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 .
Receipt is acknowledged of Applicant’s Amendment filed on 12/23/2025; and IDS filed on 12/23/2025.
Claims 1, 11-12 have been amended.
Claims 1-3, 6-7, 9-18, 92-97 are pending in the instant application.
Claims 13-14, 95-97 have been previously withdrawn from consideration.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claim 1-3, 6-7 ,9-12 and 15-18, 92-94 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 17/047,778 and 17/904,442 (reference application) in view of FENDLER et al (177Lu-PSMA Radioligand Therapy for Prostate Cancer. Journal of Nuclear Medicine Aug 2017, 58 (8) 1196-1200), MORGENSTERN et al (WO 2018/108287) and MOKHTARI et al (Combination therapy in combating cancer. Oncotarget, 2017, Vol. 8, (No. 23), pp: 38022-38043).
The co-applications recite a method for treating a cancer in a patient in need of such treatment comprising, administering to the patient a therapeutically effective amount of a compound of the formula 1 wherein the compound is complexed with a metal selected from the group consisting of 177Lu, and 225Ac (see 17/047,778 at claim 38), wherein the cancer is prostate cancer, or metastatic castration-resistant prostate cancer (see claim 39), wherein the therapeutically effective amount is from about 2 GBq to about 13 GBq (see claim 42).
The co-applications do not specifically recite using both compounds together to treat prostate cancer.
FENDLER teaches a method of treating metastatic castration-resistant prostate cancer (see abstract) comprised of: administering beta-emitter therapy, such as 177Lu-PSMA (see pg. 1197, 1st col), which reads on Applicant’s 177Lu complexed with Formula I, wherein the dosage is 3.5-7.5 GBq (see pb. 1198, under Safety), which reads on Applicant’s range of about 2-8 GBq. Additional disclosures include: alpha-emitter therapy using 225Ac-PSMA-617 has induced promising response (see pg. 1199, 1st col).
MORGENSTERN teaches the prior art had known of using alpha emitter (see [0022]), such as Ac255-PSMA-617 (see [0013]), which reads on Applicant’s 225Ac complexed with Formula I, wherein the dosage is about 7MBq (see [0055]), which is about 4 MBq.
MOKHTARI teaches the prior art had known of combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anticancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner (see abstract). A lower therapeutic dosage of each individual drug is required (see pg. 38023, 1st col).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate administering both compounds together to treat metastatic castration-resistant prostate cancer. The person of ordinary skill in the art would have been motivated to make those modifications, because it would have an additive effect, and reasonably would have expected success because both compounds treat metastatic castration-resistant prostate cancer.
The co-applications do not specifically teach the exact amounts of therapeutic agents or administration times as claimed by Applicant. The amount of a therapeutic and administration times in a method of treating prostate cancer is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of active agent and administration times in order to best achieve the desired results, such as effective treatment of the cancer and decrease of adverse effects. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of active agent amounts and administration times would have been obvious at the time of Applicant's invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112, 2nd paragraph
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.
Claim 1 is 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 the limitation "Ia-Lu". There is insufficient antecedent basis for this limitation in the claim.
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.
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) 1-3, 6-7, 9-12, 15-18, 92-94 is/are rejected under 35 U.S.C. 103 as being unpatentable over FENDLER et al (177Lu-PSMA Radioligand Therapy for Prostate Cancer. Journal of Nuclear Medicine Aug 2017, 58 (8) 1196-1200) in view of MORGENSTERN et al (WO 2018/108287) and MOKHTARI et al (Combination therapy in combating cancer. Oncotarget, 2017, Vol. 8, (No. 23), pp: 38022-38043).
FENDLER teaches a method of treating metastatic castration-resistant prostate cancer (see abstract) comprised of: administering beta-emitter therapy, such as 177Lu-PSMA (see pg. 1197, 1st col), which reads on Applicant’s 177Lu complexed with Formula I, wherein the dosage is 3.5-7.5 GBq (see pb. 1198, under Safety), which reads on Applicant’s range of about 2-8 GBq. Additional disclosures include: alpha-emitter therapy using 225Ac-PSMA-617 has induced promising response (see pg. 1199, 1st col).
FENDLER does not teach administering 225Ac-PSMA-617 in combination with 177Lu-PSMA-617.
MORGENSTERN teaches the prior art had known of using alpha emitter (see [0022]), such as Ac255-PSMA-617 (see [0013]), which reads on Applicant’s 225Ac complexed with Formula I, wherein the dosage is about 7MBq (see [0055]), which is about 4 MBq.
