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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/28/2026 has been entered.
Claims Status
The amendments and remarks filed 05/28/2026 are acknowledged.
Claims 1, 6-8, 10-12, 14-18, and 20-21 are pending.
Claims 1, 6, and 8 are amended.
Claims 2-5, 9, 13, 19, and 22 are canceled.
Claims 7, 18, and 20-21 remain with withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/05/2025.
Claims 1, 6, 8, 10-12, and 14-17 read on the elected species and are therefore under examination.
Withdrawn
The previous rejections of claims 1-2, 4-6, 8, 10-12, and 14-17 under 35 U.S.C. 103 are withdrawn. Applicant has amended claim 1 to now require administering WP1066 and an anti-CTLA-4/PD-1 therapy to overcome the rejections.
Claim Rejections - 35 USC § 112(b)
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, 6, 8, 10-12, and 14-17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “an anti-CTLA-4/PD-1 therapy”. The specification does not define the notation of “anti-CTLA-4/PD-1” and thus, it is unclear if “anti-CTLA-4/PD-1” is referring to a combination of an anti-CTLA-4 therapy and the protein PD-1, is referring to a combination of an anti-CTLA-4 therapy and an anti-PD-1 therapy, or is referring to a bispecific antibody that targets both CTLA-4 and PD-1. The limitation of “anti-CTLA-4/PD-1” is further made unclear by the limitations set forth in instant claims 6 and 8. Claims 6 and 8 further limit the “anti-CTLA-4/PD-1 therapy” to the listed options in each of the claims which include monoclonal antibodies against CTLA-4 and PD-1, respectively, but also include bispecific antibodies against both CTLA-4 and PD-1 (i.e. AK104 and XmAb20717). Therefore, the scope of this claim is indefinite.
Claims 6, 8, 10-12 and 14-17, which depend from claim 1, are therefore indefinite for the same reasons as set forth above.
For examination purposes, the Examiner is interpreting “anti-CTLA-4/PD-1” to mean a combination of an anti-CTLA-4 therapy and an anti-PD-1 therapy based on Applicant’s election set forth in the reply filed 02/05/2025 of pembrolizumab for the anti-PD-1 therapy and ipilimumab for the anti-CTLA-4 therapy.
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 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.
Claims 1, 6, 8, 10-11, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Woessner (WO 2016062722; 09/05/2024 PTO-892) in view of Guha et al., 2007 (instant PTO-892).
Regarding claims 1, 10 and 17, Woessner teaches a method of treating cancer (disease; proliferative disease) comprising administering an immunomodulator, such as an immune checkpoint inhibitor, and an antisense compound targeted to STAT3 (STAT3 inhibitor) in a subject in need thereof [page 3, lines 8-10 and page 15, lines 1-4], and that the type of cancer that the combination treatment is proposed for includes breast cancer, pancreatic cancer, and lymphoma [page 4, lines 9-14]. Woessner further teaches that the patient with cancer is administered (i) at least one immunomodulatory agent (immune checkpoint inhibitor) and (ii) an antisense compound targeted to STAT3 (STAT3 inhibitor) in pharmaceutically effective amounts [page 39, lines 24-26]. Woessner also teaches that the immunomodulator can include an anti-PD-L1 antibody, an anti-PD1 antibody, and an anti-CTLA-4 antibody [page 3, lines 10-12].
However, Woessner does not teach that the STAT3 inhibitor is WP0166. Note: the instant specification defines WP1066 as a STAT3 inhibitor [0004].
Guha teaches that administration of WP1066 significantly inhibited proliferation and induced apoptosis of pancreatic cells in vitro and significantly inhibited pancreatic cancer cell tumor growth in vivo [see page 2; Methods and Results].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Woessner and to have substituted the STAT3 inhibitor of Woessner to be the STAT3 inhibitor (i.e. WP1066) of Guha. One would have been motivated to make this modification because Guha teaches that administration of WP1066 significantly inhibited proliferation and induced apoptosis of pancreatic cells in vitro and significantly inhibited pancreatic cancer cell tumor growth in vivo. Further, it would have been obvious to make this modification because Woessner and Guha both teach STAT3 inhibitors for the treatment of pancreatic cancer, and it is prima facie obvious to substitute equivalents known for the same purpose (see MPEP 2144.06 (II)).
Claim 6 is included in this rejection because Woessner teaches that the anti-PD1 antibody can be pembrolizumab [page 3, lines 31-32 – page 4, line 1].
Claim 8 is included in this rejection because Woessner teaches that the anti-CTLA-4 antibody can be ipilimumab [page 3, lines 31-32 – page 4, line 1].
Claim 11 is included in this rejection because Woessner teaches that the method of treating cancer can decrease or retard cancer tumor growth (i.e. inhibits the survival or proliferation of cancer cells) [page 43, lines 24-25].
Claims 1, 6, 8, 10-12, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Woessner (WO 2016062722; 09/05/2024 PTO-892) in view of Guha et al., 2007 (instant PTO-892), as applied to claims 1, 6, 8, 10-11, and 17 above, and further in view of Skelton et al., 2017 (04/10/2025 PTO-892).
The teachings of Woessner and Guha are above. Further, Woessner teaches that treatment with the STAT3 inhibitor resulted in an increase in tumor infiltrating CD45+ cells [page 49, lines 23-30] and also teaches enhanced antitumor activity of combination treatment vs. single agents, and that treatment with the STAT3 inhibitor enhances the activity of immune checkpoint inhibitors [page 53, 1-4]. Woessner further teaches that the combination activity results in an increase in antitumor immune infiltrates in the tumor, which enables enhanced inhibition of tumor growth when immune checkpoints are blocked by treatment with therapeutics targeting PD-L1 and CTLA-4 [page 53, lines 4-8].
