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 .
Status of the Claims
The status of the claims are as follows:
Claims 1-25 are pending.
Claims 1-25 are rejected.
Priority
Acknowledgement is made that Instant Application 18/846,183, filed on 2024, Sept. 11, is a National Stage entry of PCT/IB2023/052,408, filed on 2023, Mar. 13, which claims priority from Provisional Application 63/319,373, filed on 2022, Mar. 13, which additionally claims priority from Provisional application 63/375,108, filed on 2022, Sept. 09, which claims foreign priority to 22315323.0, filed on 2022, Dec. 09.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2024, Sept. 11 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
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) 1-18 and 20-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Campone, (Abstract P5-11-02: Dose-Escalation Study of SAR439859, an Oral Selective Estrogen Receptor Degrader, in Postmenopausal Women with Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Cancer Res., 2020, 80, P5-11-02. doi.org/10.1158/1538-7445.SABCS19-P5-11-02) in view of NCBI clinical trial ID NCT04059484 (posted 2019, Oct. 22).
Claim 1 is directed to a method for reducing disease progression or death as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator, in a patient in need thereof, wherein the patient has ER+/HER2-advanced/metastatic breast cancer with mutated estrogen receptor 1 (ESR1), the method comprising administering to the patient amcenestrant or a pharmaceutically acceptable salt thereof.
Campone teaches a method of administering SAR439859 (hereafter referred to as “amcenestrant”) as a monotherapy to treat postmenopausal women with ER+/HER2- metastatic breast cancer, most of whom had ESR1 mutation, and who had previously been treated with endocrine therapy for ≥ 6 months (methods). The method comprising administering to the patient 400 mg amcenestrant QD (conclusions). Campone further teaches a dose-escalation study wherein subjects of the same patient population were administered amcenestrant 20 – 600 mg QD (results).
The difference between the teaching of Campone and the instant application is that Campone fails to teach the above method as reducing disease progression or death as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator.
However, NCT04059484 teaches a method of administering amcenestrant to patients with ER+/HER2- locally advanced or metastatic breast cancer with prior exposure to hormonal therapies (official title). Patients must have presented a secondary endocrine resistance to endocrine therapy, defined as progression while on endocrine therapy after at least 6 months of treatment (recruitment information; eligibility criteria). NCT04059484 further teaches a head-to-head comparison of amcenestrant against physicians’ choice of therapy, consisting of monotherapy from a list of fulvestrant, the aromatase inhibitors anastrozole, letrozole, exemestane, and the selective estrogen receptor modulator tamoxifen.
One of ordinary skill in the art would have been motivated to combine the teachings of Campone and NCT04059484 because both teachings apply the same drug (amcenestrant) in treating the same indication (ER+/HER2- metastatic breast cancer). Campone further discloses a QD dosage for expansion cohorts based on safety, PD, and PK (conclusions), and NCT04059484 is an expansion cohort to determine efficacy against other endocrine therapy options.
Although the results of NCT04059484 were not published prior to the effective filing date of the instant application, the drug (amcenestrant monotherapy), the active step of administration, the route of administration, and the same patient population (ER+/HER2- advanced/metastatic breast cancer with mutated estrogen receptor 1) are the same as taught by Campone and identical to that of instantly claimed. Furthermore, as previously discussed, Campone teaches administering between 20 – 600 mg of amcenestrant to said patient population. Therefore, the property of the amcenestrant monotherapy to reduce disease progression or death as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator in the treated patient must necessarily be present in the prior art within the disclosed dose range of 20 – 600 mg QD.
It is noted that MPEP 2112 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the present case, the burden is shifted to Applicant to prove that the method as taught by Campone would not result in reducing disease progression or death as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator, in a patient in need thereof, wherein the patient has ER+/HER2-advanced/metastatic breast cancer with mutated (ESR1).
