DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1-14 are pending in this application.
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 .
Status of Claims
Claims 1-3, 7-10, and 14 are original. Claims 4-6, and 11-13 are previously presented.
Response to Amendment
The amendment filed on 7 Jan. 2026 are entered.
Response to Arguments
In view of the approved terminal disclaimer, the rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US patent No. 11,364,235 B2, in view of NCT03867682 (ClinicalTrials.gov; published 8 Mar. 2019), Cicic et al. (WO 2018/200841 A1; published 1 Nov. 2018) and Hagemann et al. (Mol. Cancer Ther.; published 2016) is withdrawn.
In view of the approved terminal disclaimer, the rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of US patent No. 11,844,799 B2, in view of NCT03867682 (ClinicalTrials.gov; published 8 Mar. 2019), Cicic et al. (WO 2018/200841 A1; published 1 Nov. 2018) and Hagemann et al. (Mol. Cancer Ther.; published 2016) is withdrawn.
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.
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) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT03867682 (ClinicalTrials.gov; published 8 Mar. 2019), in view of Cicic et al. (WO 2018/200841 A1; published 1 Nov. 2018) for the reasons cited in the Office action filed on 7 Nov. 2025.
Applicants Arguments
Applicants assert that a person of ordinary skill in the art would not have been motivated to delay lintuzumab-AC225 administration from day 1 to days 4-6 because NCT03867682 does not suggest that such a modification would provide any benefit. Changing the timing would require redesigning the treatment protocol and would involve unpredictable effects on efficacy and safety. The examiners obviousness statement is conclusory and lacks evidentiary support. The interaction between venetoclax-induced apoptotic sensitization and radiation induced DNA damage is highly dependent on the temporal coordination of the agents.
Applicant's arguments filed 7 Jan. 2026 have been fully considered but they are not persuasive. NCT03867682 provides a dosing method for treating a human subject having AML comprising administering to the subject a regimen comprising administering venetoclax and lintuzumab-Ac225 wherein the regimen comprises about 4-8 cycles each cycle lasting from about 28 to 42 d. The regimen comprises orally administering venetoclax on days 1 and 2 of the first cycle at a ramp up dosage, and thereafter orally administering 400 mg of venetoclax daily on days 3-21 of the first cycle and days 1-21 of each subsequent cycle, and intravenously administering lintuzumab-Ac225 on day 1 of each cycle at a dose of about 0.5 µCi/kg, 1.0 µCi/kg or 1.5 µCi/kg. Qualified subjects have a blast count of ≤200/µL. Like NCT03867682, Cicic teaches venetoclax and lintuzumab-Ac225 in AML patients. At examples, Cicic provides dosing regimens for lintuzumab-Ac225 and venetoclax where dosing regimens state that lintuzumab-Ac225 may just as well be administered on day 4, 5, or 6 instead day 1. Choosing from a finite number of identified predictable solutions is an exemplary rationale for obviousness. In this case, a person of ordinary skill in the art would have expected that the administration of lintuzumab-Ac225 on day 4, 5, or 6 to be equivalent to day 1 by allowing synergistic treatment of AML. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify NCT03867682 so that lintuzumab-Ac225 gets administered on day 4, 5, or 6 instead of day 1 because administering on one of those days would have been expected to provide an equivalent method of treating AML while arriving at predictable results. In addition, Cicic describes the combination of lintuzumab-Ac225 and venetoclax as synergistic resulting in better survival rates compared to treatment with lintuzumab-Ac225 or venetoclax alone. The NCT03867682 dosing schedule administers lintuzumab-Ac225 on day 1 concomitant with a low ramp up dose of venetoclax. At day 3, the patient max dose of venetoclax. Accordingly, a person of ordinary skill in the art would have had reason and motivation to administer lintuzumab-Ac225 on an equivalent day 3, 4, or 5 because that is when the patient has been received and adjusted the full dose of venetoclax whereby providing ideal and advantageous synergistic treatment. A recognized advantage is the strongest reason to modify a prior art method and dosing schedule. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify NCT03867682 so that lintuzumab-Ac225 gets administered on day 4, 5, or 6 instead of day 1 because the administering on one of those days would have been expected to advantageously enable optimal synergistic treatment when has received and adjusted to the full dose of venetoclax.
Claim(s) 1-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT03867682 (ClinicalTrials.gov; published 8 Mar. 2019), in view of Cicic et al. (WO 2018/200841 A1; published 1 Nov. 2018), in further view of Hagemann et al. (Mol. Cancer Ther.; published 2016) for the reasons cited in the Office action filed on 7 Nov. 2025.
Applicants Arguments
Applicants assert that Hagemann does not cure the deficiencies of NCT0386768 and Cicic. Thorium-227 and actinium-225 are different isotopes with distinct physical properties. A person of ordinary skill would not have expected that the fractionation schedule developed for thorium-227 in Hagemann would be directly applicable to actinium-225. Hagemann does not address human dosing regimens. Extrapolating dosing schedules from mouse studies to human treatment protocols involves significant uncertainty due to differences in pharmacokinetics, metabolism, and disease biology between species. It has not been explained how or why a person of ordinary skill would been reasonably guided by the fractionation timing from Hagemann’s mouse studies to claimed human treatment regimen with lintuzumab-Ac225 with required expectation of success.
Applicant's arguments filed 7 Jan. 2026 have been fully considered but they are not persuasive. NCT03867682 and Cicic are not deficient for the reasons discussed above. In addition, at examples, Cicic, who teaches human subjects, provides for a normal fractional dosing regimen where 2 × 2.0 µCi/kg of lintuzumab-Ac225 gets administered one week apart and alternate fractional dosing regimens where days 18, 19, and 20 are taught as equivalent days for administering the second fractional dose of lintuzumab-Ac225. Like NCT03867682 and Cicic, Hagemann provides for radioimmunotherapy of AML using lintuzumab labeled with an alpha emitter 227Th that treats AML using mechanism as the alpha emitter 225Ac. The data presented supports lintuzumab-Th227 as an alpha pharmaceutical for the treatment of AML. At pg. 2423, Hagemann discusses lintuzumab-Ac225. At fig. 6, Hageman provides for a fractional dosing regimen of lintuzumab-Th227 wherein lintuzumab-Th227 gets administered on day 5 and day 19 of the treatment cycle. In Hagemann, the advantageous fractional dosing regimen of lintuzumab-Th227 gets compared to other single dosing regimens of lintuzumab-Th227 and the advantageous fractional dosing regimen produced an ideal duration of survival at a reduced therapeutic dose. Cicic performed human experiments based on the results obtained in animal experiments. Obviousness does not require an absolute predictability of success nor is there a requirement for conclusive proof of efficacy. See OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019). A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify NCT03867682 so that the lintuzumab-Ac225 gets administered as a fractional dose on days 5 and 19 of the treatment cycle as taught by Hagemann because the administration of lintuzumab-Ac225 on days 5 and 19 of the treatment cycle would have expect to provide an ideal duration of survival using a low or moderate dose lintuzumab-Ac225 whereby reducing radioimmunotherapy associated toxicity and/or provide the predictable outcome of synergistic treatment of AML using both venetoclax and lintuzumab-Ac225 in a treatment cycle.
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 SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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