DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 1-2, 16-21, and 23-26 are pending in this application No.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2 Mar. 2026 has been entered.
Status of Claims
Claims 1, 20-21, and 25 have been amended. Claims 3-15, and 22 are cancelled. Claim 26 is new.
Response to Amendment
The amendments filed on 2 Mar. 2026 have been entered. In reply to this Office action, the Examiner request a clean copy of the amended claims since some structures in claims 1, 20, and 21 appear to be unlined rather than crossed out.
The declaration under 37 CFR 1.132 filed 2 Mar. 2026 is insufficient to overcome the rejection of claims in the last Office action because of the reasons set forth below.
Dr. Mease declares that the application demonstrates the ability of a non-radiolabeled PSMA competing inhibitor, YC-I-27, when administered with a PSMA inhibitor to reduce uptake of the radiolabeled PSMA inhibitor in non-target organ, e.g. kidney. Tables 1-5 support the ability of non-radiolabeled YC-I-27 to reduce uptake of representative PSMA targeted agents in the kidney. As show in Table 1, the administration of 211At-labeled [Lu]VK-02-90 in combination with 0.25 nmole or 0.5 nmole cold YuC-I-27 resulted in a significant reduction of uptake, 5.0±1.6 and 2.2±0.6 respectively. The data in Table 2 demonstrate high uptake of YC-1-27 in the kidney indicating high binding affinity of YC-1-27 for PSMA. Table 3 demonstrates that while coadministration of YC-I-27 significantly reduces uptake of [125I]VK-02-90 in the kidney, it has little or no reduction of uptake in the salivary gland. Coadministration of VK-02-90 results in a significant reduction in uptake of [125I]VK-02-90-Lu in the salivary gland. Similar results were observed in a 24 h biodistribution study. Little differences were observed in a 24 h biodistribution study.
Applicant's arguments filed 2 Mar. 2026 have been fully considered but they are not persuasive. As an initial matter Pomper III (WO 2019/157037 A1; cited below) anticipates the claimed invention and so the Dr. Mease declaration is immaterial. In this case, at example 4, tables 3, 4, and 5, Pomper III provides for biodistribution studies of [125I]VK-02-90-Lu with cold blocking agents YC-I-27 and VK-02-90-Lu at 0.5 nmol, 1 nmol, and 5 nmol. The kidney uptake of [125I]VK-02-90-Lu is greatly reduced with blocking agent YC-I-27 in comparison to none. Pg. 20 provides a description of the YC-I-27 where it is stated that X includes iodine and so a person of ordinary skill in the art would have readily envisaged the claimed YC-I-27 wherein in X is I.
In the case Pomper III gets removed as prior art. A declaration of unexpected results must contain a comparison with the closest prior art in order to be effective to rebut a prima face case of obviousness. See In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). The next closest prior art after Pomper III is Wurzer (cited below) who teaches compositions and methods for imaging PSMA positive tumors comprising a radiolabeled PSMA inhibitor in amount suitable for imaging a PSMA positive tumor together with a non-radiolabeled PSMA competing inhibitor wherein the non-radiolabeled PSMA competing inhibitor advantageously provides significantly enhanced tumor to kidney ratios by saturating the PSMA binding site in the kidney but not the PSMA tumor. The Dr. Mease declaration does not contain a comparison with Wurzer to describe an unexpected result over the prior art of Wurzer.
A declaration of unexpected results must be commensurate in scope with the claims. A showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). In this case, the claimed method and composition allow for the use of any radiolabeled PSMA inhibitor. However, the experiments in the Dr. Mease declaration do not allow for the extrapolating a beneficial tumor to kidney ratio for any radiolabeled PSMA inhibitor. For example, at pg. 4298 and Fig. 3, Wurzer describes a radiolabeled DBCO3 PSMA inhibitor where when administered in the presence of a non-radiolabeled resulted in a larger kidney accumulation than tumor uptake.
