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 . Claims 21-40 filed January 09, 2025 are currently pending.
Priority
Acknowledgement is made of the continuation of Application 18101377, now U.S. Patent 12,083,129. Application 18101377 is a continuation of Application 16989528, now U.S. Patent 11,576,919. Application 16989528 claims priority to U.S. Provisional Applications 62885732 filed 08/12/2019 and 62935526 filed 11/14/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/11/2024 and 04/15/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 21, 23-25, 27-28, 31-33, 36-37, and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clinical trial NCT03959891 published online 05/30/2019.
Claim interpretation is as follows: Claim 21 is directed to a method of treating hormone receptor positive and HER2 negative locally advanced unresectable or metastatic breast cancer in a patient having hormone receptor positive and HER2 negative locally advanced unresectable or metastatic breast cancer, the method comprising administering to the patient a combination therapy over a 28-day cycle; wherein the combination therapy comprises (i) an ATP competitive AKT inhibitor, and (ii) fulvestrant or a CDK4/6 inhibitor. Applicant is reminded of MPEP 2111.03 wherein the transitional phrase "comprising" is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). In the present case, the pending claims do not exclude the administration of fulvestrant and a CDK 4/6 inhibitor in combination with the ATP competitive AKT inhibitor.
Clinical Trial NCT03959891/TAKTIC trial teaches the administration of ipatasertib, fulvestrant and palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2 negative breast cancer (pages 1-8). lpatasertib is administered once a day for days 1-21 of a 28 day schedule, palbociclib is administered once a day for 21 days of a 28 day cycle and fulvestrant is administered twice a month via injection in a 28 day cycle for the first month, then monthly for all other cycles (pages 4-6). Post-menopausal patients that comprise disease progression following treatment with endocrine therapy with palbociclib are embraced in the claimed methodology (page 8). Said patients have previously received endocrine therapy, such as tamoxifen (page 9).
Claims 21-23, 25, 31-34 and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jones (J. Clin. Oncology Vol. 37 number 15, abstract #1005, published online 05/20/2019).
Jones teaches the FAKTION clinical trial comprising treating advanced hormone receptor positive, HER2- breast cancer in post-menopausal patients who had relapse or disease progression from treatment with an aromatase inhibitor comprising administering an ATP competitive AKT inhibitor (capivasertib) in combination with fulvestrant in a 28 day cycle. The ATP competitive AKT inhibitor capivasertib was orally administered in a dose of 400 mg twice a day (bd), while fulvestrant was administered in a dose of 500 mg on day 1 and day 15 of a 28-day cycle (abstract). Jones teaches that the addition of the ATP competitive AKT inhibitor capivasertib to the fulvestrant regimen resulted in significantly longer progression-free survival and an improvement in overall survival (abstract).
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.
Claim(s) 21-23, 25, 28-34, 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Jones (J. Clin. Oncology Vol. 37 number 15, abstract #1005, published online 05/20/2019) in view of Lin (US2017/0157124 published 06/08/2017).
Jones teaches the FAKTION clinical trial comprising treating advanced hormone receptor positive, HER2- breast cancer in post-menopausal patients who had relapse or disease progression from treatment with an aromatase inhibitor comprising administering an ATP competitive AKT inhibitor (capivasertib) in combination with fulvestrant in a 28 day cycle. The ATP competitive AKT inhibitor capivasertib was orally administered in a dose of 400 mg twice a day (bd), while fulvestrant was administered in a dose of 500 mg on day 1 and day 15 of a 28-day cycle (abstract). Jones teaches that the addition of the ATP competitive AKT inhibitor capivasertib to the fulvestrant regimen in ER resistant breast cancer resulted in significantly longer progression-free survival and an improvement in overall survival (abstract).
However, Jones does not specifically teach administering the claimed ipatasertib and fulvestrant combination to the advanced hormone receptor positive, HER2- breast cancer patient.
Lin teaches treating hormone receptor positive, HER2- metastatic breast cancer in a subject in need comprising administering to said subject a therapeutically effective amount of the AKT inhibitor GDC-0068 (abstract, [0038]-[0039], [0091]-[0092], [0324]-[0325], Figures 21 and 22A-22D).