However, Woessner and Guha do not specifically teach that the patient has previously failed to respond to the administration of an immune checkpoint inhibitor.
Regarding claim 12, Skelton teaches that a combination approach to immunotherapy is needed to overcome resistance to immune checkpoint inhibitors as pancreatic ductal adenocarcinoma (PDAC) does not respond to single-agent checkpoint inhibitors [see Abstract]. Skelton also teaches that anti-CTLA-4 and anti-PD-1 antibodies can work through a complementary mechanism [page 60, left column, fourth paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have treated a patient with pancreatic cancer that has previously failed to respond to the administration of an immune checkpoint inhibitor with the method taught by Woessner and Guha. One would have been motivated to treat this patient population with the method taught by Woessner and Guha because Skelton teaches that a combination approach to immunotherapy is needed to overcome resistance to immune checkpoint inhibitors as pancreatic ductal adenocarcinoma (PDAC) does not respond to single-agent checkpoint inhibitors, and Woessner teaches that the combination treatment results in an increase in antitumor immune infiltrates in the tumor, which enables enhanced inhibition of tumor growth when immune checkpoints are blocked by treatment with therapeutics targeting PD-L1 and CTLA-4. Thus, since Skelton teaches that PDAC does not respond to single-agent checkpoint inhibitors, one skilled in the art could reasonably assume that a patient with pancreatic cancer would have failed to respond to the administration of an immune checkpoint inhibitor, but that there would be a reasonable expectation of success in treating the patient with the method (i.e. combination therapy) taught by Woessner and Guha.
Claims 1, 6, 8, 10-11, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Woessner (WO 2016062722; 09/05/2024 PTO-892) in view of Guha et al., 2007 (instant PTO-892), as applied to claims 1, 6, 8, 10-11, and 17 above, and further in view of Funakoshi et al., 2004 (04/10/2025 PTO-892).
The teachings of Woessner and Guha are above.
However, Woessner and Guha do not specifically teach further administering an anti-cancer therapy, wherein the anti-cancer therapy is chemotherapy, and wherein the chemotherapy is irinotecan.
Regarding claims 14-16, Funakoshi teaches administering irinotecan (CPT-11) to patients with metastatic pancreatic cancer with ten patients showing a partial response (PR) with a median survival rate of 7.3 months [see Abstract]. Funakoshi concludes that CPT-11 is effective for metastatic pancreatic cancer [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating pancreatic cancer, as taught by Woessner and Guha, to further comprise administering irinotecan, as taught by Funakoshi. One would have been motivated to make this modification because Funakoshi teaches that irinotecan is an effective treatment for pancreatic cancer. This follows the logic of MPEP 2144.06 which states “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 to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions for the same purpose of treating pancreatic cancer.
Response to Arguments
The previous rejections of claims 1-2, 4-6, 8, 10-12, and 14-17 under 35 U.S.C. 103 are withdrawn. However, Applicant’s remarks will be addressed to the extent that they apply to the new rejections under 35 U.S.C. 103 set forth above. On page 5 of the remarks, Applicant states that the Office concedes that FIG. 1A and Example 1 of the instant specification provides synergistic results demonstrating that the combination of WP1066 and an anti-CTLA-4/PD-1 therapy is unexpectedly better than WP1066 or the anti-CTLA-4/PD-1 therapy alone, but that the results were not commensurate in scope with the claims, and that as amended, claim 1 is not commensurate in scope with the surprising and unexpected synergistic result. Firstly, the Examiner notes that the Office never definitively stated that FIG. 1A and Example 1 of the instant specification provides synergistic results. The previous office actions stated that Figure 1A, which displays the results of Example 1, is potentially persuasive suggesting that the combination of WP1066 and a CTLA-4/PD-1 antibody is unexpectedly better than WP1066 or the CTLA-4/PD-1 antibody alone. Second, the results of Example 1 are still not commensurate in scope with the claims.
Example 1 does demonstrate synergy for the combination of WP1066, an anti-CTLA-4 antibody, and an anti-PD-1 antibody for the treatment of pancreatic ductal adenocarcinoma (PDAC), but this would not necessarily apply to the broad genus of any proliferative disease that the claims are drawn to. Further, there is no disclosure as to which anti-CTLA-4 antibody and anti-PD-1 antibody were administered and there is no expectation that the synergistic results could be extrapolated to any anti-CTLA-4 antibody and any anti-PD-1 antibody. Additionally, the Examiner cannot determine if the results are due to the specific anti-CTLA-4 antibody and specific anti-PD-1 antibody that are administered in combination with WP1066 or if the results are due to targeting the combination of STAT3, CTLA-4, and PD-1. The burden is on applicant to provide the Examiner a trend proving unexpected results, and one data point demonstrating an unexpected synergistic result for treating PDAC with an undisclosed anti-CTLA-4 antibody and an undisclosed anti-PD-1 antibody is insufficient to provide a trend that there is a synergistic effect in treating the broad genus of any proliferative disease with WP1066, any anti-CTLA-4 antibody, and any anti-PD-1 as claimed. See MPEP 716.02(b). Therefore, Applicant’s arguments of unexpected results are not persuasive to rebut the 103 rejection as a whole.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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