Regarding claims 1, 3, 6-7, and 24, Applicant is reminded that “Products of identical chemical composition cannot have mutual exclusive properties.” Any properties exhibited by or benefits from are not given any patentable weight over the prior art provided the composition is inherent. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the disclosed properties are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. The burden is shifted to the applicant to show that the prior art product does not inherently possess the same properties as the instantly claimed product.
Claim 2 is directed to a method of treating ER+/HER2- advanced/metastatic breast cancer with mutated estrogen receptor 1 (ESR1) in a patient in need thereof, the method comprising administering to the patient amcenestrant or a pharmaceutically acceptable salt thereof.
NCT04059484 teaches a method of administering amcenestrant monotherapy to patients for the treatment of ER+/HER2- locally advanced or metastatic breast cancer with mutated ESR1 (title, secondary objectives).
Claim 3 is directed to the method of claim 1, wherein the method results in a reduction of 10.0% in risk of disease progression or death as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator.
NCT04059484 teaches a method of administering amcenestrant monotherapy against fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator (trial description; study arms).
As discussed above, NCT04059484 applies the same drug through the same administration route to the same patient population as taught by Campone. Campone further teaches a method of administering between 20 – 600 mg QD of amcenestration to said patient population. Therefore, burden is shifted to Applicant to prove the method and dose taught by Campone does not inherently possess the feature of reducing the risk of disease progression by 10.0% as compared to treatment with a therapy selected from fulvestrant, an aromatase inhibitor, and a selective estrogen receptor modulator.
Claim 4 is directed to the method of claim 1, wherein the aromatase inhibitor is exemestane, letrozole, or anastrozole.
NCT04059484 teaches a method of evaluating amcenestrant monotherapy against the aromatase inhibitors anastrozole, letrozole, and exemestane (trial description; study arms).
Claim 5 is directed to the method of claim 1, wherein the selective estrogen receptor modulator is tamoxifen.
NCT04059484 teaches a method of evaluating amcenestrant monotherapy against the selective estrogen receptor modulator, tamoxifen (trial description; study arms).
Claim 6-7 is directed to the method of claim 1, wherein the method increases the progression-free survival (PFS) of the patient, wherein the median PFS is about 3.7 months.
NCT04059484 teaches a method of evaluating progression free survival in patients up to 17 months after administration of amcenestrant monotherapy.
As discussed above, NCT04059484 applies the same drug through the same administration route to the same patient population as taught by Campone. Campone further teaches a method of administering between 20 – 600 mg QD of amcenestration to said patient population. Therefore, burden is shifted to Applicant to prove the method and dose taught by Campone does not inherently possess the feature of increasing PFS of the patient, wherein the median PFD is about 3.7 months.
Claim 8 is directed to the method of claim 1, wherein amcenestrant or a pharmaceutically acceptable salt thereof is administered to the patient orally at a dose of 400 mg daily, optionally once daily.
Campone teaches daily administration of 400 mg amcenestrat to the patient (conclusions).
Claim 9 is directed to the method of claim 1, wherein amcenestrant or a pharmaceutically acceptable salt thereof is provided as a capsule or a tablet, optionally comprising 100 mg of amcenestrant per capsule or tablet.
Campone teaches a method of oral administration of amcenestrant in dose levels ranging from 20 – 600 mg (methods).
The difference between Campone and the instant application is that Campone fails to teach the oral dosage form used to deliver amcenestrant as a capsule or tablet
However, NCT04059484 teaches amcenestrant monotherapy can be administered in capsule form (trial description; intervention).
One of ordinary skill in the art would have been motivated to combine the teachings of Campone and NCT04059484 because capsules are common solid oral dosage forms that can be utilized in administering amcenestrant, which is taught by Campone to be pharmacologically effective as an oral medication.
Claim 10 is directed to the method of claim 1, wherein amcenestrant or a pharmaceutically acceptable salt thereof is administered to the patient in the morning regardless of food status.
NCT04059484 teaches a method of administering amcenestrant that was assessed when the patient was under fasted conditions as well as fed conditions (study arms, experimental).
