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 .
Election/Restrictions
Claims 1-30 are pending in the application.
Applicant’s election without traverse of the species I in the reply filed on 9/10/26 is acknowledged.
Claims 7,15,23 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 9/10/26.
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.
Claim(s) 1-6,8-14,16-22 and 24-29 is/are rejected under 35 U.S.C. 103 as being unpatentable
over McCann et al. (US 2025/0127940A1) in view of Larsen (US 2019/0177345A1), Stenberg et al. (Cancers 2022, 14, 2784, p1-19) and Stallons et al. (Mol. Cancer. Ther.; 18(5) May 2019) and in further view of Bu et al. (Front. Oncol. March 2022, Volume 12, Article 835956, p1-13) and Jalomӓki et al. (US 2025/0121103A1).
McCanns et al. (US 2025/0127940A1) discloses the method of treating a subject suffering from metastatic prostate cancer, such as metastatic castration-resistant prostate cancer with 212Pb-PSMA-I&T (p3, [0041]; p85, [0339]) that encompasses the methods of treating a.) a human subject with metastatic castration-resistant prostate cancer and b.) advanced prostate cancer of the instant claims.
The metastatic castration-resistant prostate cancer encompasses the metastatic castration-resistant prostate cancer of the instant claims 2,11 and 20.
The 212Pb-PSMA-I&T (p1, [0019]; p72, [0208-0212]) encompasses the 212Pb-PSMA-targeting ligand
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of the instant claims 6,14,22 and 29.
The treatment of metastatic prostate cancer includes inhibiting the disease, disorder or condition, i.e., partially or completely halting its progression (p82, [0297]) that encompasses the method of inhibiting the progression of metastatic prostate cancer of the instant claims.
The subjects treated for metastatic prostate cancer, such as metastatic castration-resistant prostate cancer previously received treatment with androgen receptor-axis-targeted (ARAT) therapies (p3, [0041]; p85, [0339]) that encompasses the human subject has previously received at least one androgen receptor pathway inhibitor of the instant claim 3.
The 212Pb-PSMA-I&T may be formulated as a pharmaceutical composition that is administered
in an effective amount via intravenous, etc. administration (p84, [0329]; p85, [0340]) that encompasses
the intravenous administration of the instant claims 19 and 27.
The single dosage of 212Pb comprises 50-225 MBq (p3, [0044]) and an effective amount comprises a range of about 0.1 GBq to 30 GBq per dose (p86, [0345]) that encompasses the dose of between about 60-500 MBq and 1 MBq to about 600 MBq of the instant claims.
Mccann et al. does not disclose that the subject has bone metastases/lesions wherein the metastases/lesions are treated.
Larsen (US 2019/0177345A1) discloses the treatment of prostate cancer with a PSMA targeting compounds comprising 212Pb (abstract; p1, [0002]; p2, [0037],[0041],[0044],[0050]).
The treatment includes skeletal metastases from cancers to prostate (p1, [0020]).
The 212Pb is an in vivo generator for the short-lived alpha-emitter 212Bi wherein if 212Pb-chelate taken up in bone or in tumor cells 212Bi will also be retained in the target, such as bone metastases or soft tissue metastases (p1, [0009]; p4, [0101]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the subjects having metastatic castration-resistant prostate cancer will have bone metastases/lesions that are treated via administration of the 212Pb-PSMA-I&T as Larsen teaches that skeletal metastases result from prostate cancer and are treated when 212Pb-PSMA chelates target bone, generates the alpha emitter 212Bi and therefore, 212Pb is an indirect source for irradiating the bone metastases target (p4, [0100]).
Mccann et al. does not disclose two treatment cycles separated by an interval of 7 to 14 days.
Stenberg et al. (Cancers 2022, 14, 2784, p1-19) discloses a study to assess the influence of
various factors on the in vitro and in vivo therapeutic efficacy of PSMA-targeting radioligand 212Pb-
NG001 on prostate cancer models (abstract; p3, first paragraph).
