesk teaches the synthesis of C-14 labeled 4-cyanophenol, one of ordinary skill would recognize the process extends to the synthesis of unlabeled 4-cyanophenol.
For claim 5, Podall teaches the third fluid is ethylene dichloride and Hesk teaches the fourth fluid is dimethylformamide.
The skilled artisan would have expected success in utilizing the method of Podall, as modified by Lowenthal, for the preparation 4-bromophenol since Podall teaches a process for the bromination of phenol that is substantially identical to the claimed method and Loewenthal teaches that hexane is a preferred recrystallization solvent for moderately polar compounds with a melting point in the range of 50-80°C. It is noted that hexane is the recrystallization solvent utilized in the instant specification for 4-bromophenol (pg 14).
The skilled artisan would have expected success in utilizing the method of Hesk for the preparation 4-cyanophenol from 4-bromophenol since Hesk teaches the substitution reaction is complete after 4 hours at 160°C. While Hesk teaches the synthesis of C-14 labeled 4-cyanophenol, one of ordinary skill would recognize the process extends to the synthesis of unlabeled 4-cyanophenol.
3) Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Bird (cited above), in view of Luckenbaugh (cited above), Harpp (cited above), Zhong (cited above), and Wollenweber (US 6,759,371).
The teachings of Bird, Luckenbaugh, Harpp, and Zhong are discussed above.
The combination of Bird, Luckenbaugh, Harpp, and Zhong does not teach an herbicidal composition comprising at least one ester of bromoxynil, bromoxynil, and a salt of bromoxynil.
Wollenweber teaches the missing element of the combination of Bird, Luckenbaugh, Harpp, and Zhong.
Wollenweber teaches herbicidal preparations containing at least one agrochemical agent from the group consisting of bromoxynil and its derivatives and certain alkoxylated fatty acid esters, where the use of the fatty acid esters increases the penetration of bromoxynil and its derivatives into plant leaves and to a process for controlling unwanted plant growth (col 1: 42-48). Wollenweber teaches the herbicidally effective bromoxynil component comprises one or more derivatives selected from bromoxynil alkyl esters, bromoxynil sulfates and salts thereof, bromoxynil carbonates and salts thereof, and mixtures thereof (col 6, claim 17).
The skilled artisan would have expected success in adding Wollenweber's bromoxynil and bromoxynil salts as the bromoxynil component, which may also comprise bromoxynil alkyl esters, for the bromoxynil alkyl ester taught by Bird because Wollenweber teaches that bromoxynil has little water solubility (col 1: 14-15), and one of ordinary skill would predict that the more non-polar bromoxynil alkyl esters would have even less water solubility but be effective over longer time period, and the bromoxynil salts would be predicted to have higher water solubility. The skilled artisan could have combined the bromoxynil salts and bromoxynil to the herbicidal composition of Bird in order to have a longer-lasting herbicidal effect.
4) Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Bird (cited above), in view of Luckenbaugh (cited above), Harpp (cited above), Zhong (cited above), and Foan (US 6,255,252).
The teachings of Bird, Luckenbaugh, Harpp, and Zhong are discussed above.
The combination of Bird, Luckenbaugh, Harpp, and Zhong does not teach an herbicidal composition comprising two esters of bromoxynil, namely bromoxynil heptanoate and bromoxynil octanoate.
Foan teaches the missing element of the combination of Bird, Luckenbaugh, Harpp, and Zhong.
Foan teaches mixture of herbicide esters 3,5-dibromo-4-hydroxybenzonitrile ("bromoxynil") n-octanoate and bromoxynil n-heptanoate in a molar ratio of n-octanoate to n-heptanoate of from 1:1.5 to 1.5:1, possesses an unexpectedly low melting point and high solubility in hydrocarbon oils (Abstract). Foan further teaches that a substantially 1:1 molar ratio mixture of bromoxynil octanoate and bromoxynil heptanoate possesses particularly advantageous properties in terms of ease of transportation, handling and formulation into herbicidal liquid concentrates and in the reduction of energy input necessary in the preparation of herbicidal liquid concentrates (col 2: 11-16), and the 1:1 mixture possesses herbicidal properties very similar to those of bromoxynil octanoate and formulations of the mixture may be used in the same manner and at the same rates of application as bromoxynil octanoate to control the growth of weeds (col 2: 17-22).
The skilled artisan would have expected success in substituting Foan's mixture of bromoxynil octanoate and bromoxynil heptanoate for the bromoxynil hexanoate in Bird’s herbicidal composition and method because Foan teaches that a mixture of bromoxynil octanoate and bromoxynil heptanoate provides a composition having the advantage of a low melting point (due to the phenomenon of freezing point depression) and therefore improving the ability to produce a formulation for herbicidal treatment.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL P COHEN whose telephone number is (571)270-7402. The examiner can normally be reached on M-Th 8:30-5:30; F 9-4.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup, can be reached on (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL P COHEN/Primary Examiner, Art Unit 1612
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