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
Response to Amendment
The amendment filed 12/17/2025 has been entered. Newly amended Claims 76-80 and 89 are pending in the application.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
Regarding the 103 over Bissonnette, applicant argues Bissonnette does not teach the newly added limitations of independent Claim 76 including the requirement that the inhibitor of CTLA-4 is an antibody. For this reason, the rejection is withdrawn and a new rejection is issued below.
Applicant references “unexpected” results in terms of the efficacy of the combination of HBI-8000 and CTLA-4 in Example 1 of the Specification. However, Example 1 is directed to MC38 cells. MC38 is an adenocarcinoma cell line whereas the claims are now limited to melanoma, a different form of cancer. Applicant’s arguments regarding unexpected results are not at all commensurate in scope with the narrowed claims and therefore not persuasive.
Applicant argues that the nonstatutory double patenting rejections should be withdrawn in light of the terminal disclaimer filed 12/17/2025. Applicant’s argument is persuasive and all NSDP rejections are withdrawn accordingly.
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.
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.
Claims 76-80 and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Bissonnette (WO 2017197140, Published 2017) in view of Dent (Oncotarget, 2017, Vol. 8, (No. 47), pp: 83155-83170).
Bissonnette teaches the administration of chidamide, HBI-8000, which is an “[e]pigenetic modifier…histone deacetylase inhibitors (HDACi)…successful in the treatment of some hematologic malignancies” (Para 3, 7, and 19; Page 92, Claim 81). The therapy may be second-line therapy following therapy with an anticancer drug wherein the cancer to be treated is resistant to some anticancer drug, particularly resistant to PD-1 inhibition which resulted in stable disease, partial response, complete response, or no response (Pages 86-87, Claims 40-45; Pages 89-90, Claims 70-73). The method is effective in reducing myeloid-derived suppressor cells (MDSC) or regulatory T cells in a patient wherein said patient “has been previously treated with a PD-1 inhibitor” (Para 15-16, 154; Page 89, Claim 69). A PD-1 inhibitor is an immune checkpoint inhibitor. To treat a patient as described, one of skill in the art must first necessarily identify said patient as having been resistant to a prior anti-PD-1 therapy to be selected for treatment of cancer. “The methods of treating cancers [t]herein include treating subjects who…have experienced no response to treatment, or a partial response, or stable disease, but then develop resistance to treatment with progression of disease or who have experienced a complete response to treatment, but then develop resistance to treatment with progression of disease” (Page 45, Para 136).
Bissonnette further teaches the “clinical use of immuno-oncology agents targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)…resulted in improvements over the standard of care in the treatment of many cancer types… Epigenetic modifiers such as histone deacetylase inhibitors (HDACi) have been successful in the treatment of some hematologic malignancies, but despite preclinical data demonstrating activity against solid tumors, this result has not translated to the clinic as a monotherapy. Accordingly, there is a need in the art for new therapies, including, for example, combination therapies for the treatment of cancers” (Para 3). Cancer types to be treated include melanoma (Para 117-118 and 121; Claims 36-37, 40, and 81).
Bissonnette fails to describe particular classes of CTLA-4i like antibodies as is claimed in Claim 76.
Dent teaches “Using B16 mouse melanoma cells we discovered that pre-treatment with AR42 or sodium valproate [HDAC inhibitors like HBI-8000] enhanced the anti-tumor efficacy of an anti-PD-1 antibody and of an anti-CTLA4 antibody” (Abstract). Figure 9C on page 83163 demonstrates the increased efficacy of using an anti-CTLA-4 antibody in conjunction with an HDAC inhibitor:
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Therefore, one of ordinary skill in the art appreciating that an CTLA-4i antibody is an effective anti-melanoma therapeutic as taught in Dent and Bissonette would seek to combine said therapeutic with the HDACi and PD-Li of Bissonnette to treat the same disease, melanoma. In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “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, in order to form a third composition which is to be used for the very same purpose.” It is further noted that Bissonnette teaches specifically, with respect to immune checkpoint inhibitors like PD-1, that “a significant number of tumors are either resistant or become refractory” requiring “combination therapies for the treatment of cancers” (Para 3). Therefore, motivated by the guidance provided in Bissonnette and the increased efficacy of combining CTLA4i and HDACi demonstrated by Dent, an ordinarily skilled artisan would find it obvious to form combination therapies with HDACi, like chidamide, and CTLA-4i antibodies for the treatment of melanoma in refractory patients treated with PD-1i as claimed. The same artisan would expect success in doing so, especially with respect to resistant cancers, because Bissonnette teaches combination therapies are necessary to overcome the insufficiencies of monotherapies and Dent explicitly demonstrates the efficacy of such a combination in the particular cancer claimed.
Conclusion
No claim is allowable.
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 extension fee 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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627