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 in reply to Applicant Arguments/Remarks filed on 13 March 2026. This application 18/449,793 was filed on 15 August 2023, CON of PCT/US2022/016268 filed on 14 February 2022, with PRO 63/149,941 filed on 16 February 2021. Claims 1-10, 12, 14-17, 19, 22-34 and 38-47 are canceled. Claims 11, 13 and 36 are amended. Claims 48-56 are new.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 13 March 2026 was filed after the mailing date of the application on 15 August 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 55 is objected to because of the following informalities: the phrase comprises an ESR1-mutation is used twice in the claim where one is appropriate. Appropriate correction is required.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous office action is set out below.
35 U.S.C. 102, 103, and Double Patenting
Applicant’s amendments to claims 11 and 13, further limiting the claims to inoperable cancer and the patient having disease progression during or following treatment with a CDK4/6 inhibitor in the first line (1L) or second line (2L) setting, is sufficient to overcome these rejections.
REJECTIONS – MAINTAINED & NEW
Applicant’s amendments to now independent claims 11 and 13 have resulted in the below new prior art rejections.
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 non-obviousness.
(New) Claims 11, 13, 20-21, 35-37, and 48-56 are rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (Solid forms of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidine-3-yl)amino)phenyl)-3-metyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-B]indol-2-yl)-2,2-difluoropropan-1-ol and processes for preparing fused tricyclic compounds comprising a substituted phenyl or pyridinyl moiety, including methods of their use, WO 2019/245974A1, 2019; entered in the IDS on 22 November 2023) in view of Bardia et al. (Phase Ib dose-escalation/expansion trial of Ribociclib in combination with Everolimus and Exemestane in postmenopausal women with HR+, HER2+ advanced breast cancer, Clin. Cancer Res. 2020, 26, 6417-6428).
Chung discloses methods of treating ER+, HER2+, HER2-, TN (para. 0388), locally advanced or metastatic breast cancers (para. 0390) through the administration of an effective amount of GDC-9545, which can include 30 mg (para. 0393), QD on 28-day cycles (para. 0726), in a combinational therapy (para. 0398) with CDK4/6 inhibitors Abemaciclib and Ribociclib (para. 0402), where Abemaciclib can be dosed 150-450 mg, BID daily in 28-day cycles (para. 0403), and Ribociclib can be dosed 250-750 mg, QD daily in 28-day cycles (para. 0404). The receiving patient may have previously been treated, with a 1L, 2L, 3L or more line therapy with an AKT inhibitor, CDK4/6 inhibitor, PARP inhibitor, or aromatase inhibitor (para. 0395) and may be refractory to the anti-cancer therapy (para. 0396).
Chung does not, however, disclose where the cancer is inoperable.
Bardia rectifies this deficiency by teaching the clinical design and results of a phase Ib dose-escalation/expansion study of triplet therapy with Ribociclib, mTOR inhibitor Everolimus, and endocrine therapy Exemestane for postmenopausal women with HR+, HER2-, pretreated, advanced breast cancer. Within the key inclusion data included postmenopausal and adult women (≥18 years of age) with HER2- locally advanced or metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy who experienced recurrence during, or within 12 months of ending, adjuvant treatment with letrozole or anastrozole, or progression during or within one month of stopping, letrozole or anastrozole treatment for advanced breast cancer, with radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment (pg. 6418 – Patient Population).
While the combinational therapy is different as the target includes HR+ breast cancer, the framework of treatment, utilizing a CDK4/6 inhibitor in combination with another treatment to target HER2- breast cancer, broadly reads upon the methods of claim 11 and 13.
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider the addition of inoperable cancers as an inclusive criterion in the selection of patients based on the prior clinical trial patient inclusion criteria in a clinical trial for the treatment of advanced breast cancer using a combinational therapy which included a CDK4/6 inhibitor.
With regards to the limitation of claim 20, wherein the patient is premenopausal, is met by Bardia who teaches the inclusion of both postmenopausal and adult women who are ≥18 years of age, necessarily premenopausal (pg. 6418- Patient Population).
Pertaining to the limitations of claim 21, wherein the patient is tested for the presence of a mutation of one or more of estrogen receptor, prostaglandin receptor, or Ki67, are met as Chung discloses treatment of a patient diagnosed with ER+PR+ breast cancer (para. 0728).
