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 27, 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.
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) 14, 18 – 20 and 23 were rejected under 35 U.S.C. 103 as being unpatentable over Behe et al. (US 10,130,724) in view of Pruszynski et al. (Mol Pharmaceutics, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
The amendments to the independent claim do not alter the underlying rejection as claim 20 was rejected over this combination of prior art and required the presence of norleucine (Nle), DOTA and 225Ac which are now specific options recited in claim 14.
Applicants traverse this rejection on the grounds that it would not have been obvious to replace the beta-emitting radionuclide chelated via DOTA to the gastrin analog in Behe with an alpha-emitting radionuclide such as 225Ac. While Pruszynski et al. disclosed results showing relatively low kidney accumulation for the anti-HER-2 nanobody labeled with 225Ac via DOTA, gastrin analogs have shown specific toxicity issues such as hemorrhagic gastritis, a side effect not observed by Pruszynski et al. This is further evidence that the teachings of Pruszynski et al. are of limited use when respect to a reasonable expectation of success. More recent studies, citing to Sauter et al. (cited on the IDS filed March 2, 2026) and Rottenberger et al. previously of record, PP-F11N labeled with 177Lu showed low kidney accumulation but showed significant accumulation in healthy tissue such as the stomach due to endogenous CCKBR expression. Since stomach specific uptake of PP-F11N was noted in Behe 2002a, Sauter et al. and Rottenberger et al., Applicant again asserts that the teachings of Pruszynski et al. would be of no significance and would not provide the requisite reasonable expectation of success.
These arguments are unpersuasive. Given the difference in targets between the gastrin analogs claims and the anti-HER-2 nanobody of Pruszynski et al., one of ordinary skill in the art would not expect accumulation in the stomach of the anti-HER-2-nanobody when there is no endogenous expression of that target in that tissue but would reasonably expect accumulation of gastrin analogs in tissue such as the stomach that as noted by Applicants, have endogenous CCKBR expression, the target of gastrin analogs. References must be considered as a whole and Pruszynski et al. discussed the limitations of beta-emitters and the advantages of alpha-emitters such as 225Ac for the treatment small tumors or metastases given the high linear energy transfers and short range of α-emitters. A given isotope often had simultaneous advantages and disadvantages and this does not obviate motivation to change the radioisotope used in a radiolabeled constructs. Any apparently conflicting teachings in the prior art requires the consideration of each reference for its power to suggest solutions to an artisan of ordinary skill and the degree to which one reference might accurately discredit another. Only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness. One of ordinary skill in the art would have a reasonable expectation of success that the beta-emitters in the DOTA-gastrin analogs of Behe et al. could be replaced with an α-emitter such as 225Ac as a radioistope with high linear energy and a short range as disclosed by Pruszynski et al. to produce a radiolabeled construct suitable for various uses in a subject.
Applicants also state that they have unexpectedly and surprisingly found that HE stains showed no difference between control and 225Ac-PP-F11N treated groups which indicates no signs of acute radiation during the alpha radionuclide therapy in the stomat and kidneys as shown in Example 4 in the instant application.
These statements are unpersuasive. Any evidence of unexpected results must be a comparison with the closest prior art such as ß-emitter labeled version as taught by the primary reference and not a control such as a buffer with no radioisotope. Applicants bear the burden of explaining any evidence proffered in support of alleged unexpected results (see MPEP 716.02 et seq. for a complete discussion of unexpected results) and the administration schedule was not clearly set forth. Example 4 states that samples were collected between days 11 – 26 for control but between 34 – 39 days for the 225Ac containing treatment arm (¶ [0185] of the PGPub of the instant application). It appears that the treatment protocol is that set forth in ¶ [0169] of the PGPub of the instant application with a single dose administration, and if that is considered day 1 or if day 1 is considered tumor cell implantation is not stated, and there appears to only be a single administration step. Regardless of how day 1 was defined, the samples were collected multiple weeks after the administration of the radiolabeled material, which could allow tissue damage to heal. Therapeutic efficacy of the radiolabeled constructs was observed, so it would seem to be the case that the gastrin analogs did bind to the intended target that could include binding to endogenously expressed CCKBR so one possible explanation is that any tissue damage could have healed by the time the tissue samples were obtained between days 34 and 39. One of ordinary skill in the art could reasonably expect that the short range of α-emitters compared to ß-emitters would alter the area of damage caused by binding of the α-emitter labeled gastrin analog compared to a gastrin analog labeled with a ß-emitter and without a comparison to the ß-emitter labeled analogs and an indication of what the expected results would be, if the results are in fact unexpected can be determined. Any evidence must also be reasonably commensurate in scope with the claims and no explanation as to how the allegedly unexpected behavior of the Nle containing construct labelled with 225Ac would then behave in a predictable manner for constructs labeled with 213Bi or 149Tb and containing either isoleucine or homo-norleucine has been given. Therefore even if the evidence of unexpected results was persuasive, it does not appear to be reasonably commensurate in scope with the claims and therefore the rejection is maintained.
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 14, 18 – 20 and 23 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 - 35 of copending Application No. 18/040,011 in view of Pruszynski et al. (Mol Pharmaceutics, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
Applicants indicate they will address the rejection once there is an indication of allowable subject matter.
Therefore this rejection is maintained for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection.
Claims 14, 18 – 20 and 23 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 5 and 7 of U.S. Patent No. 10,130,724 in view of Pruszynski et al. (Mol Pharmaceutics, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that as discussed in greater detail above regarding the obviousness rejection, the instant claims are patentably distinct over the claims of this patent as Pruszynski et al. would not add anything of significance and the Sauter et al. and Rottenberger et al. disclose relating to gastrin analog specific accumulation and adverse side effects.
As discussed in greater detail above, there exists a reasonable expectation of success in replacing the beta emitter of the claims of US’724 with an alpha emitter such as 225Ac and only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness and the evidence of record in support of the alleged unexpected results does not outweigh the prima facie case of obviousness.
Claims 14, 18 – 20 and 23 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of U.S. Patent No. 10,953,114 in view of Pruszynski et al. (Mol Pharmaceutics, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that as discussed in greater detail above regarding the obviousness rejection, the instant claims are patentably distinct over the claims of this patent as Pruszynski et al. would not add anything of significance and the Sauter et al. and Rottenberger et al. disclose relating to gastrin analog specific accumulation and adverse side effects.
As discussed in greater detail above, there exists a reasonable expectation of success in replacing the beta emitter of the claims of US’114 with an alpha emitter such as 225Ac and only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness and the evidence of record in support of the alleged unexpected results does not outweigh the prima facie case of obviousness.
Claims 14, 18 – 20 and 23 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7, 9 and 12 - 14 of U.S. Patent No. 11,623,014 in view of Pruszynski et al. (Mol Pharmaceutics, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed November 24, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that as discussed in greater detail above regarding the obviousness rejection, the instant claims are patentably distinct over the claims of this patent as Pruszynski et al. would not add anything of significance and the Sauter et al. and Rottenberger et al. disclose relating to gastrin analog specific accumulation and adverse side effects.
As discussed in greater detail above, there exists a reasonable expectation of success in replacing the beta emitter of the claims of US’014 with an alpha emitter such as 225Ac and only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness and the evidence of record in support of the alleged unexpected results does not outweigh the prima facie case of obviousness.
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.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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