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
Applicant's election with traverse of group I in the reply filed on 8/12/25 is acknowledged. The traversal is on the ground(s) that a search for a process of manufacturing a pharmaceutical aqueous solution of group I would be expected to uncover art relevant to groups II and III and a search for relevant art and subsequent examination would not be an undue burden. This is not found persuasive because the process as claimed can be used to make another and materially different product. The pharmaceutical aqueous solution(s) prepared via the process of manufacturing yields different 177Lu-DOTA-TATE or 177Lu-DOTA-TOC complexes wherein TATE and TOC are different peptides. The pharmaceutical aqueous solution(s) have the range of volumetric radioactivity of 250 MBq/mL to 500 MBq/mL and prepared via the process of manufacturing comprises a combination of different stabilizers in various concentrations to prevent radiolysis. The amount of stabilizer necessary to prevent radiolysis depends on the specific complex, specific volumetric radioactivity and the specific stabilizers.
The pharmaceutical aqueous solution prepared via the process of manufacturing can be used in materially different processes, such as radiotherapy and/or SPECT imaging.
The process of manufacturing and the method of treating a tumor have different designs and modes of operation.
The requirement is still deemed proper and is therefore made FINAL.
Claims 29-51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups, there being no allowable generic or linking claim. Applicant timely
traversed the restriction (election) requirement in the reply filed on 8/12/25.
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) 22-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mathur et al. (Cancer Biother. Radiopharm. 2017, 32, 266-273) in view of Chen et al. (US2007/0269375A1) and in further view of De Jong et al. (Int. J. Cancer: 92, 628-633 (2001)).
Mathur et al. (Cancer Biother. Radiopharm. 2017, 32, 266-273) discloses a bulk scale “ready-to-use” 177Lu-DOTA-TATE formulation that is safe for human use for more than 1 week (radiochemical purity [Symbol font/0x3E]98%) (abstract).
The 177Lu-DOTA-TATE encompasses the 177Lu-DOTA-TATE of the instant claims.
The protocol for synthesis comprises direct heating of 177LuCl3 with DOTA-TATE solution (0.25 mL) in ammonium acetate buffer (2.2 mL) containing gentisic acid (33 mg) (p267, Synthesis).
The gentisic acid encompasses the at least one first stabilizer against radiolytic degradation of the instant claims.
The reaction mixture was loaded onto a Sep-Pak® C18 cartridge to remove unreacted free 177Lu
and the column washed with 0.6 mL ethanol (p267, Synthesis).
The 177Lu-DOTA-TATE product was diluted with acetate buffer containing gentisic acid (1.5% w/v ≈ 15 mg/mL) to final radioactive concentration of 740 MBq/mL (ethanol content <10%)(abstract; p267, Synthesis).
The acetate buffer containing gentisic acid 1.5% w/v encompasses the at least one second stabilizer against radiolytic degradation of the instant claims.
The radiochemical purity was [Symbol font/0x3E]97.0 ± 0.5% 3 days post formulation at room temperature (Table 3) that encompasses the radiochemical purity of ≥ 95% for at least 72 h when stored at about 25[Symbol font/0xB0]C of the instant claims.
Mathur et al. does not explicitly disclose that the first stabilizer gentisic acid is present in a total amount to result in a concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution or a ratio of the concentration of the first:second stabilizers is 1:3 to 1:5 in the pharmaceutical aqueous solution.
Chen et al. (US2007/0269375A1) discloses stabilized radiopharmaceutical formulations, for imaging and radiotherapy, using stabilizers that improve the radiostability of radiotherapeutic and radiodiagnostic compounds (abstract; p11, [0137]; p12, [0143]). Radioisotopes cause radiolytic damage to the radiolabeled compound and can cause serious problems during preparation because of the destructive properties of the emissions (p1, [0015-0016]).
The design of a successful radiotherapeutic involves several critical factors: (p12, [0144-0149])
1. selection of an appropriate targeting group to deliver the radioactivity to the disease site;
2. selection of an appropriate radionuclide that releases sufficient energy to damage that disease site, without substantially damaging adjacent normal tissues;
3. selection of an appropriate combination of the targeting group and the radionuclide without adversely affecting the ability of this conjugate to localize at the disease site. For radiometals this often involves a chelating group that coordinates tightly lo the radionuclide, combined with a linker that couples said chelate to the targeting group, and that affects the overall biodistribution of the compound to maximize uptake in target tissues and minimize uptake in normal, non-target organs; and
4. selection of appropriate radiostabilizers, such that once formed, the radiotherapeutic compound does not undergo significant radiolytic decomposition prior to administration.
