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 .
Priority
The instant application claims priority as follows:
PNG
media_image1.png
104
524
media_image1.png
Greyscale
Receipt of claim amendments and arguments filed on 01/07/2026 is acknowledged.
Claims 1-6 and 8-13 are currently pending. Rejections and objections not reiterated herein have been withdrawn.
Applicant previously elected Group I, drawn to a compound of formula (I) and compositions comprising the same.
Claim 13 has been amended to be directed to a method of control, treatment and/or prevention. In the last Office action, the methods of control, treatment and/or prevention were assigned to be in Group III, which was withdrawn from further consideration. Amended claim 13 is thus, grouped in Group III, and withdrawn accordingly for the reasons discussed in the previous action.
Applicant elected compound 5, of formula
PNG
media_image2.png
186
262
media_image2.png
Greyscale
.
Accordingly, claims 9-11 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 07/15/2025.
Examination
Search and examination have not been extended.
Pursuant to MPEP 803.02, the elected species of compound was searched and was found unpatentable over the art. Therefore, examination was stopped and art has been applied against the claims. For the purpose of a compact prosecution similar compounds disclosed in the same prior art have been examined as detailed below.
Accordingly, subject matter of claims 1-6, 8 and 12 which is outside of the scope of the rejected compounds below, are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 07/15/2025.
Claims 1-6, 8 and 12 are the subject of this Final Office action.
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.
Claim(s) 1-6, 8 and 12 remain rejected under 35 U.S.C. 103 as being unpatentable over Hubsch et al. (WO 2018/087036) in view of Zitko et al. (Molecules 2018, 23, 2390), andYang et al. (J. Agric. Food Chem. 2019, 67, 13185-13194).
Applicant claims a compound of formula
PNG
media_image2.png
186
262
media_image2.png
Greyscale
and analogs wherein the phenyl ring that is represented by Q is substituted by one, two or three fluoro atoms and may be additionally substituted by chloro atoms.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Teachings of Hubsch et al.
Hubsch teaches:
PNG
media_image3.png
172
648
media_image3.png
Greyscale
At page 2:
PNG
media_image4.png
210
716
media_image4.png
Greyscale
PNG
media_image5.png
170
498
media_image5.png
Greyscale
.
In at least page 47:
PNG
media_image6.png
380
600
media_image6.png
Greyscale
.
Representative examples of the anthelmintic compounds of Hubsch wherein Q is fluoro-substituted phenyl and R2 is dimethylamino are found in Table 1 and are as follows:
PNG
media_image7.png
172
250
media_image7.png
Greyscale
,
PNG
media_image8.png
162
278
media_image8.png
Greyscale
,
PNG
media_image9.png
174
246
media_image9.png
Greyscale
,
PNG
media_image10.png
160
276
media_image10.png
Greyscale
(#30),
PNG
media_image11.png
174
246
media_image11.png
Greyscale
,
PNG
media_image12.png
164
276
media_image12.png
Greyscale
,
PNG
media_image13.png
160
278
media_image13.png
Greyscale
,
PNG
media_image14.png
162
272
media_image14.png
Greyscale
(#47),
PNG
media_image15.png
162
276
media_image15.png
Greyscale
(#49),
PNG
media_image16.png
158
276
media_image16.png
Greyscale
,
PNG
media_image17.png
202
248
media_image17.png
Greyscale
(#57),
PNG
media_image18.png
162
272
media_image18.png
Greyscale
(#81),
PNG
media_image19.png
164
276
media_image19.png
Greyscale
,
PNG
media_image20.png
200
244
media_image20.png
Greyscale
,
PNG
media_image21.png
170
270
media_image21.png
Greyscale
(#247) and
PNG
media_image22.png
170
248
media_image22.png
Greyscale
(#277). The compounds are efficacious against nematodes and their larvae.
Teachings of Zitko et al.
Zitko disclosed: “Exchanging the amide moiety for a retro-amide is a strategy successfully used in medicinal chemistry and drug design. The obligatory textbook example is the group of local anesthetics. Cinchocaine is a substituted amide of a heteroaromatic acid, therefore having the -CONH- connecting bridge between the aromatic core and the basic amino moiety in the side chain. However, significantly more populated group of local anesthetics are anilides having the retro-amide -NHCO- linker (e.g., lidocaine, trimecaine, bupivacaine). In the field of antimicrobial research, the retro-amide modification led recently to derivatives with increased activity against Candida albicans [20]. The retro-amides of classical β-lactam antibiotics and their analogues were studied as substrates and/or inhibitors of beta-lactamases [21,22,23,24].”
“Thus, the main aim of our study was to evaluate the effect of amide (-CONH-) vs retro-amide (-NHCO-) linker between the pyrazine and benzene core on in vitro antimycobacterial activity. Along with the linker exchange, we kept the variability both in the pyrazine core (R1 is H, 5-Cl, or 6-Cl) and in the benzene core (R2). Synthetic work was performed by two undergraduate students (co-authors of this paper, A.M. and O.V.) as a part of their diploma theses, therefore we kept the chemistry complexity at a suitable level.”
