DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-20 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 and a continuation in part of US application No. 16/493,668 filed on 12 Sep. 2019 (now US 11,628,229 B2) which is a 35 USC 371 National Stage filing of PCT/US2018/022160 filed on 13 Mar. 2018 and claims benefit to US provisional application No. 62/470,735 filed on 13 Mar. 2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 24 May 2023 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.
Claim 7 is 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.
Claim 7 recites the limitation "the first aqueous solvent" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 1-8, 12-14, 16, and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Med. Chem. Commun.; published 2012; see attached 892).
Regarding claims 1-8, 12-14, 16, and 20, Li et al. teach reaction scheme 1
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and reaction scheme 2
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(pgs. 1306-1307). For all reactions, the isotopic exchange was allowed to proceed for 20 min with an 18F activity of 30 mCi initial activity. The reactions are performed in 100 µL of [18F]water solution containing 15 µL of MeCN used for solubilization of the phosphoniumtrifluoroborate. The reaction was performed at room temperature for 20 min (pg. 1307). This reads on a method for preparing an 18F-labeled radiotracer compound for use in PE, the method comprising: a) providing an 18F compound ([18F]fluoride salt, [18F]F-); b) providing a target tracer compound having biological moiety (compounds 1-3) that comprises synthetic organic and inorganic small molecule and wherein the providing comprises radiolabeling and the reacting the 18F compound with comprises borate conjugation; and c) reacting the 18F compound with the target tracer compound in a second solvent that is predominantly water wherein the second solvent comprises at most 10% ACN co-solvent (margin of error) such that the fluorinated compound is 18F-labeled thereby forming the 18F-compound and wherein the providing the target tracer compound having biological moiety comprises borate conjugation and reacting the 18F compound with the target tracer compound comprises radiolabeling thereby forming the 18F-compopunds [18F/19F]1-3. Regarding claim 4, scheme 1 describes reacting the target tracer compound with KHF2 (non-radioactive fluoride compound) in a solvent the predominantly water at room temperature (mild for biological moiety), thereby forming a fluorinated tracer compound wherein the fluorinated tracer compound is non-radioactive, and wherein the biological activity of the biological moiety is preserved.
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) 1-8, 11-16, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Med. Chem. Commun.; published 2012; see attached 892).
Li et al. teach as discussed above. Li et al. teach harvesting 18F-fluoride ions in water via direct 18F-19F-exachange: radiofluorination of zwitterionic aryltrifluoroborates and in vivo stability studies (see title). Li et al. teach establishing a quick and robust radiofluorination protocol that can be implemented in water-methanol mixtures in a matter of minutes with higher specific activities. 18F-19F isotopic exchange is a strategy that has proven successful for the radiofluorination of main group molecules, including BF4- and as wells as fluorosilane derivatives. Simple stirring of [18F]water solution containing 30 mCi 18F, 1 dissolved in MeCN first and HCl at room temperature for 20 min afforded [18F/19F]1 with a % conversion of 87%. We have demonstrated that (i)18F-19F isotope exchange is a very efficient strategy for the synthesis of trifluoroborates with elevated specific activities and (ii) 18F-19F isotope exchange can be implemented directly on irradiated [18O]water alleviated the need for any time consuming drying steps (pg. 1306). When the reaction is carried out under much more concentrated conditions as in entry 7, the % conversion exceeds 90%, affording [18/19F]1 with a specific activity of 520 mCi µmol1-. When the reaction is carried out at higher 18F-fluoride/2 ratios, a comparatively high specific activity can be obtained (pg. 1307). [18/19F]1 and [18/19F]2 were injected in female nude mice and static microPET scans were obtained (used as a companion diagnostic in PET diagnostic applications) (pg. 1307; Fig. 2). The carboxylic acid functionalized derivative 3 should be amenable to simple bioconjugation protocols, opening new horizons for the radiolabeling of amine terminated biomolecules (pg. 1308).
Li et al. do not exemplify a method wherein the [18F]3 is used as a companion diagnostic or a companion therapeutic or a method wherein prior to reacting the 18F salt with the non-radioactive fluorinated compound, conjugating the non-radioactive fluorinated compound to a linker with an active functional group or method wherein the non-radioactive fluorinated compound has a functional group that acts as a linker for direct to indirect conjugation to the target tracer compound or a method wherein the target tracer compound has a functional group that acts as a linker for direct or indirect conjugation to the target tracer compound.