The stabilized radiopharmaceuticals comprising a radiometal (e.g. 177Lu, etc.); metal chelator (e.g. DTPA, DOTA, etc.) and targeting peptides, such as analogues of somatostatin (e.g. TOC) (abstract; p4, [0049],[0051]; p5, [0052]; p6,[0056],[0058]; p9, [0119-0120]; p13, [0155],[0164]).
For, 177Lu-labelled complexes, the unit dose typically ranges from about 10 mCi to about 200 mCi (p11, [0140]).
The stabilizers include gentisic acid, ascorbic acid, methionine, benzyl alcohol, etc. and mixtures thereof (p2-3, [0020],[0026]; p3, [0035]; p13-14, [0163]). The concentration of gentisic acid included in stabilized radiopharmaceutical formulations comprises 2-20 mg/ml and the concentration of ascorbic acid included in stabilized radiopharmaceutical formulations comprises 10-100 mg/ml (p13, [0166]; table 2).
A highly preferably method is to add different potential stabilizers directly to the reaction mixture during chelation (p19, [0209]).
In another approach, the stabilizers can either be added directly into reaction mixtures during radiolabeled complex preparation or added after complexation is complete, or both (p3, [0030]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the first stabilizer gentisic acid present of Mathur et al. may result in a total concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution as the specification states that the concentration of stabilizers present during complex formation is from 15 to 50 mg/mL to yield a total concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution which encompasses the 33 mg of Mathur et al. Also, Chen et al. teaches that the amount of gentisic acid and/or ascorbic acid used during complexation and after complexation comprise 2-20 mg/ml and 10-100 mg/ml, respectively.
Therefore, it would have been predictable to one of ordinary skill in the art to include a stabilizer in the 177Lu and DOTA-TATE reaction solution in a concentration effective to minimize and/or prevent radiolysis during complexation, as envisioned by Mathur et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to vary and/or optimize the amount of the second stabilizer(s) (e.g. 2-20 mg/ml gentisic acid, 10-100 mg/ml ascorbic acid) provided in the pharmaceutical aqueous solution, according to the guidance provided by Chen et al. as adding an effective amount of stabilizer during complexation and after complexation provides a composition having the desired properties such as the necessary protection against radiolytic damage and further maintain radiochemical purity of [Symbol font/0x3E]97.0 ± 0.5% 3 days post formulation at room temperature for transport and/or storage. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Mathur et al. does not explicitly disclose less than 5% ethanol, less than 2% ethanol, less than 1% ethanol or free of ethanol.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the 177Lu-DOTA-TATE of Mathur et al. will have less than 5% ethanol as the 0.6mL of ethanol present in a 177Lu-DOTA-TATE solution comprising a volume of at least 9.05-11.05 mL yields 6.63%-5.43% ethanol prior to dilution of the 177Lu-DOTA-TATE solution with acetate buffer containing gentisic acid (1.5% w/v). Therefore, it would have been predictable to one of ordinary skill in the art that the dilution of the 177Lu-DOTA-TATE solution may comprise 4.8% ethanol when diluted to a final 12.5 mL volume yielding the 7.4GBq dose or as low as 4% ethanol if the 177Lu-DOTA-TATE solution is diluted to 15 mL in the 15 mL vial.
Also, Chen et al. teaches that the addition of stabilizers or mixtures thereof during the
complexation reaction and/or after complexation does not necessarily require the addition of ethanol and therefore, pharmaceutical aqueous solution may comprise less than 2% ethanol, less than 1% ethanol or is free of ethanol.
Mathur et al. does not disclose 250-500MBq/mL.
De Jong et al. (Int. J. Cancer: 92, 628-633 (2001)) discloses a 177Lu-DOTA-TATE complex for radionuclide therapy. The treatment of CA20948 tumors in rats comprises the administration of 2 doses of 277.5 MBq 177Lu-DOTA-TATE or a single dose of 555 MBq 177Lu-DOTA-TATE (abstract; p629, Radionuclide therapy experiments using [177Lu-DOTA0,Tyr3]octreotate; p630, In vivo radionuclide therapy experiments using 177Lu-labeled somatostatin analogs).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to examine different doses of 177Lu-DOTA-TATE administered to a subject to determine the most effective dose for radionuclide therapy and it would have been predictable that the dilution of the 177Lu-DOTA-TATE complex solution of Mathur et al. allows for the varying and/or procedural optimizing of the volumetric radioactivity to 250-500 MBq/mL.