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As evidenced by CAS REGISTRY DATABASE, GDC-0068 is art-recognized as the claimed ipatasertib. Regarding claims 29-30 and 38-39, oral administration of 400 mg GDC-0068 as a hydrochloride salt is taught by Lin ([0038]-[0039], [0216], [0324]-[0325]). Administration of once a day, repeated for 7 days of a 21-day cycle is embraced within the teachings of Lin ([0216], [0325]). As shown in Figure 21 and 22A-D said hormone positive, HER2- breast cancer patient harboring a PI3K mutation (H1074R) treated with GDC-0068 had not been previously treated with a PI3K inhibitor, a MTOR inhibitor or an AKT inhibitor ([0324]-[0325], Figures 21-22). As shown in Figures 21 and 22A-22D, monotherapeutic administration of GDC-0068 resulted in stabilizing the aforementioned hormone receptor positive, HER2- metastatic breast cancer in the neoplastic patient ([0038]-[0039], [0324]-[0325], Figures 21, 22A-D).
Therefore, one of ordinary skill in the art prior to the time of the invention knowing that the combination of the AKT inhibitor capivasertib and fulvestrant is efficacious at treating advanced hormone receptor positive, HER2- breast cancer in a subject in need as taught by Jones above, said artisan would have found it prima facie obvious to substitute the AKT inhibitor capivasertib in the regimen of Jones, for an alternative AKT inhibitor, such as ipatasertib in view of Lin in order to arrive at the instantly claimed methodology.
MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
In the present case, considering the AKT inhibitor ipatasertib is art-recognized as effective at treating hormone positive, HER2- breast cancer in a subject in need, said artisan would have readily predicted that administration of a combination comprising fulvestrant and an AKT inhibitor, wherein the AKT inhibitor is ipatasertib, said regimen would have effectively treated advanced hormone receptor positive, HER2- breast cancer in the neoplastic patient.
Lastly, regarding the limitation wherein ipatasertib is administered once a day for 21 days in a 28 day cycle, the optimum dosing cycle and frequency of administration of the AKT inhibitor ipatasertib to the advanced hormone receptor positive, HER2- breast cancer patient receiving fulvestrant and ipatasertib would have been a matter well within the insight of one of ordinary skill in the art. Such a determination would have been made in accordance with a variety of factors, such as the route of administration, pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles of the combined regimen, as well as the age, weight, sex, diet and severity of the medical condition of the patient. Thus, the dosing cycle and frequency of administration regimen that would have been employed would have varied widely and, in the absence of evidence to the contrary, the current claimed specific administration regimen is not seen to be inconsistent with one that would have been determined by the skilled artisan. Furthermore, absent and evidence demonstrating a patentable difference between the compositions administered and the criticality of the claimed frequency and dosing cycles, the determination of the optimum or workable frequency of administration given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)(”[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the workable ranges by routine experimentation.”)
Claim(s) 26 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Jones (J. Clin. Oncology Vol. 37 number 15, abstract #1005, published online 05/20/2019) and Lin (US2017/0157124 published 06/08/2017) as applied to claims 21-23, 25, 28-34, 37-40 above in view of Chakravarty (WO2013/173811 published 11/12/2013).
As discussed above, the combination of Jones and Lin render obvious the treatment of advanced hormone positive, HER2- breast cancer in a subject in need comprising administering fulvestrant in combination with an AKT inhibitor, wherein the AKT inhibitor is ipatasertib.
However, the combination of Jones, Lin and Lin does not specifically teach administering the AKT inhibitor ipatasertib as a monohydrochloride salt, nor as an amorphous monohydrochloride salt.
Chakravarty teaches GDC-0068 pharmaceutical salt formulations ([0003]-[0005]). As evidenced by CAS REGISTRY DATABASE above, GDC-0068 is art-recognized as ipatasertib. Chakravarty teaches preparation of an amorphous monohydrochloride salt formulation of GDC-0068, wherein said pharmaceutical salt formulation has improved pharmaceutical properties, is a stable form of GDC-0068 and is efficacious for the treatment of cancer ([0012], [0081]-[0082], Figure 1, claim 1).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the combination of the AKT inhibitor ipatasertib and fulvestrant to treat hormone receptor positive, HER2- breast cancer in a subject in need, wherein ipatasertib is administered as an amorphous monohydrochloride salt in view Chakravarty.
MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
In the present case, it was known in the prior art that, ipatasertib, formulated as an amorphous monohydrochloride salt has improved pharmaceutical properties and is efficacious for the treatment of cancer. Accordingly, said artisan would have readily predicted that administration of ipatasertib and fulvestrant wherein ipatasertib is administered as an amorphous monohydrochloride salt would have effectively treated the hormone receptor positive, HER2- breast cancer patient.