With respect to the limitation of claim 35, wherein the patient has been previously treated with tamoxifen, is met by Chung who discloses that the patients of the described methods may have had previous treatment with one or more anti-cancer agents including tamoxifen (para. 0394).
Concerning the limitations of claim 36, wherein the patient has been previously treated with an aromatase inhibitor or an aromatase inhibitor in combination with a CDK4/6 inhibitor, are met as Chung discloses that the patients of the described methods may have been previously treated with one or more anti-cancer agents including letrozole, anastrozole, or exemestane, which are aromatase inhibitors (para. 0394).
Regarding the limitations of claim 37, wherein the patient has been previously treated with fulvestrant, is met as Chung discloses that a patient may have been previously treated with fulvestrant (para. 0395).
With regards to the limitations of claim 48, wherein the patient is premenopausal, is met by Bardia who teaches the inclusion of both postmenopausal and adult women who are ≥18 years of age, necessarily premenopausal (pg. 6418- Patient Population).
Pertaining to the limitations of claim 49, wherein the patient is tested for the presence of a mutation of one or more of estrogen receptor, prostaglandin receptor, or Ki67, are met as Chung discloses treatment of a patient diagnosed with ER+PR+ breast cancer (para. 0728).
With respect to the limitations of claim 50, wherein the patient has been previously treated with tamoxifen, is met by Chung who discloses that the patients of the described methods may have had previous treatment with one or more anti-cancer agents including tamoxifen (para. 0394).
Concerning the limitation of claim 51, wherein the patient has been previously treated with an aromatase inhibitor or an aromatase inhibitor in combination with a CDK4/6 inhibitor, are met as Chung discloses that the patients of the described methods may have been previously treated with one or more anti-cancer agents including letrozole, anastrozole, or exemestane, which are aromatase inhibitors (para. 0394).
Regarding the limitation of claim 52, wherein the patient has been previously treated with fulvestrant, is met as Chung discloses that a patient may have been previously treated with fulvestrant (para. 0395).
With regards to the limitation of claim 53, wherein the patient has not undergone breast conserving surgery or had a mastectomy before treatment with Giredestrant and Abemaciclib, is met as Bardia teaches the inclusion of women with locally advanced or metastatic breast cancer not amenable to curative treatment by surgery.
With respect to the limitation of claim 54, wherein the patient has not undergone breast conserving surgery or had a mastectomy before treatment with Giredestrant and Ribociclib, is met as Bardia teaches the inclusion of women with locally advanced or metastatic breast cancer not amenable to curative treatment by surgery.
Concerning the limitation of claim 55, wherein the ER+ and HER2-negative inoperable IaBC or mBC comprises an ESR1-mutation, is met as Chung discloses that studies have identified mutations in ESR1 (i.e., the gene that encodes for Erα) affecting the ligand-binding doman of the ER, where mutant ER can drive transcription and proliferation in the absence of estrogen, suggesting that LBD-mutant forms of ER may be involved in mediating clinical resistance to some endocrine therapies, and that ER antagonists that are efficacious against these ligand-independent, constitutively-active ER-mutated receptors may possess substantial therapeutic benefit (para. 0707). Chung also discloses that GDC-9545 also demonstrated nonclinical activity in ER-positive breast cancer models of ESR1-wildtype and ESR1-mutation bearing disease (para. 0721).
Concerning the limitation of claim 56, wherein the ER+ and HER2-negative inoperable IaBC or mBC comprises an ESR1-mutation, is met as Chung discloses that studies have identified mutations in ESR1 (i.e., the gene that encodes for Erα) affecting the ligand-binding domain of the ER, where mutant ER can drive transcription and proliferation in the absence of estrogen, suggesting that LBD-mutant forms of ER may be involved in mediating clinical resistance to some endocrine therapies, and that ER antagonists that are efficacious against these ligand-independent, constitutively-active ER-mutated receptors may possess substantial therapeutic benefit (para. 0707). Chung also discloses that GDC-9545 also demonstrated nonclinical activity in ER-positive breast cancer models of ESR1-wildtype and ESR1-mutation bearing disease (para. 0721).
(Maintained) Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Chung and Bardia as applied to claim 11, 13, 20-21, 35-37, and 48-56 above, and further in view of O’Kane et al. (A single-centre analysis of 30 patients with relapsed germ cell tumours treated with the TI-CE regimen, Bone Marrow Transplantation 2016, 51, 6, 856-859).
