DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 1, 5-14, 16, 19, 21, 25, 27-28, and 30 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12 Jan. 2026 has been entered.
Status of Claims
Claims 1, 16, 27-28, and 30 are amended. Claims 2-4, 15, 17-18, 20, 22-24, 26, 29, and 31-33 are canceled.
Response to Amendment
The amendments filed on 12 Jan. 2026 have been entered.
Response to Arguments
In view of Applicants amendments, the rejection of claims 1, 6-10, 12-16, 21, 25, and 27 under 35 USC 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017), in view of Lane et al. (Nucl. Med. Biol.; published 2008) is withdrawn.
In view of Applicants amendments, the rejection of claims 1, 5-16, 21, 25 and 27-28 under 35 USC 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017), in view of Lane et al. (Nucl. Med. Biol.; published 2008), in further view of Cao et al. (Nanoscale Res. Lett.; published 2016) and Jamous et al. (Nucl. Med. Biol.; published 2014) is withdrawn.
In view of Applicants amendments, the rejection of claims 1, 6-10, 12-16, 19, 21, 25, 27, and 30 under 35 USC 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017) and Lane et al. (Nucl. Med. Biol.; published 2018), in further view of Dapueto et al. (Bioorg. Med. Chem.; published 2015) is withdrawn.
In view of Applicants amendments, the rejection of claims 1, 5-16, 19, 21, 25, 27-28 and 30 on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US patent No. 10,130,717 B2, in view of Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014) and Dapueto et al. (Bioorg. Med. Chem.; published 2015) is withdrawn.
In view of Applicants amendments, the rejection of claims 1, 5-16, 19, 21, 25, 27-28 and 30 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US patent No. 11,197,888 B2, in view of Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014) and Dapueto et al. (Bioorg. Med. Chem.; published 2015) is withdrawn.
In view of Applicants amendments, the rejection of claims 1, 5-16, 19, 21, 25, 27-28 and 30 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of US patent No. 12,152,089 B2, in view of Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014) and Dapueto et al. (Bioorg. Med. Chem.; published 2015) is withdrawn.
New Grounds of Rejection
Claim Objections
Claim 16 is objected to because of the following informalities: “, and 186/188rhenium” should be removed from the claim and an “and” before 188rhenium to recite “, and 188rhenium”. Appropriate correction is required.
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, 5-10, 12, 16, 21, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017), in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892).
Ndinguri et al. teach LHRH-platinum conjugates for treating reproductive cancers (see title). Ndinguri et al. teach conjugation of lutenizing hormone-releasing hormone (DLys6]-LHRH) with activated cisplatin using a malonate linker that gives rise to new platinum (pt) conjugate that effectively targets tumor cells that express LHRH receptor ([0012]). Ndinguri et al. teach that LHRH, referred to as gonadotropin releasing hormone, is a decapeptide regulatory hormone comprised of sequence pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 involved in reproduction. Studies have shown that LHRH receptors are overexpressed in breast, prostate, endometrial and ovarian cancers, along with non-reproductive cancers, making LHRH peptide a good candidate for drug targeting (see [0007]). LHRH has been shown to be effective as a stand-alone treatment in certain cancers ([0008]). The mal linker may be utilized in combination with PEG groups. The targeting peptide can be endogenous LHRH or analog thereof (see [0037]). Ndinguri et al. teach the compound
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(see fig. 2). (SEQ ID: 2; (Pyr=pGlu-His-Trp-X1-X2-X3-X4-Arg-Pro-Gly-NH2 wherein X1=Ser, X2=Tyr, X3=DLys(right handed amino acid), X4=Leu, and linker is covalently bound to X3). Ndinguri et al. teach that the targeting peptide can be [D-Trp6]-LHRH, [D-Alal6]-LHRH, [Gln8]-LHRH, antide, etc ([0037]). The Pt-LHRH conjugate targets and binds to the LHRH receptors of any cancer cell or any tumor microenvironment that expresses these receptors ([0039]). Ndinguri et al. claim a method for killing or inhibiting the growth of cells in a tumor in a mammal (see claims 10-11).
