DETAILED ACTION
All rejections and objections not shown below have been withdrawn.
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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/089,965 and 63/151,468, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicate a lack of support for the structure of ring A in claim 269, some of the compounds of Table C (claim 412) and table 1b of claim 427, thus these claims were given a priority date of 10/08/2021. All other claims were given a priority date of 10/09/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/14/2026 is being considered by the examiner.
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 426, 549 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.
Regarding claims 426 and 549, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103- New Due to IDS
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.
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.
Claim(s) 1, 183-186, 189-193, 248-249, 255-257, 263, 269-270, 412-414, 522-531, 539-546 is/are rejected under 35 U.S.C. 103 as being unpatentable over Graham (Graham et al., US 10428063, 2019-10-01, IDS) in view of Barillari (Barillari et al., Classical Bioisosteres, Bioisosteres in Medicinal Chemistry, First Edition. Edited by Nathan Brown, 2012, pages 15-29).
The reference Graham teaches the following compound on column 74, wherein A R1c=R2a=R2b=R3a=R3b=R4=R7=H, A=phenyl, RcA= methyl.
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The reference Graham teaches the following compound on column 65, wherein A R1c= R3a=R3b=R4=R7=H, A=phenyl, R2a=R2b==methyl, RcA= H.
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The reference Graham teaches the following general formula (reference claim 1):
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This helps to teach claims 1, 183-186, 189-193, 248-249, 255-257, 263, 269-270, 412-414, 522-531, 539-546.
The reference Graham also teaches “The present invention relates to a method for using the compounds of the present invention and compositions thereof, to treat mammalian hyper-proliferative disorders. Compounds can be utilized to inhibit, block, reduce, decrease, etc., cell proliferation and/or cell division, and/or produce cell death e.g. apoptosis. This method comprises administering to a mammal in need thereof, including a human, an amount of a compound of this invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof; etc. which is effective to treat the disorder. Hyper-proliferative disorders include but are not limited, e.g., psoriasis, keloids, and other hyperplasias affecting the skin, benign prostate hyperplasia (BPH), solid tumours, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Those disorders also include lymphomas, sarcomas, and leukaemias.
Examples of breast cancer include, but are not limited to invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ”[50-51] and “A further aspect of the invention is the use of the compounds according to formula (I) for the treatment of cervical-, breast-, non-small cell lung-, prostate-, colon- and melanoma tumors and/or metastases thereof, especially preferred for the treatment thereof as well as a method of treatment of cervical-, breast-, non-small cell lung-, prostate-, colon- and melanoma tumors and/or metastases thereof comprising administering an effective amount of a compound of formula (I)”[49].
This helps to teach claim 414.
The reference Graham also teaches “The compounds of the present invention can be administered with pharmaceutically-acceptable carriers or auxiliaries well known in the art using any effective conventional dosage unit forms, including immediate, slow and timed release preparations, orally, parenterally, topically, nasally, ophthalmically, optically, sublingually, rectally, vaginally, and the like”[53].
This helps to teach claim 413.
The reference Graham does not teach the specific compound of the instant invention, wherein there are two nitrogens in instant ring C, the reference Graham only teaches one nitrogen in that ring.
The reference Barillari teaches bioisosteres, “The discovery and development of a candidate for clinical evaluation is along process that involves small modifications to a lead compound to improve some of its properties, such as pharmacological activity, selectivity, and pharmacokinetics. This is often achieved by the medicinal chemists by replacing a functional group with groups sharing similar physical or chemical properties and maintaining similar activity, which are defined as bioisosteres. We will hereby provide a historical overview of the development and evolution of the concepts of isosterism and bioisosterism, followed by a selection of successful examples of bioisosteric modifications reported in the literature”(page 15).
