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 .
Election/Restrictions
The rejections of record have been maintained below.
Applicant’s election without traverse of NU7441, talazoparib, BRCA2, and pancreatic cancer in the reply filed on 11/12/2025 is acknowledged.
The elected species reads on claims 1, 3, 7, 10-12, and 17.
Claims 8, 13-16, and 18-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 11/12/2025.
Priority
This application is a continuation in part of US application 17/303,457, which claims priority to US provisional application 63/032,653. There is also a divisional of ‘457 (application 18/901,200). There is also a PCT application in the patent family.
The instant application finds support from the provisional application. Therefore, the effective filing date is 5/31/2020.
Response to Arguments
Applicants’ claim amendments and Remarks of 6/11/2026 are acknowledged and have been considered.
Any rejection and/or objection not specifically addressed or modified below is herein withdrawn.
In regard to the obviousness rejection, this rejection is maintained. Applicants’ Remarks with Examiner’s Reply are summarized below:
Applicants submit that VORMOOR teaches PARP inhibitors and DNA-PKcs inhibitors are both sensitizers, and therefore an artisan would not have been motivated to combinate two sensitizers.
Applicants submit that VORMOOR teaches no benefit to and examples of using two drugs from claimed classes in conjunction with radiation.
Examiner disagrees. It would be obvious to combine these compounds to be used for the same purpose; the idea to combine flows from In re Kerkhoven.
Applicants submit that HAO teaches NU7441 as a sensitizer for pancreatic cancer cells.
Applicants submit that Zhu teaches talazoparib in pancreatic cancer.
Applicants submit that the instantly claimed combination has synergy. Applicants point out Figure 15.
Examiner has reviewed Figure 15, which shows the percent survival of wild type cells and BRCA2 mutant pancreatic cancer cells to DNA-PK and PARP inhibition in combination with radiation. Figure 15 only describes testing a single dosage (i.e. 1.5GY with 1uM NU7441 and 10 nM talazoparib).
The scope of the unexpected results (1.5GY with 1uM NU7441 and 10 nM talazoparib) given are not commensurate with the scope of the instant claims (base claim 1 is a method for treating or preventing any cancer in a subject with two or more compounds from limitation (a). Claim 1 is not limited by a dosage amount).
Furthermore, Applicants have added the limitation, which seemly says that the dosage should be lowered if the compounds are administered together than the dosage if either compound were administered alone. Figure 15 does not lower the combined dosage compared to the compounds administered alone (for example, talazoparib is administered at 10 nM no matter if administered alone or together with other agents).
MPEP 716.02 states that unexpected results a) are greater than expected results, b) show superiority of a property shared with the prior art, c) exhibit the presence of an unexpected property, and/or d) exhibit the absence of an expected property. MPEP 716.02 additionally states that unexpected results must be commensurate in scope with the claimed invention and provide a comparison with the closest prior art.
What Figure 15 shows not commensurate in scope with the claims, and as such, it is not persuasive to show unexpected results.
Applicants submit that the inventor has discovered a molecular pathway (at the top of page 7).
The claims as currently written, however, do not reflect the mechanism of action Applicants has detailed.
In regard to the double patenting rejection, rejections cannot be held in abeyance.
Response to Amendment
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 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.
Claim(s) 1, 3, 7, 10-12, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Vormoor (Vormoor et al., “Sensitizing Ewing sarcoma to chemo- and radiotherapy by inhibition of the DNA-repair enzymes DNA protein kinase (DNA-PK) and poly-ADP-ribose polymerase (PARP) ½”, Oncotarget, September 2017), in view of HAO (Hao et al., “DNA-PKcs is important for Akt activation and gemcitabine resistance in PANC-1 pancreatic cancer cells”, Biochemical and Biophysical Research Communications, August 2014), and in view of ZHU (Zhu et al., “PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications”, Molecular Cancer, May 2020).
Vormoor teaches that DNA-PK and PARP inhibitors sensitize cancer cells to chemo- and radiotherapy (abstract). This helps teach step b of claim 1.
