DETAILED ACTION
This Office action details a first action on the merits for the above-mentioned application No. Claims 1-21 are pending in this application.
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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit under 35 USC 120 as a continuation of US application No. 17/467,110 filed on 3 Sep. 2021 (now US patent No. 12,102,696 B2) and claims benefit under 35 USC 119(e) to US provisional application No. 63/074,451 filed on 3 Sep. 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 21 Nov. 2024 and 26 Sep. 2025 has been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10, 13, 17, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 10, the recitation of “(µg of DOTATATE per mCi of Copper-64)” is indefinite because it is not clear if the recitation is a required limitation and because the text inside the parentheses in context with the required concentration of Copper-64 that is 0.6 µg/mL.
Regarding claim 13, the recitation of “(decay corrected)” is indefinite because it is not clear if the recitation is a required limitation or an example.
Regarding claim 17, the recitation of “DOTATATE can be radiolabeled” is indefinite because the recitation connotes a mere possibility and it is not clear if what follows is required. The recitation of “(µg of DOTATATE per mCi of Copper-64)” is indefinite because it is not clear if the recitation is a required limitation and because the text inside the parentheses in context with the required concentration of Copper-64 that is 0.6 µg/mL.
Regarding claim 21, the recitation of “(ppm)” is indefinite because it is not clear if the recitation is required and conflicts with µg/mL when a density correction is required.
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)(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.
(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, 5, 8-9, 11-12, and 17-19 is/are rejected under 35 U.S.C. 102(a)(1),(2) as being anticipated by Kjaer et al. (US 2014/0341807 A1; published 20 Nov. 2014; see attached 892).
Regarding claims 1, 5, and 17, Kjaer et al. disclose the preparation of 64Cu-DOTATATE starting with 2-6 GBq of 64Cu as 64CuCl2 (specific activity 300-3000 TBq/mmol; RNP >99%). The labeling was performed in a sterile solution of DOTATATE (0.3 mg; mw= 1435.63 g mol-1; 0.0002 mmol) and gentisic acid (25 mg) in aq sodium acetate (1 mL; 0.4 M; pH 5.0; buffered solution) to a dry vial containing 64CuCl2 (~1 GBq; 27 mCi; 0.0000033 mmol; mw=134.45 g mol-1; 0.44 µg). (mole ratio of DOTATATE:total copper-64 is about 60:1; DOTATATE can be radiolabeled with copper-64 at a concentration of about 0.6 µg/mL). Gentisic acid was added as a scavenger to reduce radiolysis. The mixture was left at ambient temperature (connotes 20-22oC) for 10 min and then diluted with sterile water (1 mL). (27 mCi/2 mL= 13.5 mCi mL-1). The mixture was passed through a 0.22 µm sterile filter ([0033]-[0034]). The labeling of 64Cu-DOTATATE took less than 30 min and resulted in greater than 95% yield. The amount of unlabeled 64Cu in the product was less than 1% (connotes a radionuclidic purity of copper-64 in the drug product of about 99%; [0045])
Claims 8-9, 11-12, and 18-19 are product by process claims. Product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. In this case, the drug product comprising 64Cu-DOTATATE taught by Kjaer et al. is the same as the drug product in claims 8-9, 11-12, and 18-19 because the drug product of Kjaer et al. comprises structurally the same 64Cu-DOTATATE at about 13.5 mCi mL-1.
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) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kjaer et al. (US 2014/0341807 A1; published 20 Nov. 2014; see attached 892).
Kjaer et al. teach as discussed above. Kjaer et al. teach a PET tracer for imaging neuroendocrine tumors (see title). Kjaer et al. teach 64Cu-DOTATATE having the formula
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([0012]). The inventors have found that the compound is particularly useful for diagnostic use when administered with a target dose rage of 150-350 MBq (4.5-9.5 mCi) such as 150-250 MBq (4.5-6.8 mCi)([0015]).
Kjaer et al. do not expressly teach the claimed method wherein the reaction occurs in less than 10 min or 5 min or wherein the mole ratio of DOTATATE to copper-64 in the reaction solution is about 100:1 or that the reaction occurs at a temperature of less than 20oC or 15oC. Kjaer et al. do not teach the claimed method wherein the drug product is prepared by radiolabeling DOTATATE with copper-64 at a concentration of about 0.6 µg/mL.
However, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art. "[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). MPEP 2144.05.II. The reaction time is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill in the art would have arrived at a reaction time of less than 10 min or 5 min through routine experimentation in order to arrive at optimal reaction conditions. The reaction temperature is a result-effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill in the art would have arrived at a reaction temperature of less than 20oC or less than 15oC through routine experimentation in order to arrive at optimal mild reaction conditions. The mole ratio of DOTATATE to copper-64 is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill in the art would have arrived at a mole ratio of DOTATATE to copper-64 in the reaction solution of about 100:1 in order to arrive at an optimal radiochemical yield. A person of ordinary skill in the art would have arrived at a copper-64 concentration of about 0.6 µg/mL through routine experimentation in order to arrive at optimal reaction conditions.