Expected beneficial results are evidence of obviousness. See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). At [0130] Pomper (WO 2010/014933 A2; cited below) teaches that the YC-I-27 wherein X is I achieves high kidney accumulation p.i. The kidney achieves its maximal uptake at 24 h p.i. The values noted in the kidney are largely due to specific binding due to the expression of high amounts of PSMA in the proximal renal tubule. Wurzer teaches the composition and method that combines at the same time a radiolabeled PSMA inhibitor with a non-radiolabeled PSMA competing inhibitor where the non-radiolabeled PSMA competing reduces kidney uptake by saturating binding sites whereby providing optimal PSMA PET tumor to kidney ratios. A person of ordinary skill in the art would have expected the claimed methods and compositions to provide reduced kidney uptake of a radiolabeled PSMA inhibitor because the YC-I-27 wherein X=I was known to bind to PSMA binding site in kidney for at least 24 h p.i. and because Wurzer teaches that favorable kidney to tumor ratios can be achieve by co-administration of a non-radiolabeled PSMA competing inhibitor that saturates kidney binding sites.
Response to Arguments
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 12, 16, 18-21, and 23-25 under 35 USC 103 as being unpatentable over Pomper et al. (US 2011/01422760 A1; published 2011), in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016) is withdrawn.
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 12, 16, 18-21, and 23-25 under 35 USC 103 as being unpatentable over Pomper et al. (US 2011/01422760 A1; published 2011), in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016) and Pomper et al. (WO 2017/070482 A2; published 27 Apr. 2017; “Pomper et al. II”) is withdrawn.
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 10, 16, 18-21, and 23-25 under 35 USC 103 as being unpatentable over Pomper et al. (US 2011/01422760 A1; published 2011), in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016), Ray et al. (WO 2017/165473 A1; published 28 Sep. 2017) and Pomper et al. (WO 2016/065145 A2; published 28 Apr. 2016; “Pomper et al. III”) is withdrawn.
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 12, 16-21, and 23-25 under 35 USC 103 as being unpatentable over Pomper et al. (US 2011/01422760 A1; published 2011), in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016) and Pomper et al. (WO 2010/018125 A1; published 23 Sep. 2010; “Pomper et al. IV”) is withdrawn.
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 12, 16-21, and 23-25 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US patent No. 8,778,305 B2, in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016), Pomper et al. (WO 2017/070482 A2; published 27 Apr. 2017; “Pomper et al. II”), Ray et al. (WO 2017/165473 A1; published 28 Sep. 2017), Pomper et al. (WO 2016/065145 A2; published 28 Apr. 2016; “Pomper et al. III”), and Pomper et al. (WO 2010/018125 A1; published 23 Sep. 2010; “Pomper et al. IV”) is withdrawn
In view of Applicants amendments, the rejection of claims 1-2, 5-6, 8, 12, 16-21, and 23-25 on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of US patent No. 10,947,197 B2, in view of Pillarsetty et al. (J. Nucl. Med. Chem; published 2016), Pomper et al. (WO 2017/070482 A2; published 27 Apr. 2017; “Pomper et al. II”), Ray et al. (WO 2017/165473 A1; published 28 Sep. 2017), Pomper et al. (WO 2016/065145 A2; published 28 Apr. 2016; “Pomper et al. III”), and Pomper et al. (WO 2010/018125 A1; published 23 Sep. 2010; “Pomper et al. IV”) is withdrawn.
New Grounds of Rejection
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 16, 20, and 23-26 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Pomper et al. (WO 2019/157037 A1; published 15 Aug. 2019; see IDS filed on 7 Mar. 2022; “Pomper et al. III”).
Regarding claims 1, 16, 20, and 23-26, Pomper et al. disclose biodistribution experiments with biodistribution experiments with [125I]VK-02-90-Lu and [211At]VK-02-90-Lu administered to athymic mice bearing PSMA+PC3-PIP ad PSMA-PC3-flu flank xenografts with and without the YC-I-27 blocking agent at dose of 0.5, 1.0, and 5 nmol (see example 4; tables 2-8). At pg. 20, Pomper et al. teach YC-I-20 as
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wherein X is halogen including I. A person of ordinary skill in the would have readily envisaged a YC-I-27 wherein X=I. MPEP 2131.02.III.
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, 2, 16, 18-21, and 23-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wurzer et al. (Mol. Pharmaceuticals; published 16 Jul. 2018; see attached 892), in view of Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892).
