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 .
Acknowledgement of Receipt
Applicant’s Response, filed 6/25/2026, in reply to the Office Action mailed 1/27/2026, is acknowledged and has been entered. Claims 1, 23, 30, 33, 40, 45 and 55 have been amended. Claims 1, 5, 12, 16, 23, 25, 30, 33, 36, 40, 42, 45, 48, 52-56, 59 and 60 are pending, of which claims 16, 25, 48, 52 and 60 are withdrawn from consideration at this time as being drawn to a non-elected invention. Claims 1, 5, 12, 23, 30, 33, 36, 40, 42, 45, 55-56 and 59 encompass the elected invention and are examined herein on the merits for patentability.
Response to Arguments
Any rejection not reiterated herein has been withdrawn as being overcome by claim amendment. The Examiner’s response to Applicant’s arguments is incorporated below.
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, 5, 12, 23, 30, 33, 36, 40, 42, 45, 53-55, 57 and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/703,086 (reference application), for reasons set forth in the previous Office Action. Claim 59 incorporates subject matter of the rejected claims.
Response to arguments
Applicant requests the rejection be held in abeyance.
Applicant’s arguments have been fully considered. The rejection is maintained at this time as a terminal disclaimer has not been received.
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, 5, 9, 16, 23, 30, 33, 36, 42, 45, 53, 55 and 57-58 are rejected under 35 U.S.C. 103 as being unpatentable over Caravan et al. (WO 08/098056) in view of Ray (US 2017/0081298).
Caravan teaches modifications of a chelating ligand to enhance the relaxivity of a resultant metal chelate upon metal binding. These modifications include changing the donor groups (functional groups that directly coordinate to the metal ion), introducing groups that organize water in the second coordination sphere (e.g., by hydrogen bonding), and introducing groups that slow down molecular tumbling either by increased molecular weight or by targeting the metal chelate to a macromolecule (e.g., a protein).
Chelating ligands can be used to prepare non-specific metal chelates having high relaxivity, or may be modified to incorporate target binding moieties (TBMs).
Chelating ligands and metal chelates can also be useful as luminescent probes, e.g., fluorescent (or phosphorescent) probes having long fluorescence lifetimes. Finally, chelating ligands may be useful for preparing diagnostic and/or therapeutic compositions of radioactive metal ions (page 2).
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An exemplary compound is compound 42, Table 3.
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Accordingly, the compound is within the scope of the instant claims such that Z is -C(COOH)-, L is a linker and TBM is a targeting ligand; Y2 is alkylheteroaryl-COOH and Y1 and Y3 are alkyl-CO2H.
It is noted that link between the chelator and the TBM may be represented as either:
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(page 15).
Chelating ligands may be modified to incorporate one or more Target Binding Moieties (TBM), as indicated above. TBMs can include peptides, nucleic acids, or small organic molecules. TBMs allow chelating ligands and metal chelates to be bound to targets in vivo.
Caravan does not specifically recite a chelate comprising Cu-44, Cu-47, or Sc-47.
Ray teaches low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific T1-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific T1 contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics (abstract).
Magnetic resonance (MR) imaging is advantageous because it can provide anatomic, functional and molecular information concurrently. MR molecular imaging can combine the ubiquity of this established clinical modality and its high spatial resolution with molecular profiling in vivo. However, due to the intrinsically low sensitivity of MR, high local concentrations of biological targets are required to generate discernable MR contrast.
Without wishing to be bound to any one particular theory, it was thought that PSMA would be good target for MR molecular imaging agents because of the high target concentration per cell (approximately 3 μM/cell volume), as well as the extra-cellular location of the ligand binding site. The presently disclosed approach is directed toward improving the binding affinity (lowest Kd) of contrast agents for a specific molecular or cellular target so that the amount of agent needed for MR-detection will be much lesser. Accordingly, the presently disclosed approach combines a high binding affinity receptor specific ligand with multimeric Gd(III) agents as one possible solution for MR-based molecular imaging.
