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 Status
Claims 1-9, 11-13 and 15-24 are pending. Claims 12-13 and 15-24 are withdrawn. Claims 1-9 and 11 are rejected.
Election/Restrictions
Applicant’s election without traverse of Group I and the combination of BVT948 and alkylating agents in the reply filed on July 7th, 2026 is acknowledged.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicant’s elected combination is not allowable under 35 USC 103. Therefore, the Markush-type claims have been rejected and claims to the nonelected invention are held withdrawn from further consideration. Examination has been limited to claims embracing the elected species which are claims 1-9 and 11. Claims 1-9 and 11 have been examined to the extent that they are readable on the elected embodiment. Subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration.
Claims 12-13 and 15-24 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Rejections - 35 USC § 103
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) 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2004006842 A2 by Borisy et al. in view of Hwang, Bo-Mi, et al. “Protein Tyrosine Phosphatase Controls Breast Cancer Invasion through the Expression of Matrix Metalloproteinase-9.” BMB Reports, vol. 46, no. 11, Korean Society for Biochemistry and Molecular Biology - BMB Reports, 30 Nov. 2013, pp. 533–538.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The prior art teaches (title) “combinations of drugs for the treatment of neoplasms” and report that the invention features a method for treating a patient having cancer or a neoplasm by administering to the patient two compounds simultaneously (abstract).
Borisy et al. list breast cancer as one of the cancers treated according to the invention and further specify that the method includes administering a PTP1B inhibitor and one or more antiproliferative agents (page 15, line 3; page 18, lines 18-23). Regarding instant claims 1 and 7, the prior art recites various alkylating agents as suitable antiproliferative agents (page 22, Table 1).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art teaches pharmaceutical compositions to facilitate coadministration of a PTP1b inhibitor and secondary active agents such as alkylating agents; however, the disclosure is silent to the use of BVT948 as the PTP1b inhibitor.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Hwang et al. discuss the role of protein tyrosine phosphatase in breast cancer and report (abstract):
The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-κB activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.
Accordingly, a person of ordinary skill would have been motivated to test the composition of Borisy et al. with alternative PTP1b inhibitors such as BVT948 in order to optimize treatment of cancers such as breast cancer as this compound is capable of controlling breast cancer invasion (corresponding to instant claims 1-4).
Regarding instant claims 5-6 and 8-9, the claimed limitations are intended effects that would flow from use of the prior art composition. A compound and its properties are inseparable therefore the prior art composition which contains all the components of the claimed invention would have the claimed effects.
Claim(s) 11 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2004006842 A2 by Borisy et al. in view of Hwang, Bo-Mi, et al. “Protein Tyrosine Phosphatase Controls Breast Cancer Invasion through the Expression of Matrix Metalloproteinase-9.” BMB Reports, vol. 46, no. 11, Korean Society for Biochemistry and Molecular Biology - BMB Reports, 30 Nov. 2013, pp. 533–538. as applied to claims 1-9 above, and further in view of Nolan, Emma et al. “Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer.” Science translational medicine vol. 9,393 (2017): eaal4922.
Borisy et al. and Hwang et al. in combination teach a pharmaceutical composition comprising PTP1B inhibitor BVT948 and an alkylating agent for the treatment of breast cancer. Borisy et al. disclose that the prior art composition may contain additional active agents such as immunomodulators but do not discuss the checkpoint blockade components of claim 11.
Nolan et al. discuss (title) “[c]ombined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer.” The prior art reports (abstract):
BRCA1-mutated triple-negative breast cancers (TNBCs) exhibited an increased somatic mutational load and greater numbers of tumor-infiltrating lymphocytes, with increased expression of immunomodulatory genes including PDCD1 (PD-1) and CTLA4, when compared to TNBCs from BRCA1–wild-type patients. Cisplatin treatment combined with dual anti–programmed death-1 and anti–cytotoxic T lymphocyte–associated antigen 4 therapy substantially augmented antitumor immunity in Brca1-deficient mice, resulting in an avid systemic and intratumoral immune response. This response involved enhanced dendritic cell activation, reduced suppressive FOXP3+ regulatory T cells, and concomitant increase in the activation of tumor-infiltrating cytotoxic CD8+ and CD4+ T cells, characterized by the induction of polyfunctional cytokine-producing T cells. Dual (but not single) checkpoint blockade together with cisplatin profoundly attenuated the growth of Brca1-deficient tumors in vivo and improved survival. These findings provide a rationale for clinical studies of combined immune checkpoint blockade in BRCA1-associated TNBC.
Accordingly, a person of ordinary skill seeking to treat subjects with breast cancers such as BRCA1-mutated triple-negative breast cancers would have been motivated to modify the pharmaceutical composition of the combined teachings of Borisy et al. and Hwang et al. to add anti-PD-1 or anti-CTLA4 immunomodulators in order to improve therapeutic outcomes.
Conclusion
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/A.A.C./Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
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