DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-20, 24, 26, 28-31, 33-36, 39, and 41 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 371 National Stage filing of international application No. PCT/US2020/030085 filed on 27 Apr. 2020, and claims benefit under 35 USC 119(e) to US provisional application No. 62/839,085 filed on 26 Apr. 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 30 Dec. 2024 has been considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 30 Dec. 2024 is acknowledged. The traversal is on the ground(s) that Bauder (WO 2015/055316 A1) does not anticipate or render obvious the claimed formula (I) and the claimed formula (I) qualifies as a special technical feature that defines a contribution of the prior art. This is not found persuasive because Groups I-II do not contain a special technical feature that make a contribution of the prior art of Kung et al. (WO 2017/116994 A1) for the reasons cited in the rejection of claims under 35 USC 102(a)(1),(2) and 35 USC 103 below. That is, claimed formula (I) does not contain a special technical feature that defines a contribution over the prior art as set forth below.
The requirement is still deemed proper and is therefore made FINAL.
Claims 36 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II and III, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 30 Dec. 2024.
Applicant’s election without traverse of the species shown below, claims 1-4, 7-11, 15-20, 24, 26, 28, 30-31, and 33-35 in the reply filed on 3 Dec. 2025 is acknowledged.
Claims 5-6, 12-14, 29, and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 30 Dec. 2024.
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Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 16-17, 20 and 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Instant claims 16 and 17 are dependent to claim 1 require the structural fragments
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and R37a; however, those structural fragments are not defined in claim 1 or claims themselves. Claims 11 and 20 depends to claim 1 and require a R37a that is not defined in claim 1. Claim 24 depends to claim 2 and includes that A1 may be selected from -(CH2)nC(O)NH- or -(CH2CH2O)n(CH2CH2NH)n-; however, n is not defined in claims 1, 2, or 24.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The following rejection is based upon art which was found incidental to the search for the elected species. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
Claim(s) 1, 7-11, 20, 26, 30, 33, and 35 is/are rejected under 35 U.S.C. 102(a)(1),(2) as being anticipated by Kung et al. (WO 2017/116994 A1; published 6 Jul. 2017; see attached 892).
Regarding claims 1, 7-11, 20, 26, 30, and 33 Kung et al. disclose the compounds 5b
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([0130]-[0131]), and [68Ga]5b. These compounds read on compounds of instant formula I
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and a 68Ga complex thereof wherein W=
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(PSMA ligand;
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, R20=Lys, R21=Glu); R37= CH2Ph (alkyl aryl); R38=H; s=1; R33=R34=R35=R36=H; G=O; v=0; X2=O; A2=bond; B2=H; r=0; q=1; T1=T11=
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and Z=HBED (chelating moiety) and provided that Z is not Z1 or
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. Regarding claim 35, Kung et al. disclose intravenous injection of [68Ga]5b (implies a composition comprising a pharmaceutically acceptable carrier).
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.
The following rejection is based upon art which was found incidental to the search for the elected species. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
Claim(s) 1-2, 7-11, 16-20, 24, 26, 30-31, 33, and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kung et al. (WO 2017/116994 A1; published 6 Jul. 2017; see attached 892), in view of Lutje et al. (Theranostics; published 2015; see attached 892).
Kung et al. teach as discussed above. Kung et al. teach urea based prostate specific membrane antigen (PSMA) inhibitors for imaging and therapy (see title). Kung et al. teach compounds of formula IV wherein Z is a chelating moiety ([0014]). Kung et al. teach that the series with the novel phenoxy linker showed equal or better binding affinity that [68Ga]1 ([0027]). Kung et al. teach chelating moieties selected from the group consisting of DOTA, etc ([0038]). Kung et al. teach compounds 5a
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([0127]-[0128]), and [68Ga]5a. The results suggest that specific binding of [68Ga]5b was comparable to that of known compound [68Ga]1 ([0153]). The internalized activity was much higher for [68Ga]5b ([0164]-[0165]). Although [68Ga]5a demonstrated lower tumor uptake its kidney retention was the lowest which is desirable for therapeutic drug ([0168]). Only LNCaP tumor was clearly visualized with all tracers with good tumor to background contrasts ([0177]).
`Kung et al. do not further teach a compound of instant formula I wherein Z is
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where D is a divalent linking structure derived from DOTA and A1 is a bond or a compound of formulas III-A, III-B, and IV-A or a 68Ga or 177Lu complex of formula IVA.
Lütje et al. teach PSMA ligands for radionuclide imaging and therapy of prostate cancer (see title). Lütje et al. teach that to improve the pharmacokinetics of the DOTA-coupled PSMA ligands, the hydrophilicity of the ligand was increased by substitution with DOTAGA which can be labeled with both 68Ga and 177Lu and thus used for diagnostic and therapeutic purposes. DOTAGA conjugated ligand complexes showed a significantly increase affinity towards PSMA on PSMA expressing LNCaP cells compared to DOTA-conjugated PSMA ligands (pg. 1398).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compounds and compositions of Kung et al. (compounds 5a and 5b and pharmaceutical compositions thereof) by substituting the DOTA or HBED-CC chelators with DOTAGA to arrive at instant formula IV-A and optionally form 68Ga or 177Lu complexes with that compound as taught by Lütje et al. because the DOTAGA chelator and 68Ga or 177Lu complexes thereof would have been expected to advantageously enable significantly increased affinity towards PSMA and/or advantageous theranostic applications.
Claim(s) 1-4, 7-11, 15-20, 24, 26, 28, 30-31, and 33-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kung et al. (WO 2017/116994 A1; published 6 Jul. 2017; see attached 892), in view of Lütje et al. (Theranostics; published 2015; see attached 892), in further view of Abiraj et al. (Chem. Commun.; published 2008; see attached 892).
Kung et al. teach as discussed above. In addition, Kung et al. teach dimeric imaging agents (see examples 6f, 6g, 15-17).
Kung et al. do not further teach a compound of instant formula I wherein Z is
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where D is
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or a compound of formula IV-B or the elected species
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.
Abiraj et al. teach novel DOTA-based prochelator for divalent peptide vectorization (see title). Abiraj et al. teach that application of multivalent ligands showed markedly increased binding affinity with their respective receptors compared to monovalent ligands (pg. 3248). Abiraj et al. teach that DOTA based prochelators for the multivalent grafting of targeting ligands is of significant interest to develop improved targeting vectors that could find potential application in different imaging modalities (pg. 3248). Abiraj et al. teach prochelator (04)
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containing two free carboxyl groups for divalent vectorization (pg. 3248). Abiraj et al. teach deprotection of the tBu protecting groups (scheme 1). The divalent peptide conjugates showed excellent labeling properties with radiometals of interest such as 177Lu and 68Ga (pg. 3249).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Kung et al. so that the obvious DOTAGA chelator gets further modified by incorporation of a second glutamic acid radical to arrive at the elected species and a pharmaceutical composition thereof and optionally form 68Ga or 177Lu complex with that compound as taught by Kung et al. and Abiraj et al. because the second glutamic acid radical would have been expected to advantageously further increase hydrophilicity and binding affinity and advantageous enabling of multivalent constructs that optionally potentially increasing tumor uptake.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618