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 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,596,276B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of US 10,596,276B2 comprises an aqueous complex solution of 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least a first stabilizer that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The 177Lu and DOTA-somatostatin of US 10,596,276B2 comprises DOTA-TATE or DOTA-TOC that encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The process for manufacturing a pharmaceutical aqueous solution of US 10,596,276B2 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution of US 10,596,276B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 10,596,276B2 comprise ascorbic
acid and gentisic acid that encompass the ascorbic acid and gentisic acid of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 10,596,276B2 are present in a total
concentration of from 1.0 to 5.0 mg/mL that encompass the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in a total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 1.0 to 5.0 mg/mL of US 10,596,276B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of US 10,596,276B2 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of US 10,596,276B2 comprises less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 10,596,276B2 has a radiochemical purity that is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The pharmaceutical aqueous solution prepared by the process of US 10,596,276B2 encompasses the pharmaceutical aqueous solution prepared by the process of the instant claims.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. US 10,596,278B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical aqueous solution of US 10,596,278B2 comprises a complex formed by 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least two different stabilizers, such as ascorbic acid and gentisic acid that encompasses the pharmaceutical aqueous solution prepared by the process for manufacturing of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the
pharmaceutical aqueous solution.
The 177Lu and DOTA-somatostatin of US 10,596,278B2 comprises DOTA-TATE or DOTA-TOC that
encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The ascorbic acid and gentisic acid of US 10,596,278B2 encompass the ascorbic acid and gentisic acid of the instant claims.
The pharmaceutical aqueous solution of US 10,596,278B2 has a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the volumetric radioactivity of from 250 to 500 MBq/mL of the pharmaceutical aqueous solution of the instant claims.
The pharmaceutical aqueous solution of US 10,596,278B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The at least two different stabilizers of the pharmaceutical aqueous solution of US 10,596,278B2 are present in a total concentration of from 1.0 to 5.0 mg/mL that encompass the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 1.0 to 5.0 mg/mL of US 10,596,278B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of US 10,596,278B2 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of US 10,596,278B2 comprises less than 1% ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 10,596,278B2 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of
the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The pharmaceutical aqueous solution prepared by the process of US 10,596,278B2 encompasses
the pharmaceutical aqueous solution prepared by the process of the instant claims.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,904,027B2. Although the claims at issue are not
identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of US 11,904,027B2 comprises an aqueous complex solution of 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least a first stabilizer present in the total amount of 0.5 to 2 mg/mL that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The 177Lu and DOTA-somatostatin of US 11,904,027B2 comprises DOTA-TATE or DOTA-TOC that encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The process for manufacturing a pharmaceutical aqueous solution of US 11,904,027B2 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution of US 11,904,027B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 11,904,027B2 comprise gentisic
acid and ascorbic acid that encompasses the gentisic acid and ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of US 11,904,027B2 comprises DTPA that encompasses
the DTPA of the instant claims.
The ratio of the first stabilizer to the second stabilizer of the pharmaceutical aqueous solution of US 11,904,027B2 is 1:3 to 1:7 that encompasses the ratio of 1:3 to 1:5 of the first stabilizer to the second
stabilizer of the pharmaceutical aqueous solution of the instant claims.
The pharmaceutical aqueous solution of US 11,904,027B2 comprises less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 11,904,027B2 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The pharmaceutical aqueous solution prepared by the process of US 11,904,027B2 encompasses the pharmaceutical aqueous solution prepared by the process of the instant claims.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. US 12,144,873B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of treating a tumor and of treating gastroenteropancreatic neuroendocrine of US 12,144,873B2 comprises the administration of a pharmaceutical aqueous solution comprising a complex of 177Lu and DOTA-somatostatin receptor binding peptide and at least one stabilizer present in a total concentration of 0.5 mg/mL to 10.0 mg/mL that encompasses the pharmaceutical aqueous solution formed by the process for manufacturing of the instant claims comprising 177Lu and DOTA-TATE or DOTA-TOC wherein at least two stabilizers are present in a total concentration from 0.8-30 mg/mL.
The first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.5 to 10 mg/mL and the total concentration range of the summed first:second stabilizers (1:3 to 1:5) is 0.8-30 mg/mL and the total concentration of from 0.5 to 10.0 mg/mL of US 12,144,873B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The 177Lu and DOTA-somatostatin of US 12,144,873B2 comprises DOTA-TATE, DOTA-TOC, etc.
that encompasses the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The pharmaceutical aqueous solution of the methods of treating of US 12,144,873B2 comprises a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 12,144,873B2 comprise ascorbic acid that encompass the ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of US 12,144,873B2 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of US 12,144,873B2 comprises less than 2% ethanol, less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 12,144,873B2 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The pharmaceutical aqueous solution used for the methods of treating of US 12,144,873B2 encompass the pharmaceutical aqueous solution prepared by the process of the instant claims.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,151,003B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical aqueous solution of US 12,151,003B2 comprises a complex formed by 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least one stabilizer, such as ascorbic acid present in a total concentration of 0.5 mg/mL to 10.0 mg/mL that encompasses the pharmaceutical aqueous solution of the instant claims prepared by the process for manufacturing comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The ascorbic acid of US 12,151,003B2 encompasses the ascorbic acid of the instant claims.