Previously, successful radiometal-based PET (64Cu) and SPECT (111In and mTc) imaging was demonstrated using radiolabeled, urea-based PSMA inhibitors in mice. A tripartite strategy containing a: (i) PSMA targeting moiety, (ii) linker for pharmacokinetic tuning, and (iii) chelating agent to enable attachment of radionuclides was developed. This strategy included 86Y labeled DOTA conjugated agents for PET imaging and to serve as a model for radiotherapy with corresponding 90Y labeled agents. Because DOTA is a strong chelating agent for many metals the same DOTA conjugates can be used with other radiotherapeutic radionuclides, such as Lu-177, Ac-225, Bi-213, Bi-212, Pb-212, Cu-67, and Sc-47. In the presently disclosed subject matter, the same urea-linker construct was used and the number of Gd-chelates (mono-, di- and trimeric Gd) was increased to optimize relaxometric behavior or MR sensitivity as high field contrast agents as well as their binding affinity to investigate systematically the possibility of PSMA-based MR imaging of PCa (paragraph 0050-53).
In some embodiments, the metal is selected from the group consisting of Gd, Lu, Ac, Bi, Pb, Cu, In, Sc, and Y. In particular embodiments, the metal or the radiometal is selected from the group consisting of Gd-157, Lu-177, Ac-225, Bi-212, Bi-213, Pb-203/Pb-212, Cu-67, In-111, Sc-44/Sc-47, and Y-90. In yet more particular embodiments, for MRI applications, the nonradioactive metal is Gd-157 (stable isotope); for radiotherapy applications, the radiometal is selected from the group consisting of Lu-177, Ac-225, Bi-203, Pb-210, Cu-67, In-111, Sc-47, and Y-90; for PET imaging, the radiometal is selected from the group consisting of Y-86 and Sc-44; and for SPECT application, the radiometal is selected from the group consisting of Lu-177 and In-111 (paragraph 0061).
See also exemplified compounds and compounds in claim 11 bearing PSMA targeting ligands.
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide Cu-64, Cu-67, Sc-47 or Sc-44 as a radioisotope in the compounds taught by Caravan when the teaching of Caravan is taken in view of Ray. While Caravan exemplifies gadolinium complexes, rather than radioactive copper or scandium, Ray further teaches that the chelating ligands may be useful for preparing diagnostic and/or therapeutic compositions of radioactive metal ions. One would have been motivated to provide Cu-64, Cu-67, Sc-47 or Sc-44 with a reasonable expectation of success because it is known from Ray that a given chelate, e.g. DOTA, may be used for magnetic resonance imaging when gadolinium is complexed, but DOTA conjugates can be used with other radiotherapeutic radionuclides, such as Cu-64, Lu-177, Ac-225, Bi-213, Bi-212, Pb-212, Cu-67, and Sc-47 or for PET imaging, the radiometal is selected from the group consisting of Y-86 and Sc-44.
It would have been further obvious to provide -CH2-C(=O)NH- equivalent to position Z1 of the instant claims, as Caravan readily teaches that a DOTA chelator can be conjugated to a targeting ligand by -CH2-C(=O)NH- or -C(COOH)- and a linker at the stated position (page 15).
It would have been further obvious to provide a DUPA ligand for targeting PSMA because Caravan teaches conjugation of chelating agents to target binding moieties, and Ray teaches that the prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of prostate and other forms of cancer (paragraph 0003), and urea-based metal/radiometal-based agents to maintain high binding affinity for PSMA. Consequently, metal or radiometal conjugated carbamate scaffold can also be utilized for imaging and therapy of PSMA-expressing cells and tissues (paragraph 0008).
Claim(s) 1, 5, 9, 12, 23, 30, 33, 36, 40, 42, 45, 53-55 and 57-59 are rejected under 35 U.S.C. 103 as being unpatentable over Babich et al. (US 2015/0078998) in view of Gateau (US 2010/0247448) and Ray (US 2017/0081298).
