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
This Office Action is a response to Applicant’s Amendment and Remarks filed February 12, 2026.
Claims 2-11 have been canceled. Claims 1, 12 and 13 have been amended.
Claims 1 and 12-14 are pending in the instant application.
Accordingly, claims 1 and 12-14 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Drawings
In the previous Office Action mailed November 21, 2025, the Drawings were objected to because some Drawings referenced the colors, "red line"; "green line"; and "yellow line" without an accompanying petition. This objection is withdrawn in view of Applicant’s Amendment to the Specification filed February 12, 2026 to remove any reference to color Drawings.
Claim Objections
In the previous Office Action mailed November 21, 2025, claim 12 was objected to for containing a typographical error This objection is withdrawn in view of Applicant’s Amendment to claim 12 filed February 12, 2026 to correct the typographical error.
Claim Rejections - 35 USC § 102
In the previous Office Action mailed November 21, 2025, claims 1-4, 7 and 12 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by So, D. (Oncogene, Springer Nature, 2018 Vol. 37:5191-5204). This rejection is moot against claims 2-4 and 7 in view of Applicant’s Amendment filed February 12, 2026 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed February 12, 2026.
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In the previous Office Action mailed November 21, 2025, claims 1-4 and 7-11 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (Cancer Sci. 2014 Apr;105(4):445-54.Epub 2014 Mar 17, plus Supplemental Data). This rejection is moot against claims 2-4 and 7-11 in view of Applicant’s Amendment filed February 12, 2026 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed February 12, 2026.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed November 21, 2025, claims 13 and 14 were rejected under 35 U.S.C. 103 as being unpatentable over either So, D. (Oncogene, Springer Nature, 2018 Vol. 37:5191-5204) or Zhang et al. (Cancer Sci. 2014 Apr;105(4):445-54.Epub 2014 Mar 17) in view of U.S. Patent Publication 20070037865 A1. This rejection is withdrawn in view of Applicant’s Amendment to the claims filed February 12, 2026.
Applicant's amendment necessitated the new ground(s) of rejection present below:
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 12-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 recites the phrase, “the method comprising”. There is insufficient antecedent basis for this limitation in the claim because the preamble of the claim is drawn to a “SIRT1 inhibitor” and therefore never makes reference to a method. Correction is required.
Claim Interpretation
Claim 1 has been amended and is now drawn to a SIRT1 inhibitor or antagonist for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof, the method comprising administering a pharmaceutical composition comprising EX527 in combination with a chemotherapeutic drug, wherein the chemotherapeutic drug is doxorubicin or cisplatin. As detailed above, there is insufficient antecedent basis for the phrase, “the method comprising” in claim 1. For examination and prior art purposes, the Examiner will interpret claim 1 to mean: A SIRT1 inhibitor or antagonist for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof, comprising a pharmaceutical composition comprising EX527 in combination with a chemotherapeutic drug, wherein the chemotherapeutic drug is doxorubicin or cisplatin.
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 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 § 102
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 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shin et al. (Cancer Res; 74(1) January 1, 2014, pages 298-308, plus Supplementary Figure S4).
The claim is drawn to a SIRT1 inhibitor or antagonist for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof, comprising a pharmaceutical composition comprising EX527 in combination with a chemotherapeutic drug, wherein the chemotherapeutic drug is doxorubicin or cisplatin. For further explanation, see section titled, “Claim Interpretation” above. NOTE and REMINDER: The claim is drawn to a composition and not a method of using a composition.
Shin et al. disclose EX527 in combination with the chemotherapeutic drugs, doxorubicin and cisplatin. See Shin et al. Figures 1E and Supplementary Figure S4.
While Shin et al. does not necessarily teach the EX527 SIRT1 inhibitor in combination with doxorubicin and cisplatin is for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof, Applicant is reminded that a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). In the instant case, the present claim does not overcome Shin et al. since the composition itself is taught and suggested in the prior art.
