DETAILED ACTION
Notice of Pre-AIA or AIA Status
This Office action details a first action on the merits for the above referenced application No. Claims 1-19 are pending in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/31/2025, 08/04/2025, 09/16/2025, 09/18/2025, 10/29/2025 and 12/05/2025 was noted and the submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 06/18/2025. These drawings are acknowledged.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 9, 10, and 12-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carolyn Anderson et al. (Method in Enzymology, 386, 237-261, 2004).
Anderson discloses a review of copper radio-nuclide production and copper radiopharmaceutical development for PET imaging and targeted radiotherapy (abstract). Anderson discloses that copper-64 can be effectively produced by both reactor-based and accelerator-based methods. For producing high-specific activity 64Cu, fast neutrons are used to bombard the target in a (n, p) reaction. In one embodiment, discloses that cyclotron production of ⁶⁴Cu has the advantage of being very economical and allows for production of very large amount >3 Ci of reasonably high-specific activity material 860 Ci/mmol (page 240). After bombardment, the 64Cu is separated from the target nickel in a one-step procedure using 0.5 N HCl solution (page 242). Anderson discloses that longer-lived copper radionuclides, such as 64Cu and 67Cu have been utilized for development of copper-labeled biologic molecules, for tumor targeting using monoclonal antibodies, peptides, biomolecules. The radiometal is connected to these targeting molecules via a bifunctional chelator (BFC)(DOTA), which consists of a chelator to complex the radiometal and a functional group for attachment to the targeting molecule (page 245 and Fig 3-5). The radiolabeling was complete within 90 sec at 99.7% radiochemical purity (page 252). Additional disclosure includes that utilizing the cyclotron conditions described earlier, the yields of ⁶⁴Cu are dependent on the amount of ⁶⁴Ni on the target and the length of the bombardment. The specific activity of the ⁶⁴Cu ranges from 47.4 to 474 GBq/umol (1280 to 12,800 mCi/umol). The interest in copper radionuclides for PET imaging and targeted radiotherapy of cancer, particularly the use of 64Cu, is increasing. Copper -64 has attractive decay properties for PET imaging and therapy, and can be used in a wide variety of applications.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Welch et al. (US 6011,825) in view of Carolyn Anderson et al. (Methods in Enzymology, 386, 237-261, 2004), Mushtaq et al. (J Radioanal Nucl Chem, 284, 265-271, 2010), Gaehle Gregory et al., (Washington University in St. Louis, Oct 22, 2019) and Miguel A. Avila-Rodriguez et al., (Applied Radiation and Isotopes, 65, 1115-1120, 2007).
Welch discloses production of radionuclides suitable for use in radio-diagnostic agents such as PET imaging agents and radiotherapeutic agents and/or compositions. In a preferred application, a biomedical cyclotron has been used to produce over 500 mCi of Cu having a specific activity of over 300 mCi/mu of Cu (abstract). Welch discloses that the amount of ⁶⁴Cu required for imaging agents ranges from about 3 mCi to about 10 mCi when administered, and therefore, the amount of ⁶⁴Cu produced for preparing the compositions is preferably ranges from at least about 10 mCi to at least about 30 mCi (Col 13 line 10-15). In one embodiment discloses that the radionuclidic purity of the accelerator produced ⁶⁴Cu is dependent upon the isotopic composition of the target material and the energy of the charged-particle beam. An irradiation time of 4 hours produces about 20% of the saturation yield. In a preferred method, the beam energy is at least about 5 MeV and the beam currents are sufficient to produce at least about 10 mCi of ⁶⁴Cu and more preferably sufficient to produce at least about 100 mCi of ⁶⁴Cu within about 36 hours (Col. 13 line 55+). Additionally, compounds which can be radiolabeled with ⁶⁴Cu includes lipophilic copper chelates, monoclonal antibodies and antibody fragments and small peptides that can be used in both diagnosis and therapy. For example, discloses the preparation of ⁶⁴Cu-labeled TETA-octreotide radiolabeled compounds using 64CuCl. The specific activity and radio-chemical purity of several preparations of ⁶⁴Cu-labeled TETA-octreotide ranges from >90% to 100% (Col. 27 and
Table 7).
Welch fails to disclose composition comprising from about 4 Ci to about 50 Ci of 64-Cu, and bifunctional chelating agent DOTA.
Anderson discloses a review of copper radio-nuclide production and copper radiopharmaceutical development for PET imaging and targeted radiotherapy (abstract). Anderson discloses that copper-64 can be effectively produced by both reactor-based and accelerator-based methods. For producing high-specific activity ⁶⁴Cu, fast neutrons are used to bombard the target in a (n, p) reaction. In one embodiment, discloses that cyclotron production of ⁶⁴Cu has the advantage of being very economical and allows for production of very large amount >3 Ci of reasonably high-specific activity material 860 Ci/mmol (page 240). Anderson discloses that longer-lived copper radionuclides, such as 64Cu and 67Cu have been utilized for development of copper-labeled biologic molecules, for tumor targeting using monoclonal antibodies, peptides, biomolecules. The radiometal is connected to these targeting molecules via a bifunctional chelator (BFC)(DOTA), which consists of a chelator to complex the radiometal and a functional group for attachment to the targeting molecule (page 245 and Fig 3-5). Additional disclosure includes that utilizing the cyclotron conditions described earlier, the yields of ⁶⁴Cu are dependent on the amount of ⁶⁴Ni on the target and the length of the bombardment. The specific activity of the ⁶⁴Cu ranges from 47.4 to 474 GBq/umol (1280 to 12,800 mCi/umol).