However, it would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Li et al. so that the 18F-labeled radiotracer prepared from a target tracer compound that was prepared by reacting the target tracer compound with a non-radioactive fluorinated compound in aqueous solvent is used as a companion diagnostic for diagnostic applications as taught by Li et al. because it would have been expected to advantageously enable in vivo whole body PET imaging diagnostic applications that facilitate treatment.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Li et al. so that prior to reacting the 18F salt with the non-radioactive fluorinated compound, conjugating the non-radioactive compound 3 having a carboxyl for direct conjugation gets conjugated a biomolecule having amine reactive group as taught by Li et al. because it would have been expected to advantageously enable 18F-labeling of amine terminated biomolecules whereby facilitating there in vivo imaging.
Claim(s) 1-16, and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Med. Chem. Commun.; published 2012; see attached 892), in view of Blom et al. (J. Label Compd Radiopharm.; published 2009; see attached 892) and Perrin et al. (WO 2009/012596 A1; published 2009; see IDS filed on 24 May 2023).
Li et al. teach as discussed above.
Li et al. do not further teach a method wherein the 18F salt is K18F or 18F-K222/K2CO3 or a fluorinated compound of the formula
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Blom et al. teach 18F/19F exchange in fluorine containing compounds for potential use in 18F-labeling strategies (see title). Blom et al. teach that multi-fluorinated molecules containing an electron withdrawing group were successfully labeled at room temperature, whereas monofluorinaed as well as those containing electron-donating groups required heating for the exchange reaction to take place (see abstract). Blom et al. teach incorporation yields for reaction of hexafluorobenzne 8, 11, and 16 with NCA [18F]fluoride at room temperature (Fig. 1, table 3). Blom et al. teach [K/K222]+18F- (pg. 509).
Perrin et al. teach substituted aryl-fluoroborates as imaging agents (see title). Perrin et al. teach exemplary linking groups for coordination to biomolecules included
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(pg. 32). Perrin et al. teach biomolecules include peptides, antibodies, etc (pg. 33). Perrin et al. teach 84, RT 9-089 and CH-01-059 (pg. 41). Perrin et al. teach the NHS activated molecule
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(pg. 44). Perrin et al. teach aqueous solvent (pgs. 46,53). Perrin et al. teach [18F]-NaF (pg. 59).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Li et al. by so that the 18F salt is a 18F-K222/K2CO3 salt as taught by Blom et al. because the 18F-K222/K2CO3 salt would have been expected to provide an source of [18F]fluoride advantageously including a solubilizing krypton,. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Li et al. so that the fluorinated compound is a compound of formula
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wherein FG NHS ester, each X=C, Y=F and Z= Cl, Br, or NO2 as taught by Blom et al. and Perrin et al. because that fluorinated compound would have been expected to provide a fluorinated organic prosthetic group comprising electron withdrawing substituents that enable mild 18F exchange labeling of biomolecules under mild conditions.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Med. Chem. Commun.; published 2012; see attached 892), in view of Blom et al. (J. Label Compd Radiopharm.; published 2009; see IDS filed on 24 May 2023) and Perrin et al. (WO 2009/012596 A1; published 2009; see attached 892), in further view of Jacobson et al. (Bioconjugate Chem.; published 2015; see IDS filed on 24 May 2023).
Li et al. teach as discussed above.
Li et al. do not further teach a target tracer compound that has a functional group that reacts with 18F-labeled compound via aromatic nucleophilic substitution.
Blom et al. teach as discussed above.
Perrin et al. teach as discussed above.
Jacobson et al. teach novel method for radiolabeling and dimerizing thiolated peptides (see title). Jacobson et al. teach that the hexafluorobenzene reacts with thiols to produce a unique perfluorinated linkage. This reaction was modified to produce a dimeric 18F-RGD-tetrafluorobenzene RGD, an integrin ανβ3 receptor ligand (see abstract, Fig. 30.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Li et al. so that the non-radioactive fluorinated compound has a functional group such as a thiol that reacts with the 18F-labeled compound via aromatic nucleophilic substitution as taught by Jacobson et al. because it would have been expected to advantageously enable an 18F-labeled biomolecule radiotracer formed from a biomolecule having a reactive thiol group.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,628,229 B2, in view of Li et al. (Med. Chem. Commun.; published 2012; see attached 892), Blom et al. (J. Label Compd Radiopharm.; published 2009; see IDS filed on 24 May 2023) and Perrin et al. (WO 2009/012596 A1; published 2009; see attached 892).