Wurzer et al. teach the using subcutaneous murine LNCaP xenografts, the influence of molar activity (mass dose) on the uptakes in tumor, kidney, salivary, and background muscle was analyzed by means of ROI based quantification of small animal PET imaging data. Molar activity/cold mass had the most pronounced influence of PET uptakes. A overall high amount of active compound (12 pmol vs 2 nmol) resulted in remarkable reduction of kidney-to-tumor ratio from 11.4 to 1.4 respectively, at 60 min p.i. (see abstract). Wurzer et al. teach that excessive uptake of PSMA-targeted radiotherapeutics may lead to renal insufficiency or impairment. Current development of PSMA-targeting radiotherapeutics for PCa aims to reduce such critical, dose limiting off-target accumulation while maintaining or improving tumor uptake (pg. 4296). For saturable targets, the amount and density of available receptors in tissues determines the respective uptakes (pg. 4297). The impact of total administered mass of bioactive compound of selected critical uptakes was assessed by injecting each compound with slightly different molar activities of approximately 1200 and 8 MBq/nmol, equivalent to doses of 12 pmol and 2 nmol. With one exception (68Ga-DBCO3) kidney accumulations are reduced to a larger extent than tumor uptakes. Kidney to tumor ratios are dramatically improved upon lowering the AM. Co-injection of large amounts of unlabeled compound appears to be a promising strategy for tuning of kidney-to tumor ratios, which should be as low as possible to radiation related kidney damage (pg. 4298). Wurzer et al. teach PET imaging studies where low molar activities were adjusted by the addition of 2.2 nmol of the respective unlabeled compounds to the injection syringes. Imaging was performed 60 min p.i on a Siemens Inveon small animal PET system (pg. 4301).
Wurzer et al. do not teach in instant method of imaging PSMA positive tumors or cells wherein the non-radiolabeled PSMA competing inhibitor is YC-I-27 wherein X=I optionally wherein the radiolabeled PSMA inhibitor is [131/125I]YC-I-2 or optionally wherein the radiolabeled PSMA inhibitor comprises 211At or the claimed pharmaceutical composition and kit wherein the non-radiolabeled PSMA inhibitor is YC-I-27 wherein X=I.
Pomper et al. teach PSMA-binding agents and uses thereof (see title). Pomper et al. teach YC-I-27
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(3) and [125I]YC-I-S7
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([125I]3) ([0071]). Pomper et al. teach prostate cancer including metastasized prostate cancer and renal cell tumors (see [0074]). Examples of therapeutically effective radioisotopes include 131I and 211At ([0083]). Other embodiments provide for kits comprising a compound of the invention ([0084]). Pomper et al. teach the preparation of [125I]3 (pg. 32). Pomper et al. teach ex vivo biodistribution and imaging of compound [125I]3 where SCID mice were injected with [125I]3 via the tail vein. Table 2 oulines the ex vivo rodent tissue distribution results of [125I]3. The blood, kidney, urinary bladder, spleen and PSMA+ PC-3 PIP tumor display high uptake at the initial, 30 min pi time point. The kidney achieved its maximal uptake at 24 h pi. The values in the kidney are largely due to specific binding rather than renal clearance due to the expression of high amounts of PSMA in the proximal renal tubule (see example 19, table 2). Pomper et al. teach in vivo biodistribution imaging. Fig. 3 shows a SPECT imaging of radiopharmaceutical uptake at 4 h.i. The very intense uptake in the kidneys is consistent with the ex vivo biodistribution data (example 22; Fig. 3). Pomper et al. teach target/non-target ratios for compound 3. The high and prolonged uptake in the tumor and kidney due to specific binding to PSMA ([0142]-[0144]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to the method and composition of Wurzer et al. (method and composition for imaging PSMA positive tumors wherein the method comprises administering to a subject a radiolabeled PSMA inhibitor (e.g. 68Ga-KuE3) in an amount suitable for imaging a PSMA positive tumor in combination with a non-radiolabeled PSMA inhibitor (e.g. KuE3) in an amount suitable for reducing the uptake of the radiolabeled PSMA inhibitor in a non-target organ such as the kidneys compared to uptake of the radiolabeled PSMA inhibitor in the one or more non-target organs when the radiolabeled PSMA inhibitor is administered without the non-radiolabeled PSMA competing inhibitor wherein the PSMA positive tumor or cell is a prostate tumor or cell wherein the method further comprises taking a PET image and wherein the radiolabeled PSMA inhibitor and non-radiolabeled PSMA inhibitor are administered at the same time and wherein the method reduces the side effect of renal toxicity) so that competing non-radiolabeled PSMA inhibitor used in the method and composition is YC-I-27 where X=I and optionally so that the radiolabeled PSMA inhibitor is [125I]YC-I-27 or [131I]YC-I-27 as taught by Pomper et al. because the use of YC-I-27 as a competing non-radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theragnostic SPECT imaging and radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Wurzer et al. by further forming a kit comprising the obvious radiolabeled PSMA inhibitor and non-radiolabeld competing inhibitor as taught by Pomper et al. the kit would have been expected to enable facile distribution and assembly of the obvious composition. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Wurzer et al. so that the radiolabeled PSMA inhibitor comprises 211At as taught by Pomper et al. because the 211At would have been expected to advantageously enable radiotherapy of PSMA positive tumors.
