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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1 – 3, 6, 10, 13, 17, 20, 27, 30, 32, 34 – 35, 38, 88 – 91, 93, and 105) drawn to a compound, or pharmaceutically acceptable salt thereof, having a structure of formula (I),
PNG
media_image1.png
102
354
media_image1.png
Greyscale
wherein X1-2, Y, Ring A, and Ring B, are defined and the species election of
PNG
media_image2.png
200
400
media_image2.png
Greyscale
in the reply filed on October 14th, 2025 is acknowledged.
Claim 108 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (a method of inhibiting cyclin dependent kinase 19 (CDK19)), there being no allowable generic or linking claim. Additionally, claims 3, 6, 10, 13, 17, 20, 27, 30, 32, and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected chemical species. Election was made without traverse in the reply filed on October 14th, 2025. Hence claims 1 – 2, 34 – 35, 88 – 91, 93, and 105 are being examined on the merits herein.
However upon searching the elected species;
PNG
media_image2.png
200
400
media_image2.png
Greyscale
the elected species was found to be free of the prior art. Thus the search was expanded to rejoin chemical species with the following features: instant Ring A is unsubstituted pyridinyl, instant Ring B is substituted phenyl, instant X1 is N, instant X2 is S, and instant Y is S as defined by instant claim 1.
While chemical species having instant Ring A is unsubstituted pyridinyl, instant Ring B is substituted phenyl, instant X1 is N, instant X2 is S, and instant Y is S are rejoined; these chemical features are not encompassed by claims 3, 6, 10, 13, 17, 20, 27, 30, 32, and 38. Thus claims 3, 6, 10, 13, 17, 20, 27, 30, 32, and 38 are still withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected chemical species or rejoined chemical species wherein instant Ring A is unsubstituted pyridinyl, instant Ring B is substituted phenyl, instant X1 is N, instant X2 is S, and instant Y is S. Nonetheless, the election of species has been modified to only rejoin chemical species wherein instant Ring A is unsubstituted pyridinyl, instant Ring B is substituted phenyl, instant X1 is N, instant X2 is S, and instant Y is S. Thus the restriction requirement set forth in the office action mailed August 15th, 2025 is maintained.
Hence claims 1 – 2, 34 – 35, 88 – 91, 93, and 105 are being examined on the merits herein.
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.
Claim 105 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 105, recite, “the compound of claim 1 having a structure as recited in Table A,” in line 1; without stating the chemical name or chemical structure. Applicant is reminded that, where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). (See MPEP 2173.05(s)).
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, 34 – 35, 88, and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rosenthal et. al. ((2013), Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase, Bioorg. Med. Chem. Lett., 23, 5660-5666).
Regarding claims 1 – 2, 34 – 35, 88, and 90, Rosenthal et. al. teach compound 7a of the structure
PNG
media_image3.png
200
400
media_image3.png
Greyscale
(claim 1) (page 5663 column 1 table 3); wherein instant ring A is an unsubstituted 4-pyridine (claims 2 and 34); instant X1 is N; instant X2 is S; instant Y is S; instant ring B is phenyl (claims 35 and 90) wherein instant RB is Cl (claim 88) in the 3 and 4 position of the phenyl ring. Thus Rosenthal et. al. teach a compound that anticipates instant claims 1 – 2, 34 – 35, 88, and 90.
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 89 is rejected under 35 U.S.C. 103 as being unpatentable over Rosenthal et. al. ((2013), Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase, Bioorg. Med. Chem. Lett., 23, 5660-5666) in view of Lima et. al. ((2005), Bioisosterism: A Useful Strategy for Molecular Modification and Drug Design, 12, 23 – 49).
The teachings of Rosenthal et. al. as they relate to claim 1, from which claim 89 depend, are given previously in this office action and are fully incorporated here.
However, Rosenthal et. al. fails to teach a compound wherein instant Ring B is
PNG
media_image4.png
200
400
media_image4.png
Greyscale
(claim 89).
Nevertheless, Lime et. al. teach that bioisosterism is a strategy of Medicinal Chemistry for the rational design of new drugs, applied with a lead compound (LC) as a special process of molecular modification (page 23 column 1 paragraph 1). Furthermore, Lime et. al. teach that the success of this strategy in developing new substances which are therapeutically attractive has observed a significant growth in distinct therapeutic classes, being amply used by the pharmaceutical industry to discover new analogs of therapeutic innovations commercially attractive, and also as a tool useful in the molecular modification (page 23 column 1 paragraph 2). Moreover, Lime et. al. teach that there may be innumerous reasons for the use of bioisosterism to design new drugs, including the necessity to improve pharmacological activity, gain selectivity for a determined receptor or enzymatic isoform subtype – with simultaneous reduction of certain adverse effects -, or even optimize the pharmacokinetics the LC might present (page 23 column 1 paragraph 3). Additionally, Lima et. al. teach that -OH, -NH2, -CH3, -OR, -F,-Cl,-Br, -I, -SH, -Si3, -SR, and -PH2, are classical monovalent bioisostere equivalents (page 25 column 1 Table 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the 4-Cl of compound 7a of Rosenthal et. al. in view of Lima et. al. that is to, replace the 4-Cl for a 4-F. One or ordinary skill in the art would have been motivated to make this modification to improve pharmacological activity, gain selectivity for a determined receptor or enzymatic isoform subtype – with simultaneous reduction of certain adverse effects -, or even optimize the pharmacokinetics the compound 7a. One ordinary skill in the art would have had a reasonable expectation of success because -F and -Cl are known in the art classical monovalent bioisostere equivalents.
