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 .
Priority
The instant application, filed 01/05/2026, is a 371 filing of PCT/US22/36351, filed 07/07/2022, which claims domestic priority to provisional US application nos. 63/278,526, filed 11/12/2021, and 63/219, 802, filed 07/08/2021
Amendments and Claim Status
The amendment filed on 06/01/2026 is acknowledged and entered.
Claim 7 is amended;
Claims 3, 8-17, 20, 22, 28, 32, 37, and 38 are cancelled;
Claims 1, 2, 4-7, 18, 19, 21, 23-27, 29-31, 33, 35, and 36 are pending.
Information Disclosure Statement
The Information Disclosure Statements filed on 12/20/2024 and 11/25/2025 are acknowledged and found to be in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election without traverse of the following species in the reply filed on 06/01/2026 is acknowledged.
Species A: Applicant elects trastuzumab as a specific HER2 anticancer agent;
Species B: Applicant elects the brain as a location in which metastasis has been detected;
Species C: Applicant elects ribociclib as a specific additional anticancer agent
Species D: Applicant elects letrozole as the inhibitor which the subject was previously treated with
Species E: Applicant elects a tablet as a form of a pharmaceutical composition
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species does not make a contribution over the prior art of record.
Status of Claims
Claims 1, 2, 4-7, 18, 19, 21, 23-27, 29-31, 33, 35, and 36 are pending in the instant application. Claims 19, 23, 26, and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 1, 2, 4-7, 18, 21, 24, 25, 29-31, 33, 35, and 36 read on an elected invention and species and are therefore under consideration in the instant application.
Drawings
The drawings filed on 01/05/2024 are objected to under 37 CFR § 1.83(a) for the following reasons:
The different data types are indistinguishable in Figures 2 and 19. The original figures rely on color-coding of the data, a feature not available in the black and white drawings. The figures must be remade with shapes or line-types used to clearly distinguish the different data points. Alternatively, the data can be broken up into two or more figures, so as to separate the data into a more digestible form.
The different data types are indistinguishable in Figures 7, 8, and 11A. The Figures have overlapping data points with large error bars which the identity of each individual symbol. In many cases, the data points lie on top of each other, because the y-axis is improperly sized. The figures must be remade so that the different data is clearly distinguishable. For example, the y-axis in Figure 11A may be made from 0-2200 to allow for better separation of the tata at the lower y-axis points.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claims 1, 2, 4, 18, 21, 24, 25, 29-31, 33, 35, and 36 are rejected under 35 U.S.C. § 103 as being unpatentable over Myles et al. (US 20190247372 A1, published August 15, 2019, cited in applicant IDS filed 12/20/2024) hereinafter Myles, in view of Arciero et al. (Clinical Breast Cancer, Volume 19, Issue 4, published every 14 2019, cited in applicant IDS filed 12/20/2024), hereinafter Arciero.
The instant claims are drawn to a method of treating cancer determined to have ER+/HER2+ comprising the administration of Compound 1, also known as CAS Registry Number: RN 2092925-89-6. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2092925-89-6, Entered STN: 20 Apr 2017] in combination with a HER2 inhibitor, elected to be trastuzumab. The instant claims are further drawn to a method further comprising an additional anticancer agent elected to be ribociclib. Further, the claims are drawn to a patient previously treated with the aromatase inhibitor, elected to be letrozole. Finally, the claims are drawn to a pharmaceutical composition administered in the instantly claimed method in the form elected to be a tablet.