The study shows that a significant increase in treatment response is observed in mice that
received repeated injections compared to the corresponding single dose. The mice were injected intravenously either with a single administration or with two administrations 3 or 14 days apart (abstract; p, 2.9, Therapeutic Effects of 212Pb-NG001 in Mice with PC-3 PIP and C4-2 Xenografts).
Stallons et al. (Mol. Cancer. Ther.; 18(5) May 2019, 1012-1021) discloses a dose range-finding study that showed that fractionating the dose was optimal and allowed for a cumulative dose that would be toxic if given as a single injection (p1020, left column, last paragraph; p1021, right column, first paragraph). The efficacy of 212Pb-DOTAMTATE was enhanced by giving three treatment cycles and reducing time between injections to two weeks (abstract). Decreasing the time between drug injections from three weeks to two weeks improved efficacy (p1013, left column, first full paragraph). The study suggests that a fractioned dose of drug is optimal as it allows the same cumulative dose but with recoverable hematologic effects (p1017, left column, first paragraph).
Larsen further discloses that the compounds can be used in a single treatment or in a repeated treatment fashion (p16, [0269]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to intravenously administer the 212Pb-PSMA-I&T of Mccann et al. in fractionated doses every two weeks in a repeated fashion for the advantages of optimization, a significant increase in treatment response and recoverable hematologic effects between doses.
Mccann et al. does not disclose PET and/or scintigraphy imaging and ECOG performance status of 0,1 or 2.
Mccann et al. further discloses that 177Lu-PSMA I&T is analogously used to that of the 212Pb-
PSMA I&T (p77, [0244-0245]; p78, [0254]; p85, [0339]).
Bu et al. (Front. Oncol. March 2022, Volume 12, Article 835956, p1-13) discloses the method of treatment of metastatic castration-prostate cancer with 177Lu-PSMA I&T that provides tumor remission
and bone metastasis (abstract; Table 2).
68Ga-PSMA-11 PET/CT imaging was done to evaluate tumor metastasis (p2, 68Ga-PSMA-11
PET/CT Acquisition and Interpretation).
The 177Lu-PSMA I&T was administered every 10 (± 2) weeks followed by whole body SPECT/CT
and scintigraphy imaging 48 h post injection (p3, left column, first and second paragraph; p4, Post-Therapy Scintigraphy).
The patients had an ECOG of 0-2 and may have been previously given Abiraterone (Table 1).
Jalomӓki et al. (US 2025/0121103A1) discloses a method of treating cancer and improved progression-free survival and radiographic progression-free survival of a patient via administration of 177Lu-PSMA RLT to chemo naïve patients (abstract; FIG. 17; p33, [0363],[0365]; p34, [0387]).
The patients are determined to be mCRPC with PSMA positive metastatic disease based upon
imaging prior to administration of 177Lu-PSMA I&T (p31, [0357-0358]; p33, [0365],[0368]).
The patients are determined to be positive via PSMA-PET scans (e.g. [68Ga]Ga-PSMA-11 or
[18F]DCFPyL) (p31, [0357]; p51, [0497]; p55, [0563]).
The patients may be treatment naïve (chemo naïve) or not treatment naïve (Figure 17; p33,
[0363],[0369]; p91, [0996-0097]) and had previous ARAT therapy (FIG. 17; p51, [0493-0496]). The patients have ECOG Performance Status 0-1 (p75, [0796]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to monitor bone lesion progression in mCRPC patients having ECOG 0-2 after 212Pb-PSMA-I&T treatment of Mccann et al. as Bu et al. and Jalomӓki et al. teach of evaluating tumor remission and bone metastasis in patients having ECOG 0-2 or 0-1 Performance Status via comparing pretherapy PET/CT imaging of metastases and post 177Lu-PSMA I&T therapy SPECT/CT and scintigraphy imaging and Mccann et al. teaches that 212Pb-PSMA-I&T and 177Lu-PSMA I&T are analogously used
for mCRPC treatment. It would have been predictable to use the standard protocol for monitoring bone lesion progression with 177Lu-PSMA I&T for the method of monitoring bone lesion progression with212Pb-PSMA-I&T.