Ndinguri et al. do not teach the claimed LHRH composition comprising a tridendate structure comprised of three amines and a metal or halide nuclide wherein the three amines retain the metal or halide nuclide wherein the metal or halide nuclide is 99mTc, 186Re, or 188Re.
Babich et al. teach that selective targeting of cancer cells with radiopharmaceuticals is challenging. Radionuclides known to be useful for radioimaging and radiotherapy include 186Re, 188Re, and 99mTc. The invention provides bifunctional molecules that comprises a specific homing bioactive molecule covalently tethered to Pt, 186Re, 188Re or 99mTc as tumor selective imaging agents ([0004], [0060]). Babich et al. teach compound 7
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(pg. 14) and Re-(7)
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(pg. 17) and the compound
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([0040], example 2). (Those compounds read on a linker and a tridentate structure comprised of three amines and a metal optionally wherein the three amines retain the metal and wherein the metal is rhenium and wherein the linker comprises an amino alkyl carboxylic acid wherein the alkyl is 11 carbons in length and wherein the tridentate structure is covalently linked to the linker). The present invention provides for a pharmaceutical composition comprising at least one metal complex of formula I ([0012]-[0014], [0016]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify LHRH composition of Ndinguri et al. (LHRH composition comprising a LHRH peptide, a linker, and a bidentate structure comprising a metal such as Pt) by substituting the bidentate structure retaining the metal with a tridentate structure comprising three amines and wherein the three amines retain 99mTc, 186Re or 188Re as taught by Babich et al. because the tridentate structure capable of retaining Pt and 99mTc-, 186Re- or 188Re-complexes thereof would have been expected to advantageously enable radionuclide imaging and therapy of cancer. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Ndinguri et al. so that the linker of the obvious LHRH composition comprises an amino alkyl carboxyl wherein the alkyl is of between 1 and 25 carbons in length as taught by Ndinguri et al. and Babich et al. because that linker would have been expected to provide an equivalent linker advantageously capable of directly attaching the obvious tridentate chelator to a Lys of the LHRH composition. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Ndinguri et al. by further administering the obvious 99mTc-, 186Re- or 188Re-LHRH complexes to a cell or subject to label a LHRH receptor on a cell or determine LHRH receptor expression in a subject whereby allowing binding and detecting as taught by Ndinguri et al. and Babich et al. because it would have been expected to enable imaging and/or therapy of LHRH expressing tumor cells optionally in vivo.
Claim(s) 1, 5-14, 16, 21, 25, and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017), in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892), in further view of Lane et al. (Nucl. Med. Biol.; published 2008), and Jamous et al. (Nucl. Med. Biol.; published 2014).
Ndinguri et al. teach as discussed above.
Ndinguri et al. do not further teach a tridentate structure that is a diethyltriamine or compounds of instant formulas (I) and (II) further having a PEG linker comprising between 1-25 EG units.
Babich et al. teach as discussed above.
Lane et al. teach 99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GPR receptor (see title). Lane et al. teach that 99mTc is ideally suited as a diagnostic radiometal for in vivo tumor targeting due to its ideal physical characteristics (see abstract). Lane et al. teach the new chelator DTMA and the conjugation of DTMA to NH2-(X)-BBN(7-14)NH2 wherein X is amino acid or a pharmacokinetic modifier (see abstract). Lane et al. teach that 99mTc is a versatile radiometal for use in molecular imaging of human tumors and Lane et al. teach the isolink radiolabeling kit. Tridentate ligand frameworks occupy all three binding sites of the fac-[99mTc(CO)3]+ metal fragment alleviating possible transmetalation reactions, thus offering higher quality SPECT images (see pg 264). Lane et al. teach the DTMA-(X)-BBN(7-14)NH2 structure
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(see Fig. 1) and [99mTc(CO)3-DTMA-(X)-BBN(7-14)-NH2]+
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(see scheme 2). [Re(CO)3-DTMA-(X)-BBN(7-14)NH2]+ conjugates were prepared by addition of an aqueous solution of [Re(Br)3(CO)3]2- (see pg. 267). DTMA-(X)-BBN(7-14)NH2 formed well-defined conjugates in good yield upon radiolabeling with the [99mTc(H2O)3(CO)3 precursor. All the conjugates displayed high affinity and selectivity for the GrPRr in vitro and in vivo (see pg. 271). Lane et al. teach the DTMA ligand provided effective containment of the fac-[99mTc(CO)3]+ metal center (see pg. 270).