Babich teaches compounds according to Formula I and Formula II are potent inhibitors of PSMA activity.
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The chelator D includes any linear, branched, cyclic, or alicyclic, aliphatic polyaza/polycarboxylic acid moiety that is capable of forming a metal complex with a radionuclide (paragraph 0024). Various chelators are shown in paragraph 0033.
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An exemplary synthetic scheme is set forth in Scheme 1 as an illustration of the general synthetic route for GUL-HEX-EDTA-DOTA and GUG-HEX-EDTA-DOTA analogs.
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In one aspect, the synthesis and methods for using PSMA selective
Indium, Ytterbium, Gallium, Copper and Lutetium, Gadolinium and Iron complexes
of Formula I compounds or Formula II compounds as novel radiopharmaceuticals
for the treatment and imaging of cancer cells is provided (paragraph 0041).
Pharmaceutically acceptable carriers are taught (paragraph 0060).
Metal complexes of any of the compounds of Formula II may also be provided. Specifically provided are radionuclide complexes of Formula II compounds. Illustrative radionuclides are moieties selected from the group consisting of 111In, 90Y, 68Ga, 64Cu, 153Gd, 155Gd, 157Gd, Fe and 177Lu (paragraph 0017).
The term radionuclide refers to an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide can undergo radioactive decay and in the process emit subatomic ionizing particles. Illustrative of subatomic ionizing particles without limitation are alpha (.alpha.) particles, beta (.beta.) particle and gamma (.gamma.) rays. Illustrative radionuclides may include, but are not limited to 111In, 90Y, 68Ga, 64Cu, 171Lu, 153/157/158Gd, or Fe. However, the term is not limited to these four radionuclides (paragraph 0054).
Babich does not specifically teach wherein the chelator is a picolinate-pendant triazacylononane complexing scandium.
Gateau teaches ligand for metals, in particular lanthanides, of the general formula (I). The invention relates moreover to the ligands and the complexes grafted to a molecule of biological interest, as well the contrast agents and the pharmaceutical compositions including at least one of these molecules.
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Exemplary compounds are shown:
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The favorable electronic relaxation properties observed for the gadolinium complex by NMR and PER indicate that, after grafting to a macromolecule, relaxivity greater than that of the commercial contrast agents might be reached (paragraph 0086).
Preferable metal ions include gadolinium, terbium, europium, neodymium, erbium and ytterbium (paragraph 0062). Development of radiotracers is also contemplated (paragraph 0077). The invention also corresponds to the pharmaceutical compositions, including at least one ligand and/or one complex, grafted or not to a molecule of interest and/or a contrast agent as defined previously, useable in a diagnostic method and in particular a medical imaging method (paragraph 0078).
In another particular embodiment of the present invention, the ligands and/or the complexes as described in the present application may moreover be grafted to a molecule of biological interest.
The molecules of interest according to the invention correspond in particular to the biomolecules such as the nucleotides, the polypeptides, the deoxyribonucleic (DNA) and ribonucleic (RNA) acids, the antibodies or any other active molecule of biological and/or medicinal interest. It may be any molecule which an experimenter wishes to detect inside a living system, using in vivo or in vitro techniques, and using the magnetic properties of the metal and the intrinsic optical properties of the metal or the possible fluorescence conferred by the ligand (paragraph 0063-0064).
An additional grafting step to a molecule of interest is advantageous. The molecule of interest may be grafted at numerous points on the ligand or the complex by any suitable reaction from available functions arranged on the complex and in particular from alkyl or aryl radicals present on the structure and as shown above (paragraph 0071).
Ray teaches low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific T1-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific T1 contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics (abstract). Magnetic resonance (MR) imaging is advantageous because it can provide anatomic, functional and molecular information concurrently. MR molecular imaging can combine the ubiquity of this established clinical modality and its high spatial resolution with molecular profiling in vivo. However, due to the intrinsically low sensitivity of MR, high local concentrations of biological targets are required to generate discernable MR contrast.
