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 .
DETAILED ACTION
This Office Action is Responsive to the Response to Election/Restriction filed 03/24/2026.
The preliminary amendment filed 05/20/2024 amended claims 6-7, 23, 31, 34, and 38, and cancelled claims 5, 9-12, 17-18, 24-29, 32-33, and 35-37.
Claims 1-4, 6-8, 13-16, 19-23, 30, 31, 34, and 38 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant’s election without traverse of a) Group I, the method, b) Osimertinib as the EFGR-TK inhibitor species; and c)
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as the proliferating cell nuclear antigen inhibitor, in the reply filed on 03/24/2026, is acknowledged.
Claim 16 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claims 1-4, 6-8, 13-15, 19-23, 30, 31, 34, and 38 are examined on the merits herein.
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 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 1-4, 6-8, 13-15, 19-23, 30, 31, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/049206 to Malkas (published 2017, PTO-892) in view of Martens (Small Molecules in Oncology, published 2018, PTO-892).
Malkas teaches compounds of instant formulas (A), (I), (II), (III), (IV) and (V), and species of instant claim 30 (pgs. 189-192, claims 1-5; pgs. 199-201, claims 77-83), and specifically exemplifies
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, AOH1996(pg. 201, claim 83; pg. 181, Table 3).
Malkas teaches compositions comprising these compounds and further comprising a pharmaceutically acceptable excipient, and an anti-cancer agent (pg. 201, claims 85-86).
Malkas teaches a method of treating cancer by administering these compounds, wherein the cancer is non-small cell lung cancer, leukemia, lung cancer, colon cancer, a central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, or breast cancer (pg. 202, claims 89-95).
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, AOH1996, is exemplified as selectively killing neuroblastoma and small cell lung cancer (SCLC) at below micromolar concentrations, and exemplified as treating breast cancer, colon cancer, CNS cancer, leukemia/myeloma, melanoma, ovarian cancer, prostate cancer, renal cancer, and non-small cell lung cancer (NSCLC) ([0023]; [0024]; [0571]-[0573]).
Malkas teaches gefitinib, erlotinib, panitumumab, vandetanib, afatinib, canertinib, neratinib, dacomitinib, lapatinib and others as the anti-cancer agent, wherein these agents are EGFR inhibitors or EGFR targeted therapy ([0077]).
Regarding claim 1, while Malkas teaches a method of treating cancer by administering a compound of Formula A and an anticancer agent, wherein the instantly claimed EGFR-TK inhibitors are taught as anticancer agents, it differs from that of instant claim 1 in that it does not specifically exemplify the combination of a compound of Formula (A) and a EGFR-TK inhibitors.
Martens teaches gefitinib, afatinib, and osimertinib as EGFR-TKI inhibitors have been approved for patients with NSCLC, wherein the TKI benefit is mainly based on tumor control and overall survival rather than rapid tumor responses and complete remission rates (pg. 2, Introduction; pg. 211).
Martens teaches that lung cancer belongs to the most frequent tumor entities in Western countries. Only 15% of lung cancer patients survive 5 years after diagnosis. Therefore, the development of new agents with different efficacy mechanisms compared to conventional chemotherapy has encouraged the pharmaceutical development (pg. 5).
Martens teaches that EGFR mutations have been found in 10% up to 17% of NSCLC patients (pg. 5). The mutations are mainly within the exons 19 and 21, such as exon 19 deletion L858R (pg. 6, 1st paragraph). Martens teaches that gefitinib shows clear superiority in patients with EGFR-mutated NSCLC with significant improvement in progression free survival (pg. 242, 1st full paragraph).
Martens teaches gefitinib as positively associated with clinical benefits such as tumor response, health-related quality of life and increased survival. Patients treated with gefitinib experienced a lower treatment-related toxicity and better improvement in quality of life (pg. 6, 3rd paragraph). Gefitinib significantly improves symptoms related to lung cancer (pg. 24, 4th paragraph).
Martens teaches that for the first-line treatment of metastatic NSCLC, those who are non-smokers, those with EGFR mutations and/or with bronchioloalveolar cell carcinoma histology have promising efficacy with EGFR-TKI first-line therapy (pg. 7, 1st paragraph). Martens teaches that L858R mutations possess increased affinity for tyrosine kinase inhibitors such as gefitinib, erlotinib, afatinib, and Osimertinib (pg. 237; pg. 238, Table 1).
Martens teaches that the main limitation of the widespread benefits of EGFR TKIs is the development of resistance in patients with EGFR-mutated NSCL. Resistance mutations, such as EGFR-T790M abrogates the inhibitor effects of first generation EGFR TKI (pg. 243, 4.4).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add gefitinib to the methods of treating SCLC or NSCLC by administering AHO1996, in Malkas, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Malkas exemplifies a method of treating SCLC or NSCLC by administering AHO1996,
-Malkas teaches that additional anti-cancer agents can be added to its methods, and specifically teaches gefitinib as such an agent,
-Martens teaches gefitinib as approved for the treatment of NSCLC, and teaches gefitinib as positively associated with clinical benefits such as tumor response, health-related quality of life and increased survival, and teaches that patients with gefitinib experienced a lower treatment-related toxicity and better improvement in quality of life.