Furthermore, the recitation, “for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof” is nothing more than an intended use. Applicant is also reminded that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, EX527 in combination with the chemotherapeutic drugs, doxorubicin and cisplatin disclosed by Shin et al. is capable for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof and therefore meets the functionality recited in Applicant’s claimed invention, absent some evidence to the contrary.
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Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (Cancer Sci 105 (2014) 445-454, plus Supplementary Figure S1, submitted and made of record with the Office Action filed November 21, 2025).
The claim is as described above.
Zhang et al. disclose EX527 in combination with the chemotherapeutic drug, cisplatin. See Supplementary Figure S1.
While Zhang et al. does not necessarily teach the EX527 SIRT1 inhibitor in combination with cisplatin is for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof, Applicant is reminded that a chemical composition and its properties are inseparable. In this example, the prior art teaches the identical chemical structure of the claims and therefore the properties applicant discloses and/or claims are necessarily present. See In re Spada as discussed above. Therefore, the present claim does not overcome the prior art since the composition itself is known as taught by Zhang et al.
Furthermore, the recitation, “for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof” is nothing more than an intended use. Applicant is also reminded that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, EX527 in combination with the chemotherapeutic drug, cisplatin disclosed by Zhang et al. is capable for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof and therefore meets the functionality recited in Applicant’s claimed invention, absent some evidence to the contrary.
Response to Arguments
In response to these 35 USC § 102 rejections for anticipation, Applicants may want to argue that the references do not teach enhanced sensitivity or synergy. Applicants may want to support this argument with the 37 C.F.R. § 1.132 Declaration filed on February 12, 2026 which supposedly evidences that EX527 combined with cisplatin results in tumor volume and tumor weight reductions that exceed the additive effects of each agent alone. Applicant’s Declaration and the anticipated argument would not be persuasive as it would appear that Applicant is arguing against limitations not found in the instant claims. Nowhere do the claims recite or require any degree of enhanced sensitivity or synergy. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, Applicant's anticipated arguments and Declaration regarding synergy would appear to be misplaced.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 1, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over either Shin et al. (Cancer Res; 74(1) January 1, 2014, pages 298-308, plus Supplementary Figure S4) or Zhang et al. (Cancer Sci 105 (2014) 445-454, plus Supplementary Figure S1, submitted and made of record with the Office Action filed November 21, 2025) in view of U.S. Patent Publication 20070037865 A1 (submitted and made of record with the Office Action mailed November 21, 2025).
The claims are as described above.
Shin et al. is relied upon as discussed above
Zhang et al. is relied upon as discussed above.
Neither Shin et al. nor Zhang et al. teach the EX527 SIRT1 inhibitor or antagonist is in a release tablet form.
Patent Publication 20070037865 teaches SIRT1 modulating compounds, including SIRT1 inhibitors. See Example 2 and Table 5. Patent Publication 20070037865 teaches the SIRT1 modulators of their invention are prepared as pharmaceutical compositions for oral administration and may be suitably formulated to give controlled release of the active inhibitor compound, such as release tablets.
Regarding claims 13 and 14 which recite, “immediate release tablets from 80 to 120 mg” or :wherein the pharmaceutical composition is used in a dosage of one tablet/day”, Applicant is reminded that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. Also see MPEP 2144.05. In other words, it is not inventive to discover the optimum or workable ranges by routine experimentation and optimization.
Before the effective filing date of the claimed invention, EX527 in combination with the chemotherapeutic drugs, doxorubicin and/or cisplatin was known, taught and suggested by the prior art of either Shin et al. or Zhang et al.
The skilled artisan would have been motivated to modify the EX527 SIRT1 inhibitor of either Shin et al. or Zhang et al. to include the release tablet of Patent Publication 20070037865 to give controlled release of the inhibitor drug.
A person of ordinary skill in the art would have expected reasonable success of making the SIRT1 inhibitor/antagonist of Applicant's claimed invention using the successful teachings and suggestion of either Shin et al. or Zhang et al.
Therefore, the subject matter of claims 1, 13 and 14 is obvious over either Shin et al. or Zhang et al. in view of U.S. Patent Publication 20070037865.