Vormoor teaches rucaparib (PARP inhibitor) and NU7441 (elected species of DNA-PKs inhibitor) separately sensitize Ewing sarcoma cell lines to chemo- and radiation therapy (table 1 on page 113422). This helps teach NU-7441 of claim 11 and rucaparib of claim 12.
Vormoor teaches that “NU7441 potentiated the effects of ionizing radiation in both cell lines, causing a 3-fold reduction in cell survival” (page 114323).
Vormoor does not teach pancreatic cancer or talazoparib. Vormoor does not administer a DNA-PK and PARP inhibitor together.
HAO teaches that NU-7441 (elected species of DNA-PKcs inhibitor) enhanced gemcitabine-induced cytotoxicity and apoptosis in PANC-1 pancreatic cancer cells (abstract). This helps teach pancreatic cancer of claim 10, and NU-7441 of claims 1, 11, and 17.
HAO also teaches that DNA-PKcs inhibitors were shown to enhance the cytotoxicity induced by radiation and a number of chemo-drugs (i.e., etoposide and doxorubicin) in vivo and in vitro (Introduction).
HOA does not teach talazoparib.
ZHU teaches that four of the 13 patients with pancreatic cancer showed clinical benefit using talazoparib (Talazoparib). This helps teach talazoparib of claims 1, 12, and 17.
ZHU teaches that a family history of pancreatic cancer is an essential risk factor, and germline BRCA2 mutations comprise the highest proportion of known reasons for inherited pancreatic cancer (page 2). This helps teach claims 7 and 10.
The artisan would have found it obvious to combine NU-7441 (DNA-PKcs inhibitor) and talazoparib (PARP inhibitor). HAO teaches that NU-7441 enhanced gemcitabine-induced cytotoxicity and apoptosis in PANC-1 pancreatic cancer cells (abstract). ZHU teaches that talazoparib is useful in treating pancreatic cancer (Talazoparib). It is prima facie obvious to combine one cancer treatment (NU-7441) with another (talazoparib) in order to form a composition to be used for the very same purpose (treating pancreatic cancer). This teaches claim 1 step a.
"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). See MPEP 2144.06(I).
The artisan would have been motivated to administer radiation therapy to the subject sometime before/during/after administering claim 1’s step b. Vormoor teaches that “NU7441 potentiated the effects of ionizing radiation in both cell lines, causing a 3-fold reduction in cell survival” (page 114323). The artisan would expect that NU-7441 to maintain its effectiveness for treating pancreatic cancer. The artisan would be motivated to use NU-7441 to sensitive cancer cells to radiation therapy (Vormoor abstract). This teaches claim 1 and claim 10 (pancreatic cancer). This also teaches claims 11-12 and 17.
The artisan would have expected to administer NU-7441 and talazoparib either sequentially or concurrently from the natural conclusion that there are physically only two ways to administer two compounds, together at the same time or one after another. This teaches claim 3.
The artisan would be motivated and expected to treat a cancer with a BRCA2 mutation because for people with family history of pancreatic cancer, this is the most common mutation (ZHU page 2). This teaches claim 7.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 10 and 12 are provisionally rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 18/901,200 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims.
Ref. claims 1 and 3 anticipate instant claims 1, 3, and 12. AG120 is an IDH inhibitor and Olaparib is PARP inhibitor.
Ref claim 1 anticipates diffuse intrinsic pontine glioma , which is a cancer of instant claim 10.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 10 and 12 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claim 20 of copending Application No. 17/303,457 (reference application). Although the claims at issue are not identical since the instant application (“instant”) is drawn to a method of use of the compound of the reference patent (“reference”), they are not patentably distinct from each other because both instant and reference are drawn to the same underlying compound. Sun Pharmaceutical Industries, Ltd. vs. Eli Lilly and Company, 611 F.3d 1381 (Fed. Cir. 2010).
Ref. claim 20 teaches instant claims 1, 3, and 12. AG120 is an IDH inhibitor and Olaparib is PARP inhibitor.
Ref claim 1 teaches that the ref composition is useful in treating diffuse intrinsic pontine glioma (ref specification page 23 “Section e”), which is a cancer of instant claim 10.
It would have been obvious to use the reference composition in a method of treating diffuse intrinsic pontine glioma.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
THIS ACTION IS MADE FINAL. 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 GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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