Jamous et al. teach PEG spacers of different length influence the biological profile of bombesin-based radiolabeled antagonists (see title). Jamous et al. teach that GRPR was shown to be expressed with high density on several types of cancers. Among the studied analogs the PEG4 and PEG6 showed significantly better properties (see abstract; Fig. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Ndinguri et al. so that the obvious tridentate structure is a diethylenetriamine and/or so that the LHRH composition comprises the structure set forth in instant formula I as further taught by Lane et al. because that chelator and composition would have been expected to eliminate destabilization of metal center by transmetalation reactions and enable high quality imaging and therapy of LHRH expressing cancers. It would have been obvious to a person of ordinary skill in the art to further modify Ndinguri et al. by further incorporating a PEG4 or PEG6 spacer to arrive at a compound of instant formula II because the further incorporating would have been expected to advantageously enable a LHRH conjugate having improved properties including tumor to kidney ratios.
Claim(s) 1, 5-10, 12-14, 16, 19, 21, 25, 27, and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ndinguri et al. (US 2017/0157263 A1; published 8 Jun. 2017), in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892), and Lane et al. (Nucl. Med. Biol.; published 2008), in further view of Dapueto et al. (Bioorg. Med. Chem.; published 2015).
Ndinguri et al. teach as discussed above.
Ndinguri et al. do not further teach a LHRH composition wherein the LHRH peptide is dimerized through the metal nuclide or a compound of instant formula III.
Babich et al. teach as discussed above.
Lane et al. teach as discussed above.
Dapueto et al. teach as technetium glucose complex as potential cancer imaging agents (see title). Dapueto et al. teach 99mTc-IDAG
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(see Fig. 1). Dapueto et al. teach that the preparation of the 99mTc-IDAG complex was accomplished through a simple procedure in a similar way as previously described. The final complex of the 99mTc-IDA radiopharmaceuticals is an octahedral structure with two IDA molecules bounded to one technetium atom with oxidation state of +3 (see pg. 4255). Dapueto et al. teach that the IDAG is formed by a tridentate ligand proper for Tc(III) coordination. Radiolabeling was achieved with high radiochemical yield using a simple and quick labeling strategy for both derivatives. Complexes demonstrated excellent stability up to 5 h after labeling (>80%) and provide to be hydrophilic (pg. 4258).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the compounds of Ndinguri et al. by further forming a dimer complex with the 99mTc to arrive at a compound of instant formula III wherein n=1 and X=99mTc as taught by Dapueto et al. because the dimer complex would have been expected to advantageously enable a homobifunctional LHRH conjugate formed in high yield and is extremely stable, the homobifunctional LHRH conjugate enabling SPECT imaging of LHRH expressing cancers.
Applicants Arguments
Applicants assert that Ndinguri does not indicate that the cisplatin at the end of the linker could broadly be replaced by anything. Replacing the linker of Ndinguri with the linker of Lane makes two major structural changes. Ndinguri is under an obligation to expressly teach that changing the structure would affect linkage as one of ordinary skill in the art already knows of unpredictability and change in pharmacological effect with changes in structures. In the present rejection there is no direction or suggestion provided in any reference that would allow one skilled in the art to arrive at the present invention and the general knowledge of those skilled in the art provides guidance that making changes has a not always predictable effect on the pharmacological attributes of the resulting structure. Claim 1 has been amended so that platinum species are no longer an option and as discussed Ndinguri limits substitution to another cytotoxic drug in the platinum family. Claim 16 does not include technetium as an option. Cao, Jamous and Dapueto fail to overcome the deficiencies of Ndinguri and Lane.