Mushtaq discloses production of low and high specific activity 64Cu by irradiating natural copper and zinc in reactor (abstract). Mushtaq discloses that maximum activity of 64Cu was produced by 63Cu (n,y) 64Cu reaction and after one day irradiation 89Ci (3293 GBq) of 64Cu is obtained (page 268). The activity of 64 can be further slightly increased with the increase of irradiation time (Fig 2). Table 2 and 3 discloses the nuclear reaction cross sections leading to production of 64 Cu and radionuclidic impurities including 67Cu and 68Zn. The specific activity of 64Cu is 3.83 X 10 mCi/mg. Additional disclosure includes that the specific activity of 64Cu can be increased by irradiating enriched 63Cu in high neutron flux.
Gregory discloses an efficient high yielding Cu-64 manufacturing process to produce Cu-64 in high yields of > 7.5 Ci reliably with the specific activity expected to routinely exceed 300 mCi/ug (abstract).
Avila-Rodriguez discloses simultaneous production of high specific activity ⁶⁴Cu with 11.4 MeV protons on enriched ⁶⁴Ni nuclei (abstract). In one experiment, a thin-target irradiated for 8h at 30uUA yielded ~1Ci of ⁶⁴Cu, while a thick target reached the Ci level in 4.5h of bombardment and a total activity >13 Ci of ⁶⁴Cu was produced in over 60 production runs, sufficient to satisfy local demand and distribution to external users (page 1118, 3.4 Experimental target yields). In Table 2 shows the relative quantities of radionuclidic impurities associated with the production ⁶⁴Cu and a radionuclidic purity
>99% for ⁶⁴Cu at the time of their application, as confirmed by Y-ray spectroscopy and half-life measurement (page 1119). Additional disclosure includes that the large population of biomedical (10<Ep<18) cyclotrons evenly distributed in the US, and the high target yields in the production of 64Cu achieved at these energies, forms a potential network of distribution of 64Cu to satisfy the growing demand of this radionuclide.
In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) ("mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled." 531 F.2d at 1053, 189 USPQ at 148.). (See MPEP 2144.) In the instant case the prior art already suggests scaling up the production of 64Cu to greater than 3 Ci. Thus, the scaling up of such a process and the resulting large quantities of product produced by such a scale up still appears to be obvious in view of the prior art of record.
It would have been prima facie obvious to scale up the production of Cu and generate a composition comprising high specific activity and radionuclidic purity by routine experimentation. There appears to be no criticality in obtaining high specific activity and radionuclidic purity of ⁶⁴Cu, since the prior art recognizes and obtains the desired quantities or amounts and radioactivity. Further, Avila-Rodriguez teaches that the production of the 64Cu radionuclide in a small biomedical cyclotron with 11.4 MeV protons has proven to be very efficient with an experimental thick target saturation yield of 159 mCi/UA (96% enrichment) and specific activity as high as 25 Ci/umol (page 1120). One having ordinary skill in the art would have been motivated to do this because the references demonstrate how to obtain sufficient quantities of radionulclides by irradiating for a period of time with sufficient beam energy.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,521,762, over claims 1-21 of U.S. Patent No. 11,581,103, over claims 1-15 of U.S. Patent No. 11,798,701, over claims 1, 10, 11, 21 and 28 of U.S. Patent No. 11,972,874, over claims 1, 2, 11, 18, 19 and 29-30 of U.S. Patent No. 11,978,569, over claims 1-8 and 13-27 of U.S. Patent No. 12,237,092, over claims 1-25 of U.S. Patent No. 12,148,542, over claims 1-27 of U.S. Patent No. 12,288,627, over claims 1-20 and 25-30 of U.S. Patent No. 12,315,649, over claims 1-30
of U.S. Patent No. 12,462,943. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined claim is either anticipated, 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). Although the conflicting claims are not identical, they are not patentably distinct from each other because both the issued claims and the examined claims teach compositions containing from about 2 Ci to 15 Ci of copper-64 (64Cu)and the radionuclidic purity of the 64Cu is greater than 99%. Thus, the claims are readily envisaged by the teaching of the prior art and the claims are properly included in the rejection.
Claims 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of Copending application No. 19/195,850, over claims 1-4, 6-13, 15-21 and 23-25 of Copending Application No. 18/733,537, over claims 1-29 of Copending Application No. 18/745,925 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the Copending application claims and the examined claims teach compositions containing from about 2 Ci to 15 Ci of copper-64 (64Cu), specific activity from about 100 mCi ⁶⁴Cu/ugCu to about 3800 mCi ⁶⁴Cu/ugCu and the radionuclidic purity of the 64Cu is greater than 95%. Thus, the claims are readily envisaged by the teaching of the prior art and the claims are properly included in the rejection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
It is respectfully requested to applicant to file all appropriate terminal disclaimers including any that applicant is aware and have not been listed in this office action.
Conclusion
No claims are allowed at this time.
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/J.R.S/ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618