“As a continued effort to extend the knowledge of SAR of N-phenylpyrazine-2-carboxamides as antimycobacterial agents, we designed a series of N-(pyrazin-2-yl)benzamides, which can be regarded retro-amide analogues (Figure 1).”
PNG
media_image23.png
152
556
media_image23.png
Greyscale
Figure 1. Design of title compounds inspired by previously published N-phenylpyrazine-2-carboxamides with antimycobacterial activity.
Teachings of Yang et al.
Yang disclosed that in searching for novel fungicidal leads, fluxapyroxad derivatives were designed and synthesized by the inversion of carbonyl and amide groups.
PNG
media_image24.png
122
340
media_image24.png
Greyscale
Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
The only difference between the compounds of the prior art cited above and claimed compounds of formula (I) is the replacement of the amide linker with a reverse-amide linker. That is, the amide (-CONH-) vs retro-amide (-NHCO-) linker between the quinoline and chromane core.
The difference between the elected species and the tri-fluorinated compounds of Hubsch above is additionally, the position of a fluorine atom on the phenyl ring Q.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
The level of ordinary skill in the art is high. Someone preparing these compounds would be trained in organic chemistry and would recognize the very close structural similarity and would expect these compounds to have similar properties. One of ordinary skill would have been motivated to make reverse-amide (-NHCO-) linker derivatives of the compounds of Hubsch above because “exchanging the amide moiety for a retro-amide is a strategy successfully used in medicinal chemistry and drug design” with the aim of obtaining derivatives with similar or increased activity. This replacement is a research technique routinely used before the filing date of the instant invention.
Regarding the elected species of formula
PNG
media_image2.png
186
262
media_image2.png
Greyscale
, it would have been obvious to make the reverse-amide analog compound wherein Q is a 2,3,5-trifluorophenyl ring as in the elected species in view that Hubsch disclosed the compounds wherein Q is 2,3,6-trilfuorophenyl, 3,4,5-trifluorophenyl, 2,4,5-trifluorophenyl and 2,3,4-trilfuorophenyl as follows:
PNG
media_image21.png
170
270
media_image21.png
Greyscale
,
PNG
media_image14.png
162
272
media_image14.png
Greyscale
(#47),
PNG
media_image17.png
202
248
media_image17.png
Greyscale
(#57), and
PNG
media_image18.png
162
272
media_image18.png
Greyscale
(#81).
The claimed compounds have exactly the same formula and the same use as the compounds of Hubsch; they are analogs possessing chemical and pharmacological similarities. There would have been a high expectation of success due to that the prior at teaches how to prepare and use the compounds which share the same groups.
In addition, MPEP 2144.09 states: A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c) and (d).
Under the Supreme Court rationales in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007), here at least exemplary rationales (A) through (D) apply:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results.
Applicant’s arguments have been carefully considered but were found unpersuasive.
Applicant argues that Hubsch does not disclose the carboxamide moiety as a linking moiety but as an essential part of general formula (I), and that it therefore does not teach or suggest replacing the carboxamide group by an “inverted amide”. In response, Hubsch disclosed the carboxamide moiety as part the compounds, and it is still there in the inverted amide or retro-amide claimed. The carboxamide moiety is still present but inversely attached.
Regarding Zitko, Applicant argues that it relates to antibacterial and antifungal compounds and that one of skill would not refer to Zitko to arrive at antihelminthic compounds. In response, Zitko is evidence of the knowledge and skill in the pesticide art. One of skill would refer to Hubsch to arrive at antihelminthic compounds of the quinolyl-chromane carboxamide type. Zitko teaches and evidences that inverting the amide in useful compounds is a validated strategy that is used to obtain more compounds for the same use. Note that Yang is also evidence:
PNG
media_image25.png
40
734
media_image25.png
Greyscale
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant additionally argues that Zitko teaches away from retro-amides because it teaches that the retro-amide leads to deterioration or loss of the compound’s activity. In response, Zitko does not teach away from the motivation to use a retro-amide strategy because for their compounds, the inversion of the amide linker usually leads to decrease or loss of activity, “but the remaining active retro-amides are more selective and probably also less toxic to mammalian cells (HepG2) in comparison with the pattern amides (N-phenylpyrazine-2-carboxamides)”. See also the last paragraph which provides motivation to make and test retro-amides:
PNG
media_image26.png
124
688
media_image26.png
Greyscale
Regarding Yang, Applicant argues that it relates to antifungal activity of compounds and that one of skill would not refer to Yang to arrive at antihelminthic compounds. In response, Yang is evidence of the knowledge and skill in the pesticide art. One of skill would refer to Hubsch to arrive at antihelminthic compounds of the quinolyl-chromane carboxamide type. Yang teaches and evidences that inverting the amide in useful compounds is a validated strategy in the art that is used to obtain more compounds for the same use.