MOKHTARI teaches the prior art had known of combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anticancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner (see abstract). A lower therapeutic dosage of each individual drug is required (see pg. 38023, 1st col).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate administering 225Ac-PSMA-617 in combination with 177Lu-PSMA-617. The person of ordinary skill in the art would have been motivated to make those modifications, because it would have an additive effect in treating metastatic castration-resistant prostate cancer, and reasonably would have expected success because both compounds treat metastatic castration-resistant prostate cancer.
The references do not specifically teach the exact amounts of therapeutic agents or administration times as claimed by Applicant. The amount of a therapeutic and administration times in a method of treating prostate cancer is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of active agent and administration times in order to best achieve the desired results, such as effective treatment of the cancer and decrease of adverse effects. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of active agent amounts and administration times would have been obvious at the time of Applicant's invention.
Note, Applicant’s specification provides no experimental data, but only a prophetic example (see Applicant’s only example at [0221]) stating: “Patients with PSMA positive scans will be administered a single dose of Compound Ia-Ac on day 1, cycle 1 of the clinical regimen of 7.4 GBq Compound Ia-Lu, administered 6 weekly for a maximum of 5 cycles. Subjects will be reviewed weekly for assessment of adverse events (onset, duration, grade and relatedness to treatment) during cycle 1 only. DLT will be determined by AE on cycle 1 only”.
Response to Arguments
Applicant argues that the Examiner has failed to support the assertion that a compound of formula I-Lu and I-Ac would have been expected to "have an additive effect." In contrast to the combination therapy described in Fendler, where the RL T and the androgen-deprivation therapy or chemotherapy would be working to address the same cancer but using different mechanisms, both I-Lu and I-Ac contain the same binding ligand. However, even though the compounds of both I-Lu and I-Ac contain the same binding ligand, the claimed combination provides a therapeutic benefit not reasonably expected from the cited art, as shown in Meyer, for example, which is discussed below. 1 Accordingly, the Examiner has failed to articulate why a person of ordinary skill in the art would have expected the compounds recited in amended claim 1 to have an additive effect when the binding ligand for each of the compounds is of the same formula. Applicants further submit (1) that a person of ordinary skill in the art considering the alleged combination of references would not have arrived at the method recited in the amended claims with a reasonable expectation of success, and (2) the alleged combination of references fails to teach each and every element of the amended claims. No motivation to modify Fendler to arrive at the claimed method with a reasonable expectation of success.
The Examiner finds this argument unpersuasive, because the binding ligands are targeting ligands that targets the prostate; thus, both have to target the same area of interest, such as the prostate, to treat prostate cancer. The two different active agents are Lu and Ac, wherein MOKHTARI teaches the prior art had known of combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anticancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner (see abstract). A lower therapeutic dosage of each individual drug is required (see pg. 38023, 1st col). Combination therapy is common practice in treating cancer or any other ailments.
Applicant argues that the claimed method provides a benefit not realized from the alleged combination of Fendler and Morgenstern. As discussed in Rathke. It was interestingly found that combining I-Lu with I-Ac still led to promising anti-tumor activity, but at a lower rate of reported xerostomia. See id A person of ordinary skill in the art considering the alleged combination would not have reasonably been able to predict that maintaining efficacy while also decreasing the amount ofl-Ac relative to what is exemplified in Morgenstern would be possible by combining the therapy with I-Lu.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, Applicant’s specification provides no experimental data, but only a prophetic example (see Applicant’s only example at [0221]) stating: “Patients with PSMA positive scans will be administered a single dose of Compound Ia-Ac on day 1, cycle 1 of the clinical regimen of 7.4 GBq Compound Ia-Lu, administered 6 weekly for a maximum of 5 cycles. Subjects will be reviewed weekly for assessment of adverse events (onset, duration, grade and relatedness to treatment) during cycle 1 only. DLT will be determined by AE on cycle 1 only”.
Applicant argues that neither Fendler nor Morgenstern provide any teaching on how dosing or timing of various therapeutics can affect the method. Although Fendler discloses a protocol, Fendler fails to provide any details as to how the protocols can be varied to affect the results. Accordingly, Fendler does not contain any disclosure "of the relationship of the variable" (i.e., dosing/time) "and the result in the prior art" according to a standard articulated by the Federal Circuit.
The Examiner finds this argument unpersuasive, because the prior art teaches these active agents treats prostate. Additionally, Applicant’s specification provides no experimental data, but only a prophetic example (see Applicant’s only example at [0221]) stating: “Patients with PSMA positive scans will be administered a single dose of Compound Ia-Ac on day 1, cycle 1 of the clinical regimen of 7.4 GBq Compound Ia-Lu, administered 6 weekly for a maximum of 5 cycles. Subjects will be reviewed weekly for assessment of adverse events (onset, duration, grade and relatedness to treatment) during cycle 1 only. DLT will be determined by AE on cycle 1 only”.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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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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/JAKE M VU/Primary Examiner, Art Unit 1618
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