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 .
Applicants' arguments, filed March 23, 2026 and March 24, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Response to Amendment
The declarations under 37 CFR 1.132 filed March 23, 2026 and March 24, 2026 are insufficient to overcome the rejection of claims 19, 32 – 37, 44 – 46, 48 and 49 based upon Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) as set forth in the last Office action because: there remains insufficient evidence of unexpected results compared to the closest prior art and that is reasonably commensurate in scope with the instant claims. The 4 page declaration by Julie Nonnekens filed March 24, 2026 is a new declaration that is discussed in detail below. The 9 page declaration by Julie Nonnekens, with a signature date of May 6, 2025 filed March 23, 2026 is the same declaration that has been filed on July 31, 2025 (9 pages) and May 6, 2025 (6 pages) with the extra pages being enlarged versions of the graphs that until the most recent submission, the various samples could not be differentiated from one another but finally can be distinguished in the copy of record. Therefore, the totality of the data can now be evaluated but remains insufficient as discussed herein.
The 4 page declaration states that given the short half-life of PARP inhibitors and ineffectiveness as part of monotherapy would lead one of ordinary skill in the art to anticipate that PARPi administration alone for days prior to administration of co-therapy may yield unwanted toxicities, causing potentially deleterious effects in the treated patient without therapeutic benefit. PRRT (peptide receptor radionuclide therapy) requires accumulation within the tumor while minimizing non-target radiosensitization of health tissues, informing the timing of administration. Certain types of co-therapy at the same time or prior to PRRT administration would increase unwanted adverse effects as PRRT radionuclide clearance from non-target healthy tissue would not be allowed. The claimed regimen was carried out showed no difference in tumor control when PARP was administered 3 – 10 day post-PRRT compared to PRRT-only. This lack of efficacy and the known effects on monotherapy with the agents alone would have led the person of ordinary skill in the art to expect PARPi therapy initiated days prior to PPRT would lack therapeutic efficacy for producing unwanted side effects in patients.
These statements are unpersuasive. The applied prior art in the obviousness rejection of record is not PARPi monotherapy and PRRT monotherapy that are combined to render the claimed method using both treatments obvious. Rather, the applied prior art teaches that the synergistic sensitization of somatostatin receptor expressing cells to PRRT with olaparib (in the culture media for the cells at the same time the PRRT materials was added, p 1822, col 2, ¶ 4), a condition which would not be met by olaparib administration being given after the PRRT. While instant claim 1 is met by a single administration of olaparib 2 days prior to PRRT, that is not the experimental conditions tested which better aligns with dependent claim 29 in which the olaparib is administered daily for 14 days so on the day of PRRT therapy, the patient is administered both olaparib and PRRT and on subsequent days only olaparib. Both drugs are given on the day of PRRT therapy although in the -2 day test condition, olaparib PARPi alone was administered for 2 days. In line with the teachings of the applied Nonnekens reference as to the use of PARP inhibitors to enhance the efficacy of radiation (p 1822, col 1, ¶ 2), Schaefer et al. (Nucl med Commun, 2011) assessed the radiosensitizing capabilities of two different PARP inhibitors in combination with either external beam radiation or a radiolabeled antibody and found that both inhibitors to “highly radiosensitizing agents when used before external beam radiation and 131I-tositumomab” (emphasis added; conclusion section of abstract). Similarly, Al-Ejeh et al. (J Nucl Med, 2013) discloses the clinical trials using the strategies of PARP inhibition and anti-EGFR (epidermal growth factor receptor) strategies did not reach their promise in treating triple negative breast cancer but the combination of anti-EGFR radioimmunotherapy, chemotherapy and PARP inhibitors led to the eradication of established metastases (abstract). When the declaration by one of the named inventors and the apparent state of the art is considered, although there is a difference in treatment outcome when olaparib administration begins 2 days before PRRT administration and is continued for 14 days as compared to olaparib administration that begins 3 days after (and also continued for 14 days) PRRT, that evidence does not outweigh the prima facie case of obviousness as there is no comparison with co-administration beginning at the same time, there appears to be multiple indications that radiation-based therapy of various types in combination with PARP inhibition, which can be administered before the radionuclide containing therapy, can produce better results, even when the individual therapies themselves are not strongly therapeutic to establish that the results observed are in fact unexpected.