Myles teaches Compound 1 (claim 71) administered in a method of treating ER+ breast cancer (claims 76 and 77). The method further comprises the administration of Compound 1 in combination with another anticancer agent (claim 79), wherein the anticancer agent is herceptin, also known as trastuzumab (paragraph [0054]) (see instant claim 1 and 21). Myles teaches the use of the compounds in the treatment of metastatic breast cancer (paragraph [0051]). Myles teaches the method used to treat patients who have previously progressed in the presence of therapy with an aromatase inhibitor, specifically naming letrozole as the previously used anticancer agent (paragraph [0052], see instant claim 25). Myles further teaches that Compound 1 can be co-administered with the CDK4/6 inhibitor, ribociclib in combination with the HER2 inhibitor hereceptin (trastuzumab) (paragraph [0306], see instant claims 18, 24, and 24). Myles further teaches the compound as a pharmaceutically acceptable composition comprising a pharmaceutically acceptable salt and a carrier (paragraphs [0269- 0271], see instant claims 29 and 30). The disclosure by Myles explicitly enumerates formulations administered as tablets (paragraph [0289], see instant claim 31), with a daily dosage of between 10-500mg per day (paragraph [0277], see instant claim 33). The method comprises the oral delivery of the composition (claim 75, see instant claim 35), and is administered once daily (paragraph [0277], see instant claim 36).
Myles fails to teach the administration of compound 1 to a subject with both ER+ and HER2+ status. Myles fails to teach brain cancer as a specific metastatic manifestation of breast cancer.
The deficiencies of Myles are remedied by Arciero, who establishes that HER2+ breast cancer patients are also most often indicated for ER+ breast cancer. Within the comparative study put forth, 70% of the cohort of breast cancer patients studied were found to be both ER+ and HER2+ (Table 1). Arciero teaches that brain metastasis is a clinically significant complication in breast cancer patients characterized as being ER+/HER2+ (Table 3, Figure 2, see instant claims 1, 2, and 4,). Breast cancer patients of the ER+/HER2+ population are associated with poor outcomes (Table 5), and are described as being a recognized population of unmet need in successful cancer treatment (page 242, final paragraph).
A person of ordinary skill in the art would be motivated to modify the patient population treated using the method taught by Myles to treat ER+/HER2+ patients with brain metastasis as taught by Arciero, in order to apply a known and successful ER+ therapy to a cohort of breast patients who are frequently characterized as also being HER2+ (Table 1 of Arciero), wherein brain metastasis is documented in significant clinical presentation of the breast cancer population.
Regarding claim 33, the disclosure by Myles teaches a range of daily doses of compound 1 which overlap with that of the instant claims. It is noted that the courts have stated,
where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see 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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that,
“where 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). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claims 5-7 are rejected under 35 U.S.C. § 103 as being unpatentable over Myles (see earlier citation) in view of Arciero (see earlier citation) as applied to claims 1, 2, 4, 18, 21, 24, 25, 29-31, 33, 35, and 36, above, in view of Kotecha et al. (NeuroOncol Adv, Volume 3, Issue 1, published January 16, 2021), hereinafter Kotecha.
The instant claims are further drawn to method further comprising patients with the same or different HER2 status of a primary tumor associated with breast cancer and metastasis, elected to be in the brain.
The teachings of Myles and Arciero are as set forth above.
Myles and Arciero fail to teach a comparison of HER2 status between a primary tumor and a corresponding metastasis in the brain.
The deficiencies of Myles and Arciero are remedied by Kotecha, who teaches that both HER2 concordance and discordance occurs in breast cancer patients with metastasis to the brain. In a cohort of patients that also included ER+/HER+ status (Table 1), the disclosure analyzes HER2 expression in metastatic breast cancer brain metastasis compared to primary tumors The disclosure teaches that 88% of patients retain the same HER2 status at both sites (Figure 4, see instant claims 5 and 6), while 12% had discordance in HER2 between the primary and brain metastasis (Abstract, Figure 4, see instant claim 7). The disclosure determined that breast cancer brain metastasis exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients (Abstract).
A person of ordinary skill in the art would be motivated to further modify the ER+/HER2+ brain metastasis population of Myles in view of Arciero to account for HER2 status of the brain metastasis relative to the primary tumor as taught by Kotecha because Kotecha demonstrates that both concordant and discordant HER2 status are documented, art-recognized outcomes in breast cancer brain metastasis. A person of ordinary skill developing a method of treating breast cancer with HER2+ status, which is known to metastasize to the brain, would necessarily encounter, and be motivated to account for patients presenting with both the same and different HER2 status between their primary tumor and brain metastasis.
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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