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 – 9, 11 – 14, and 16 – 20) drawn to a compound of Formula I,
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wherein R1-6, q, Ring A, Ring B, Z, and Y are defined and the species election of N-(3-(5-(2-((5-acrylamido-2-methoxyphenyl)amino)pyridin-4-yl)-2-(methylthio)-1H-imidazol-4-yl)phenyl)-2-((1-oxoisoindolin-2-yl)methyl)benzamide of structure
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in the reply filed on October 10th, 2025 is acknowledged.
Claims 21 – 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (a method of inhibiting the activity of EGFR), there being no allowable generic or linking claim. Additionally, claims 7, and 16 – 17, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected compounds species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 10th, 2025.
However, upon the initial search the elected specie
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was found to be free of the prior art; therefore, the search was expanded, and all non-elected species were rejoined. Thus the election of species required in the Restriction Requirement mailed August 11th, 2025 is withdrawn; but, the restriction between Groups I and Group II is maintained.
Hence claims 1 – 9, 11 – 14, and 16 – 20 are being examined on the merits herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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.
Claim Objections
Claims 6 – 8, and 17 – 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 103
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 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 – 2, 4 – 5, 9, 11 – 14, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Günther et .al. ((2017), Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site, J. Med. Chem., 60, 5613 – 5637) in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
Regarding claims 1 – 2, 4 – 5, 9, 11 – 14, and 20, Günther et .al. teach that pathologically increased EGFR activity is closely linked to tumorigenesis and tumor cell growth in general and has been identified as a key driver for the onset and progression of nonsmall cell lung cancer (NSCLC) in particular (page 5613 column 1 paragraph 1). Additionally, Günther et .al. teach that insights into the SAR of trisubstituted pyridinylimidazoles as EGFR inhibitors (page 5614 column 2 paragraph 1). Specifically, Günther et .al. teach compound 19a of structure
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(page 5621 Table 2) wherein A is pyridine; B is phenyl (claim 2); Z=O and Y are absent; R1 is CH3 (claim 4); R2 is phenyl substituted with -OCH3 and NHC(O)C2 alkenyl (claim 5); R3 is H (claim 9); and R6 is H (claim 13). Furthermore, Günther et .al. teach that compound 19a had IC50 values of <1 nM for wild type EGFR, <1 nM for L858R mutant EGFR, and <1 nM for L858R/T790M mutant EGFR. Moreover, Günther et .al. teach that in the Mass Spectrometry Experiments a mixture of 52 µM of protein with 100 µM of inhibitor, which includes compound 19a, in buffer (claim 20) 25 mM TRIS, 250 mM NaCl, 10% glycerol, 1 mM TCEP, pH 8 was performed (page 5626 column 1 paragraph 2).
However, Günther et .al. fails to teach a compound wherein ring B has an amino group wherein R4 is H (claims 1, 11 – 12, and 14).
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (page 2529 column 1 paragraph 1). Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties (page 2529 column 1 paragraph 1). Moreover, Meanwell teach that F, OH, NH2, and CH3 are classical monovalent bioisosteres (page 2530 column 1 Table 1). Thus Meanwell suggest the ability to substitute F for NH2 with a reasonable expectation that compounds with either F or NH2 would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify compound 19a of Günther et .al. in view of Meanwell, that is to substitute the F atom for an NH2 group. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both F and NH2 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Günther et. al. ((2017), Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site, J. Med. Chem., 60, 5613 – 5637) and Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591) as applied to claims 1 – 2, 4 – 5, 9, 11 – 14, and 20, above, and further in view of Ali et. al. ((2014), Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, 150 – 169).
The teachings of Günther et. al. and Meanwell as they relate to claim 1, from which claim 16 depend, are given previously in this office action and are fully incorporated here.
However, the prior art of Günther et. al. and Meanwell fail to teach a compound wherein B is a thiophene of the structure
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(claim 16).
Nevertheless, Ali et. al. teach that Isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules (page 150 column 1 paragraph 1). Furthermore, Ali et. al. teach that this approach is now commonly used in advance drug design to optimize lead compound by rational molecular modification in order to improve its pharmacokinetic i.e. absorption, distribution, metabolism and excretion (ADME) or pharmacodynamic i.e. receptor, enzyme or channel level behavior (page 150 column 1 paragraph 1). Specifically, Ali et. al. teach that benzene/phenyl of structure
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is a ring equivalent to thiophene of the structure
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(page 153 column 1 Figure 1). Thus Ali et. al. suggest the ability to substitute a phenyl/benzene ring for a thiophene ring with a reasonable expectation that compounds with either ring system would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify compound 19a of Günther et .al. in view of Meanwell, that is to substitute the F atom for an NH2 group, in further view of Ali et.al. that is to replace the phenyl ring of B with a thiophene ring. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both phenyl/benzene and thiophene are ring equivalents and would be reasonable expected to at least have the same biological properties.
Conclusion
Claims 1 – 2, 4 – 5, 9, 11 – 14, 16, and 20 are rejected. Claims 6 – 8, and 17 – 19 are objected.
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.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627