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.
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.
Claim(s) 19, 37, 48 and 49 were rejected under 35 U.S.C. 103 as being unpatentable over Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Applicants reference the contents of the various declarations and state that the data presented clearly support the unexpected effects of the claimed dosage regimen of claim 19 and is therefore patentable.
These arguments are unpersuasive. As discussed in greater detail above, the evidence of record in support of the alleged unexpected results does not outweigh the prima facie case of obviousness as the evidence is at least not reasonably commensurate in scope with the claims and that olaparib administration 2 days prior to PRRT results in an unexpected improvement over administering both drugs at the same time. Therefore the rejection is maintained for the reasons of record.
Claim(s) 32 – 36, 44 and 45 were rejected under 35 U.S.C. 103 as being unpatentable over Nonnekens et al. as applied to claims 19, 37, 48 and 49 above, and further in view of Strosberg et al. (NEJM, January 12, 2017). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Applicants do not present any specific arguments regarding Strosberg et al. for the Examiner to address herein.
Claim(s) 46 was rejected under 35 U.S.C. 103 as being unpatentable over Nonnekens et al. and Strosberg et al. as applied to claims 19, 32 – 36, 37, 44, 45, 48 and 49 above, and further in view of Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Applicants do not present any specific arguments regarding Koch et al. for the Examiner to address herein.
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.
Due to the abandonment of Application No. 18/819,282 since the mailing of the previous Office Action, the provisional non-statutory double patenting rejection based on this application has been withdrawn.
Also since the mailing of the previous Office Action on September 22, 2025, Application No. 18/927,058 issued as Patent No. 12,491,272 on December 9, 2025. Therefore the provisional non-statutory double patenting rejection based on this application is now a non-provisional nonstatutory double patenting rejection based on issued Patent No. 12,491,272.
Regarding the non-provisional and provisional nonstatutory double patenting rejections, Applicants state that the pending claims are non-obvious over the cited references. The Examiner stipulated that successful demonstration of non-obviousness would likewise overcome the rejections for nonstatutory double patenting.
As discussed in greater detail above, the non-obviousness of the instant claims over Nonnekens et al. has not been established and similarly, the non-obviousness over the claims of the issues patents or patent applications has not been demonstrated so these rejections are maintained for the reasons of record.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 24 of U.S. Patent No. 10,596,276 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 25 of U.S. Patent No. 10,596,278 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 16 of U.S. Patent No. 11,904,027 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 30 of U.S. Patent No. 12,151,003 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 30 of U.S. Patent No. 12,168,063 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 30 of U.S. Patent No. 12,415,003 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 - 48 of copending Application No. 17/331,927 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 19, 32 – 37, 44 – 46, 48 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 21 of copending Application No. 18/494,042 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 - 21 of copending Application No. 18/597,037 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 19, 32 – 37, 44 – 46, 48 and 49 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 20 of U.S. Patent No. 12,491,272 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
Application 18/927,058 issued as U.S. Patent No. 12,491,272 on December 9, 2025, after the mailing of the previous Office Action on September 22, 2025. Therefore the provisional nonstatutory double patenting rejection based on the application has been converted to a non-provisional nonstatutory double patenting rejection based on the issued patent.
Claims 19, 32 – 37, 44 – 46, 48 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 - 52 of copending Application No. 19/084,265 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 19, 32 – 37, 44 – 46, 48 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 - 50 of copending Application No. 19/231,931 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 19, 32 – 37, 44 – 46, 48 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 – 25, 27 – 36 and 38 - 44 of copending Application No. 19/234,864 in view of Nonnekens et al. (Theranostics, 2016; cited on May 21, 2021 IDS) and optionally further in view of Strosberg et al. (NEJM, January 12, 2017) and Koch et al. (Mol Imaging, 2014). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed September 22, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
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 Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Nissa M Westerberg/Primary Examiner, Art Unit 1618
Prosecution Insights