DETAILED ACTION
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 .
Application Status
The amendment filed on 11/10/2025 in response to the Non-Final rejection of 5/15/2025 is acknowledged and has been entered.
Claims 20-22, 28-31 and 39-47 are currently pending and under consideration.
Information Disclosure Statement
The Information Disclosure Statements filed on 5/09/2025 and 11/10/2025 have been considered except when lined through.
Rejections Maintained, but amended in view of the Amendments
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 (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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 20-22, 28-31 and 39-47 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Miyano et al. (US 2018/0303817 A1, 10/25/2018) in view of Katoh, Masaru (Nature Reviews Clinical Oncology; 16; 2019, pp. 105-122, published online October 26, 2018) and Bardia et al. (Future Oncol. 2019; 15(28): 3209-3218).
Miyano teach a composition comprising the instantly claimed compound or a pharmaceutically acceptable salt thereof and an excipient (paragraph 0010, (1) and (6)). The publication further teaches a method of treating breast cancer comprising administering said composition in a patient in need thereof (paragraph 0010, (4)). With regards to the compound, the publication teaches that the instantly claimed compound has FGFR inhibitory activity (paragraph 0001). With regards to the salt of the instantly claimed compound, the publication teaches that the preferred pharmaceutical salt is a 1.5 succinate (paragraph 0019). With regards to the breast cancer, the publication teaches that breast cancer is one that expresses FGFR (FGFR1, FGFR2 or FGFR3) and includes, but is not limited to, locally advanced breast cancer, metastatic breast cancer and recurrent breast cancer (paragraph 10, (8)-(9) and paragraph 23). Moreover, the publication teaches in vivo inhibitory activity of the instantly claimed compound in mice injected with MFM223 human breast cancer cell line (Example 1).
The publication does not specifically teach that the composition or method of treatment further comprises the estrogen receptor antagonist fulvestrant or elacestrant or that the combination is administered simultaneously or separately.
Katoh teach fibroblast growth factor receptors as treatment targets in clinical oncology (Title). Moreover, the publication teaches that alterations in FGFRs 1-4 can lead to the development and/or progression of cancer and therefore are targetable using small molecules of antibodies (abstract). Moreover, Katoh teach that:
“Combination strategies, involving the concurrent administration of FGFR-targeted therapies with other agents, might prevent or delay the expansion of treatment-resistant clones and also have the potential to enhance the antitumour effects of FGFR-targeted therapies. Data from preclinical studies indicate that anti-FGFR antibodies, cytotoxic agents, ER-targeted or other endocrine therapies… are all applicable for use in combination with FGFR inhibitors.” (page 117, Combination therapies)
With regards to the endocrine therapies, Katoh teaches that selective ER modulators (tamoxifen), selective ER degraders (fulvestrant) and aromatase inhibitors (anastrozole, exemestane and letrozole) are all approved for patients with ER-positive breast cancer (page 117, Endocrine therapies). Moreover, Katoh teach that
“FGFR1 amplification and treatment induced FGFR1 overexpression occur preferentially in patients with letrozole-resistant ER-positive breast cancer, whereas fulvestrant and the multi-kinase FGFR inhibitor lucitanib have synergistic effects on two PDX models of ER-positive, HER2-negative, FGFR1-amplified breast cancer. These finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.” (page 117, Endocrine therapies, 2nd full paragraph).
Bardia et al. teach that elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast caner previously treated with endocrine therapies including fulvestrant and/or CDK4/6 inhibitor therapy, and in those with ESR1 mutations known to confer endocrine resistance.
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 include an estrogen receptor antagonist such as fulvestrant or elacestrant in the method taught by Miyano whether within the composition or by sequential/simultaneous administration in view of the teachings of Katoh and Bardia et al.. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Katoh teaches past finding clearly support the concept of combining endocrine therapies with FGFR inhibitors; and
"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) (citations omitted)
Moreover, 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 optimize when the combination would be administered to a patient. One of ordinary skill in the art would have been motivated to make such an optimization, with a reasonable expectation of success, because:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In response to the above rejection, Applicants submits a declaration under 37 CFR 1.132 by one of the inventors, Satoshi Kawano. The declaration under 37 CFR 1.132 filed on 11/10/2025 has been carefully considered, but is not found persuasive.