Chung teaches a method of treating ER+ and HER2- breast cancer utilizing a combination therapy of GDC-9545, dosed QD on a 28-day cycle, and co-administration of Abemaciclib or Ribociclib, dosed BID on the same 28-day cycle, for patients who have been previously treated with a 1L or 2L line therapy with a CDK4/6 inhibitor and are refractory to the anti-cancer therapy, while Bardia teaches the inclusion of patients with inoperable cancers.
They do not, however, teach the application of this dosing regimen over a range of 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 30, 36, 42, 48, 54, 60, and 72 cycles.
O’Kane rectifies this deficiency by teaching a TI-CE regimen applied from 1998 to 2015 at the National Adult SCT center at St James’s Hospital in Dublin. The TI aspect, two cycles of taxol (paclitaxel/ifosfamide) followed by three cycles of the CE aspect (carboplatin/etospide) as a means to treat germ cell tumors, common malignancies in young men between 15-35 years. With a cohort of 30 patients, a total of 81 out of a planned 90 cycles were performed, with a 72% survival rate (discussion). A prima facie case of obviousness necessarily exists when the prior art range overlaps or touches a claimed range, such as in the instant application. MPEP § 2144.05.
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider an extended treatment period to observe the longitudinal outcomes including ORRs, survival rates, and AEs.
(Maintained) Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Chung and Bardia as applied to claim 11, 13, 20-21, 35-37, and 48-56 above, and further in view Lambertini et al. (Adjuvant anti-HER2 therapy, treatment-related amenorrhea, and survival in premenopausal HER2-positive early breast cancer patients, J. Natl. Cancer Inst. 2019, 111, 1djy094).
Chung teaches a method of treating ER+ and HER2- breast cancer utilizing a combination therapy of GDC-9545, dosed QD on a 28-day cycle, and co-administration of Abemaciclib or Ribociclib, dosed BID on the same 28-day cycle, for patients who have been previously treated with a 1L or 2L line therapy with a CDK4/6 inhibitor and are refractory to the anti-cancer therapy, while Bardia teaches the inclusion of patients with inoperable cancers.
Chung does not teach wherein the patient is premenopausal.
Lambertini overcomes this delinquency by teaching treating a cohort of HER2-positive early breast cancer patients, a total of 2862 premenopausal women, receiving adjuvant Lapatinib and/or Trastuzumab treatment in the BIG2-06 phase III trial. Approximately 73% of patients were observed to have treatment-related amenorrhea with a statistically significant associated survival benefit (abstract).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to potentially recruit a cohort of similar premenopausal women to see if there is a similar occurrence of treatment-related amenorreha and corollary to therapeutic efficacy and survival rates.
(Maintained) Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Chung and Bardia as applied to claim 11, 13, 20-21, 35-37 and 48-56 above, and further in view Jerzak et al. (HR+/HER2- advanced breast cancer treatment in the first-line setting: expert review, Curr. Oncol. 2023, 30, 5425-5447) and Shao et al. (MR imaging phenotypes and features associated with pathogenic mutation to predict recurrence or metastasis in breast cancer, BMC Cancer 2023, 23, 97, 1-13).
Chung teaches a method of treating ER+ and HER2- breast cancer utilizing a combination therapy of GDC-9545, dosed QD on a 28-day cycle, and co-administration of Abemaciclib or Ribociclib, dosed BID on the same 28-day cycle, for patients who have been previously treated with a 1L or 2L line therapy with a CDK4/6 inhibitor and are refractory to the anti-cancer therapy, while Bardia teaches the inclusion of patients with inoperable cancers.
Jerzak teaches routinely performing ER/PR testing during the first-line treatment of HR+/HER2- advanced breast cancer while administering Ribociclib and aromatase inhibitor therapy as part of a simplified approach to monitoring breast cancer detection and tracking of progression during the therapy period (abstract, Fig. 3).
Shao teaches genetic testing for breast-related gene mutations in 54 patients with breast cancers alongside comparative evaluation of tumors. Ki67 was observed o have a near significant difference between pathogenic mutations and non-pathogenic mutations where women younger than 40 had more pathogenic gene mutations than women over 40. Pathogenic mutations were therefore more likely to be associated with the TN phenotype than another and were observed in more unfavorable biological behavior in cancer. Additionally, these pathogenic mutations, including Ki67, were more likely to be associated with recurrence or metastasis (results).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to combine any experimental therapy, such as the claimed GDC-9545 and Abemaciclib combination, with monitoring of ER, PR, and Ki67 levels to provide corollary data possibly predictive of patient outcomes.
