DETAILED ACTION
Notice of Pre-AIA or AIA Status
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 (i.e., changing from AIA to pre-AIA ) 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.
Current Status of 18/552,326
This Office Action is responsive to the amended claims received 6 May 2024.
Claims 1-18 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/IL2022/050321 (22 March 2022) and IN 202131013524 (26 March 2021) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The Examiner has determined, for the purposes of the instant action, that the effective filing date of the instant claims is 22 March 2022, because sufficient support was not found in earlier-filed documents (specifically, instant claim 14).
Information Disclosure Statement
The information disclosure statement (IDS) received on 25 September 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 1. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. References to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01(VII).
Claim Objections
Claims 12 and 13 is objected to because of the following informalities: Each of these claims recites the phrase “comprising the steps of”. In each case, this phrase should be amended to “further comprising the steps of”, because steps were already presented in a parent claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 6, 8-10, and 14-17 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 and 6 each recite “(HPLC, area%)”. It is unclear to the reader whether the language within parentheses is a required limitation or serves as an example. This renders claims 2, 6, and 15-17 indefinite. Applicant may choose to replace the phrase “(HPLC, area%)” with “, as determined by HPLC area %”.
Claims 8 and 16 each contain the phrase “wherein the solvent(s) is (are) selected from”. These parentheses cause it to be unclear whether these claims require a single solvent or multiple solvents. This renders claims 8-10 and 16-17 indefinite. Applicant may choose to replace the phrase “wherein the solvent(s) is (are) selected from” with the phrase “wherein the one or more solvents are selected from”.
Claim 14(c) shows, within the structure shown, that the ethyl carbamate is shown, but this is not stated in the text above the structures. This causes it to be unclear if the ethyl carbamate specifically is a required limitation of the claim. This renders claim 14 indefinite. Applicant may choose to add the word “ethyl” to the text description to claim 14, step (c).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 5-6, 11-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
WANG (Cited by Applicant in IDS of 25 September 2023; Wang, B.; Mao, Y.; Liu, X.; et al. “New and convergent synthesis of saflufenacil” J Heterocyclic Chem. 2020; 57: 151-156).
WANG generally teaches the synthesis of saflufenacil, an herbicide (abstract). Within this herbicide synthesis, WANG teaches the synthesis of 2‐chloro‐4‐fluoro‐5‐nitrobenzoic acid from 2‐chloro‐4‐fluorobenzoic acid (Scheme 1 and Scheme 2; last paragraph of page 151 to first paragraph of page 152). Section 3.3, on page 154 of WANG teaches the following details of this reaction: 2‐chloro‐4‐fluorobenzoic acid (0.57 mol) was added to a stirred solution of concentrated sulfuric acid, cooled by an ice bath; nitric acid (0.89 mol) was then added while the solution was kept below 30 degrees C; the reaction was then heated to 40-50 degrees C and stirred for another 2 hours; the reaction was then cooled to room temperature and poured into 2 liters of ice water; the solid product was filtered and determined to be 99.56 % pure. The nitric acid is present in a 56 % molar excess, as compared to the starting material.
The Examiner determines that the 99.56 % pure product of WANG reads on the essentially pure form of 2‐chloro‐4‐fluoro‐5‐nitrobenzoic acid instantly claimed.
WANG does not teach the presence of 2‐chloro‐4‐fluoro‐3‐nitrobenzoic acid or 3,5-dinitro-2‐chloro‐4‐fluoro‐benzoic acid. All of the positive steps required by instant claim 1, that can be accomplished by one of ordinary skill in the art, such as performing the nitration reaction with a particular starting material, are taught by WANG. In other words, because the method of performing the reaction of instant claim 1 is anticipated by WANG, the direct outcome of the reaction, including minor products not taught by WANG, must be anticipated as well. Similarly, all of the positive steps that can be performed by the artisan, as required in instant claims 1 and 5, are anticipated as shown above. Because the method of performing the steps of instant claims 1 and 5 is anticipated by WANG, the direct outcome of these steps in instant claim 6 must be anticipated as well.