Claim(s) 1, 2, 16, 18-21, and 23-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wurzer et al. (Mol. Pharmaceuticals; published 16 Jul. 2018; see attached 892), in view of Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), in further view of Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”).
Wurzer et al. teach as discussed above.
Wurzer et al. do not further teach that the PSMA positive tumor is a primary clear cell renal carcinoma.
Pomper et al. teach as discussed above.
Pomper et al. II teach PSMA targeting compounds and uses thereof (see title). Pomper et al. II teach that clear cell carcinoma expresses significantly more PSMA in its vasculature (see [0004]). Pomper et al. II teach detection and eradication of primary tumor ([0007]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Wurzer et al. so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Claim(s) 1, 2, 16, 18-21, and 23-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pillarsetty et al. (J. Nucl. Med; published 2016), in view of Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), and Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”).
Pillarsetty et al. teach the effect of specific activity on the uptake of [68Ga]-DKFZ-PSMA11 in tumor and other organs (see title). Biodistribution studies revealed that the PC3-PIP tumor uptake of mice injected with 100 µCi of [68Ga]-DP at a specific activity of 180, 50, 11 mCi/µmol were 10.41±1.16, 8.08±0.93, and 9.61±2.87 %ID/g, respectively. The corresponding kidney uptake values were 90.52±19.98, 48.08±10.17, and 16.39±5.40 %ID/g, respectively. A more than 16-fold decrease of specific activity had not significant effect on tumor uptake of [68Ga]-DP11. The drastic decrease of renal uptake with decreasing specific activity is probably due to saturation of binding sites in well perfused kidneys whereas tumor uptake appears limited by delivery of [68Ga]DP11. Administering a larger mass may therefore decrease renal toxicity of PSMA targeted radionuclide therapy.
Pillarsetty et al. do not teach in instant method of imaging PSMA positive tumors or cells wherein the non-radiolabeled PSMA competing inhibitor is YC-I-27 wherein X=I optionally wherein the radiolabeled PSMA inhibitor is [131/125I]YC-I-27 or optionally wherein the radiolabeled PSMA inhibitor comprises 211Ator the claimed pharmaceutical composition and kit wherein the non-radiolabeled PSMA inhibitor is YC-I-27 wherein X=I. Pillarsetty et al. do not further teach that the PSMA positive tumor is a primary clear cell renal carcinoma.
Pomper et al. teach as discussed above.
Pomper et al. II teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to the method and composition of Pillarsetty et al. (method and composition for imaging PSMA positive tumors wherein the method comprises administering to a subject a radiolabeled PSMA inhibitor ([68Ga]-DKFZ-PSMA11) in an amount suitable for imaging a PSMA positive tumor in combination with a non-radiolabeled PSMA inhibitor (DKFZ-PSMA11) in an amount suitable for reducing the uptake of the radiolabeled PSMA inhibitor in a non-target organ such as the kidneys compared to uptake of the radiolabeled PSMA inhibitor in the one or more non-target organs when the radiolabeled PSMA inhibitor is administered without the non-radiolabeled PSMA competing inhibitor wherein the PSMA positive tumor or cell is a prostate tumor or cell wherein the radiolabeled PSMA inhibitor and non-radiolabeled PSMA inhibitor are administered at the same time and wherein the method reduces the side effect of renal toxicity) so that competing non-radiolabeled PSMA inhibitor used in the method and composition is YC-I-27 where X=I and optionally so that the radiolabeled PSMA inhibitor is [125I]YC-I-27 or [131I]YC-I-27 and optionally so that imaging is PET or SPECT imaging as taught by Pomper et al. because the use of YC-I-27 as a competing none radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theragnostic SPECT imaging and radiotherapy of PSMA positive tumors and because the PET or SPECT imaging would have been expected to provide non-invasive in vivo imaging and localization of tumor tissue. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Pillarsetty et al. by further forming a kit comprising the obvious radiolabeled PSMA inhibitor and non-radiolabeld competing inhibitor as taught by Pomper et al. the kit would have been expected to enable facile distribution and assembly of the obvious composition. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Pillarsetty et al. so that the radiolabeled PSMA inhibitor comprises 211At as taught by Pomper et al. because the 211At would have been expected to advantageously enable radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Pillarsetty et al. so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Claim(s) 1-2, 16-21, and 23-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pomper et al. (WO 2019/157037 A1; published 15 Aug. 2019; see IDS filed on 7 Mar. 2022; “Pomper et al. III”), in view of Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), and Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”).