The reference Barillari teaches the following bioisosteres (pages 18 and 19) and “The substitution of phenyl ring with pyridine is widely used to improve metabolic stability”(page 19):
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Graham with Barillari to achieve a compound of the instant invention because one of ordinary skill in the art would recognize -N= and -CH= as bioisosteres which by definition are likely to have similar activity and thus be useful to treat cancer. One would be motivated to make the change because it is standard practice in the development of a drug candidate for clinical evaluation to do small modifications to a lead compound to improve some of its properties, such as pharmacological activity, selectivity, and pharmacokinetics. This is often achieved by the medicinal chemists by replacing a functional group with groups sharing similar physical or chemical properties and maintaining similar activity, which are defined as bioisosteres (as taught by Barillari). One would have a reasonable expectation of success because -N= and -CH= are known bioisosteres and because swaps of N for ring C have been successful before (as taught by Barillari, page 19).
Claim(s) 1, 415-417 and 425-427 is/are rejected under 35 U.S.C. 103 as being unpatentable over Graham (Graham et al., US 10428063, 2019-10-01, IDS) in view of Barillari (Barillari et al., Classical Bioisosteres, Bioisosteres in Medicinal Chemistry, First Edition. Edited by Nathan Brown, 2012, pages 15-29) further in view of ROBICHAUX (ROBICHAUX et al., WO 2018094225 A1, 2018-05-24, IDS).
The Graham and Barillari has been discussed supra (and are incorporated herein by reference) and do not disclose EGFR cancer(claims 415-417, 425-427).
The reference ROBICHAUX teaches “Approximately 10-15% of NSCLCs harbor activating EGFR mutations. For the majority of these patients whose tumors have "classical" sensitizing mutations (L858R and exon 19 deletions), TKIs such as gefitinib and erlotinib provide dramatic clinical benefit, with approximately 70% experiencing objective responses (OR), improved progression free survival (PFS), and quality of life compared to chemotherapy alone (Maemondo et al, 2010). However, approximately 10-12% of EGFR mutant NSCLC tumors have an in-frame insertion within exon 20 of EGFR (Arcila et al, 2012), and are generally resistant to EGFR TKIs. In addition, 90% of HER2 mutations in NSCLC are exon 20 mutations (Mazieres et al, 2013). Together, EGFR and HER2 exon 20 mutations comprise approximately 4% of NSCLC patients. The data thus far suggests that available TKIs of HER2 (afatinib, lapatinib, neratinib, dacomitinib) have limited activity in patients with HER2 mutant tumors with many studies reporting OR rates below 40% (Kosaka et al, 2017), although some preclinical activity is observed in HER2 mouse models treated with afatinib (Perera et al, 2009)”[0005] and “A method of treating cancer in a subject comprising administering an effective amount of poziotinib to the subject, wherein the subject has been determined to have one or more EGFR exon 20 mutations”(reference claim 1).
This help to teach claims 415-417, 425-427.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Graham and Barillari with ROBICHAUX because Graham teaches its compounds (and Barillari teaches bioisosteres would have similar activity) for treatment of NSCLC and ROBICHAUX teaches the treatment of NSCLCs harbor activating EGFR mutations as a subset of this patient population. One would be motivated to treat this population because it is 10-15% of NSCLCs patients. One would have a reasonable expectation of success because Graham teaches its compounds for treatment of NSCLC.
Allowable Subject Matter
Claims 196, 198-200, 215, 221, 232, 272, 532-538, 547-548 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.
Claims 550-553 are allowable.
Response to Arguments
Applicant's arguments filed 04/14/2026 have been fully considered but they are not persuasive.
The applicants argue that the indefiniteness from the phrase ‘for example’ has been removed from claims 426. This argument is not persuasive because claim 426 includes the following which is language that means for example: e.g. and exemplary and exemplified.
Conclusion
Claims 1, 183-186, 189-193, 248-249, 255-257, 263, 269-270, 412-414, 415-417, 425-427, 522-531, 539-546, 549 are rejected.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 04/14/2026 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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