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Claims 1 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over So, D. (Oncogene, Springer Nature, 2018 Vol. 37:5191-5204) (submitted and made of record on the Information Disclosure Statement filed January 24, 2025) (Supplemental Data and Figures submitted and made of record with the Office Action mailed November 21, 2025) in view of Regalado Porras et al. (Reports of Practical Oncology & Radiotherapy Volume 23, Issue 6, November–December 2018, Pages 533-539).
The claims are as described above.
So, D. teaches that cervical cancer cells undergo massive death by SIRT1 knockdown. See Abstract. So, D. teach that SiHa cells (HPV-infected cervical cancer) were treated with the SIRT1 inhibitor EX-527 (100 mM) for 48 hours and cancer cell growth was inhibited. See Supplementary Fig. S1, f and g.
So, D. conclude that SIRT1 could therefore be a target for the effective treatment of cervical treatment. See last sentence of Abstract and concluding paragraph on page 5201.
So, D. also teach that invasive squamous carcinoma in uterine cervix is usually treated with a combination of chemotherapy, surgery, and/or radiation therapy. See page 5201, left column, second full paragraph.
So, D. does not teach the chemotherapy is doxorubicin or cisplatin.
Regalado Porras et al. teach that cervical cancer is closely associated with human papilloma virus (HPV) infection and the standard of care is radiotherapy in combination with cisplatin-based chemotherapy.
Before the effective filing date of the claimed invention So, D. taught and suggested the EX527 SIRT1 inhibitor as an effective treatment of HPV-infected cervical cancer treatment.
The skilled artisan would have been motivated to modify the teachings of So, D. to include chemotherapy and/or radiation therapy since both So, D. and Regalado Porras et al. confirm that a combination treatment can be expected to provide better curative, beneficial and additive results than monotherapy.
A person of ordinary skill in the art would have expected reasonable success of making and using the EX527 SIRT1 inhibitor/antagonist in combination with a chemotherapeutic drug and/or radiotherapy since the standard of care in most cervical cancers involves systemic platinum-based chemotherapy with concomitant radiotherapy.
Therefore, the subject matter of claims 1 and 12 is obvious over So, D. in view of Regalado Porras et al.
Response to Arguments
In response to these 35 USC § 103 rejections for obviousness, Applicants may want to argue that the references do not teach enhanced sensitivity or synergy. Applicants may want to support this argument with the 37 C.F.R. § 1.132 Declaration filed on February 12, 2026 which supposedly evidences that EX527 combined with cisplatin results in tumor volume and tumor weight reductions that exceed the additive effects of each agent alone. The Declaration and the anticipated argument would not be persuasive as it would appear that Applicant is arguing against limitations not found in the instant claims. Nowhere do the claims recite or require any degree of enhanced sensitivity or synergy. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, Applicant's anticipated arguments and Declaration regarding synergy would appear to be misplaced.
Furthermore, the recitation, “for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof” is nothing more than an intended use. Applicant is also reminded that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, EX527 in combination with the chemotherapeutic drugs, doxorubicin and/or cisplatin disclosed by either Shin et al. or Zhang et al. is capable for use in treating a human papilloma virus (HPV) induced tumor in a subject in need thereof and therefore meets the functionality recited in Applicant’s claimed invention, absent some evidence to the contrary.
Further, regarding the 37 C.F.R. § 1.132 Declaration filed on February 12, 2026, it is not found persuasive since both Shin et al. and Zhang et al. disclose EX527 in combination with the chemotherapeutic drugs, doxorubicin and/or cisplatin.
Regarding So. D. and Regalado Porras et al., both references confirm that a combination treatment can be expected to provide better results than monotherapy. Applicant is reminded that, "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex lnc., 550 U.S. 398,416 (2007). That is, the rationale for combination therapy is obvious when it does nothing more than yield predictable results of additive therapy.
Turning to the facts, the presumption of obviousness applies here, and none of the anticipated means for rebutting it has been shown. In view of the foregoing, when all the evidence is considered, the totality of the anticipated rebuttal evidence of non-obviousness fails to outweigh the evidence of obviousness made of record. Thus, it is maintained that the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635