Applicant additionally argues that Yang teaches away from retro-amides because the retro-amide 5f of fluxapyroxad shows inferior antifungal activity as compared to fluxapyroxad. In response, the result of retro-amide 5f in Yang would not discourage the artisan from using the retro-amide technique because of all the positive results in Yang. They explain in the abstract that their “studies showed that 5i was worthy of further investigation as a promising fungicide candidate.”
Additionally, at page 13191 they explain:
“In general, most of the compounds displayed considerable to excellent fungicidal activities against eight phytopathogens in vitro at 50 μg/mL (Table 1).”
“Most of these compounds were highly active against B. cinerea, R. cerealis, and S. sclerotiorum. As shown in Table 1, 5c, 5d, and 5j showed over 90% inhibitory rate against B. cinereal, which was comparable to that of boscalid and fluxapyroxad. For G. zeae, 5i and 5j showed better activity than the positive controls. Compounds
5i, 5p, 5q, and 5s displayed higher activity against P. infestans than boscalid and fluxapyroxad; 5h, 5i, 5j, 5p, 5q, 5r, and 5s exhibited excellent activities against P. sasakii, which were better than boscalid and fluxapyroxad. Eight compounds showed over 86% inhibitory rate against R. cerealis; boscalid and fluxapyroxad only showed 35 and 86% inhibitory rates respectively. All compounds exhibited excellent activities
against S. sclerotiorum.”
“Compounds 5i and 5q displayed excellent activities against P. infestans and P. sasakii, with EC50 values lower than the positive control fluxapyroxad. Nine compounds exhibited better fungicidal activity against R. cerealis than fluxapyroxad; especially, 5i showed excellent fungicidal activity with the EC50 value of 4.61 μg/mL, which was more active than that of fluxapyroxad with its EC50 value of 16.99 μg/mL.” See page 13192.
Thus, the artisan would have been motivated to make the reverse-amide (-NHCO-) compounds of the compounds of Hubsch since “exchanging the amide moiety for a retro-amide is a strategy successfully used in medicinal chemistry and drug design” with the aim of obtaining derivatives with similar or increased activity. At least both Zitko and Yang provided the motivation to use the reverse-amide technique.
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 1-6, 8 and 12 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 11 of U.S. Patent No. 10,889,573 in view of Zitko et al. (Molecules 2018, 23, 2390), Yang et al. (J. Agric. Food Chem. 2019, 67, 13185-13194). Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds and compositions as claimed in the rejected claims are prima facie obvious over claims 1-6 and 11 of the patent.
The disclosure of the patent teaches the particular compounds that represent patented claims 1-6 and 11. Examples of the anthelmintic compounds wherein Q is fluoro-substituted phenyl and R2 is dimethylamino are found in Table 1 of the patent as described above and are particular embodiments of the invention claimed in the reference patent.
Ascertainment of the difference between the conflicting application and the claims. (MPEP §2141.02)
The instant claims differ from the conflicting patented claims in the replacement of the amide linker with a reverse-amide linker (that is the amide (-CONH-) vs retro-amide (-NHCO-) linker between the quinoline and chromane core for the examples of the compounds covered by the patented claims.
Finding of prima facie obviousness--rational and motivation. (MPEP §2142-2413)
What is covered by the patented claims was exemplified in the patent.
One of ordinary skill would have been motivated to make reverse-amide (-NHCO-) linker derivatives of the compounds of Hubsch above because “exchanging the amide moiety for a retro-amide is a strategy successfully used in medicinal chemistry and drug design” with the aim of obtaining derivatives with similar or increased activity. This replacement is a research technique used routinely used before the filing date of the instant invention.
Regarding the elected species of formula
PNG
media_image2.png
186
262
media_image2.png
Greyscale
, it would have been obvious to make the reverse-amide analog compound wherein Q is a 2,3,5-trifluorophenyl ring as in the elected species in view that the patent disclosed the compounds wherein Q is 2,3,6-trilfuorophenyl, 3,4,5-trifluorophenyl, 2,4,5-trifluorophenyl and 2,3,4-trilfuorophenyl as follows:
PNG
media_image21.png
170
270
media_image21.png
Greyscale
,
PNG
media_image14.png
162
272
media_image14.png
Greyscale
(#47),
PNG
media_image17.png
202
248
media_image17.png
Greyscale
(#57), and
PNG
media_image18.png
162
272
media_image18.png
Greyscale
(#81).
The claimed compounds have exactly the same formula and same use as the patented compounds.
In addition, MPEP 2144.09 states: A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08,
This rejection is proper under MPEP 804 II. B. 2. (a):
Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because ONLY "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Applicant’s arguments are the same as for the 103 rejection above. Thus, the examiner’s response to arguments above is incorporate herein.
Conclusion
Claims 1-8 and 12 are rejected.
Not every piece of prior art found in the search has been applied against the instant claims. See MPEP 904.03.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
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, Clinton Brooks can be reached at 571-270-7682. 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.
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621 03/27/2026
Prosecution Insights