Pomper et al. III teach as discussed above. Pomper et al. III teach PSMA targeted radiohalogenated urea-polyaminocarboxylates for cancer radiotherapy (see title). Pomper et al. III teach a kit for treating one or more PSMA tumors or cells wherein the kit comprises a compound of formula (I) and further comprises a blocking agent (pg. 5). Pomper et al. III teach that astatine-211 has attractive properties for radiopharmaceutical therapy (pg. 7). Pomper et al. III teach prostate tumor or cell (pg. 19). Pomper et al. III teach that the blocking agent YC-I -27
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wherein X is halogen, including iodine (pg. 20). In some embodiments, the blocking agent is administered at the same time (pg. 21). Co-injection of a small amount of non-radioactive urea or -DOTA compound with [125I/211At]VK-02-90-Lu further reduces the uptake of radioactivity in the kidneys and lacrimal glands which are problematic normal organs for radiopharmaceutical therapy (pg. 47). Pomper et al. III teach biodistribution experiments with [125I]VK-02-90-Lu and [211At]VK-02-90-Lu administered to athymic mice bearing PSMA+PC3-PIP ad PSMA-PC3-flu flank xenografts with and without the YC-I-27 blocking agent at dose of 0.5, 1.0, and 5 nmol (see example 4; tables 2-8).
Pomper et al. III do not expressly teach the claimed method, composition and kit for imaging and treatment of PSMA positive tumor or cell such as prostate tumor or cells comprising the non-radiolabeled PSMA competing inhibitor that is the YC-I-27 having an X= I and optionally wherein the method comprising taking an image such as a PET or SPECT image. Pomper et al. do not further teach that the PSMA positive tumor is primary clear cell renal carcinoma.
Pomper et al. teach as discussed above.
Pomper et al. II teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Pomper et al. III (method, composition and kit for imaging a PSMA positive tumor or cell comprising radiolabeled PSMA imaging including [125I]VK-02-90-Lu and [211At]VK-02-90-Lu and the YC-I-27 blocking agent at the same time) so that the non-radiolabeled competing PSMA inhibitor is YC-I-27 wherein X=I and optionally so that the radiolabeled PSMA inhibitor is [125/131I]YC-I-27 as taught by Pomper et al. because the YC-I-27 wherein X= I is a competing non-radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theragnostic SPECT imaging and radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Pomper et al. III so that the method further comprises taking an image such as a PET or SPECT image or further comprises reducing the renal toxicity as taught by Pomper et al. III and Pomper et al. because the PET or SPECT imaging would have been expected to enable in vivo localization of the PSMA expressing tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-20 of U.S. Patent No. 12,2332,137 B1 so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Applicants Arguments
Applicants refer to the Dr. Mease declaration. As provided on page 30 of the application as originally filed YC-I-27 demonstrated high uptake and retention in kidneys and was chosen as an initial competing PSMA binding agent to reduce the renal uptake of radiolabeled PSMA inhibitors. Fig. 2 of the application demonstrates that co-injection of YC-I-27 selectively blocks the kidney uptake of a different PSMA binding radioligand, e.g. [125I]VK-02-90-Lu at an early time point. The inventors unexpectedly found that YC-I-27 had relatively little or no reduction of uptake in the salivary gland. Coadministration of different PSMA of a different inhibitor, e.g. cold VK-02-90 resulted in a significant reduction in uptake of [125I]VK-02-90-Lu in the salivary gland. This demonstrates the unpredictability of selecting a cold blocking agent for reducing uptake in non-target organs. Neither Pomper nor Pillarsety teach the use of YC-I-27 for reducing uptake of a radiolabeled PSMA inhibitor in a kidney of a subject when imaging a PSMA positive tumor or treating a disease associated with PSMA. At [0077], Pomper merely mentions that the imaging method further disclosed therein is suitable for imaging studies of PSMA inhibitors by studying competitive binding of non-radiolabeled inhibitors. Pillarsetty showed that a decrease of specific activity had no significant effect on tumor uptake of the 68Ga imaging agent and tha a decrease of renal uptake with decreasing specific activity is probably due to saturation of binding sites in the kidneys.
