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 23-38 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 11/18/2024, 01/16/2025, 06/13/2025, 09/30/2025, 10/20/2025 and 08/31/2026 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 09/18/2024. These drawings are acknowledged.
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) 23-38 are rejected under 35 U.S.C. 103 as being unpatentable Fugazza et al. (US 2014/0171637) in view of Cvet et al. (US 2016/0303258), Ballinger et al. (WO 2012/063028), and Matthias et al. (Bioconjugate Chem. 2012, 23, 688-697).
Fugazza discloses a process for the preparation of complexes of 68Ga wherein the complexing reaction between a chelator-functionalized molecule and 68Ga is carried out in a buffer formic acid/formate aqueous solution optionally in the presence of a compound capable of sequestering metal cations, wherein a commercial generator of 68Ga is eluted with an eluate containing acid directly into a vial containing buffer formate, and a base; a chelator-functionalized molecule is added into the vial and the reaction vial is heated for a short time and the product is collected (abstract, 0050 and 0052). Preferred chelates for the complexation of Ga-68 according to the invention can be chosen among: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tretraacetic acid ("DOTA") and its derivatives, 1,4,7-triazacyclononane-1,4,7-triyltriacetic acid ("NOTA") and its derivatives, 3,6,9,15 tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triecetic acid ("PCTA") and its derivatives (0025). In one embodiment, the acid eluate is an aqueous solution of HCI, while the base is an aqueous solution of NaOH and the complexing reaction is carried out in a pH range between 3 and 4.5 (0054). Additional disclosure includes that the use of formate buffer guarantees a suitable pH even if variations in the eluate acidity occur and, in this way reduces, the amount of not complexed Ga-68 due to a too low or a too high pH resulting in high content of free ⁶⁸Ga³⁺ or ⁶⁸Ga hydroxides respectively. Moreover, the addition of a sequestering agent allows to bring down the amount of chelator-functionalized molecule needed to obtain a complete Ga-68 complexation.
Fugazza fails to disclose free radical scavenger, chelator compound of formula (I) and a biological targeting agent such as prostate specific membrane agent (PSMA) in the composition.
Cvet discloses composition comprising radiolabeled compounds a chelating moiety capable of binding a radioactive atom, wherein the chelating moiety comprises a macrocycle, e.g., a macrocycle comprising an O and/or a N, DOTA, NOTA, one or more amines, one or more ethers, one or more carboxylic acids, EDTA, DTPA, TETA, DO3A, PCTA, or desferrioxamine, and (c) a linker moiety that covalently attaches the amino-terminus of the amino acid sequence of the peptide to the chelating moiety, wherein the compound is capable of binding to guanylyl cyclase C (GCC) (abstract and 0008). In one embodiment, the composition has a ratio of about 1:100 to 1:10,000 of Gallium-68-bound compounds to unbound compounds (0021). In embodiments composition comprises buffer such as citrate, acetate, or phosphate and a radioprotectant such as human serum albumin (HSA) or ascorbate. Other radioprotectants are known in the art and can also be used in the formulation buffer, i.e., free radical scavengers (phenol, sulfites, glutathione, cysteine, gentisic acid (reads on free radical scavenger), nicotinic acid, ascorbyl palmitate, HOP(:O)H2I glycerol, sodium formaldehyde sulfoxylate, Na2S2O, Na2S2O3, and SO2, etc) (0247). Additional disclosure includes the compounds and compositions that can be used to detect and quantify GCC-expressing cells associated with cancerous disorders such as solid tumors, soft tissue tumors, and metastatic lesions. Examples of solid tumors that express GCC include malignancies, e.g., sarcomas, adenocarcinomas, and carcinomas, of the various organ systems.
Ballinger discloses bilunctional compounds having a tripodal hydroxypyridinone
chelating portion conjugated to a targeting group so that the compounds target specific
cells or tissue in subject (abstract). In one embodiment, the bifunctional compounds
includes
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85
258
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or salts thereof; wherein one of X and Y is
C-Q and the other is NR; wherein R1 is a chelating group capable of chelating a
radionuclide and is selected from:
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172
494
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wherein R, R²; R³and R⁴ are independently hydrogen or an optionally substituted CI -7
alkyl group: B is a linker group for linking the chelating group to the reactive group
represented by the formula:
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83
193
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A* is a reacted reactive group that is coupled to T, T being a targeting group capable of binding to a target of interest in the subject (page 3 and 4). Additional disclosure includes that the bifunctional conjugate compounds provide a tripodal hexadentate tris (hydroxypyridinone) chelating portion, which is able to chelate metallic radionuclides in a very short time and is able to do so at room temperature at physiological pH. The quick and low temperature labelling of the chelating group allows the bifunctional molecule to be coupled both to a radionuclide with a short half-life, such as 68Ga through the chelating portion and to a temperature sensitive targeting group (page 6, line 4-20). The imaging probes (68Ga) has the property of
binding to the hydroxypyridinone groups of the chelating portion and can be used in PET imaging techniques.
