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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/28/2026 has been entered.
The office acknowledges Applicants arguments and amendments in response to the office action dated 12/01/2025. The IDS filed on 1/28 and 2/13/2026 has been considered and signed.
Claims 1, 14, 16, 93, and 102 have been amended. Claims 6-13, 15, 1-35, 41-76, 76, 78, 83-92, 94-101, 110-137, 140-141 have been canceled. Applicants arguments have been fully considered. The rejections not reiterated from previous office actions are hereby withdrawn. Arguments, which are directed to withdrawn rejections, are thus rendered moot. In light of the amendments and further search necessitated the new rejections in this action. The action is made non-final. For the sake of compact prosecution filing of terminal disclaimers was discussed with applicant’s representative, Yi Shi and no agreement was reached. Claims 1-5, 14, 16, 36-40, 77, 79-82, 93, 102-109, and 138-139 are pending and are examined based on the merits herein.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 1-5, 14, 16, 36-40, 77, 79-82, 93, 102-109, and 138-139 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 11-12, 15-16, 21-23 of U.S. 10899742 (‘742) in view of Angus et al. (Cancer Treatment Reviews 2017, 52, 33-40) and Andrew et al. (IDS: WO2018102725A1).
The instant claims are directed to:
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The dependent claims are directed to specific somatic ER mutations, specific breast cancer type, metastatic or locally advanced, additional cancer agents, and method of claim 1 along with palbociclib (claim 77). Claim 93 is to the method of treating breast cancer with I-c and includes the step of selecting the subjects for the treatment.
‘742 reference claims are directed to a method of treating breast cancer in a subject comprising administering to a subject in need thereof a composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound having the structure:
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or a pharmaceutically acceptable salt, enantiomer, stereoisomer, isotopic derivative, or prodrug of any of the foregoing. The composition further comprises an effective amount of at least one additional anti-cancer agent, including FLT-3 inhibitor, CDK inhibitor (claim 21), palbociclib (see claims 11, 15). The dependent claims are limited to specific additional cancer agents to be used in the method.
The reference claims are silent in teaching that the breast cancer is associated with somatic ER mutations as claimed.
Angus teach that mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC) (Abstract). The reference teaches that recent NGS efforts revealed that somatic ESR1 mutations in the LBD were more frequently present in metastatic lesions than previously thought. In preclinical models to evaluate the role of ESR1 mutations in endocrine resistance, it was demonstrated that cell lines transfected with a D538G, Y537S, L536Q, Y537N, Y537C, S463P or E380QESR1 mutationexert activity in the absence of estrogen [6,10–15] (Fig. 1) (See p 33, col. 2, last para). It is taught that “ESR1 mutations in metastatic tissue of MBC patients. In 5/13 (38%) ER positive MBC patients, who failed on multiple lines of endocrine treatment, a D538G ESR1 mutation was reported [12]. Furthermore, Jeselsohn et al. [5] detected in 9/76 (12%) ER-positive meta static tumors ESR1 mutations (Y537N/C/S and D538G) using NGS, whereas none of the 115 ER-negative tumors they assessed had such mutations.” (See p 35, col. 1, para 2).
Andrew et al. discloses compounds that are modulators of estrogen receptor, inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor, e.g. the treatment of breast cancer (See abstract, [0003]). The reference teach the following exemplary compound:
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It is noted that this compound 411 is the compound of formula Ic as in the instant claim. Further taught is that the compound(s) can be administered orally [0317] and in an oral dosage of 25-250 mg [0333].
A person skilled in the art from the teachings of Angus would have found it obvious that (i) ESR1 mutations such as D538G, Y537S, Y537N, Y537C are associated with ER positive metastatic tumors in breast cancer subjects and (ii) 38% of ER positive metastatic breast cancer patients had somatic mutations, e.g. D538G. A person skilled in the art would have found it obvious to administer the compound of the reference claims (which is formula Ic of the instant invention) to a breast cancer subject with ESRI somatic mutations, e.g. D538G and treat the same with a reasonable expectation of success and derive therapeutic benefits. As to the amount, the reference claim is not explicit in teaching the therapeutic amount. However Andrew teaches the compound 411 as an exemplary compound, an inhibitor of estrogen receptor and its use in the diseases including breast cancer, oral dosage amount includes 25-250 mg. Thus a skilled artisan would have found it obvious to administer the compound of formula Ic orally in an amount of e.g. 25 mg (that falls within the instantly claimed amount) to patients with breast cancer that has somatic mutations, e.g. D538G to treat and provide therapeutic benefits. Thus claims 1-3 would have been obvious over the reference claims and the prior art teachings. As to claim 4, ER+/HER- is a subtype of breast cancer. A person skilled in the art would have found it obvious to try administering a therapeutically effective amount of formula (Ic) to a subject with ER+/HER breast cancer to achieve therapeutic effects. As to claims 5, 138 Angus teach ER positive breast cancers are metastatic. Thus a skilled artisan would have found it obvious to treat metastatic breast cancer with an effective amount of compound of formula Ic from the reference claims and the prior art. As to claims 14, 16, A person skilled in the art from the reference claims teaching would have found it obvious to administer the compound Ic as a free base form or as a pharmaceutically acceptable salt. As to claims 36-40, the reference claims teach the additional cancer agent therapy, e.g. FLT-3 inhibitor, CDK inhibitor, and palbocilib. Though the reference claims is not explicit in teaching the CDK inhibitor as CDK 4/6, it teaches everolimus as an additional anti-cancer agent which is a CDK 4/6 inhibitor. Claims 77, 79-82 are addressed by the combined teachings of the reference claims and the prior art for the reasons stated above. As to claim 93, though the reference claims are not explicit in teaching selecting a breast cancer subject based on the subject’s somatic ER tumor biomarker status, from Angus a skilled artisan would have found it obvious to select the patients with specific biomarkers, e.g. D538G mutation to provide therapy. It is within the skill of an artisan to measure and test the biomarkers as taught in Angus. Claims 93, 102-109, 139 would have been obvious from the combined teachings of the reference claims and the prior art for the reasons stated above.