Applicant's arguments filed 2 Mar. 2026 have been fully considered but they are not persuasive. The Dr. Mease declaration was found ineffective for the reasons discussed above. At example 4, Pomper III anticipates the claimed invention.
In addition, Pomper ‘933 teaches that YC-I-27 exhibits high uptake and retention in the kidneys due specific binding to PSMA binding sites. Accordingly, a person of ordinary skill in the art would have known before the effective filing date that the YC-I-27 wherein X=I is a suitable non-radiolabeled PSMA competing inhibitor for blocking kidney PSMA binding sites. Wurzer teaches a method and compositions that combines radiolabeled PSMA inhibitors with non-radiolabeled PSMA competing inhibitors in an amount suitable for reducing the uptake of the radiolabeled PSMA inhibitor in the kidneys to provide beneficial tumor to kidney ratios and reduced renal toxicity. 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 modify Wurzer so that the compositions and methods use YC-I-27 wherein X=I as the non-radiolabeled PSMA competing inhibitor because the YC-I-27 wherein X=I would have been expected to advantageously enable specific binding to the kidney PSMA binding sites over a prolonged period time whereby reducing renal toxicity and providing beneficial tumor to kidney ratios.
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).
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Claims 1-2, 16-21, and 23-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,2332,137 B1, in view of Pillarsetty et al. (J. Nucl. Med; published 2016), Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), and Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”).
Claims 1-20 of U.S. Patent No. 12,2332,137 B1 claim compounds of formula
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and claim methods for treating one or more PSMA expressing tumors or cells, the methods comprising administering or contacting one or more PSMA expressing tumors or cells with an effective amount of a compound of claim 1 wherein the PSMA expressing tumor or cell is a prostate tumor or cell wherein the method further comprises administering a blocking agent in combination with the compound of formula (I) wherein the blocking agent reduces accumulation of the compound of formula (I) in one more PSMA expressing cells wherein the off target organ is the kidney wherein the blocking agent is YC-I-27 wherein X is a halogen and kit further comprising the blocking agent and wherein the radiolabeled PSMA inhibitor comprises 211At.
Claims 1-20 of U.S. Patent No. 12,2332,137 B1 do not claim the instant method, composition and kit wherein the non-radiolabeled PSMA competing inhibitor is YC-I-27 wherein X =I and optionally is combined at the same time and optionally wherein the radiolabeled PSMA inhibitor is [131/125I]YC-I-27 and optionally wherein the PSMA positive tumor or cell is a primary clear cell renal carcinoma optionally wherein the method comprising taking an imaging optionally by PET or SPECT and optionally reduces one or more side effects of renal toxicity.
Pillarsetty et al. teach as discussed above.
Pomper et al. teach as discussed above.
Pomper et al. II teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-20 of U.S. Patent No. 12,2332,137 B1 so that the non-radiolabeled competing PSMA inhibitor is YC-I-27 wherein X=I and optionally so that the radiolabeled PSMA inhibitor is [125/131I]YC-I-27 as taught by Pomper et al. because the YC-I-27 wherein X= I is a competing non-radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theranostic SPECT imaging and radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-20 of U.S. Patent No. 12,2332,137 B1 so that the method further comprises taking an image such as a PET or SPECT image or further comprises reducing the renal toxicity as taught by Pillarsetty et al. and Pomper et al. because the PET or SPECT imaging would have been expected to enable in vivo localization of the PSMA expressing tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-20 of U.S. Patent No. 12,2332,137 B1 so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Claims 1-2, 16-21, and 23-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11,813,340 B2, in view of Pillarsetty et al. (J. Nucl. Med; published 2016), Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), and Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”).
Claims 1-31 of U.S. Patent No. 11,813,340 B2 claim compounds of formula (I) such as
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optionally wherein X is 211At and methods for treating one or more PSMA expressing tumors are cells such as a prostate tumor or cell, the method comprising administering or contacting one or more PSMA expressing tumors or cells with an effective amount of a compound of claim 1 wherein the method further comprises administering a blocking agent with the compound of formula (I) wherein the blocking agent reduces accumulation of the compound of formula (I) in one or more PSMA expressing cells in an off target organ such as the kidney or salivary gland wherein the PSMA blocking agent is YC-I-27 wherein X is halogen and a kit further comprising the blocking agent and method for imaging one or more PSMA tumors or cells.