The Declarant asserts that as described in example 1 of the patent application, administration of either Compound A alone or fulvestrant alone inhibited tumor growth in an in vivo model of breast cancer, whereas the combined administration of Compound A and fulvestrant inhibited tumor growth to a significantly greater degree (see Table 1 and Fig.1 of the specification). The Declarant further provides Table 2 which shows an expected and actual measured tumor volume after treatment with the combination of Compound A and fulvestrant, wherein the expected is calculated by first multiplying the control group tumor volume measured on a given day by the percent of control tumor volume resulting from the treatment with Compound A and then further multiplying that number by the percent of control tumor volume resulting from treatment with fulvestrant.
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In view of the results above, the Declarant asserts that the experimental findings in Example 1 of the patent application demonstrate that the inhibition of tumor growth resulting from combination treatment with Compound A and fulvestrant was synergistic, exceeding that which would have been expected from the combination based upon the mere addition of the compounds individual efficacies.
The Declarant further provides a second experiment of administration of Compound A, elacestrant or a combination of Compound A and elacestrant to ST2056 mice, a patient-derived in vivo xenograft tumor model. Similar to the results above, the Declarant provides the changes in the average tumor volume after administration of Compound A, elacestrant or a combination of compound A and elacestrant (Table 3), as well as, expected and actual measured tumor volume after treatment with the combination of compound A and elacestrant (Table 4, reproduced below):
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. Similar to above, the Declarant asserts that these experimental findings demonstrate that the inhibition of tumor growth resulting from combination treatment with Compound A and elacestrant was synergistic.
In response to Declarants assertions, the Examiner appreciates Declarants analysis and does not dispute, on its face, that the combination of Compound A and fulvestrant or elacestrant significantly reduced tumor volume as compared the compounds’ individual efficacies. However, the examiner does not fully agree that the results would not have been expected for the following reasons:
First, both of the in vivo models use xenografts with some type of resistance to anti-estrogen therapy.
The combination with fulvestrant used OD-BRE-0438 which is a PDX preclinical tumor model which shows resistance to hormone therapy treatment (fulvestrant) in the presence and absence of estrogen supplementation (see De Boisferon et al (Cancer Research 2021; 81(13))).
The combination with elacestrant used ST2056 model which is a patient-derived xenograft model of CDK4/6 inhibitor resistant HR+/HER2- breast cancer which is derived from a patient that progressed on 1L abemaciclib + fulvestrant, 2L fulvestrant and 3L investigational therapy (see Brown et al. (Cancer Res. 2023; 83: P6-10)).
This is important because it would be reasonably expected that the model would not perform well to the anti-estrogen therapy because of the resistance which could overinflate the combination treatment since each xenograft shows some form of resistance to anti-estrogen therapy and therefore, it would be expected to achieve low inhibition rates for the anti-estrogen therapies. Secondly, at the time of filing, FGFR inhibitors were known in the art to overcome a variety of acquired resistance in ER+ breast cancers. For example, Formisano et al. (Clin. Cancer Res 2017; 23(20): 6138-6150) teach the association of FGFR1 with ERa maintains ligand-independent ER transcription and mediates resistance to estrogen deprivation in ER+ breast cancer (title). In particular, Formisano et al. teach that growth of ER+/FGFR1-amplified cells and PDXs was more potently inhibited by fulvestrant and lucitanib (a FGFR tyrosine kinase inhibitor) combined than each drug alone (Abstract, Results section). For example, Formisano et al. teach that all mice bearing TM00368 xenografts exhibited a >= 50% reduction in tumor size from baseline after 3 weeks of treatment with the combination of fulvestrant and lucitanib (page 6148, 2nd column, 1st full paragraph). Moreover, Formisano et al. (Nature Communications 2019;10:1373, referred to herein as Formisano 2 ) used an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant to identify FGFR1 as a mechanism of drug resistance (Abstract). In particular, Formisano 2 found that this resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor lucitanib, wherein addition of another FGFR inhibitor erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient derived xenografts (Abstract). In view of the above, it would seem reasonable to expect a significant reduction in tumor volume in these two in vivo models when using the combination. Please note: Since there is no side by side comparisons of another FGFR inhibitor and fulvestrant or elacestrant in the SAME tumor models, it is difficult to determine whether the difference asserted by the Declarant would be significant.
Applicants arguments mirror those of the Declarants which have been addressed above.