Claims 1-15 of U.S. Patent No. 11,628,229 B2 claim a method of preparing an 18F-alebeld radiotracer compound for use in PET, the method comprising: a) providing a target tracer compound having a biological moiety, b) providing a non-radioactive, PFA compound, c) reacting the target tracer compound and the water soluble PFA in a first aqueous solvent that is predominantly water , thereby forming a modified PFA-compound wherein the modified PFA target tracer compound is non-radioactive and wherein the biological activity of the biological moiety is preserved, d) providing an 18F salt, and e) reacting the 18F salt with the PFA-modified target tracer compound in a second solvent that is predominantly water at a second ambient temperature that is mild for the biological moiety wherein the 18F isotope of the 18F salt replaces the 19F isotope of the PFA thereby forming 18F labeled wherein the first ambient temperature and the second ambient temperature is about 37oC wherein the biological activity of the biological moiety is preserved wherein the target tracer compounds is an MRI agent and wherein the target tracer compound comprises a functional group that reacts with the PFA via aromatic nucleophilic substitution and wherein the second aqueous solvent comprises about 1%-10% vol of co-solvent wherein the co-solvent is DMSO and wherein the 18F salt is Na18F and wherein the PFA compound is
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Claims 1-15 of U.S. Patent No. 11,628,229 B2 do not claim reacting the target tracer compound with a non-radioactive fluorinated compound in a solvent that is predominantly water at a temperature that is mild for the biological moiety thereby forming a fluorinated target tracer compound wherein the fluorinated target tracer compound is non-radioactive and wherein the biological moiety is preserved. Claims 1-15 of U.S. Patent No. 11,628,229 B2 do not claim a compound formula
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. Claims 1-15 of U.S. Patent No. 11,628,229 B2 do not claim that the 18F-tracer compound is used as a companion diagnostic or companion therapeutic compound for the treatment of disease or claim conjugating the non-radioactive compound to a linker with an active functional group.
Li et al. teach as discussed above.
Blom et al. teach as discussed above.
Perrin 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 further modify claims 1-15 of U.S. Patent No. 11,628,229 B2 by further reacting the target tracer compound with a non-radioactive fluorinated compound in a solvent that is predominantly water at a temperature that is mild for the biological moiety thereby forming a fluorinated target tracer compound wherein the fluorinated target tracer compound is non-radioactive and wherein the biological moiety is preserved as taught by Li et al., Blom et al. and Perrin et al. because the further reacting would have been expected to enable a non-radioactive fluorinated target tracer compound advantageously capable of 19F-18F exchange reaction. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-15 of U.S. Patent No. 11,628,229 B2 so that the fluorinated compound is a compound of formula
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wherein FG NHS ester, each X=C, Y=F and Z= Cl, Br, or NO2 as taught by Blom et al. and Perrin et al. because that fluorinated compound would have been expected to provide a fluorinated organic prosthetic group comprising electron withdrawing substituents that enable mild 18F exchange labeling of biomolecules under 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 1-15 of U.S. Patent No. 11,628,229 B2 so that the 18F-labeled radiotracer is used as a companion diagnostic for diagnostic applications as taught by Li et a, Blom et al., and Perrin et al. because it would have been expected to advantageously enable in vivo PET imaging of the biomolecule. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compound so that prior to reacting the 18F salt with the non-radioactive fluorinated compound, conjugating the non-radioactive fluorinated compound to a linker with an active functional group that acts as a linker for direct conjugation to the target tracer compound or so that the non-radioactive fluorinated compound has a functional group that acts as a linker for direct conjugation to the target tracer compound as taught by Li et al., Blom et al. and Perrin et al. because it would have been expected to advantageously enable 18F-labeling of reactively terminated biomolecules such as amine or thiol terminated biomolecules whereby facilitating there in vivo imaging and treatment.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/SEAN R. DONOHUE/
Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618