Applicant's arguments filed 12 Jan. 2026 have been fully considered but they are not persuasive. Ndinguri provides a LHRH composition for the treatment of cancer comprising the SEQ ID NO: 2 peptide, a linker attached to the DLys and a bidentate structure and a Pt metal wherein the bidentate structure retains the Pt metal. Regarding the bidentate structure and Pt metal, at [0039], Ndinguri teaches that the proteases in the tumor microenvironment effective cleave the warhead, i.e. cisplatin, carboplatin, or other platinum drug or derivative to achieve more effective concentration of the target agent in the targeted area. Babich provides for compositions for the treatment of cancer comprising a specific receptor homing molecule, a linker, optionally an amino alkyl carboxylic acid, and a tridentate structure comprised of three amines wherein the amines, in addition to retaining a Pt warhead, advantageous retain 99mTc, 186Re and 188Re whereby enabling radionuclide imagining and therapy in addition to Pt therapy. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the LHRH composition of Ndinguri by substituting the bidentate structure retaining the Pt metal with Babich’s tridentate structure comprised of three amines and metal therein the three amines retain the metal and wherein the metal is 99mTc, 186Re or 188Re because those modifications would have been expected to enable radionuclide imaging and therapy in addition to Pt therapy. Modification of the LHRH composition of Ndinguri by substituting the bidentate structure retaining the metal with the tridentate structure of Babich would not have required substituting the mal linker. Regarding linker substitution, Ndinguri teaches that aliphatic linkers other than the mal linker may be used, either alone or in combination with other linkers. Babich provides for the amino alkyl carboxyl linker that enable attached the obvious tridentate chelator to a receptor homing agent using a carboxyl analogous to the Mal linker exemplified by Ndinguri. It would have been obvious to a person of ordinary skill in the art with a reasonable expectation of success to substitute the Mal linker exemplified by Ndinguri with amino alkyl carboxyl linker because that linker would have been expected to provide an equivalent linker suitable for attaching the tridentate chelator to the Dlys of the LHRH peptide. Regarding the diethylenetriamine tridentate structure, at pg. 270, Lane teaches that the diethylenetriamine tridentate structure eliminates destabilization of the metal center by transmetalation reaction. The diethylenetriamine tridentate structure provided effective containment of the metal center. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Ndinguri so that the obvious tridentate structure is the diethylenetriamine tridentate structure as further taught by Lane because that tridentate structure would have been expected to advantageously enable containment of the metal center.
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, 5-14, 16, 19, 21, 25, 27-28, and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,130,717 B2, in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892), Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014), and Dapueto et al. (Bioorg. Med. Chem.; published 2015).
Claims 1-16 of U.S. Patent No. 10,130,717 B2 claim the compound
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and similar compounds wherein the hormone domain comprises SEQ ID NO 1 (Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly) or [D-Lys6]-LHRH comprising Pyr and methods for slowing the growth of cancer cells expressing a receptor for LHRH and method for lessening the incidence of metastasis of cancer cells in mammal.
Claims 1-16 of U.S. Patent No. 10,130,717 B2 do not claim a LHRH composition comprising the tridendate structure of three amines and metal and where the three amines retain the metal or a linker that comprises an amino alkyl carboxylic acid wherein the alkyl is between 1 to 25 carbons or a tridendate structure that is a diethylenetriamine or a metal that is a radionuclide such as 99mTc. Claims 1-16 of U.S. Patent No. 10,130,717 B2 do not claim the structure
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. Claims 1-16 of U.S. Patent No. 10,130,717 B2 do not claim a method for labeling an LHRH on a cell or determining LHRH expression in a subject.
Babich et al. teach as discussed above.
Lane et al. teach as discussed above.
Jamous et al. teach as discussed above.