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 20-22, 28-31 and 39-47 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No 11,219,619 in view of Miyano et al. (US 2018/0303817 A1, 10/25/2018), Katoh, Masaru (Nature Reviews Clinical Oncology; 16; 2019, pp. 105-122, published online October 26, 2018) and Bardia et al. (Future Oncol. 2019; 15(28): 3209-3218).
The US Patent claims a method of treating hepatocellular carcinoma, comprising administering the instantly claimed compound or a pharmacological acceptable salt thereof (claim 1).
The US Patent does not claim that the cancer is breast and that the instantly claimed compound is administered in combination with the estrogen receptor antagonist fulvestrant or elacestrant or that the combination is administered simultaneously or separately.
Miyano teach a composition comprising the instantly claimed compound or a pharmaceutically acceptable salt thereof and an excipient (paragraph 0010, (1) and (6)). The publication further teaches a method of treating breast cancer comprising administering said composition in a patient in need thereof (paragraph 0010, (4)). With regards to the compound, the publication teaches that the instantly claimed compound has FGFR inhibitory activity (paragraph 0001). With regards to the salt of the instantly claimed compound, the publication teaches that the preferred pharmaceutical salt is a 1.5 succinate (paragraph 0019). With regards to the breast cancer, the publication teaches that breast cancer is one that expresses FGFR (FGFR1, FGFR2 or FGFR3) and includes, but is not limited to, locally advanced breast cancer, metastatic breast cancer and recurrent breast cancer (paragraph 10, (8)-(9) and paragraph 23). Moreover, the publication teaches in vivo inhibitory activity of the instantly claimed compound in mice injected with MFM223 human breast cancer cell line (Example 1).
Katoh teach fibroblast growth factor receptors as treatment targets in clinical oncology (Title). Moreover, the publication teaches that alterations in FGFRs 1-4 can lead to the development and/or progression of cancer and therefore are targetable using small molecules of antibodies (abstract). Moreover, Katoh teach that:
“Combination strategies, involving the concurrent administration of FGFR-targeted therapies with other agents, might prevent or delay the expansion of treatment-resistant clones and also have the potential to enhance the antitumour effects of FGFR-targeted therapies. Data from preclinical studies indicate that anti-FGFR antibodies, cytotoxic agents, ER-targeted or other endocrine therapies… are all applicable for use in combination with FGFR inhibitors.” (page 117, Combination therapies)
With regards to the endocrine therapies, Katoh teaches that selective ER modulators (tamoxifen), selective ER degraders (fulvestrant) and aromatase inhibitors (anastrozole, exemestane and letrozole) are all approved for patients with ER-positive breast cancer (page 117, Endocrine therapies). Moreover, Katoh teach that
“FGFR1 amplification and treatment induced FGFR1 overexpression occur preferentially in patients with letrozole-resistant ER-positive breast cancer, whereas fulvestrant and the multi-kinase FGFR inhibitor lucitanib have synergistic effects on two PDX models of ER-positive, HER2-negative, FGFR1-amplified breast cancer. These finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.” (page 117, Endocrine therapies, 2nd full paragraph).
Bardia et al. teach that elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast cancer previously treated with endocrine therapies including fulvestrant and/or CDK4/6 inhibitor therapy, and in those with ESR1 mutations known to confer endocrine resistance.
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 treat breast cancer and include an estrogen receptor antagonist in the method claimed in the US Patent whether within the composition or by sequential/simultaneous administration in view of the teachings of Miyano, Katoh and Bardia et al. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Miyano teaches that the claimed compounds are FGFR inhibitors and breast cancer as a target for FGFR inhibitors and,
Katoh teaches past finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.
"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) (citations omitted)
Claims 20-22, 28-31 and 39-47 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17 and 23 of U.S. Patent No 8,933,099 in view of Miyano et al. (US 2018/0303817 A1, 10/25/2018), Katoh, Masaru (Nature Reviews Clinical Oncology; 16; 2019, pp. 105-122, published online October 26, 2018) and Bardia et al. (Future Oncol. 2019; 15(28): 3209-3218).
The US Patent claims a pharmaceutical composition comprising the instantly claimed compound or a pharmaceutically acceptable salt thereof and a method of treating non-small-cell lung carcinoma, comprising administering the instantly claimed compound or a pharmacological acceptable salt thereof (claim 1).
The US Patent does not claim that the cancer is breast and that the instantly claimed compound is administered in combination with the estrogen receptor antagonist fulvestrant or elacestrant or that the combination is administered simultaneously or separately.