Claims 1-31 of U.S. Patent No. 11,813,340 B2 do not claim the instant method, composition and kit wherein the non-radiolabeled PSMA competing inhibitor is YC-I-27 wherein X =I and optionally is combined at the same time and optionally wherein the radiolabeled PSMA inhibitor is [131/125I]YC-I-27 and optionally wherein the PSMA positive tumor or cell is a primary clear cell renal carcinoma optionally wherein the method comprising taking an imaging optionally by PET or SPECT and optionally reduces one or more side effects of renal toxicity.
Pillarsetty et al. teach as discussed above.
Pomper et al. teach as discussed above.
Pomper et al. II teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-31 of U.S. Patent No. 11,813,340 B2 so that the non-radiolabeled competing PSMA inhibitor is YC-I-27 wherein X=I and optionally so that the radiolabeled PSMA inhibitor is [125/131I]YC-I-27 as taught by Pomper et al. because the YC-I-27 wherein X= I is a competing non-radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theranostic SPECT imaging and radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-31 of U.S. Patent No. 11,813,340 B2 so that the method further comprises taking an image such as a PET or SPECT image or further comprises reducing the renal toxicity as taught by Pillarsetty et al. and Pomper et al. because the PET or SPECT imaging would have been expected to enable in vivo localization of the PSMA expressing tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-31 of U.S. Patent No. 11,813,340 B2 so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Claims 1-2, 16-21, and 23-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839, in view of Pillarsetty et al. (J. Nucl. Med; published 2016), Pomper et al. (WO 2010/014933 A2; published 4 Feb. 2010; see attached 892), and Pomper et al. (WO 2010/108125 A1; published 23 Sep. 2010: “Pomper et al. II”). This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839 claim compounds of formula (I) wherein X is 211At and a method for treating one or more PSMA expressing tumors or cells such as prostate tumor or cell.s, the method comprising contacting the one or more PSMA expressing tumors or cells with an effective amount of the compound wherein the method further comprises administering a blocking agent such as a PSMA based blocking agent in combination with the compound of formula (I) wherein the blocking agent reduces accumulation of the compound of formula (I) in one or more PSMA expressing cells in an off target organ such as kidney.
Claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839 do not claim the instant method, kit, and composition wherein the non-radiolabeled PSMA competing inhibitor is YC-I-27 wherein X =I and optionally is combined at the same time and optionally wherein the radiolabeled PSMA inhibitor is [131/125I]YC-I-27 and optionally wherein the PSMA positive tumor or cell is a primary clear cell renal carcinoma optionally wherein the method comprising taking an imaging optionally by PET or SPECT and optionally reduces one or more side effects of renal toxicity.
Pillarsetty et al. teach as discussed above.
Pomper et al. teach as discussed above.
Pomper et al. II teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839 so that the non-radiolabeled competing PSMA inhibitor is YC-I-27 wherein X=I and optionally so that the radiolabeled PSMA inhibitor is [125/131I]YC-I-27 as taught by Pomper et al. because the YC-I-27 wherein X= I is a competing non-radiolabeled PSMA inhibitor would have been expected to advantageously provide saturation of the PMSA binding sites of the kidneys over a prolonged period of time whereby enabling reduced renal toxicity along with high tumor kidney ratios and because the [125I]YC-I-27 and [131I]YC-I-27 would have been expected to provide theranostic SPECT imaging and radiotherapy of PSMA positive tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839 so that the method further comprises taking an image such as a PET or SPECT image or further comprises reducing the renal toxicity as taught by Pillarsetty et al. and Pomper et al. because the PET or SPECT imaging would have been expected to enable in vivo localization of the PSMA expressing tumors. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-3, 5-7, 9, 15-19, 21-23, 25-26, 33-34, and 37 of copending Application No. 18/966,839 so that the PSMA positive tumor is a primary clear cell renal carcinoma as taught by Pomper et al. II because it would have been expected to advantageously enable detection and eradication of clear cell renal carcinoma expressing PSMA.
Conclusion
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/SEAN R. DONOHUE/
Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618