Mccann et al. does not disclose progression free survival for at least a period of 6 months or working group 3.
Jalomӓki et al. further discloses that the primary objective of the study is to prospectively assess
the efficacy of 177Lu-PSMA I&T on the improvement of progression free survival (PFS) and radiographic progression free survival (rPFS) compared to standard of care hormone therapy (p33, [0365]; p49, [0455],[0460]; p50, [0464]; p93, [01041],[1053]). The rPFS after administration of 177Lu-PSMA RLT is at least 6-12 months (p34, [0387]; p56, [0595]).
The time from randomization to radiographic progression is determined by Prostate Cancer Working Group 3 criteria (bone lesion status) (p49, [0455]; p51, [0485]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the 212Pb-PSMA-I&T mCRPC treatment of Mccann et al. will provide a rPFS of at least 6-12 months as determined via PCWG3 after administration of 177Lu-PSMA RLT as taught by Jalomӓki et al. wherein 212Pb-PSMA-I&T and 177Lu-PSMA I&T are analogously used for the treatment of mCRPC, as taught by Mccann et al. and therefore, it would have been predictable to assess the efficacy of the analogous 212Pb-PSMA-I&T on the improvement of PFS or rPFS via PCWG3.
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 1-6,8-14,16-22 and 24-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12,419,977B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating PSMA-expressing prostate cancer of U.S. Patent No. 12,419,977B2 with the compound of
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comprising a 212Pb encompasses the method of treating a human with mCRPC or method of treating advanced prostate cancer with the 212Pb compound
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of the instant claims. The compound
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comprising a 212Pb of U.S. Patent No. 12,419,977B2 encompasses the 212Pb compound
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of the instant claims, has an analogous structure, the same properties and is capable of the same functions, such as use in the methods of the instant claims.
Claims 1,2,6,9,11,14,17-20,22 and 25-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 12-22,25,28,29 and 34-39 of copending Application No. 19/507,046 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method for treating mCRPC cancer with a
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compound comprising 212Pb of copending Application No. 19/507,046 that is administered in a dosage interval at about 1 to about 3 weeks with an activity per dose of between about 1 MBq to 20000 MBq encompasses the method of treating a human with mCRPC or method of treating advanced prostate cancer with at least two treatment cycles separated by an interval of 7 to 14 days and at an activity per dose of between about 60 MBq to 500 MBq or one to four weeks with an activity per dose of between about 1 MBq to 600 MBq.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct
claims have not in fact been patented.
Claims 1-6,8-14,16-22 and 24-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/279,675 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating PSMA-expressing prostate cancer of copending Application No. 19/279,675 with the compound of
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comprising a 212Pb encompasses the method of treating a human with mCRPC or method of treating advanced prostate cancer with the 212Pb compound
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of the instant claims. The compound
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comprising a 212Pb copending Application No. 19/279,675 encompasses the 212Pb compound
comprising a
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of the instant claims, has an analogous structure, the same properties and is capable of the same functions, such as use in the methods of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1,2,4,6,9,11,14,17-20,22 and 24-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-14,17,18,31-35,44,47,48 and 50-52 of copending Application No. 19/210,753 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method of preventing the formation of a metastatic bone lesion in a human subject having prostate cancer with
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or
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comprising 212Pb of copending Application No. 19/210,753 that is administered in an amount of about 75 MBq per dose, about 100 MBq per dose, about 150 MBq per dose or about 200 MBq per dose about once every week, about one every two weeks, etc. encompasses the method of treating a human with mCRPC or method of treating advanced prostate cancer with the 212Pb compound of the instant claims administered in two treatment cycles separated by an interval of 7 to 14 days and at an activity per dose of between about 60 MBq to 500 MBq. The methods of copending Application No. 19/210,753 prevents the formation of bone lesions that encompasses the result of no progression of bone lesions of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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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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/MELISSA J PERREIRA/Examiner, Art Unit 1618
