DETAILED ACTION
This office action is in response to applicant’s filing dated February 19, 2026.
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 .
Status of Claims
Claims 1-12, 15, and 17-23 are pending in the instant application. Acknowledgement is made of applicant’s remarks filed February 19, 2026. Claims 13, 14, and 16 were previously cancelled.
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a compound of the formula of claim 1, in the reply filed on February 19, 2026 is acknowledged.
Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 19, 2026.
Applicant’s election without traverse of the elected compound:
PNG
media_image1.png
94
249
media_image1.png
Greyscale
As the elected compound of formula (I) in the reply filed on February 19, 2026 is acknowledged.
Compound is a compound of formula (I) wherein X is -CR6, Y is -CR6, Z is -CR6, ring A is a fused bicyclic heteroaryl (benzoxazole), R1 is hydrogen, R4 is phenyl, wherein the phenyl is optionally substituted with 1 to 3 groups selected from R7 (phenyl substituted with one R7 group), R5 is hydrogen, R2 is -SO2Rg (-SO2(C1-C4)alkyl), R3 is cyano, R6 is hydrogen, R7 is (C1-C4)alkyl (methyl) and Rg is (C1-C4)alkyl (methyl). Compound has been found to be free of prior art. Thus, examination has been expanded to encompass the expanded species:
PNG
media_image2.png
72
159
media_image2.png
Greyscale
Where X = Cl
The expanded species is a compound of formula (I) wherein X is -CR6, Y is -CR6, Z is -CR6, ring A is a fused bicyclic heteroaryl (benzoxazole), R1 is hydrogen, R4 is phenyl, wherein the phenyl is optionally substituted with 1 to 3 groups selected from R7 (phenyl substituted with one R7 group), R5 is hydrogen, R2 is halo (chloro), R3 is nitro, R6 is hydrogen, and R7 is (C1-C4)alkyl (ethyl).
Claims 1-2, 6-7, 9-12, 15, and 17-22 are read on the elected compound.
Claims 1-2, 6-8, 10-12, 15, and 17-22 are read on the expanded species.
Claims 3-5 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 19, 2025.
Claims 1-2, 6-12, 15, and 17-22 are presently under examination as they relate to the elected species:
PNG
media_image1.png
94
249
media_image1.png
Greyscale
and the expanded species:
PNG
media_image2.png
72
159
media_image2.png
Greyscale
Where X = Cl
Priority
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 20 and 21 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 20 and 21 recites the limitation "R7" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 1 mentions R7 as a part of the Markush claim defining a compound of formula I. However, Claim 1 does not specify the location of R7 in formula I, as such it is unclear as to what R7 refers to. For the purposes of examination, R7 will be interpreted as a substituent on R4 if a cyclic substituent is chosen.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 6-12, 15, and 17-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of formula (I) wherein Ring A is a benzoxazole, benzoxazole-2-d, imidazo[1,2-a]pyridine, benzimidazole, 2H-benzotriazole, iso-quinoline, or benzothiazole; X, Y, and Z are all N or two of which are N and one is CH; R1 and R5 are hydrogen, halo, a (C-1-C4)alkyl; R4 is a hydrogen, halo, a (C-1-C4)alkyl, or a phenyl optionally substituted with a hydrogen, halo, or (C-1-C4)alkyl group as R7, and R2, R3, Rg, Rh, X1, and Ri are substituted as described does not reasonably provide enablement for the full scope of variables of Ring A, X, Y, Z, R1, R4, R6, and R7 in the instant claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of the formula (I) or a pharmaceutically acceptable salt thereof.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to compounds of the formula:
PNG
media_image3.png
113
206
media_image3.png
Greyscale
allowing for myriad combinations of variables as described in the claims with only the aryl amide in common between the myriad of compounds.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Tautermann (V, Quantum Mechanics in Drug Discover, Humana Press, 2020, Chapter 1, pp. 1-17), teaches drug discovery is a very challenging, cost-intensive, and in terms of investment risky endeavor; on average, it takes 10–15 years and an investment of more than 2.5 billion dollars to get a new drug to the Market; especially the clinical phases cause extremely high costs and late-stage failures, especially in phase II studies, are quite common (page 1, 1st paragraph). Tautermann teaches the largest attrition in clinical phases is observed in phase II studies; the main goal is the assessment of the efficacy of the compound yielding a clinical proof of concept; a recent analysis from four major pharma companies revealed that the cause for attrition in phase II is mainly caused by lack of efficacy followed by safety issues; efficacy for a certain indication is usually preclinically tested in animal models; however, the translatability from animal models to the human situation is not always given; there are several reasons for this; often the disease condition cannot adequately be induced in animals (page 3, last paragraph). Tautermann teaches small molecules have several advantages, such as being cell and brain permeable, the lower cost of goods in their production, and oral administration; however, they are not always the easiest path forward for challenging targets; especially in the case of difficult or so far undrugable targets, new design strategies are required to be successful (page 5, last paragraph). Thus, Tautermann further establishes that the state of the art of drug design is highly unpredictable.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts where R4- was not defined as mentioned above in the present application.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
Claim Rejections - 35 USC § 102
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.