Claim(s) 21-22, 24-25, 27, 32, 36 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Morikawa (Clinical Cancer Research Vol. 21 pages 3591-3596. Published 2015) and Lin (US2017/0157124 published 06/08/2017)
Morikawa (Clinical Cancer Research Vol. 21 pages 3591-3596. Published 2015) teaches treating ER+/HER2- metastatic breast cancer patients who had received 2-lines of chemotherapy comprising administering the CDK 4/6 inhibitor palbociclib. Morikawa teaches oral administration in a dose of 125 mg palbociclib for days 1-21 of a 28 day cycle. Stabilized disease was achieved in 21% of said ER+ breast cancer patients and said patients resulted in an increase of median progression free survival of 3.8 months compared to control patients (abstract, page 3593 left col.)
The difference between the presently claimed methodology and that of Morikawa is that Morikawa does not teach administering an ATP competitive AKT inhibitor in combination with palbociclib.
Lin teaches treating hormone receptor positive, HER2- metastatic breast cancer in a subject in need comprising administering to said subject a therapeutically effective amount of the AKT inhibitor GDC-0068 (abstract, [0038]-[0039], [0091]-[0092], [0324]-[0325], Figures 21 and 22A-22D).
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As evidenced by CAS REGISTRY DATABASE, GDC-0068 is art-recognized as the claimed ipatasertib. Regarding claims 29-30 and 38-39, oral administration of 400 mg GDC-0068 as a hydrochloride salt is taught by Lin ([0038]-[0039], [0216], [0324]-[0325]). Administration of once a day, repeated for 7 days of a 21-day cycle is embraced within the teachings of Lin ([0216], [0325]). As shown in Figure 21 and 22A-D said hormone positive, HER2- breast cancer patient harboring a PI3K mutation (H1074R) treated with GDC-0068 had not been previously treated with a PI3K inhibitor, a MTOR inhibitor or an AKT inhibitor ([0324]-[0325], Figures 21-22). As shown in Figures 21 and 22A-22D, monotherapeutic administration of GDC-0068 resulted in stabilizing the aforementioned hormone receptor positive, HER2- metastatic breast cancer in the neoplastic patient ([0038]-[0039], [0324]-[0325], Figures 21, 22A-D).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to incorporate GDC-0068/ ipatasertib to a regimen comprising the CDK 4/6 inhibitor palbociclib to treat hormone receptor positive, HER2 negative metastatic breast cancer in patients in need in view of Lin, arriving at the presently claimed methodology. Motivation to administer palbociclib and ipatasertib together flows logically from the very fact each agent or combination of agents was known in the prior art to have the same therapeutic utility of treating ER+/HER2- metastatic breast cancer in a subject in need and, in turn, raises the reasonable expectation of success, that when combined, a composition comprising palbociclib and ipatasertib would be efficacious at treating ER+/HER2- metastatic breast cancer in a subject in need. The instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that 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 (MPEP 2144.06).
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 21, 23-33, 35-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,576,919.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following. Claims 1-19 of U.S. Patent 11,576,919 are directed to the administration of ipatasertib, fulvestrant and palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2 negative breast cancer in a subject in need wherein the combination is administered over a 28 day cycle and said subject does not have a history of type (I) diabetes, type (II) diabetes or inflammatory bowel disease but does have a history of being treated with an aromatase inhibitor or tamoxifen (claims 13-14). Claims 18-19 of U.S. Patent 11,576,919 further embrace the administration of ipatasertib as an amorphous hydrochloride salt, which overlaps with the methodology of instant claims 26 and 35.
Claims 21-23, 25-33, 35-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,083,129
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following. Claims 1-19 of U.S. Patent 12,083,129 are directed to the administration of ipatasertib and fulvestrant for the treatment of patients with locally advanced or metastatic HR+/HER2 negative breast cancer in a subject in need wherein the combination is administered over a 28 day cycle and said subject has a history of being treated with a CDK 4/6 inhibitor (palbociclib, abemaciclib, ribociclib) and an aromatase inhibitor or tamoxifen (claims 10, 13-14). Claims 18-19 of U.S. Patent 12,083,129 further embrace the administration of ipatasertib as an amorphous hydrochloride salt, which overlaps with the methodology of instant claims 26 and 35.
Conclusion
In view of the rejections set forth above, no claim is allowed.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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