Detailed Action
The present office action is in response to amendments filed 10 Jun 2025.
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
Claims 1-4, 10, 12, 29, 35, 49-50 and 74 of the pending application have been examined on the merits. Claims 5-6, 14-15, 17, 19, 21-22, 27, and 33 of the pending application remain withdrawn. Acknowledgement is made of the amendments filed on 10 Jun 2025. Acknowledgement is made of the cancellation of claims 7-9, 11, 13, 16, 18, 20, 23-26, 28, 30-32, 34, 36-48, and 51-73.
Priority
The priority date for the instant application remains 17 Apr 2019.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 30 Jan 2025, 05 Mar 2025, and 10 Jun 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Acknowledgement is made of the amendments filed 10 Jun 2025.
The rejection of claim 63 under 35 USC § 101 is rendered moot following applicant amendments.
All rejections pertaining to claims 9 and 30 are rendered moot following applicant amendments.
The rejection of claims 1-4, 10, 12, 29, 35, 49-50, 63, and 74 under 35 USC § 103 over US 2018/0147279 (provided in IDS 09/09/24) and Wu et al. (OncoTargets Therapy, 2016, 9:6137-6145; provided in the office action mailed 10 Dec 2024) is rendered moot following applicant amendments.
The rejections of claims 1-4, 10, 12, 29, 35, 49-50, 63, and 74 under 35 USC § 102(a)(1) over Zeng et al. (J Thorac Onco, 2018, 13:e93-e95; provided in the office action mailed 10 Dec 2024), hereinafter Zeng, and Kobayashi et al. (Clin Cancer Res, 2015, 21:5305-5313; provided in IDS 09/09/24), hereinafter Kobayashi, are rendered moot following applicant amendments.
Regarding the rejections of claims 1-4, 10, 12, 29, 35, 49-50, 63, and 74 under 35 USC § 102(a)(1) over Heigener et al. (Oncologist, 2015, 20:1167-1174; provided in the office action mailed 10 Dec 2024), hereinafter Heigener, applicant's arguments filed 10 Jun 2025 have been fully considered but they are not persuasive.
Applicant argues that Heigener does not reject the instant claims on the grounds that the reference does not disclose that the subject being administered afatinib to treat non-small cell lung cancer (NSCLC) had no mutations at C797 and T790.
Applicant’s arguments are not persuasive because any non-wild type mutations in the references are disclosed and by not explicitly mentioning that there were mutations at C797 and T790 on EGFR exon 20, the reference inherently treats NSCLC in subjects with the wild type at positions C797 and T790 of EGFR exon 20. Heigener reports uncommon EGFR mutations using data directly from physicians who had patients in a larger clinical study, the Compassionate Use Program, and further teaches that a 55% of patients had exon 20 mutations (showing testing of exon 20) and that 30 patients had T790M mutations, none of which were paired with the E709X mutations (pg. 1168, column 2). By not stating mutations found for positions C797 and T790 of EGFR exon 18, Heigener inherently teaches the treatment of NSCLC in a patient with wild type C797 and T790. This analysis has been amended to the rejections found in the office action dated 10 Dec 2024 which have been restated below.
In light of the discussion above, the rejection of claims 1-4, 10, 12, 29, 35, 49-50, 63, and 74 under 35 USC § 102(a)(1) as anticipated by Heigener is maintained for the reasons of record and restated below.
Claim Rejections - 35 USC § 112(b)
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 1 and 35 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.
Claim 1 claims a method of treating cancer in a subject comprising administering a quinazolinamine derivative TKI to the subject and further limits the subject to having “been determined to have one or more EGFR TKI resistant mutations, wherein the subject has been determined to not have a mutation at residues C797 and T790” before limiting the allowable mutations to a Markush group of positions. The mutated positions, however, include “one or more EGFR exon 20 mutations located at one or more residues selected from the group consisting of A763, S768, H773, D770, C775, L792, C797, S811, and R776…” Claim 1 both limits the subject to not have a mutation at the C797 residue, but also allows for the C797 residue to be mutated. A person of skill in the art would thus be unclear as to whether the C797 residue can be mutated or not. Applicant may overcome this rejection by amending the claim to clarify whether the C797 residue can be mutated or not. This new grounds of rejection is made necessary following applicant amendments.
In the interest of compact prosecution, examiner is interpreting claim 1 to mean the C797 residue must be determined not to have been mutated in the subject.
Claim 35 recites the limitation "wherein the one or more EGFR TKI resistant mutations are selected from the group consisting of E709X, G724S, L718X, L861Q, T8541, V8431, and/or L792X, wherein X is any amino acid." There is insufficient antecedent basis for this limitation in the claim, specifically, the E709 residue may only be a E709A mutation in the claim (claim 1) that claim 35 is dependent on. Applicant may overcome this rejection by amending E709X to be E709A in claim 35. This new grounds of rejection is made necessary following applicant amendments.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 10, 12, 29, 35, 49-50, 63, and 74 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Heigener.
Heigener teaches that treatment with EGFR TKI is standard in patients with metastatic NSCLC harboring activating mutations (pg. 1167, column 1). Heigener also teaches, however, that the efficacy of first-generation reversible EGFR-TKIs like erlotinib and gefitinib on tumors with uncommon EGFR mutations is reportedly lower than in common mutations (pg. 1167, column 2). Heigener further reports data from the Compassionate Use Program (CUP) which enrolls patients with advanced NSCLC that were ineligible to participate in other actively accruing afatinib phase III trials (pg. 1168, column 1). Heigener reports the patient demographics included 60 patients with 66 uncommon mutations, of which 4 had E709X mutations (pg. 1168, column 2). Of the four patients with E709X mutations, three had E709K+L858R mutations and one had E709A+G719A mutations (pg. 1168, column 2 and Table 3). Specifically, Heigener teaches that the patients with E709K+L858R EGFR mutations were treated with afatinib for 0.8, 7.1, and 12.2 months and the patient with an E709A+G719A EGFR mutation was treated with afatinib for 16.7 months (pg. 1171, Table 3). Heigener concludes by teaching afatinib is clinically active in many TKI-pretreated patients with NSCLC harboring uncommon EGFR mutations and that pronounced activity was observed with E709X mutations (pg. 1172, column 2).
Heigener reports uncommon EGFR mutations using data directly from physicians who had patients in a larger clinical study, the Compassionate Use Program, and further teaches that a 55% of patients had exon 20 mutations (showing testing of exon 20) and that 30 patients had T790M mutations, none of which were paired with the E709X mutations (pg. 1168, column 2). By not stating mutations found for positions C797 and T790 of EGFR exon 18, Heigener inherently teaches the treatment of NSCLC in a patient with wild type C797 and T790.
Thus, by treating patients harboring E709A mutations with afatinib, Heigener’s teachings anticipate the instant claims. Therefore, claims 1-4, 9-10, 12, 29-30, 35, 49-50, 63, and 74 are rejected.
Conclusion
No claim is allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625