Miyano teach a composition comprising the instantly claimed compound or a pharmaceutically acceptable salt thereof and an excipient (paragraph 0010, (1) and (6)). The publication further teaches a method of treating breast cancer comprising administering said composition in a patient in need thereof (paragraph 0010, (4)). With regards to the compound, the publication teaches that the instantly claimed compound has FGFR inhibitory activity (paragraph 0001). With regards to the salt of the instantly claimed compound, the publication teaches that the preferred pharmaceutical salt is a 1.5 succinate (paragraph 0019). With regards to the breast cancer, the publication teaches that breast cancer is one that expresses FGFR (FGFR1, FGFR2 or FGFR3) and includes, but is not limited to, locally advanced breast cancer, metastatic breast cancer and recurrent breast cancer (paragraph 10, (8)-(9) and paragraph 23). Moreover, the publication teaches in vivo inhibitory activity of the instantly claimed compound in mice injected with MFM223 human breast cancer cell line (Example 1).
Katoh teach fibroblast growth factor receptors as treatment targets in clinical oncology (Title). Moreover, the publication teaches that alterations in FGFRs 1-4 can lead to the development and/or progression of cancer and therefore are targetable using small molecules of antibodies (abstract). Moreover, Katoh teach that:
“Combination strategies, involving the concurrent administration of FGFR-targeted therapies with other agents, might prevent or delay the expansion of treatment-resistant clones and also have the potential to enhance the antitumour effects of FGFR-targeted therapies. Data from preclinical studies indicate that anti-FGFR antibodies, cytotoxic agents, ER-targeted or other endocrine therapies… are all applicable for use in combination with FGFR inhibitors.” (page 117, Combination therapies)
With regards to the endocrine therapies, Katoh teaches that selective ER modulators (tamoxifen), selective ER degraders (fulvestrant) and aromatase inhibitors (anastrozole, exemestane and letrozole) are all approved for patients with ER-positive breast cancer (page 117, Endocrine therapies). Moreover, Katoh teach that
“FGFR1 amplification and treatment induced FGFR1 overexpression occur preferentially in patients with letrozole-resistant ER-positive breast cancer, whereas fulvestrant and the multi-kinase FGFR inhibitor lucitanib have synergistic effects on two PDX models of ER-positive, HER2-negative, FGFR1-amplified breast cancer. These finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.” (page 117, Endocrine therapies, 2nd full paragraph).
Bardia et al. teach that elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast cancer previously treated with endocrine therapies including fulvestrant and/or CDK4/6 inhibitor therapy, and in those with ESR1 mutations known to confer endocrine resistance.
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 treat breast cancer and include an estrogen receptor antagonist in the method claimed in the US Patent whether within the composition or by sequential/simultaneous administration in view of the teachings of Miyano, Katoh and Bardia et al.. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Miyano teaches that the claimed compounds are FGFR inhibitors and breast cancer as a target for FGFR inhibitors and,
Katoh teaches past finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.
"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) (citations omitted)
Claims 20-22, 28-31 and 39-47 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-19, 24, 26 and 28 of copending Application No. 17/918,829 alone or in view Katoh, Masaru (Nature Reviews Clinical Oncology; 16; 2019, pp. 105-122, published online October 26, 2018) and Bardia et al. (Future Oncol. 2019; 15(28): 3209-3218).
Copending application no. 17/918,829 claims a method of treating breast cancer that has developed resistance to CDK4/6 inhibitors and estrogen receptor antagonist comprising administering the claimed compound or alternatively a method of treating breast cancer comprising administering the claimed compound in combination with a CDK4/6 inhibitor and an estrogen receptor antagonist (Claims 16-18 of the copending application). The application further claims that the pharmacological salt is 1.5 succinate,(claim 19), the estrogen receptor antagonist is tamoxifen, fulvestrant and mepitiostane (claims 24), the breast cancer is locally advanced, metastatic, recurrent or unresectable (claim 26) and expresses FGFR1, FGFR2 or FGFR3 (claim 28).
The copending application overlaps in scope to at least the instantly claimed invention wherein the second agent is an estrogen receptor antagonist. Please note: The instant claims contain comprising language which could allow for the inclusion of the third compound.
The copending application does not specifically teach that the estrogen receptor antagonist is elacestrant.