Dapueto 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 1-16 of U.S. Patent No. 10,130,717 B2 by substituting the Pt-mal linker complex with a 99mTc(CO)3-DTMA- or 186/188Re(CO)3-DTMA- linker complex to a compound of instant formula I wherein n=1 and x=99mTc or 186/188Re as taught by Babich et al. and Lane et al. because those complexes would have been expected provide high quality imaging and therapy of LHRH expressing tumors.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-16 of U.S. Patent No. 10,130,717 B2 by further incorporating a PEG spacer to arrive at instant formula II wherein X=99mTc and n is 1, 4 or 6 as taught by Jamous et al. because the further incorporating would have been expected to result in a LHRH conjugate having improved properties including tumor to kidney ratios.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-16 of U.S. Patent No. 10,130,717 B2 by further forming a dimer complex with the 99mTc to arrive at a compound of instant formula III wherein n=1 and X=99mTc as taught by Dapueto et al. because the dimer complex would have been expected to advantageously enable a homobifunctional LHRH conjugate formed in high yield and is extremely stable, the homobifunctional LHRH conjugate enabling SPECT imaging of LHRH expressing cancers.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-16 of U.S. Patent No. 10,130,717 B2 by further administering the obvious 99mTc(CO)3-DTMA-(PEG)-LHRH (dimer) to a cell or subject to label a LHRH receptor on a cell or determine LHRH expression in the subject whereby allowing the obvious 99mTc(CO)3-DTMA-(PEG)-LHRH (dimer) to bind to the LHRH receptor and then detect the radionuclide by SPECT as taught by Babich et al. and Lane et al. because it would have been expected to advantageously enable high quality SPECT detection of LHRH expressing tumor cells or tissue optionally in vivo.
Claims 1, 5-14, 16, 19, 21, 25, 27-28, and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,197,888 B2, in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892), Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014), and Dapueto et al. (Bioorg. Med. Chem.; published 2015).
Claims 1-14 of U.S. Patent No. 11,197,888 B2 claim a compound comprising a LHRH alalog such as [DLys6]-LHRH and SEQ ID NOS 1 (Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly) and 2, a cytotoxic platinum chemotherapeutic agent, wherein the linker comprises malonate and wherein the linker further comprises a PEG group and methods for lessening the incidents of metastasis of cancer cells or for causing apoptosis of cancer cells.
Claims 1-14 of U.S. Patent No. 11,197,888 B2 do not claim a LHRH composition comprising the tridendate structure of three amines and metal and where the three amines retain the metal or a linker that comprises an amino alkyl carboxylic acid wherein the alkyl is between 1 to 25 carbons or a tridendate structure that is a diethylenetriamine or a metal that is a radionuclide such as 99mTc, 186Re, or 188Re. Claims 1-14 of U.S. Patent No. 11,197,888 B2 do not claim the structure
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. Claims 1-14 of U.S. Patent No. 11,197,888 B2 do not claim a method for labeling an LHRH on a cell or determining LHRH expression in a subject.
Babich et al. teach as discussed above.
Lane et al. teach as discussed above.
Jamous et al. teach as discussed above.
Dapueto 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 1-14 of U.S. Patent No. 11,197,888 B2 by substituting the Pt-mal linker complex with a 99mTc(CO)3-DTMA- or 186/188Re(CO)3-DTMA- linker complex to a compound of instant formula I wherein n=1 and x=99mTc or 186/188Re as taught by Babich et al. and Lane et al. because those complexes would have been expected provide high quality imaging and therapy of LHRH expressing tumors.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-14 of U.S. Patent No. 11,197,888 B2 by further incorporating a PEG spacer to arrive at instant formula II wherein X=99mTc and n is 1, 4 or 6 as taught by Jamous et al. because the further incorporating would have been expected to result in a LHRH conjugate having improved properties including tumor to kidney ratios.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-14 of U.S. Patent No. 11,197,888 B2 by further forming a dimer complex with the 99mTc to arrive at a compound of instant formula III wherein n=1 and X=99mTc as taught by Dapueto et al. because the dimer complex would have been expected to advantageously enable a homobifunctional LHRH conjugate formed in high yield and is extremely stable, the homobifunctional LHRH conjugate enabling SPECT imaging of LHRH expressing cancers.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-14 of U.S. Patent No. 11,197,888 B2 by further administering the obvious 99mTc(CO)3-DTMA-(PEG)-LHRH (dimer) to a cell or subject to label a LHRH receptor on a cell or determine LHRH expression in the subject whereby allowing the obvious 99mTc(CO)3-DTMA-(PEG)-LHRH (dimer) to bind to the LHRH receptor and then detect the radionuclide by SPECT as taught by Babich et al. and Lane et al. because it would have been expected to advantageously enable high quality SPECT detection of LHRH expressing tumor cells or tissue optionally in vivo.