The 177Lu and DOTA-somatostatin of US 12,151,003B2 comprises DOTA-TATE or DOTA-TOC that encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The pharmaceutical aqueous solution of US 12,151,003B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The stabilizer of the pharmaceutical aqueous solution of US 12,151,003B2 is present in a total concentration of from 0.5 to 10.0 mg/mL that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.5 to 10.0 mg/mL of US 12,151,003B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of US 12,151,003B2 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of US 12,151,003B2 comprises less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 12,151,003B2 has a radiochemical purity the is
maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of US 12,151,003B2 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,161,732B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of US 12,161,732B2 comprises an aqueous complex solution of 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least one stabilizer that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The 177Lu and DOTA-somatostatin of US 12,161,732B2 comprises DOTA-TATE, DOTA-TOC, etc. that encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The process for manufacturing a pharmaceutical aqueous solution of US 12,161,732B2 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution of US 12,161,732B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The at least one stabilizer of the pharmaceutical aqueous solution of US 12,161,732B2 comprises ascorbic acid that encompass the ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of US 12,161,732B2 comprises DTPA that encompasses the DTPA of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 12,161,732B2 is present in a total concentration of 0.5 to 10.0 mg/mL that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.5 to 10.0 mg/mL of US 12,161,732B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of US 12,161,732B2 comprises less than 2% ethanol, less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 12,161,732B2 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of US 12,161,732B2 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
Claims 22-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 12,168,063B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of US 12,168,063B2 comprises an aqueous complex solution of 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least one stabilizer that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The process for manufacturing a pharmaceutical aqueous solution of US 12,168,063B2 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution of US 12,168,063B2 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The at least one stabilizer of the pharmaceutical aqueous solution of US 12,168,063B2 comprises ascorbic acid that encompass the ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of US 12,168,063B2 comprises DTPA that encompasses the DTPA of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of US 12,168,063B2 are present in a total concentration of from 0.5 to 10.0 mg/mL that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.5 to 10.0 mg/mL of US 12,168,063B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of US 12,168,063B2 comprises less than 1% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 2% ethanol, less than 1% ethanol
or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of US 12,168,063B2 has a radiochemical purity the is
maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of US 12,168,063B2 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
Claims 22-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22,26-28,30,31,34-39 and 45-62 of copending Application No. 18/927,047 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of 18/927,047 comprises an aqueous complex solution of 177Lu and DOTA-TATE in the presence of at least one stabilizer, such as gentisic acid or ascorbic acid in an amount to result in a concentration of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE in the presence of at least a first stabilizer, such as gentisic acid or ascorbic acid in a total amount to result in a concentration of 0.2 to 5 mg/mL.
The process for manufacturing a pharmaceutical aqueous solution of 18/927,047 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The aqueous dilution solution of 18/927,047 comprises at least one stabilizer, such as gentisic
acid or ascorbic acid in an amount to result in a total concentration of 0.5 to 10 mg/mL. The sum of the first and second stabilizer results in a total concentration of 0.7 to 15 mg/mL in the pharmaceutical aqueous solution that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.7 to 15.0 mg/mL of US 12,168,063B2 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of 18/927,047 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The at least one stabilizer of the pharmaceutical aqueous solution of 18/927,047 comprises ascorbic acid that encompass the ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of 18/927,047 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of 18/927,047 comprises less than 5% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 2% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of 18/927,047 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of 18/927,047 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/494,042 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of 18/494,042 comprises an aqueous complex solution of 177Lu and DOTA-somatostatin receptor binding peptide in the presence of at least one stabilizer, such as gentisic acid or ascorbic acid that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer, such as gentisic acid or ascorbic acid in a total amount to result in a concentration of 0.2 to 5 mg/mL.
The 177Lu and DOTA-somatostatin of 18/494,042 comprises DOTA-TATE, DOTA-TOC, etc. that encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The process for manufacturing a pharmaceutical aqueous solution of 18/494,042 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution of 18/494,042 comprises stabilizers in a total concentration of 0.2 to 20 mg/mL that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL that results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.2 to 20.0 mg/mL of 18/494,042 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of 18/494,042 delivers 5.0 to 10 GBq that encompasses
the 7.4 GBq ± 10% of the instant claims.