Without wishing to be bound to any one particular theory, it was thought that PSMA would be good target for MR molecular imaging agents because of the high target concentration per cell (approximately 3 μM/cell volume), as well as the extra-cellular location of the ligand binding site. The presently disclosed approach is directed toward improving the binding affinity (lowest Kd) of contrast agents for a specific molecular or cellular target so that the amount of agent needed for MR-detection will be much lesser. Accordingly, the presently disclosed approach combines a high binding affinity receptor specific ligand with multimeric Gd(III) agents as one possible solution for MR-based molecular imaging.
Previously, successful radiometal-based PET (64Cu) and SPECT (111In and mTc) imaging was demonstrated using radiolabeled, urea-based PSMA inhibitors in mice. A tripartite strategy containing a: (i) PSMA targeting moiety, (ii) linker for pharmacokinetic tuning, and (iii) chelating agent to enable attachment of radionuclides was developed. This strategy included 86Y labeled DOTA conjugated agents for PET imaging and to serve as a model for radiotherapy with corresponding 90Y labeled agents. Because DOTA is a strong chelating agent for many metals the same DOTA conjugates can be used with other radiotherapeutic radionuclides, such as Lu-177, Ac-225, Bi-213, Bi-212, Pb-212, Cu-67, and Sc-47. In the presently disclosed subject matter, the same urea-linker construct was used and the number of Gd-chelates (mono-, di- and trimeric Gd) was increased to optimize relaxometric behavior or MR sensitivity as high field contrast agents as well as their binding affinity to investigate systematically the possibility of PSMA-based MR imaging of PCa (paragraph 0050-53).
In some embodiments, the metal is selected from the group consisting of Gd, Lu, Ac, Bi, Pb, Cu, In, Sc, and Y. In particular embodiments, the metal or the radiometal is selected from the group consisting of Gd-157, Lu-177, Ac-225, Bi-212, Bi-213, Pb-203/Pb-212, Cu-67, In-111, Sc-44/Sc-47, and Y-90. In yet more particular embodiments, for MRI applications, the nonradioactive metal is Gd-157 (stable isotope); for radiotherapy applications, the radiometal is selected from the group consisting of Lu-177, Ac-225, Bi-203, Pb-210, Cu-67, In-111, Sc-47, and Y-90; for PET imaging, the radiometal is selected from the group consisting of Y-86 and Sc-44; and for SPECT application, the radiometal is selected from the group consisting of Lu-177 and In-111 (paragraph 0061).
See also exemplified compounds and compounds in claim 11 bearing PSMA targeting ligands.
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide a dota/tacn chelator having one or two picolinate arms such as bpatcn or Hno1pa2py as a functionally equivalent ligand which is conjugated to a
compounds according to Formula I and Formula II as potent inhibitors of PSMA activity taught by Babich when the teaching of Babich is taken in view of Gateau and Ray. For example, Babich teaches the following targeting moiety-linker for conjugation to a chelator.
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While Babich does not specifically recite a picolinate pendant tacn/dota chelator, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to substitute such a chelator as bpatcn or Hno1pa2py as a functionally equivalent chelator to those set forth in Babich. Upon conjugation of bpatcn or Hno1pa2py to the targeting moiety-linker of Babich above, one would arrive at an amide bond linked conjugate of the instant claims.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. ___, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. One such rationale includes the simple substitution of one known element for another to obtain predictable results. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. See MPEP 2143.
In the instant case, the substituted components (chelators) and their functions were known in the art at the time of the instant invention. One of ordinary skill in the art could have substituted one known chelator for another, and the results of the substitution would have been predictable, that is conjugation of the chelator to targeting agent for use as a PSMA targeted contrast agent. Further Gateau teaches the benefit of favorable relaxation properties with picolinate pendant chelates, and may be used as radiotracers, and each of Babich, Gateau and Ray teach macrocyclic chelators for radionuclides.