Katoh teach fibroblast growth factor receptors as treatment targets in clinical oncology (Title). Moreover, the publication teaches that alterations in FGFRs 1-4 can lead to the development and/or progression of cancer and therefore are targetable using small molecules of antibodies (abstract). Moreover, Katoh teach that:
“Combination strategies, involving the concurrent administration of FGFR-targeted therapies with other agents, might prevent or delay the expansion of treatment-resistant clones and also have the potential to enhance the antitumour effects of FGFR-targeted therapies. Data from preclinical studies indicate that anti-FGFR antibodies, cytotoxic agents, ER-targeted or other endocrine therapies… are all applicable for use in combination with FGFR inhibitors.” (page 117, Combination therapies)
With regards to the endocrine therapies, Katoh teaches that selective ER modulators (tamoxifen), selective ER degraders (fulvestrant) and aromatase inhibitors (anastrozole, exemestane and letrozole) are all approved for patients with ER-positive breast cancer (page 117, Endocrine therapies). Moreover, Katoh teach that
“FGFR1 amplification and treatment induced FGFR1 overexpression occur preferentially in patients with letrozole-resistant ER-positive breast cancer, whereas fulvestrant and the multi-kinase FGFR inhibitor lucitanib have synergistic effects on two PDX models of ER-positive, HER2-negative, FGFR1-amplified breast cancer. These finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.” (page 117, Endocrine therapies, 2nd full paragraph).
Bardia et al. teach that elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast cancer previously treated with endocrine therapies including fulvestrant and/or CDK4/6 inhibitor therapy, and in those with ESR1 mutations known to confer endocrine resistance.
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 include elacestrant in the method claimed by the copending application whether within the composition or by sequential/simultaneous administration in view of the teachings of Katoh. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Katoh teaches past finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.
"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) (citations omitted)
This is a provisional nonstatutory double patenting rejection.
Claims 20-22, 28-31 and 39-47 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No 12,414,945 (previously US Application 15/771,193) in view of Katoh, Masaru (Nature Reviews Clinical Oncology; 16; 2019, pp. 105-122, published online October 26, 2018) and Bardia et al. (Future Oncol. 2019; 15(28): 3209-3218).
The US patent claims a method of treating breast cancer comprising administering the claimed compound. The patent further claims that the pharmacological salt is 1.5 succinate and the breast cancer is locally advanced, metastatic, recurrent or unresectable.
The patent does not specifically claim administration of an estrogen receptor antagonist.
Katoh teach fibroblast growth factor receptors as treatment targets in clinical oncology (Title). Moreover, the publication teaches that alterations in FGFRs 1-4 can lead to the development and/or progression of cancer and therefore are targetable using small molecules of antibodies (abstract). Moreover, Katoh teach that:
“Combination strategies, involving the concurrent administration of FGFR-targeted therapies with other agents, might prevent or delay the expansion of treatment-resistant clones and also have the potential to enhance the antitumour effects of FGFR-targeted therapies. Data from preclinical studies indicate that anti-FGFR antibodies, cytotoxic agents, ER-targeted or other endocrine therapies… are all applicable for use in combination with FGFR inhibitors.” (page 117, Combination therapies)
With regards to the endocrine therapies, Katoh teaches that selective ER modulators (tamoxifen), selective ER degraders (fulvestrant) and aromatase inhibitors (anastrozole, exemestane and letrozole) are all approved for patients with ER-positive breast cancer (page 117, Endocrine therapies). Moreover, Katoh teach that
“FGFR1 amplification and treatment induced FGFR1 overexpression occur preferentially in patients with letrozole-resistant ER-positive breast cancer, whereas fulvestrant and the multi-kinase FGFR inhibitor lucitanib have synergistic effects on two PDX models of ER-positive, HER2-negative, FGFR1-amplified breast cancer. These finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.” (page 117, Endocrine therapies, 2nd full paragraph).
Bardia et al. teach that elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast cancer previously treated with endocrine therapies including fulvestrant and/or CDK4/6 inhibitor therapy, and in those with ESR1 mutations known to confer endocrine resistance.
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 include to include an estrogen receptor antagonist in the method claimed by the US Patent whether within the composition or by sequential/simultaneous administration in view of the teachings of Katoh and Bardia. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Katoh teaches past finding clearly support the concept of combining endocrine therapies with FGFR inhibitors.
In response to the double patenting rejections set forth above, Applicants reiterate the arguments above which incorporate the assertions within the Declaration. Such arguments have been considered but are not found persuasive for the reasons above and incorporated herein.
Conclusion
Therefore, 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.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626