Claims 1-5, 14, 16, 36-39, 93, 102-108, and 138-139 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-48 of US 11597720 (‘720) in view of Angus et al. (Cancer Treatment Reviews 2017, 52, 33-40) and Andrew et al. (IDS: WO2018102725A1).
The instant claims as above.
‘720 reference claims are directed to the following compound (or its isomer), its composition, its use in a method of treating breast cancer with an effective amount of the compound. The composition further comprises an effective amount of at least one additional anti-cancer agent, including FLT-3 inhibitor, CDK inhibitor (claim 7). The dependent claims are limited to specific additional cancer agents to be used in the method.
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The reference claims are silent in teaching that the breast cancer is associated with somatic ER mutations as claimed.
Angus and Andrew’s teachings discussed as above.
A person skilled in the art from the teachings of Angus would have found it obvious that (i) ESR1 mutations such as D538G, Y537S, Y537N, Y537C are associated with ER positive metastatic tumors in breast cancer subjects and (ii) 38% of ER positive metastatic breast cancer patients had somatic mutations, e.g. D538G. A person skilled in the art would have found it obvious to administer the compound of the reference claims (which is formula Ic of the instant invention) to a breast cancer subject with ESRI somatic mutations, e.g. D538G and treat the same with a reasonable expectation of success and derive therapeutic benefits. As to the amount, the reference claim is not explicit in teaching the therapeutic amount. However Andrew teaches the compound 411 as an exemplary compound, an inhibitor of estrogen receptor and its use in the diseases including breast cancer, oral dosage amount includes 25-250 mg. Thus a skilled artisan would have found it obvious to administer the compound of formula Ic orally in an amount of e.g. 25 mg (that falls within the instantly claimed amount) to patients with breast cancer that has somatic mutations, e.g. D538G to treat and provide therapeutic benefits. Thus claims 1-3 would have been obvious over the reference claims and the prior art teachings. As to claim 4, ER+/HER- is a subtype of breast cancer. A person skilled in the art would have found it obvious to try administering a therapeutically effective amount of formula (Ic) to a subject with ER+/HER breast cancer to achieve therapeutic effects. As to claims 5, 138 Angus teach ER positive breast cancers are metastatic. Thus a skilled artisan would have found it obvious to treat metastatic breast cancer with an effective amount of compound of formula Ic from the reference claims and the prior art. As to claims 14, 16, A person skilled in the art from the reference claims teaching would have found it obvious to administer the compound Ic as a free base form or as a pharmaceutically acceptable salt. As to claims 36-39, the reference claims teach the additional cancer agent therapy, e.g. FLT-3 inhibitor, CDK inhibitor. Though the reference claims is not explicit in teaching the CDK inhibitor as CDK 4/6, it teaches everolimus as an additional anti-cancer agent which is a CDK 4/6 inhibitor. As to claim 93, though the reference claims are not explicit in teaching selecting a breast cancer subject based on the subject’s somatic ER tumor biomarker status, from Angus a skilled artisan would have found it obvious to select the patients with specific biomarkers, e.g. D538G mutation to provide therapy. It is within the skill of an artisan to measure and test the biomarkers as taught in Angus. Claims 93, 102-108, 139 would have been obvious from the combined teachings of the reference claims and the prior art for the reasons stated above.
Claims 40, 77, 79-82, 109 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-48 of US 11597720 (‘720) in view of Angus et al. (Cancer Treatment Reviews 2017, 52, 33-40) and Andrew et al. (IDS: WO2018102725A1) and further in view of Beaver et al. (IDS: Clinical Cancer Research, 2015, 4760-66).
The rejection above is incorporated herein. The reference claims, Angus and Andrew as discussed above and they do not teach palbociclib in the method.
Beaver et al. teach that palbociclib is approved for treatment of breast cancer in postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer and palbociclib is used in combination with antiestrogen letrozole is (abstract).