(Maintained) Claims 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Chung and Bardia as applied to claim 11, 13, 20-21, 35-37 and 48-56 above, and further in view Harbeck et al. (Breast cancer, Nat. Rev. Dis. Primers 2019, 5, 1, 66).
Chung teaches a method of treating ER+ and HER2- breast cancer utilizing a combination therapy of GDC-9545, dosed QD on a 28-day cycle, and co-administration of Abemaciclib or Ribociclib, dosed BID on the same 28-day cycle, for patients who have been previously treated with a 1L or 2L line therapy with a CDK4/6 inhibitor and are refractory to the anti-cancer therapy, while Bardia teaches the inclusion of patients with inoperable cancers.
Harbeck teaches the mainstay of treatment for HR+/HER2- advanced breast cancer in postmenopausal women prior to 2016 being either endocrine therapy with Tamoxifen, aromatase inhibitors (Anastrozole, Exemestane, or Letrozole) or Fulvestrant. Since 2016, Harken notes that CDK4/6 inhibitors, beginning with Pabociclib, emerged as first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women, followed by Ribociclib in 2018 and Abemaciclib in 2019. Ribociclib was further approved for first-line treatment in premenopausal women in 2020. These studies are done in comparison to vehicle cohorts in clinical trials, i.e., patients who receive either a placebo or no treatment (management).
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to design experiments, utilizing the claimed combination therapy, with patient cohorts as described above, with a vehicle cohort, and other cohorts that had received the established standard-of-care treatments including endocrine therapy agents or CDK4/6 inhibitors which have been established for the past two decades.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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.
(Maintained) Claims 11 and 13 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 9 of co-pending Application No. 18/449,807 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both applications claim QD dosing of GDC-9545 at least 30 mg, in the case of the instant application, or at 10, 30, 50, or 100 mg in the case of 18/449/807, QD dosing, on a 28-day cycle, in combination with either Abemciclib/Ribociclib or Ipatasertib. With regards to the inclusion criteria for patient population, both applications require HER2-negative locally advanced or metastatic breast cancer. Abemeciclib and Ribociclib have been reported by Harbeck to have been used as standard-of-care adjuvant therapy in conjunction with endocrine therapy. Kim et al. (Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomized, double-blind, placebo-controlled, phase 2 trial, Lancet Oncol. 2017, 18, 1360-1372) has explored Ipatasertib in combination with Paclitaxel as a first-line therapy for metastatic TN breast cancer. Both illustrate the potential benefits of using a combination approach toward breast cancer therapy with other theranostic agents without obvious liabilities.
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider utilizing either Abemciclib/Ribociclib or Ipatasertib in combination with GDC-9545 to explore their synergistic therapeutic effects for breast cancer treatments.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
Claims 11, 13, 18, 20-21, 35-37 and 48-56 are rejected under 35 U.S.C. 103. Claim 11 and 13 are rejected as NDSP. Claim 55 is objected to.
Response to Arguments
The office kindly thanks the Applicant for their consideration and arguments to the previous office action. Responses are detailed below.
Applicant’s arguments, see pg. 6, line 1, filed 13 March 2026, with respect to the rejection(s) of claim(s) 11 and 13 under 35 U.S.C. 102(a)(1) and 35 U.S.C.(a)(2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of newly found prior art reference Bardia et al. (Phase Ib dose-escalation/expansion trial of Ribociclib in combination with Everolimus and Exemestane in postmenopausal women with HR+, HER2+ advanced breast cancer, Clin. Cancer Res. 2020, 26, 6417-6428).
On page 5-6, Remarks, the Applicant argues:
…Chung fails to anticipate the claims because it fails to teach the claimed 28-day cycle for GDC-9545. While Chung describes a 28-day cycle for Abemaciclib, it does not include a cycle time for GDC-9545. Furthermore, Chung fails to describe the patient population as presently amended…
In response to Applicant’s arguments, Chung does teach a 28-day cycle for GDC-9545, in para. 0724, where patients were enrolled in a single-agent GDC-9545 dose-escalation stage. Here continuous once daily dosing was commenced during the treatment period starting on Cycle 1 Day 1. The starting dose was 10 mg, administered to patients by mouth continuously in 28-day cycles. Six patients were initiated in the initial dose 10 mg, QD 28-day cycles (para. 0726).