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.
Claims 1-2, 6-8, 10-12, 15, and 17-19, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Orsi et al (U, Journal of Medicinal Chemistry, 2022; 65, 21, 14843-14863).
Regarding claims 1-2, 6-8, 10-12, 15, 17-19, Orsi teaches of compound 6a:
PNG
media_image2.png
72
159
media_image2.png
Greyscale
Compound BAY-4931 is a compound of formula (I) wherein X is -CR6, Y is -CR6, Z is -CR6, ring A is a fused bicyclic heteroaryl (benzoxazole), R1 is hydrogen, R4 is phenyl, wherein the phenyl is optionally substituted with 1 to 3 groups selected from R7 (phenyl substituted with one R7 group), R5 is hydrogen, R2 is halo (chloro), R3 is nitro, R6 is hydrogen, and R7 is (C1-C4)alkyl (ethyl) (pp. 14843, paragraph 1, abstract figure).
Thus, Orsi anticipates the compounds of claims 1-2, 6-8, 10-12, 15, 17-19.
Regarding claim 22, Orsi examined the pharmaceutical activity of compound BAY-4931 through developing pharmaceutical compositions comprising the pharmaceutically acceptable carriers of water and formic acid and compound BAY-4931 which were applied to a mass spectrometry covalent binding assay (pp. 14850, Table 5 and pp. 14858, paragraph 21). As such, Orsi anticipates a pharmaceutical composition of claim 22.
Claims 1-2, 9, 12, 15, 17, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garofalo et al. (WO 2021007477).
Regarding claims 1-2, 9, 12, 15, and 17, Garofalo et al. teaches of compound 125 (WO 2021007477, pp. 216):
PNG
media_image4.png
123
190
media_image4.png
Greyscale
Compound 125 is a compound of formula (I) wherein X is -CR6, Y is -CR6, Z is -CR6, ring A is a fused bicyclic heteroaryl (1-H Indazole), R1 is hydrogen, R4 is a 4- to 6- membered heterocyclyl, R5 is hydrogen, R2 is -ORg where Rg is hydrogen, R3 is cyano, and R6 is hydrogen (WO 2021007477, pp. 216).
Thus, Garofalo anticipates the compounds of claims 1-2, 9, 12, 15, and 17.
Regarding claim 22, Garofalo claims a pharmaceutical composition of WO 2021007477 Claim 1, where Compound 125 is an exemplified embodiment. and at least one pharmaceutically acceptable carrier (WO 2021007477, pp. 553, claim 50). Thus Garofalo anticipates the pharmaceutical composition of claim 22 in the instant application.
Conclusion
Claims 1-2, 6-12, 15, and 17-22 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON RAFANAN ULLMAN whose telephone number is (571)272-6623. The examiner can normally be reached 7:30 am to 5:00 pm M-F.
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, Amy Clark can be reached at (571) 272-1310. 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.
/AARON RAFANAN ULLMAN/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
Prosecution Insights