Claims 11 and 13 is directed to the method of claim 1, wherein the breast cancer is advanced breast cancer or metastatic breast cancer.
NCT04059484 teaches a method of administering amcenestrant to patients with ER+/HER2-, locally advanced or metastatic breast cancer (official title).
Claim 12 is directed to the method of claim 1, wherein the advanced breast cancer is locally advanced cancer that is not amenable to radiation therapy or surgery in a curative intent.
NCT04059484 teaches a method of administering amcenestrant monotherapy to patients in need, wherein patients must have locally advanced breast cancer not amenable to radiation therapy or surgery in a curative intent, and/or metastatic disease (recruitment information; eligibility criteria).
Claims 14-15 are directed to the method of claim 1, wherein the patient is a pre- or post-menopausal woman, or a man.
Campone teaches a method of administering amcenestrant monotherapy to postmenopausal women with ER+/HER2- metastatic breast cancer (title).
The difference between the teaching of Campone and the instant application is that Campone fails to teach a method of administering amcenestrant monotherapy to a pre-manopausal woman or a man.
However, NCT04059484 teaches a method of administering amcenestrant monotherapy to patients with ER+/HER2- locally advanced or metastatic breast cancer, wherein the patient is either male or female (recruitment information; eligibility criteria).
One of ordinary skill in the art would be motivated to combined the teaching of Campone and NCT04059484 because NCT04059484 expands upon the limited patient population taught by Campone, thereby supporting amcenestrant monotherapy as an effective treatment option for nearly all adult patients with ER+/HER2- locally advanced or metastatic breast cancer.
Claim 16 is directed to the method of claim 1, wherein the patient is resistant to endocrine therapy.
NCT04059484 teaches a method of administering amcenestrant monotherapy to patients in need, wherein the patient must present a secondary endocrine resistance to endocrine therapy defined as progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer (recruitment information; eligibility criteria).
Claim 17 is directed to the method of claim 1, wherein the patient has been previously treated with at least one line, optionally one or two lines, of endocrine therapy for advanced breast cancer, optionally wherein the patient's breast cancer progressed during or after treatment with the previous endocrine therapy.
NCT04059484 teaches a method of administering amcenestrant to patients in need, wherein patients must have received no more than 1 targeted therapy regiment for advanced/metastatic disease (recruitment information; eligibility criteria).
Claim 18 is directed to the method of claim 17, wherein the patient has been previously treated with adjuvant endocrine therapy and relapsed after the first two years of the adjuvant endocrine therapy or within 12 months of completing the adjuvant endocrine therapy.
NCT04059484 teaches a method of administering amcenestrant to patients in need, wherein patients must have presented a secondary endocrine resistance to endocrine therapy defined as progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy (recruitment information; eligibility criteria).
Claims 20-21 are directed to the method of claim 1, wherein the patient has been previously treated with chemotherapy or targeted therapy, wherein the treatment is for advanced or metastatic disease.
NCT04059484 teaches a method of administering amcenestrant to patients in need, wherein patients must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease (recruitment information; eligibility criteria). Therefore, the disclosed method necessarily includes patients who had been previously treated with chemotherapy or targeted therapy.
Claim 22 is directed to the method of claim 1, wherein the patient has been previously treated with a CDK4/6 inhibitor.
NCT04059484 teaches a method of administering amcenestrant to patients in need, wherein patients must have had prior treatment with a CDK 4/6 inhibitor (recruitment information; eligibility criteria).
Claim 23 is directed to the method of claim 1, wherein the patient has not been previously treated with an mTOR inhibitor and/or with a SERD other than fulvestrant.
NCT04059484 teaches a method of administering amcenestrant to patients in need, wherein patients were excluded for having prior treatment with mammalian target of rapamycin inhibitors (mTOR) or any other SERD compound, except fulvestrant (recruitment information; eligibility criteria).