Claims 91 and 93 are rejected under 35 U.S.C. 103 as being unpatentable over Rosenthal et. al. ((2013), Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase, Bioorg. Med. Chem. Lett., 23, 5660-5666) and Lima et. al. ((2005), Bioisosterism: A Useful Strategy for Molecular Modification and Drug Design, 12, 23 – 49) as applied to claims 89 above.
The teachings of Rosenthal et. al. as they relate to claims 1 and 90, from which claims 91 and 93 depend, are given previously in this office action and are fully incorporated here. Moreover, the teachings of Lima et. al. as they relate to claim 89, are given previously in this office action and are fully incorporated here.
However, the prior art of Rosenthal et. al. and Lima et. al. fails to teach a compound wherein ring B is
PNG
media_image5.png
200
400
media_image5.png
Greyscale
(claim 91), wherein instant R1 are in the meta position and Y1 is an C1-C6alkyloxy (claim 93).
[AltContent: rect][AltContent: oval] Nevertheless, as mentioned above, Lima et. al. teach that -OH, -NH2, -CH3, -OR, -F,-Cl,-Br, -I, -SH, -Si3, -SR, and -PH2, are classical monovalent bioisostere equivalents (page 25 column 1 Table 1). Thus it would have been obvious to one of ordinary skill in the art to substitute the prior art Cl atom with the instant recitation -OR group as known in the art monovalent bioisostere equivalents. Moreover, in regard to instant claim 91 limitation that instant R1 is in the meta position
PNG
media_image5.png
200
400
media_image5.png
Greyscale
(circled); the only difference between the instant compound and the prior art compound of 7a
PNG
media_image3.png
200
400
media_image3.png
Greyscale
of Lima et. al. is the position of the -Cl atom; the ortho position (squared). Thus given that the only structural difference between a compound species of the instant claims and the prior art compound of 7a is the position of one of the instant R1 substituents both compounds are position isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).(MPEP 2144.09(II)).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the 4-Cl of compound 7a of Rosenthal et. al. in view of Lima et. al. that is to, replace the 4-Cl with an C1-C6alkyloxy such as -OCH3. Additionally, it would have been obvious to further move the instant R1 from the ortho position to the meta position. One of ordinary skill in the art would have been motivated to make this modification to improve pharmacological activity, gain selectivity for a determined receptor or enzymatic isoform subtype – with simultaneous reduction of certain adverse effects -, or even optimize the pharmacokinetics the compound 7a. One of ordinary skill in the art would have had a reasonable expectation of success because -Cl and -OCH3 are known in the art classical monovalent bioisostere equivalents.
Claim 105 is rejected under 35 U.S.C. 103 as being unpatentable over Rosenthal et. al. ((2013), Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase, Bioorg. Med. Chem. Lett., 23, 5660-5666) and Lima et. al. ((2005), Bioisosterism: A Useful Strategy for Molecular Modification and Drug Design, 12, 23 – 49) as applied to claims 89 above.
The teachings of Rosenthal et. al. as they relate to claim 1, from which claim 105 depend, are given previously in this office action and are fully incorporated here. Moreover, the teachings of Lima et. al. as they relate to claim 89, are given previously in this office action and are fully incorporated here.
However, the prior art of Rosenthal et. al. and Lima et. al. fails to teach a compound of structure
PNG
media_image6.png
200
400
media_image6.png
Greyscale
, that is instant A32; wherein instant Y is O (claim 105).
Nevertheless, Lima et. al. further teach that -O-,-S-,-Br, -I, -SH, and -PH2, are classical divalent bioisostere equivalents (page 25 column 1 Table 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to further modify instant Y position of the modified compound 7a of Rosenthal et. al. and Lima et. al. that is to, replace the O atom for a S atom. One or ordinary skill in the art would have been motivated to make this modification to improve pharmacological activity, gain selectivity for a determined receptor or enzymatic isoform subtype – with simultaneous reduction of certain adverse effects -, or even optimize the pharmacokinetics the compound 7a. One ordinary skill in the art would have had a reasonable expectation of success because O and S are known in the art classical divalent bioisostere equivalents.
Conclusion
Claims 1 – 2, 34 – 35, 88 – 91, 93, and 105 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627