Regarding claim 12: Each of the steps of instant claim 12 is clearly shown within Scheme 1 of WANG. Formula A1 and Formula A2 of instant claim 12 are shown as compounds 10 and 11 of WANG respectively.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 11-13, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Cited by Applicant in IDS of 25 September 2023; Wang, B.; Mao, Y.; Liu, X.; et al. “New and convergent synthesis of saflufenacil” J Heterocyclic Chem. 2020; 57: 151-156).
Teachings of WANG are discussed within the rejections above.
Regarding claim 2: It would be obvious to one of ordinary skill in the art to adjust the amounts of the reagents, the reaction temperature, and the reaction time for the nitration reactions taught by WANG. There is no minimum amount of adjustment required by instant claim 2. WANG anticipates claim 1, as described above, and the positive step of adjusting the reaction parameters would have been obvious to one of ordinary skill in the art, as a form of routine experimentation. The outcome, being an HPLC area ratio, must be determined by the positive steps that can be performed by one of ordinary skill in the art. Because those positive steps are anticipated and rendered obvious by WANG, the outcome of those steps must be rendered obvious.
Regarding claims 4 and 18: WANG teaches heating a reaction, as described in instant claim 4, to 40-50 degrees C and stirring for 2 hours. Instant claim 4 teaches heating the reaction to at least 55 degrees C and holding that temperature for 3 hours. These values of temperature and time taught by WANG are close to the instantly claimed values, and the instantly claimed values are not taught to be critical by the instant specification or claims. It would have been obvious to one of ordinary skill in the art to vary the reaction temperature and time, taught by WANG, and to arrive at the instantly claimed values of reaction temperature and time. See MPEP 2144.05 (I). WANG teaches isolation of the crude product after crystallization in cold water, as described in the rejections above.
Regarding claim 13: Instant claim 13 is not directly taught by WANG. The condensation reaction of instant step 13(a) is very similar to reaction “f” of Scheme 2 of WANG, which yields compound the nitro-bearing compound 16 of WANG. Compound 16 is then reduced according to WANG to yield compound 17, which is identical to the instantly claimed compound of Formula B1. The coupling reaction required by instant claim 13, step “b1”, is very similar to the coupling taught as reaction “e” within Scheme 1 of WANG. The same 2-dimethylamino-4-(trifluoromethyl)-6H,1,3-oxazine-6-one is taught by WANG to be coupled to the same amine position as instantly claimed. However, the amine compound of Scheme 1 of WANG (compound 8), shown below, has not yet had the sulfonamide moiety added onto it. The instantly required methylation step is taught as reaction “j” of Scheme 2 of WANG.
PNG
media_image1.png
92
119
media_image1.png
Greyscale
To arrive at the reaction instantly claimed in claim 13, one of ordinary skill in the art would need to modify Scheme 2 of WANG by incorporating the oxazine coupling reaction “e” of Scheme 1 of WANG, which is simply an alternate method of producing the pyrimidine ring of the final product. The artisan would also need to perform the “f” reaction of Scheme 2 of WANG using the acid instead of the acid chloride derivative.
It would have been obvious to one of ordinary skill in the art to look at the two synthetic schema of WANG and envision moving around interchangeable parts of the synthesis, for the purpose of improving yields within the synthesis. One of ordinary skill in the art would immediately envision the reaction using the carboxylic acid when presented with the acid chloride reaction shown as reaction “f” in Scheme 2 of WANG.
Claims 1-13 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Cited by Applicant in IDS of 25 September 2023; Wang, B.; Mao, Y.; Liu, X.; et al. “New and convergent synthesis of saflufenacil” J Heterocyclic Chem. 2020; 57: 151-156)
in view of:
BAUMANN (Baumann, J.S. “Solvent Selection for Recrystallization” Journal of Chemical Education Volume 56 Issue 1 Page 64 1979).
Teachings of WANG are discussed within the rejections above.
WANG does not specifically teach recrystallization of saflufenacil for the purpose of purification. WANG does teach that saflufenacil is soluble in toluene (section 3.10).