As such, an ordinary skilled artisan would have been motivated to make such an addition to predictably arrive at a more therapeutically effective and potent method of treating SCLC and NSCLC that increases quality of life and survival.
Moreover, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980), MPEP 2144.06.
Regarding claims 2-3, the combination of Malkas and Martens teach gefitinib.
Regarding claim 4, while the combination of Malkas and Martens teach a method of treating SCLC and NSCLC by administering AOH1996 and gefitinib, it differs from that of instant claim 4, in that it does not teach osimertinib.
Martens further teaches that EGFR-mutated advanced NSCLC treated with first generation EGFR-TKIs, such as gefitinib, results in resistance, wherein 60% of the resistances are due to a T790M mutation.
Martens teaches osimertinib as a EGFR-TKI that irreversibly binds both EGFR activating mutations and T790M, while sparing wild-type EGFR. As such, osimertinib is more efficacious than platinum-based chemotherapy for EGFR T790M-positive NSCLCs. Martens further teaches osimertinib as outperforming gefitinib as first-line treatment of EGFR-mutated, ex19del or L858R, advanced NSCLCs (pg. 258).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the gefitinib of the combination of Malkas and Martens, with osimertinib, to arrive at instant claim 4. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Martens teaches osimertinib as outperforming gefitinib as first-line treatment of EGFR-mutated, ex19del or L858R, advanced NSCLCs, and
-Martens teaches Osimertinib as treating NSCLC that becomes resistant to treatment with gefitinib.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a more effective method of treating NSCLC and a method of treating EGFR-resistant NSCLC.
Regarding claim 6, the combination of Malkas and Martens teach lung cancer.
Regarding claims 7-8, the combination of Malkas and Martens teach treating L858R, ex19del, and T790M mutations in patients with NSCLC.
Regarding claim 13, the combination of Malkas and Martens teaches treating EGFR-TK resistant cancer.
Regarding claims 14-15, Malkas teaches that the compound of the invention can be administered alone or can be co-administered to the patient, wherein coadministration includes simultaneous or sequential administration of the compound individually or in combination ([0104]).
Regarding claim 19, as evidenced by pg. 2 of the instant specification, compounds of instant formulas (I)-(V) and (A) are PCNA inhibitors.
Regarding claims 20-23, and 30, Malkas teaches these generic compounds and species.
Regarding claim 31, the combination of Malkas and Martens teach gefitinib and osimertinib.
Regarding claim 34, the combination of Malkas and Martens teaches lung cancer.
Regrading claim 38, the combination of Malkas and Martens teaches an EGFR mutation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 13-15, 19-23, 30, 31, 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,555,070 (PTO-892) in view of WO 2017/049206 to Malkas (published 2017, PTO-892) and Martens (Small Molecules in Oncology, published 2018, PTO-892).
Claims 1-4, 6-8, 13-15, 19-23, 30, 31, 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-42 of U.S. Patent No. 10,913,706 (PTO-892) in view of WO 2017/049206 to Malkas (published 2017, PTO-892) and Martens (Small Molecules in Oncology, published 2018, PTO-892).
Claims 1-4, 6-8, 13-15, 19-23, 30, 31, 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 14-15, 17-19, 22-23 of U.S. Patent No. 11,345,656 (PTO-892) in view of WO 2017/049206 to Malkas (published 2017, PTO-892) and Martens (Small Molecules in Oncology, published 2018, PTO-892).
Claims 1-4, 6-8, 13-15, 19-23, 30, 31, 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 18-19 of U.S. Patent No. 12,054,447 (PTO-892) in view of WO 2017/049206 to Malkas (published 2017, PTO-892) and Martens (Small Molecules in Oncology, published 2018, PTO-892).
US Patent No. 10,555,070 claims a method of treating cancer, such as lung cancer, by administering a compound of instant Formulas (I), (II), or (A), and species of instant claim 30.
‘070 claims pharmaceutical compositions comprising these compounds and an anticancer agent.
US Patent No. 10,913,706 claims a method of treating cancer, such as lung cancer, by administering compounds of instant Formulas (II), (III), (V), (A), and species of instant claim 30.
‘070 claims pharmaceutical compositions comprising these compounds and an anticancer agent.
US Patent No. 11,345,656 claims a method of treating cancer by administering compounds of instant Formulas (IV), and (A), wherein Formula (A) is a species of instant claim 30.
‘656 claims pharmaceutical compositions comprising these compounds and an anticancer agent.
US Patent No. 12,054,447 claims a method of treating cancer by administering a compounds of instant Formulas (III) and (IV).
‘447 is a compound of instant Formula (A), wherein in Formula (III), z1 and z3 are 0, R2 and R3 are H, A is phenyl, z2 is 1, R4 is -OR14, wherein R14 is H, and B is 2-naphthyl.
‘447 claims pharmaceutical compositions comprising these compounds and an anticancer agent.
