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 .
Response to Arguments
Applicant’s arguments, see Pages 2-3, filed 02/10/2026, with respect to the rejection(s) of claims 1-3 and 10-18 under Cvet et al. (US Patent No. 20160303258) in view of Frank et al. (US 20040067924 A1), Imura (US 20220259698 A1) and Roesch (DE 102012019714 A1) as well as the 103 rejections of claims 1-3 and 16 over Imura (US 20220259698 A1) have been fully considered and are persuasive with the amendment of claim 1. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Imura (US 20220259698 A1), Roesch (DE 102012019714 A1) and Frank et al. (US 20040067924 A1).
The teachings of Imura, Roesch and Frank from the previous office action reads to the limitations of amended claim 1 of water-soluble solvent agent and buffering agent.
As to the teachings of Roesch Applicant argues (Page 2) “Roesch teaches the use of ammonium acetate or HEPES as the buffer, which is different from the buffer defined in claim 1 of present application”, and “68Ga is the only radioactive metal demonstrated”. It is noted ammonium acetate is a salt of claimed buffer “acetic acid and a salt thereof” as well as being cited as the buffer in claim 11 of claimed invention. Additionally, a prior art does not need to show each and every working example to be of relevant art as Roesch teaches the claimed metal radioactive isotopes of 225Ac and 89Zr per MPEP (I): A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
As to the teaching of Frank, applicant argues (Page 2), Frank teaches the radioactive metal in the absence of organic solvents and sites para. 0083. It is noted para. 0083 states “the complexes were prepared by mixing 0.063 mL of an aqueous solution (20 mM) of chelant with 225Ac chloride solution in 0.1M HCl. When complexation was performed at pH=6, the pH of the reaction mixture was set using 50% tetramethylammonium acetate.
Applicant has added claims 19-20, no new matter was added. Claims 1-3 and 10-20 is now evaluated on its merits.
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.
Claims 1-3 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over Imura (US 20220259698 A1), published August 18th 2022, with a Foreign Priority date of July 30th 2019 in view of Roesch (DE 102012019714 A1) and Frank et al. (US 20040067924 A1).
Regarding claims 1-3 and 10-20, Imura teaches a method for synthesizing a zirconium complex, in which a complex of radioactive zirconium such as 89Zr is mixed with a chelating agent, a solvent containing an organic substance, a buffer of , water and a chelating agent containing a structure represented by General Formula (1)
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, wherein R1-19 reads to the structural limitations of claimed invention (relevant to claims 2-3) (abstract, para. 001, 0011). Of the organic solvent Imura teaches the substance selected from the group consisting of dimethylsulfoxide (DMSO), N,N-dimethylformamide (DMF), N-methylformamide (NMF), N-methylpyrrolidone (NMP), and urea, wherein the substance is 1 vol % or more and 95 vol % or less (para. 0012-0013). In Figure 3, Imura teaches the organic solvent as DMSO with a concentration of 50% by volume (relevant to claim 16) and buffer agent of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) with a concentration of about 0.25 mol/L (relevant to claim 10) and DOTA ligand at 10-4 mol/l which formulates to 100 µmol/l (relevant to claim 20) (para. 0057). In synthesizing the zirconium complex above Imura teaches the reaction is done in a temperature of 35° C or more (relevant to claim 13) (para. 0014). In the above structure Imura teaches one of R5-20 , wherein the molecular probe is a protein, a peptide, or a low-molecular weight organic compound (para. 0018). Of the peptides attached Imura teaches PSMA-617 which has a molecular mass of 1042.15 Da (relevant to claim 14).
Imura fails to teach the complex with metal ion of 225Ac and buffer of sodium acetate, ammonium acetate and tetramethylammonium.
Roesch teaches the preparation of metal-labeled compounds, comprising a metal-ligand of DOTA or NOTA (para. 0009), organic solvents of acetonitrile, DMSO (dimethyl sulfoxide), DMF (N, N-dimethylformamide), metal isotopes selected from a group which includes 225Ac or 89Zr and buffer selected from a group containing ammonium acetate and HEPES (relevant to claim 11) (para. 0021). Roesch additionally teaches the organic solvents at a concentration of 5 to 80% by volume (relevant to claim 17-19) (para. 0020).
Frank teaches 225Ac complexes with functionalized chelants, their conjugates and their use for targeted radiotherapy (para. 0002). Frank teaches the chelating agent of DOTA (para. 0050) linked to a biological carrier selected from a group which consist of a peptide (para. 0057). Frank additionally teaches in each example the complexes were prepared by mixing 0.063 mL of an aqueous solution (20 mM) of chelant with 225Ac and mixture with tetramethylammonium acetate of concentration 0.2 M (relevant to claim 12) (para. 0083).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have constructed a radio labeled metal complex containing claimed ligand, water, buffers of sodium acetate, ammonium acetate or tetramethylammonium, water-soluble organic solvent of DMSO or acetonitrile and radioactive metal of 225Ac or 89Zr. One would be motivated to do so from the teachings of Imura, Roesch and Frank of radioactive metal complex comprising 225Ac or 89Zr, DOTA ligand, buffers of sodium acetate, ammonium acetate and tetramethylammonium, water-soluble organic solvent of DMSO or acetonitrile. The teaching of Roesch provides support that each metal is interchangeable thus one could swap out 225Ac or 89Zr, claimed buffers and solvents with the teachings of Imura, Roesch and Frank for claimed invention. Three is a reasonable expectation of constructing a radio labeled metal complex containing claimed ligand, water, buffers of sodium acetate, ammonium acetate or tetramethylammonium, water-soluble organic solvent of DMSO or acetonitrile and radioactive metal of 225Ac or 89Zr from the teachings of Imura, Roesch and Frank.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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