Claim 24 is directed to the method of claim 1, wherein the patient experiences no clinically significant bradycardia, QTc prolongation, or visual disturbances.
NCT04059484 teaches a method of administering amcenestrant to human patients in need thereof.
As discussed above, NCT04059484 applies the same drug through the same administration route to the same patient population as taught by Campone. Campone further teaches a method of administering between 20 – 600 mg QD of amcenestration to said patient population. Therefore, burden is shifted to Applicant to prove the method and dose taught by Campone does not inherently possess the feature of causing no clinically significant bradycardia, QTc prolongation, or visual disturbances in patients.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Campone in view of by NCBI clinical ID NCT04059484, in further view of Osbourne (Mechanisms of Endocrine Resistance in Breast Cancer. Annu. Rev. Med., 2011, 62, 233-247. Doi: 10.1146/annurev-med-070909-182917).
Claim 19 is directed to the method of claim 18, wherein the previous adjuvant endocrine therapy is selected from treatment with tamoxifen, fulvestrant, or an aromatase inhibitor, optionally wherein the aromatase inhibitor is exemestane, letrozole, or anastrozole.
The teachings of Campone in view of NCT04059484 are discussed above and incorporated herein by reference.
The difference between the teaching of Campone in view of NCT04059484 and the instant application is that Campone in view of NCT04059484 fails to teach administering amcenestrant to patients with previous adjuvant endocrine therapy, wherein the adjuvant endocrine therapy is selected from treatment with tamoxifen, fulvestrant, or an aromatase inhibitor, optionally wherein the aromatase inhibitor is exemestane, letrozole, or anastrozole.
However, Osbourne teaches that tamoxifen, fulvestrant, letrozole, and anastrozole are common and effective endocrine therapy options (page 237, left column, paragraph 2; page 241, right column, paragraph 2; page 241, left column, paragraphs 3-4).
One of ordinary skill in the art would have been motivated combined the teachings of Campone in view of NCT04059484 with Osbourne because one could most effectively expand the potential patient population by evaluating amcenestrant in patients whose previous adjuvant endocrine therapy included the most common treatment options of advanced or metastatic breast cancer. Therefore, said skilled artisan would have found it prima facie obvious to administer amcenestrant to patients with previous adjuvant therapy with tamoxigen, fulvestrant, or an aromatase inhibitors, thereby arriving at the current invention.
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Campone in view of by NCBI clinical ID NCT04059484, in further view of Celanovic (US 2024/0173293 A1, published 2024, May 30; claims priority to Provisional Application 63/155,687, filed on 2021, Mar. 2).
Claim 25 is directed to an article of manufacture or kit, comprising amcenestrant and instructions for use for treating ER+/HER2- breast cancer in the method of claim 1.
The teachings of Campone in view of NCT04059484 are discussed above and incorporated herein by reference.
The difference between the method taught by Campone in view of NCT04059484 and the present claim is that Campone in view of NCT04059484 fails to teach an article of manufacture or kit comprising amcenestrant with instructions for use in treating ER+/HER2- breast cancer in the method of claim 1.
However, Celanovic teaches articles of manufacture, e.g., kits, comprising one or more dosages of amcenestrant and/or palbociclib or a pharmaceutically acceptable salt thereof, and instructions for patients (e.g., for treatment in accordance with a method described herein) (page 6, paragraph 0071).
A person of ordinary skill in the art would be motivated to combine the teachings of Campone in view of NCT04059484 with the teachings of Celanovic because Campone in view of NCT04059484 teaches a method of administering amcenestrant as an effective treatment of ER+/HER2- breast cancer in a clinical setting. The same method could be administered by the patients themselves in the comfort of their homes, should it be manufactured into a kit with instructions for ease of use. Celanovic teaches such kits comprising amcenestrant. Therefore, said skilled artisan would have found it obvious to manufacture a kit comprising amcenestrant for self-administration by the patient, thereby arriving at the current invention.
Conclusions
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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