Eder discloses synthesis, in vitro binding analyses, and biodistribution data of the radiogallium labeled PSMA - inhibitor Glu-NH-CO-NH-Lys (Ahx)-HBED-CC in comparison to the corresponding DOTA conjugate. (Glu-NH-CONH-Lys(Ahx)-HBED-CC; (is also called DKFZ-PSMA-11) (abstract). Typically, 0.1-1 nmol of Glu-NH-CO-NH- Lys(Ahx)- HBED-CC (7, in 0.1 MHEPES buffer pH 7.5) or 1 nmol of the DOTA conjugates (8/12, in 0.1 M HEPES buffer pH 7.5) were added in a volume of 100 uL to a mixture of 10 UL 2.1 M HEPES solution and 10 uL [⁶⁸Ga]Ga³+ eluate (560-100 MBq). The pH of the labeling solution was adjusted to 4.2. Depending on the chelator, the reaction mixture was incubated either at ambient temperature or at 80 °C for 2 min. The radiochemical yield (RCY) was determined using RP-HPLC (page 690). Additional disclosure includes that 68Ga complex of the HBED-CC ligand exhibited higher specificity for PSMA expressing tumor cells resulting in improved in vivo properties ⁶⁸Ga labeled Glu-NH-CO- NH-Lys(Ahx)-HBED-CC (DKFZ-PSMA-11) showed fast blood and organ clearances, low liver accumulation, and high specific uptake in PSMA expressing organs and tumor. It could be demonstrated that the PET-imaging property of a urea-based PSMA inhibitor could significantly be improved with HBED-CC.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate bifunctional chelator compounds (hydroxypyridinone) as taught by Ballinger into Fugazza's radiopharmaceutical composition. The person of ordinary skill in the art would have been motivated to make those modifications because Ballinger leaches that the bifunctional compounds may use a range of different chemistries and techniques for linking the biological moiety, targeting group, label, protein or polypeptides to the bifunctional compounds and/or for introducing further groups and properties into the bifunctional compounds (page 23 lines 15-23} and reasonably would have expected success because the bifunctional compounds are particularly useful for in vivo imaging applications such as cell death imaging, for example useful bifunctional compounds for the detection of apoptosis, in medical or research applications, for example in the field of oncology.
It would have been obvious to one of ordinary skill in the art at the time of invention to incorporate DKFZ-PSMA-11 targeting agent into Fugazza's radiopharmaceutical composition. The person of ordinary skill in the art would have been motivated to make those modifications because Eder teaches that ⁶⁸Ga complex of the HBED-CC ligand exhibited higher specificity for PSMA expressing tumor cells resulting in improved in vivo properties ⁶Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (DKFZ- PSMA-11) showed fast blood and organ clearances, low liver accumulation, and high specific uptake in
PSMA expressing organs and tumor. It could be demonstrated that the PET-imaging property of a urea-based PSMA inhibitor could significantly be improved with HBED-CC (abstract) and reasonably would have expected success because HBED-CC complex [⁶⁸Ga], proved to superior in comparison to the respective 68Ga-DOTA complex and the possibility of an efficient room-temperature labeling procedure in combination with the advantages of ⁶Ga as a PET radionuclide may allow the development of a kit-formulated radiopharmaceutical for the targeted imaging of prostate cancer.
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 22-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,826,436, over claims 1-7 of U.S. Patent No. 12.036,292 and, over claims 1-7 of U.S. Patent No. 12.109,277. Although the claims at issue are not identical, they are not patentably distinct from each other because each of the instant claims are drawn to composition comprising a chelator capable of chelating with a gallium radionuclide and optionally linked toa biological targeting agent. The claims differ in that those of the patented invention are directed to method of preparing a same complex comprising a radioisotope of gallium for use in a medical imaging procedure. Furthermore, according to MPEP 2112.01, if the compositions (conjugates) are of identical composition, then they cannot have mutually exclusive properties. In other words, chemical composition and its properties are inseparable. Thus, the characteristics associated with Applicant's invention would also be applicable to the composition of the patent invention. Hence, the inventions disclose overlapping subject matter.
It is respectfully requested of 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
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