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 .
Response to Arguments
Applicant’s arguments, see Page 1, filed 11/14/2025, with respect to the 102 rejections of claims 1-3, 25, 47, 49, 51-65 and 70 under Abe et al. (US patent No. 20200253975), Hasako et al. (WO 2020138400 A1) as well as the 103 rejection over claims 4-5, 15-16, 26-27, 36-38, 68-69 and 71 over Abe et al. (US patent No. 20200253975) in view of Hastings et al. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer, Thoracic Tumors, August 2019, Pages 1311-1320 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Miyadera et al. (US Patent No. 20190262345), (US Patent No. 20200253975), Hasako et al. (WO 2020138400 A1) and Hastings et al. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer, Thoracic Tumors, August 2019, Pages 1311-1320.
The teachings of Miyadera, Hasako, Ade and Hastings from the previous office action is obvious to the claimed invention.
Applicants remarks over the 102 rejection of claims 1-3, 25, 36-37, 39-40, 42, 57-67 and 70 over Miyadera et al. (US Patent No. 20190262345) are not persuasive. The teachings of Miyadera from the previous office action reads to the amended limitations of claim 1 of a method of treating cancer having exon 20 D770_N771insX mutation.
Applicants has canceled claims 39-42 and added claim 72, no new matter was added. Claims 1-5, 15-16, 25-27, 36-38, 47, 49 and 51-72 is pending. Claims 1-5, 15-16, 25-27, 36-38, 47, 49 and 51-72 is now evaluated on its merits.
Claim Rejections - 35 USC § 102
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 1-5, 15-16, 25-27, 36-38, 52, 57-67, 70 and 72 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Miyadera et al. (US Patent No. 20190262345).
Regarding claims 1-5, 15-16, 25, 36-38, 52, 57-67, 70 and 72, Miyadera teaches an administration of once, twice or three times a day oral antitumor agent for treating a malignant and non-malignant tumor patient expressing EGFR having exon 20 insertion mutation comprising (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide at a dosage of 0.1 to 1000 mg per day (relevant to claims 2-5, 15-16, 25-27, 38) (abstract, para. 0017, 0101). Of the malignant tumors, Miyadera teaches non-small cell lung cancer (relevant to claims 57-61) (para. 0063) and patients that were previously treated and not treated with a known EGFR exon 20 insertion mutation inhibitor that shows to be insufficient (relevant to claims 62-67 and 70) (para. 0048).
Miyadera additionally teaches exon 20 point mutations of D770_N771insSVD, D770_N771insG, H773_V774insNPH, V769_D770insASV, N771_P772insN, H773_V774insH (relevant to claim 72) (para. 0028, 0111) and in test example 8, Miyadera administers (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide for 28 consecutive days (relevant to claims 36-37) (para. 0155) and treating the malignant tumor with a step of predicting the success of chemotherapy (para. 0106). Further, the EGFR may also have a mutation other than exon 20 insertion mutation (such as exon 19 deletion mutation, L858R mutation, or L790M mutation) (relevant to claim 52) (para. 0069).
In terms of claim 1 the teachings of Miyadera of D770_N771insG, N771_P772insN and H773_V774insH reads to the limitations D770_N771insX, N771_P772insX and H773_V774insX of claim 1 as it is known in the art the distinction of “X” in an EGFR mutation represents any amino acid.
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.
Claims 47, 49, 51 and 55-56 are rejected under 35 U.S.C. 103 as being unpatentable over Miyadera et al. (US Patent No. 20190262345) in view of Abe et al. (US Patent No. 20200253975).
The teachings of Miyadera for the above 102 rejection of claims 1-5, 15-16, 25-27, 36-38, 52, 57-67, 70 and 72 are incorporated herein by reference.
Miyadera fails to teach the treatment further by the presence of one or more EGFR exon 18 mutation, exon 21 mutation and T790M mutation.
Abe teaches an oral antitumor agent for treating a malignant tumor patient expressing EGFR, such as malignant non-small cell lung cancer, having at least one mutation selected from the group consisting of G719X mutation of exon 18, E709X mutation of exon 18, L861X mutation of exon 21 and T790M comprising administration of (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide or a salt thereof from about 0.05 to 1000 mg per dosage unit form (relevant to claims 47, 49, 51 and 55) (abstract). Abe additionally teaches the EGFR may also have a mutation other than exon 18 mutation (such as exon 19 deletion mutation, L858R mutation, or L790M mutation) (relevant to claim 56) (para. 0071-0072).