On page 6, Remarks, the Applicant argues:
…the office has only rejected dependent claims 18, 20, 21, 29 and 34-37 under 35 U.S.C. 103. For completeness of response, Applicant disagrees should the Office consider raising such a rejection to claims 11 or 13. Chung alone or taken in combination with any other cited references is insufficient to render claims 11 or 13 as obvious. Applicant addressed the shortcomings of Chung above. Chung provides no teaching or suggestion to a person of ordinary skill to administer GDC-9545 in a 28-day cycle. Chung teaches that the administration of Abemaciclib and Ribociclib are 28- and 21-days, respectively. However, such administration regimens do not lead a person of ordinary skill to select the 28-day cycle of administration for GDC-9545 at the claimed 30 mg dose. Thus, a person of ordinary skill had no pointer to select administering GDC-9545 as claimed. Furthermore, Applicant amended claims 11 and 13 to recite treatment of specific patient populations not taught or suggested by Chung or any other cited art. Accordingly, a person of ordinary skill lacked motivation to arrive at the instant claims… Claims 18, 20, 21, 29, and 34-37 depend from claim 11, which as set forth herein is both novel and non-obvious….
As stated above, the rejections of claims 11 and 13 were withdrawn as the amendments to those claims do indeed overcome those rejections. Also as stated above, new grounds of rejection have been made in view of newly found prior art reference Bardia. While Chung does not provide dose administration cycles in the embodiments description of the art, they do provide exemplary cases in para. 0724 & 0726 where they utilize a 28-day, QD daily dosing regimen in clinical trials to enrolled patients. Additionally, the 30 mg dose, while not exactly specified by Chung, is a specific dose listed within the possible effective amounts (para. 0393). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range). A prima facie case of obviousness necessarily exists when the prior art range overlaps or touches a claimed range, such as in the instant rejection. MPEP § 2144.05.
On page 7, Remarks, the Applicant argues:
…the ‘807 application, as noted by the Office, claims GDC-9545 in combination with an entirely different agent, Ipatasertib. Ipatasertib is an AKT inhibitor targeting a different pathway from the CDK4/6 inhibitors disclose in the instant application. A person of ordinary skill had no teaching or suggestion or motivation to arrive at the instant combination in view of the ‘807 application, which discloses agents with different mechanism of action and inhibition. There is no suggestion in the ‘807 application that points a person of ordinary skill to substitute Ipatasertib with Abemaciclib or Ribociclib. There is also no suggestion that such a substitution would maintain efficacy when treating the instantly claimed patient population…
In response to the Applicant’s argument, that there is no motivation or suggestion to arrive the instant combination, the Examiner rebuts that the instant application aims to treat breast cancers utilizing a multi-vector approach and ultimately is the framework behind the instant application. Combining therapies with different mechanism of actions to overcome the resistances that can arise, such as from the ESR1 mutation as exemplified in the instant application, supports the idea of synergistic combinational therapies. Additionally, AKT is a well-known target in the PI3K/Akt signaling pathway that runs adjacent to another privileged MAPK pathway and is well documented to undergo gain or loss of function mutations (Harbeck – fig. 2). Indeed, the fact that Kim utilizes an AKT inhibitor in their combinational therapy approach to treating breast cancer supports the idea that AKT inhibitors can be used synergistically with therapies who do not have the same mode of action.
Applicant’s suggestion that there is no evidence such a substitution would maintain efficacy when treating the instantly claimed population is unconvincing on the face of the argument. As the patient population, as amended in claims 11 and 13, are now stated to include patients who had previously had L1 or L2 CDK4/6 inhibitor therapies and also saw disease progression, it seems more likely that an orthogonal vector treatment such as an AKT inhibitor combined with GDC-9545 would be efficacious to this patient population than the combination of CDK4/6 inhibitors with GDC-9545. Indeed, Alves et al. (Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine-therapy-resistant breast cancer, Nat. Comm. 2021, 12, 5112), used here only to support the Examiner’s response, illustrates results of AKT inhibitor efficacy in impairing breast cancer cells, preventing progression, and reducing metastasis of tumor xenografts resistant to a combination of CDK4/6i-fulvestrant or fulvestrant alone (abstract). As such, it appears obvious to the Examiner that it is more likely that the combination therapy from application 18/449,807 will be more efficacious for the patient population of the instant application than the combination therapy claimed.
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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