The at least one stabilizer of the pharmaceutical aqueous solution of 18/494,042 comprises
ascorbic acid that encompass the ascorbic acid of the instant claims.
The pharmaceutical aqueous solution of 18/494,042 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of 18/494,042 may comprise ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 2% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-50 of copending Application No. 19/231,931 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical aqueous solution of 19/231,931 comprises a complex of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least one stabilizer, such as ascorbic acid or gentisic acid present in a total concentration of 0.7 mg/mL to 15.0 mg/mL that encompasses the pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least a first stabilizer that is present in the total amount of 0.2 to 5 mg/mL in the pharmaceutical aqueous solution.
The 177Lu and DOTA-TATE or DOTA-TOC of 19/231,931 encompass the 177Lu and DOTA-TATE or DOTA-TOC of the instant claims.
The pharmaceutical aqueous solution of 19/231,931 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The pharmaceutical aqueous solution of the methods of treating of 19/231,931 comprises a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the volumetric radioactivity of
from 250 to 500 MBq/mL of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of 19/231,931 comprise ascorbic acid and gentisic acid that encompass the ascorbic acid and gentisic acid of the instant claims.
The stabilizers of the pharmaceutical aqueous solution of 19/231,931 is present in a total concentration of from 0.7 to 15.0 mg/mL that encompasses the first stabilizer is present in the pharmaceutical aqueous solution of the instant claims in the total amount of 0.2 to 5 mg/mL and results in a total concentration range of the summed first:second stabilizers (1:3 to 1:5) of 0.8-30 mg/mL. The total concentration of from 0.7 to 15.0 mg/mL of 19/231,931 falls within the total concentration of 0.8-30 mg/mL of the instant claims.
The pharmaceutical aqueous solution of 19/231,931 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of 19/231,931 comprises less than about 5% ethanol that encompasses the less than 5% ethanol, less than 1% ethanol or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of 19/231,931 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of 19/231,931 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-31,34-39,45,46 and 48-59 of copending Application No. 18/927,058 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the process for manufacturing a pharmaceutical aqueous solution of 18/927,058 comprises an aqueous complex solution of 177Lu and DOTA-TATE or DOTA-TOC in the presence of at least one stabilizer, such as gentisic acid or ascorbic acid in an amount to result in a concentration of about 0.5 to about 2 mg/mL in the pharmaceutical aqueous solution that encompasses the process for manufacturing a pharmaceutical aqueous solution of the instant claims comprising an aqueous complex solution of 177Lu and DOTA-TATE in the presence of at least a first stabilizer, such as gentisic acid or ascorbic acid in a total amount to result in a concentration of 0.2 to 5 mg/mL.
The process for manufacturing a pharmaceutical aqueous solution of 18/927,058 comprises the step of diluting the complex solution with an aqueous dilute solution comprising at least one stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL that encompasses the step of diluting the complex solution with an aqueous dilute solution comprising at least one second stabilizer to yield the pharmaceutical aqueous solution with a volumetric radioactivity of from 250 to 500 MBq/mL of the instant claims.
The ratio of the first stabilizer to the second stabilizer of the pharmaceutical aqueous solution of 18/927,058 is 1:3 to 1:7 that encompasses the ratio of 1:3 to 1:5 of the first stabilizer to the second stabilizer of the pharmaceutical aqueous solution of the instant claims
The pharmaceutical aqueous solution of 18/927,058 delivers 7.4 GBq ± 10% that encompasses the 7.4 GBq ± 10% of the instant claims.
The at least one stabilizer of the pharmaceutical aqueous solution of 18/927,058 comprises ascorbic acid or gentisic acid that encompass the ascorbic acid or gentisic acid of the instant claims.
The pharmaceutical aqueous solution of 18/927,058 comprises DTPA that encompasses the DTPA of the instant claims.
The pharmaceutical aqueous solution of 18/927,058 comprises less than about 5% ethanol or is free of ethanol that encompasses the less than 5% ethanol, less than 2% ethanol, less than 1% ethanol
or is free of ethanol of the instant claims.
The pharmaceutical aqueous solution of 18/927,058 has a radiochemical purity the is maintained at ≥95% for at least 72h when stored at 25°C that encompasses the radiochemical purity of the instant claims that is maintained at ≥95% for at least 72h when stored at 25°C.
The method of treating a tumor of 18/927,058 utilizes the pharmaceutical aqueous solution prepared by the method of the instant claims stated above.
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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/MELISSA J PERREIRA/Examiner, Art Unit 1618