Regarding claims 7-9 and 15-17: BAUMANN teaches recrystallization to be a well-known technique to purify compounds within organic chemistry (title). BAUMANN teaches toluene to be a common solvent used for the recrystallization of aryl compounds (results section).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to use the technique of recrystallization from toluene (as taught by BAUMANN) on the compound of WANG (saflufenacil), for the purpose of purifying the compound of WANG. The artisan would have expected success, because recrystallization is a well-known technique, and WANG teaches saflufenacil to be soluble in toluene.
Regarding claims 10: One of ordinary skill in the art would have been motivated to vary the ratio of the recrystallization solvent to the crude product for the purpose of effecting purification without losing too much of the desired compound. One of ordinary skill in the art would have reasonably arrived at a ratio within the instantly claimed range. See MPEP 2144.05(II)(A).
Claims 1-6, 11-14, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over:
WANG (Cited by Applicant in IDS of 25 September 2023; Wang, B.; Mao, Y.; Liu, X.; et al. “New and convergent synthesis of saflufenacil” J Heterocyclic Chem. 2020; 57: 151-156)
in view of:
URCH (WO 2015/040409 A2; International Publication Date 26 March 2015).
Teachings of WANG are discussed within the rejections above.
Regarding claim 14: Instant claim 14 requires the esterification of 2-chloro-4-fluoro-5-nitrobenzoic acid to act as a protecting group, and the pyrimidine ring is then built from the earlier nitro group (as shown in instant claim 14) through a carbamate intermediate. The ester is then deprotected and 2-[methyl(sulfamoyl)amino]propane is coupled with the free carboxylic acid (step “f” of instant claim 14). The addition of a methyl group finally affords the saflufenacil product.
Scheme 2 of WANG teaches the same synthetic pathway to build the pyrimidine ring from the earlier nitro group as is shown in instant claim 14; however, Scheme 2 of WANG has already functionalized the carboxylic acid with 2-[methyl(sulfamoyl)amino]propane before the pyrimidine ring is built. There are additional differences: a carboxylic acid reaction is instantly claimed instead of using the acid chloride (Scheme 2 of WANG) and an ethyl carbamate is instantly claimed instead of a methyl carbamate (WANG). But these options would be trivial for one of ordinary skill in the art to immediately envision.
URCH teaches the final reaction in the synthesis of saflufenacil to be the addition of 2-[methyl(sulfamoyl)amino]propane to 2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]benzoic acid (Page 40). This is a direct teaching that the pyrimidine ring can be built earlier within the synthesis of saflufenacil, and the carboxylic acid can be functionalized at the end.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to rearrange the synthesis of WANG to build the pyrimidine portion of the compound first and then functionalize the carboxylic acid portion, as is taught to be a viable strategy by URCH, for the purpose of improving the yield of the synthetic scheme and decreasing unwanted reaction products. The artisan would have expected success in this strategy, because both WANG and URCH teach synthetic schema for the same product.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 5, 7, 8, 10, 11, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1, 3, 5, 7, 8, 9, 20, and 22 of copending Application No. 19/108,010 (referred to below as the ‘010 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claim 1 of the ‘010 application teaches a process comprising the steps of: reacting 2-chloro-4-fluorobenzoic acid with sulfuric acid and nitric acid, separation of the crude product, and recovering 2-chloro-4-fluoro-5-nitrobenzoic acid in an essentially pure form.
The ‘010 application does not teach the presence of 2‐chloro‐4‐fluoro‐3‐nitrobenzoic acid or 3,5-dinitro-2‐chloro‐4‐fluoro‐benzoic acid. All of the positive steps required by instant claim 1, that can be accomplished by one of ordinary skill in the art, such as performing the nitration reaction with a particular starting material, are taught by the ‘010 application. In other words, because the method of performing the reaction of instant claim 1 is anticipated by the ‘010 application, the direct outcome of the reaction, including minor products not taught, must be anticipated as well. Claims 3, 5, 7, 8, 9, 20, and 22 of the ‘010 application read on instant claims 3, 5, 7, 8, 10, 11, 13 respectively, and are identical or nearly identical in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ANDREW D KOSAR can be reached at (571)272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625