Regarding claim 1, while ‘070, ‘706, ‘656, and ‘447 claim a method of treating cancer by administering a compound of instant formulas (I)-(V) and/or (A) and an anticancer agent, it differs from that of instant claim 1 in that it does not teach EGFR-TK inhibitors as the anticancer agent.
Malkas and Martens are applied as discussed above and incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select SCLC or NSCLC as the cancer treated and gefitinib as the anticancer agent, in the methods of ‘070, ‘706, ‘656, and ‘447, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-‘070, ‘706, ‘656, and ‘447 teach a method of treating lung cancer by administering instant formulas (I)-(V) and/or (A) and an anti-cancer agent,
-Malkas exemplifies a method of treating SCLC and NSCLC by administering AHO1996, instant Formula (A),
-Malkas teaches that additional anti-cancer agents can be added to its methods, and specifically teaches gefitinib as such an agent,
-Martens teaches gefitinib as approved for the treatment of NSLC, and teaches gefitinib as positively associated with clinical benefits such as tumor response, health-related quality of life and increased survival, and teaches that patients with gefitinib experienced a lower treatment-related toxicity and better improvement in quality of life.
As such, an ordinary skilled artisan would have been motivated to make such selections to predictably arrive at a therapeutically effective method of treating NSCLC that increases quality of life and survival.
Regarding claims 2-3, gefitinib is taught.
Regarding claim 4, while the combination of ‘070, ‘706, ‘656, or ‘447, and Malkas and Martens teach a method of treating SCLC or NSCLC by administering AOH1996 and gefitinib, they differ from that of instant claim 4, in that they do not teach osimertinib.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the gefitinib of the combination of -‘070, ‘706, ‘656, or ‘447, and Malkas and Martens, with osimertinib, to arrive at instant claim 4. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Martens teaches osimertinib as outperforming gefitinib as first-line treatment of EGFR-mutated, ex19del or L858R, advanced NSCLCs, and
-Martens teaches osimertinib as treating NSCLC that becomes resistant to treatment with gefitinib.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a more effective method of treating NSCLC and a method of treating EGFR-resistant NSCLC.
Regarding claim 6, lung cancer is taught.
Regarding claims 7-8, the combination of ‘070, ‘706, ‘656, or ‘447, and Malkas and Martens teach treating L858R, ex19del, and T790M mutations in patients with NSCLC.
Regarding claim 13, the combination of ‘070, ‘706, ‘656, or ‘447, and Malkas and Martens teaches treating EGFR-TK resistant cancer.
Regarding claims 14-15, Malkas teaches that the compound of the invention can be administered alone or can be co-administered to the patient, wherein coadministration includes simultaneous or sequential administration of the compound individually or in combination ([0104]).
Regarding claims 19-23, and 30, ‘070, ‘706, ‘656, and ‘447, claim the instantly claimed compounds
Regarding claim 34, lung cancer is taught.
Regrading claim 38, the combination of 070, ‘706, ‘656, or ‘447, and Malkas and Martens teaches an EGFR mutation.
Claims 1-3, 6, 15, 19-23, 30-31, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,435,030 (PTO-892).
Although the claims at issue are not identical, they are not patentably distinct from each other
‘030 claims a method of treating cancer, such as lung cancer by administering a pharmaceutical composition comprising compounds of instant Formula (I), (II), (A), and the species of instant claim 30, and an EGFR inhibitor.
‘030 claims gefitinib, afatinib, and erlotinib as anti-cancer agents, as recited in instant claim 1.
‘030 claims lung cancer as the cancer.
Claims 4, 7-8, 13-14, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,435,030 (PTO-892), as applied to claims 1-3, 6, 15, 19-23, 30-31 and 34, above and further in view of WO 2017/049206 to Malkas (published 2017, PTO-892) and Martens (Small Molecules in Oncology, published 2018, PTO-892).
‘030, Malkas and Martens are applied as discussed above and incorporated herein.
‘030 differs from that of instant claim 4 in that it does not teach a method of treating NSCLLC by administering osimertinib as the EGFR-TK inhibitor.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the gefitinib of ‘030, with osimertinib, to arrive at instant claim 4. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Malkas exemplifies a method of treating NSCLC by administering a compound of instant formula (A), which is claimed by ‘030,
-Martens teaches osimertinib as outperforming gefitinib as first-line treatment of EGFR-mutated, ex19del or L858R, advanced NSCLCs, and
-Martens teaches osimertinib as treating NSCLC that becomes resistant to treatment with gefitinib.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a more effective method of treating NSCLC and a method of treating EGFR-resistant NSCLC.
Regarding claims 7-8, the combination of ‘030, and Malkas and Martens teach treating L858R, ex19del, and T790M mutations in patients with NSCLC.
Regarding claim 13, the combination of ‘030, and Malkas and Martens teaches treating EGFR-TK resistant cancer.
Regarding claims 14, Malkas teaches that the compound of the invention can be administered alone or can be co-administered to the patient, wherein coadministration includes simultaneous or sequential administration of the compound individually or in combination ([0104]).
Regrading claim 38, the combination of ‘030, and Malkas, and Martens teaches an EGFR mutation.
Conclusion
No claims are allowed.
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/LAUREN WELLS/Examiner, Art Unit 1622
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