Claims 1, 5-14, 16, 19, 21, 25, 27-28, and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,152,089 in view of Babich et al. (WO 2013/103813 A1; published 11 Jul. 2013; see attached 892), Lane et al. (Nucl. Med. Biol.; published 2008), Jamous et al. (Nucl. Med. Biol.; published 2014), and Dapueto et al. (Bioorg. Med. Chem.; published 2015).
Claims 1-17 of U.S. Patent No. 12,152,089 B2 claim a method for delivering a cytotoxic chemotherapeutic agent to a cell that expresses a LHRH receptor comprising administering a LHRH analog; a cytotoxic platinum chemotherapeutic agent; and a linker wherein the linker comprises mal and PEG and wherein the LHRH analog is selected from [DLys6]-LHRH or SEQ ID No 1 and 2.
Claims 1-17 of U.S. Patent No. 12,152,089 B2 do not claim a LHRH composition comprising the tridendate structure of three amines and metal and where the three amines retain the metal or a linker that comprises an amino alkyl carboxylic acid wherein the alkyl is between 1 to 25 carbons or a tridendate structure that is a diethylenetriamine or a metal that is a radionuclide such as 99mTc, 186Re, or 188Re. Claims 1-17 of U.S. Patent No. 12,152,089 B2 do not claim the structure
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214
384
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,
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260
353
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, or
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188
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. Claims 1-17 of U.S. Patent No. 12,152,089 B2 do not claim a method for labeling an LHRH on a cell or determining LHRH expression in a subject.
Babich et al. teach as discussed above.
Lane et al. teach as discussed above.
Jamous et al. teach as discussed above.
Dapueto 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 1-17 of U.S. Patent No. 12,152,089 B2 by substituting the Pt-mal linker complex with a 99mTc(CO)3-DTMA- or 186/188Re(CO)3-DTMA- linker complex to a compound of instant formula I wherein n=1 and x=99mTc or 186/188Re as taught by Babich et al. and Lane et al. because those complexes would have been expected provide high quality imaging and therapy of LHRH expressing tumors.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-17 of U.S. Patent No. 12,152,089 B2 by further incorporating a PEG spacer to arrive at instant formula II wherein X=99mTc, or 186/188Re and n is 1, 4 or 6 as taught by Jamous et al. because the further incorporating would have been expected to result in a LHRH conjugate having improved properties including tumor to kidney ratios.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-17 of U.S. Patent No. 12,152,089 B2 by further forming a dimer complex with the 99mTc to arrive at a compound of instant formula III wherein n=1 and X=99mTc as taught by Dapueto et al. because the dimer complex would have been expected to advantageously enable a homobifunctional LHRH conjugate formed in high yield and is extremely stable, the homobifunctional LHRH conjugate enabling SPECT imaging of LHRH expressing cancers.
Applicants Arguments
Applicants assert that the overcoming the 35 USC 103 rejections concurrently overcomes the nonstatutory double patenting rejections for at least the same reasons.
Applicant's arguments filed 12 Jan. 2026 have been fully considered but they are not persuasive. A rejection of claims under 35 USC 103 has not been overcome for the reasons discussed above. The claims are rejected on the ground of nonstatutory double patenting for reasons discussed above.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618