Therefore it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered the treatment taught by Miyadera to treat NSCLC wherein the NSCLC additionally has an EGFR exon 18 mutation, EGFR exon 21 mutation and T790M mutation. One would have been motivated to do so from the teachings of Miyadera on administering S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide to treat NSCLC exon 20 insertion, exon 19 deletion and L858R mutations and the teachings of Abe of S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide to treat NSCLC G719X mutation of exon 18, E709X mutation of exon 18, L861X mutation of exon 21 and T790M.
The teachings of Miyadera and Abe are to the same therapeutic to treat the same cancer, thus there would be a reasonable expectation of treating NSCLC characterized by exon 20 mutation, exon 18 mutations of G719X and E709X, exon 19 mutation, exon 21 mutation of L861X, L858R and T790M from the teachings of Miyadera and Abe.
Claims 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Miyadera et al. (US Patent No. 20190262345) in view of Hasako et al. (WO 2020138400 A1)
The teachings of Miyadera for the above 102 rejection of claims 1-5, 15-16, 25-27, 36-38, 52, 57-67, 70 and 72 are incorporated herein by reference.
Miyadera fails to teach the treatment further characterized by the presence of one or more EGFR exon 20 point/substitution mutation of T790X, L792X and S768X.
Regarding claims 53-54, Hasako teaches an antitumor agent for treating a malignant tumor patient expressing EGFR having at least one mutation in non-small-cell lung cancer selected from the group consisting of a point exon 20 mutation of L792X comprising administration of (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide at 0.05 to 1000 mg per dosage unit form (abstract, para. 0035).
Therefore it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered the treatment taught by Miyadera to treat NSCLC wherein the NSCLC additionally has an EGFR 20 point/substitution mutation of L792X. One would have been motivated to do so from the teachings of Miyadera on administering S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide to treat NSCLC exon 20 insertion mutation and the teachings of Hasako of S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide to treat NSCLC exon 20 mutation of L792X. The teachings of Miyadera and Hasako are to the same therapeutic to treat the same cancer expressing exon 20 mutations. There is a reasonable expectation of treating NSCLC expressing exon 20 point mutations as expressed in claim 1 and exon 20 mutation of L792X by administration of S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide from the teachings of Miyadera and Hasako.
Claims 68-69 and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Miyadera et al. (US Patent No. 20190262345) in view of Hastings et al. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer, Thoracic Tumors, August 2019, Pages 1311-1320.
The teachings of Miyadera for the above 102 rejection of claims 1-5, 15-16, 25-27, 36-38, 52, 57-67, 70 and 72 are incorporated herein by reference.
Miyadera fails to teach the treatment wherein the patient have been previously treated with immunotherapy, not previously treated with chemotherapy and is newly diagnosed.
Hastings teaches immune checkpoint inhibitors (ICIs) from clinical evidence suggests that EGFR mutant lung cancers rarely derive benefit from treatment with ICIs and rates of positivity for potential predictors of response to ICIs, such as tumor mutation burden (TMB) and concurrent programed death-ligand 1 (PD-L1) plus CD8+ tumor infiltrating lymphocyte expression, are low (intro, 1st para).
Therefore it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered the treatment of (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide taught by Miyadera to treat patients that were previously treated with immunotherapy, not previously treated chemotherapy and is newly diagnosed. One would have been motivated to do so from the teachings of Miyadera of administration to patients who were resistant to EGFR TKI’s and the teachings of Hastings on ICIs being used as an alternative to EGFR mutant lung cancer resistance of EGFR TKI’s, showing low to no benefit. Additionally one would treat a patient population who have been newly diagnosed and previously been treated with ICI’s to test the efficacy of the drug on patients who had already been treated with multiple medications. There is a reasonable expectation of treating lung cancer expressing exon 20 insertion mutation wherein the patients were previously treated with in immunotherapy, not previously treated with chemotherapy and newly diagnosed from the teachings of Miyadera and Hastings.
Conclusion
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627