A person skilled in the art from Beaver would have found it obvious to add palbociclib as an additional anti-cancer agent in the method along with the compound of reference claims to treat breast cancer, e.g. ER+/HER- type to provide synergistic or additive therapeutic effects. Claims 77, 79, 80-81, 82 are addressed by the combined teachings of the reference claims and the prior art because (i) the reference claims teach the compound Ic in treating breast cancer in general (ii) Angus teach ESR1 mutations such as D538G, Y537S, Y537N, Y537C are associated with ER positive metastatic tumors in breast cancer subjects and 38% of ER positive metastatic breast cancer patients had somatic mutations, e.g. D538G (iii) Beaver teach palbociclib is used in combination therapy for ER+/HER breast cancer type. Thus the claims would have been obvious over the combined reference claims and the prior art.
Claims 1-5, 14, 16, 36, 39-40, 77, 79-82, 93, 102-105, 108-109, and 138-139 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of US 12208095 (‘095) or claims 1-70 of co-pending Application No.18988049 (‘049) in view of Angus et al. (Cancer Treatment Reviews 2017, 52, 33-40) and Andrew et al. (IDS: WO2018102725A1).
The instant claims as above.
‘095 reference claims are directed to a method of treating metastatic breast cancer in a subject, comprising administering to the subject an effective amount of palbociclib and an effective amount of a compound of Formula (I-c) or a pharmaceutically acceptable salt thereof, wherein the effective amount of the compound of Formula (I-c), or a pharmaceutically acceptable salt thereof, is about 10 mg to about 1000 mg.
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The method of claim 1, wherein the metastatic breast cancer is ER+, HER2−. The dependent claims are limited to specific dosage amounts, pharmacokinetic parameters, dosage regimen and administrative regimen.
‘049 reference claims are directed to a method of treating breast cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, the therapeutically effective amount of the compound of Formula (I) is about 10 mg to about 1000 mg. Claims 10-11 recite the compound of formula (I-c), the compound administered orally. The method of claim 1, wherein the metastatic breast cancer is ER+, HER2−. The dependent claims are limited to specific dosage amounts, pharmacokinetic parameters, dosage regimen and administrative regimen.
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The reference claims are silent in teaching that the breast cancer is associated with somatic ER mutations as claimed.
Angus and Andrew’s teachings discussed as above.
A person skilled in the art from the teachings of Angus would have found it obvious that (i) ESR1 mutations such as D538G, Y537S, Y537N, Y537C are associated with ER positive metastatic tumors in breast cancer subjects and (ii) 38% of ER positive metastatic breast cancer patients had somatic mutations, e.g. D538G. A person skilled in the art would have found it obvious to administer the compound of the reference claims (which is formula Ic of the instant invention) to a breast cancer subject with ESRI somatic mutations, e.g. D538G and treat the same with a reasonable expectation of success and derive therapeutic benefits. As to the amount, the reference claim is not explicit in teaching the therapeutic amount. However Andrew teaches the compound 411 as an exemplary compound, an inhibitor of estrogen receptor and its use in the diseases including breast cancer, oral dosage amount includes 25-250 mg. Thus a skilled artisan would have found it obvious to administer the compound of formula Ic orally in an amount of e.g. 25 mg (that falls within the instantly claimed amount) to patients with breast cancer that has somatic mutations, e.g. D538G to treat and provide therapeutic benefits. Thus claims 1-4 would have been obvious over the reference claims and the prior art teachings. A person skilled in the art would have found it obvious to try administering a therapeutically effective amount of formula (Ic) to a subject with ER+/HER breast cancer to achieve therapeutic effects. As to claims 5, 138 Angus teach ER positive breast cancers are metastatic. Thus a skilled artisan would have found it obvious to treat metastatic breast cancer with an effective amount of compound of formula Ic from the reference claims and the prior art. As to claims 14, 16, a person skilled in the art from the reference claims teaching would have found it obvious to administer the compound Ic as a free base form or as a pharmaceutically acceptable salt. As to claims 36, 39-40, the reference claims teach the additional cancer agent therapy, e.g. FLT-3 inhibitor, CDK inhibitor, and palbocilib. Though the reference claims is not explicit in teaching the CDK inhibitor as CDK 4/6, it teaches everolimus as an additional anti-cancer agent which is a CDK 4/6 inhibitor. Claims 77, 79, 80-81, 82 are addressed by the combined teachings of the reference claims and the prior art for the reasons stated above. As to claim 93, though the reference claims are not explicit in teaching selecting a breast cancer subject based on the subject’s somatic ER tumor biomarker status, from Angus a skilled artisan would have found it obvious to select the patients with specific biomarkers, e.g. D538G mutation to provide therapy. It is within the skill of an artisan to measure and test the biomarkers as taught in Angus. Claims 93, 102-105, 108-109, 139 would have been obvious from the combined teachings of the reference claims and the prior art for the reasons stated above.
Note: In regards to the rejection over co-pending application, 18988049, this is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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/Umamaheswari Ramachandran/ Primary Examiner, Art Unit 1627