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide Sc-47 or Sc-44 or Cu-67 as a radioisotope in the compounds taught by Babich and Gateau when the teachings of Babich and Gateau are taken in view of Ray. While Babich and Gateau do not specifically recite scandium, one would have been motivated to provide Sc-47 or Sc-44 with a reasonable expectation of success because it is known from Ray that a given chelate, e.g. DOTA, may be used for magnetic resonance imaging when gadolinium is complexed, but DOTA conjugates can be used with other radiotherapeutic radionuclides, such as Lu-177, Ac-225, Bi-213, Bi-212, Pb-212, Cu-67, and Sc-47 or for PET imaging, the radiometal is selected from the group consisting of Y-86 and Sc-44. Further Babich teaches that the radionuclide can undergo radioactive decay and in the process emit subatomic ionizing particles, including alpha, beta or gamma radiation and is not particularly limited. Each of Babich, Gateau and Ray are directed to targeted bifunctional chelators, including for radioactive metal, which may include scandium as taught by Ray. With regard to the length of the alkyl chain in the linker taught by Babich, see MPEP 2144. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Response to arguments
Applicant argues that amended claim 1 no longer recites a copper complex. Accordingly, the rejection over Guillou in view of Gasser is no longer applicable.
As such, the rejection over Guillou in view of Gasser is withdrawn.
Applicant argue that I. A POSA could not have predicted the superior properties possessed by the scandium complex recited in claim 1. Applicant asserts that none of the cited references addresses the coordination and stability challenges described above, nor do they conduct any experiments on a scandium (III) complex to provide an understanding of the aqueous coordination and radiochemistry of scandium (III). Applicant argues that a POSA would not have known that pairing scandium (III) with the chelators taught in the cited references would yield a complex exhibiting the rapid, low-temperature radiolabeling and high in vivo stability required for the scandium theranostic isotope pair. Nor is Applicant required to compare the claimed scandium (III) complex with any complex disclosed in the cited references, because the cited references neither teach nor address these requirements. Applicant contends that the compound recited in the claimed metal complex in claim 1 is an optimal bifunctional chelator for scandium isotopes, fulfilling criteria 1-4. Applicant argues that a POSA would have had no basis to predict that the claimed picolinate-functionalized chelator would form a kinetically inert Sc (III) complex under the mild conditions recited. The Examiner's contrary conclusion appears to rest on impermissible hindsight, reconstructing the claimed invention from the roadmap supplied by the present specification rather than from the teachings of the prior art.
Applicant’s arguments have been fully considered but are not found to be persuasive. See MPEP 716.02. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C).
With regard to arguments directed to hindsight reasoning, see MPEP 2145 “[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
Applicant further argues that the claims are commensurate in scope with the allegation of unexpected results. Applicant asserts that the present invention employed "picolinic acid donor arms to increase the number of coordinating donors and impart additional rigidity to formed complexes." Applicant notes that the specification further indicates that "picolinate-functionalized triazamacrocycle chelates have been shown to exhibit high kinetic inertness and slow interconversion of RRRA- to SSSδ- complex isomers...' " (Page 77 of the Specification).
Applicant’s arguments have been fully considered but are not found to be persuasive. It is respectfully submitted that the compound picaga-dupa in Figure 7 of the instant specification is encompassed by the instant claims including coordination chemistry set forth in the figure and for which data is asserted, but the claims are inclusive a large number of potential number of coordinating donors and impart additional rigidity to formed complexes asserted by Applicant to allow for unexpected results; for example variable Y1 if H or R4 as alkyl, etc. would not be coordinating, etc. as well as other differences such as fewer coordination sites with alklylCOOH or alkylCOOR4; alkylheteroaryl, etc; various tetraazacyclononane-based complexes, etc. The arguments have been fully considered but the rejections are maintained at this time.
Conclusion
No claims are allowed at this time.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEAH H SCHLIENTZ whose telephone number is (571)272-9928. The examiner can normally be reached Monday-Friday, 8:30am - 12:30pm EST.
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/LHS/
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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