Claim(s) 1-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kjaer et al. (US 2014/0341807 A1; published 20 Nov. 2014; see attached 892), in view of Zeng et al. (US 2017/0297008 A1; published 19 Oct. 2017; see attached 892).
Kjaer et al. teach as discussed above.
Kjaer et al. do not further teach that non-radioactive copper is added to reaction mixture optionally in an amount that is from 0.1-30 µg/mL (ppm) of non-radioactive copper.
Zeng et al. teach Cu(I)-catalyzed azide-alkyne cycloadditions (CuAAC) ligands and methods for carrying out Cu(I)-catalyzed azide-alkyne cycloaddition reactions (see title). Zheng et al. teach that non-radioactive copper contaminants will drastically adversely affect the corresponding radiopharmaceuticals ([0036]). Zeng et al. teach that 64Cu2+ (100 uCi) was added to a non-radioactive Cu2+ solution and the resulting carrier added 64Cu was then mixed with 1.5 eq of FTBTT; the mixture was passed through a fluorous resin after a 5 min incubation. It is anticipated that removal of toxic copper species after CuAAC can be greatly simplified.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Kjaer et al. so that non-radioactive copper is added to the reaction mixture as taught by Zeng et al. because the addition of non-radioactive copper would have been expected to advantageously enable assessing the removal of toxic copper species. The concentration of non-radioactive copper is a result effective variable. A person of ordinary skill in the art would have arrived at 0.1-30 µg/mL of non-radioactive copper in order to arrive at an amount of non-radioactive copper that enable assessing removal of toxic copper species.
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 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12,102,696 B2, in view of Kjaer et al. (US 2014/0341807 A1; published 20 Nov. 2014; see attached 892), and Zeng et al. (US 2017/0297008 A1; published 19 Oct. 2017; see attached 892).
Claims 1-7 of U.S. Patent No. 12,102,696 B2 claim a drug product for use in positron emission tomography comprising 64Cu-DOTATATE wherein the drug product comprises a molar ratio of total DOTATATE:total 64Cu of about 125:1 to about 1:1 or optionally about 75:1 and is a single dose vial containing 148 MBq of 64Cu-DOTATATE at calibration date and time in 4 mL solution volume wherein the radiochemical purity of the drug product is >96% or >99%
Claims 1-7 of U.S. Patent No. 12,102,696 B2 do not claim the instant method for radiolabeling DOTATATE comprising reacting copper-64 optionally at a concentration of about 0.6 µg/mL with a buffered solution comprising DOTATATE wherein the reaction occurs in less than 15 min, optionally less than 10 min or 5 min, at a temperature of less than or equal to 30oC, 20oC or 15oC; and wherein the mole ratio of total DOTATATE:total Copper-64 is about 125:1 to about 1:1, optionally about 100:1 or wherein the radionuclidic purity in the drug product is about 99% or wherein the drug product has an isolated RCY of about 95% and optionally wherein radiolabeling is carried out at a pH from about 4.5 to 7.0 and optionally wherein non-radioactive copper (0.1-30 µg/mL) is added to the reaction mixture. Claims 1-7 of U.S. Patent No. 12,102,696 B2 do not claim the claimed drug products wherein radioactive concentration of the drug product is about 5-15 mCi/mL.
Kjaer et al. teach as discussed above.
Zeng et al. 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 1-7 of U.S. Patent No. 12,102,696 B2 so that the drug product comprising 64Cu-DOTATATE gets made by reacting copper-64 at a concentration of about 0.6 µg/mL with a buffered solution of DOTATATE wherein the reaction occurs in less than 15 min, 10 min or 5 min at a temperature of less than or equal to 30oC, 25oC, 20oC, or 15oC and wherein the mole ratio of total DOTATATE:total Copper-64 is about 125:1 to about 1:1 or about 100:1 optionally wherein the drug product has an isolated RCY of about 95% and optionally wherein the radiolabeling is carried out at a pH of about 5 and optionally wherein the radioactive concentration of the drug product is about 5-15 mCi/mL as taught by claims 1-7 of U.S. Patent No. 12,102,696 B2 and Kjaer et al. because that drug product and preparation methods would have been expected to advantageously enable optimized drug product at effective concentration prepared under optimized and mild conditions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-7 of U.S. Patent No. 12,102,696 B2 so that non-radioactive copper is added to the reaction mixture as taught by Zeng et al. because the addition of non-radioactive copper would have been expected to advantageously enable assessing the removal of toxic copper species. The concentration of non-radioactive copper is a result effective variable. A person of ordinary skill in the art would have arrived at 0.1-30 µg/mL of non-radioactive copper in order to arrive at an amount of non-radioactive copper that enable assessing removal of toxic copper species.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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