DETAILED ACTION
This Office Action details a non-final action on the merits for the above referenced application No. Claims 1-5, 7-10, 12, 14-18, 23-24, and 27-28 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Aug. 2026 has been entered.
Status of Claims
Claims 1 and 15 are amended. Claims 6, 11, 13, 19-22, and 25-26 are cancelled. Claims 27-28 are new.
Response to Amendment
The claim amendments filed on 12 Aug. 2026 have been entered.
Response to Arguments
In view of Applicants amendments, the rejection of claim 15 under 35 USC 112(d) as being of improper dependent form for failing to further limit the subject matter upon which it depends is withdrawn.
In view of Applicants amendments, the rejection of claims 1-3, 7-18, and 23-24 under 35 USC 103 as being unpatentable over Babiche t al. (WO 2018/187631 A1; published 11 Oct. 2018), in view of Donnelly et al. (WO 2010/063069 A1; published 10 Jun. 2010) and Berkman et al. (WO 2018/098390 A1; published 31 May 2018) is withdrawn.
In view of Applicants amendments, the rejection of claims 1-3, 7-18, and 23-24 under 35 USC 103 as being unpatentable over Babich et al. (WO 2018/187631 A1; published 11 Oct. 2018), in view of Donnelly et al. (WO 2010/063069 A1; published 10 Jun. 2010) and Berkman et al. (WO 2018/098390 A1; published 31 May 2018), in further view of Zeglis et al. (US 2016/0331852 A1; published 17 Nov. 2016) is withdrawn.
New Grounds of Rejection
Claim Objections
Claim 2 is objected to because of the following informalities: “a tumor-specific cell surface protein” is recited twice in the claim. Appropriate correction is required.
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 2 and 14 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.
Regarding claim 2, the recitation of an overexpressed peptide receptor is indefinite because it is not clear what qualifies as an overexpressed peptide receptor.
Regarding claim 14, instant claim 14 is dependent to cancelled claim 13.
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) 1-3, 7-10, 12, 14-18, and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Babich et al. (WO 2018/187631 A1; published 11 Oct. 2018), in view of Donnelly et al. (WO 2010/063069 A1; published 10 Jun. 2010) and Berkman et al. (WO 2018/098390 A1; published 31 May 2018).
Babich et al. teach trifunctional constructs with tunable pharmacokinetics useful in imaging and anti-tumor therapies (see title). Babich et al. teach compounds for the treatment of for example prostate cancer (see abstract). Babich et al. teach the compound RPS-063 of the formula
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wherein n=2 having a PSMA IC50 (nM) of 1.5±0.3 and a max tumor uptake (%ID/g) of 30.0±6.9 ([0233], table 2, pg. 88).
(This reads in part on a compound of instant formula (IV) or (V) wherein TTD is PSMA GUL tumor targeting domain,
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wherein o’=0; P4=P5=P6=H and W4=-(CH2)s-NH-C(O)-, and s=2; X1 is absent; p=0; q=2; L1=-O(CH2CH2O)f’-CH2CH2C(O)-, f’=2; sarc=Lys-DOTA chelator containing domain; L2=absent; BBD is a blood protein binding domain of formula
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where Y1=Y2=Y4=Y5=H, w=1, v=1, X3=O, u=0, and t=2 and where the BBD comprises a 4-iodophenylalkanoic acid/2-(4-iodophenyl acetic acid) and a pharmaceutical composition comprising an effective amount of a compound suitable for imaging or detecting prostate cancer
Babich et al. teach compounds of formula (I)
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wherein ABD is an antigen binding domain and wherein R1-R3 are suitably for example
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wherein Tox is a cytotoxin containing domain or imaging agent containing domain such as
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([0092]) and Alb is an albumin binding moiety (pg. 18). The antigen binding domain may be a tumor targeting moiety including PSMA, SSTR2, bombesin, etc ([0084]). The albumin binding domain may be
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([0086]) or
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([0087]). Babich et al. teach chelators selected from the group consisting of NOTA, etc ([0090]). Metal ions for tox and/or rad may be 177Lu, etc ([0087]). Babich et al. teach that L1 may be -O(CH2CH2O)r’-CH2CH2C(O)- and L2 may be –(CH2CH2O)s-CH2CH2C(O)- ([0094]-[0095]).
Babich et al. teach a pharmaceutical composition comprising a pharmaceutically acceptable carrier and composition comprising an effective amount of a compound therein for detecting PSMA expressing cancer including prostate cancer or for treating cancer including prostate cancer (pgs 125-126). Babich et al. teach methods comprising administering to a subject an effective amount of the for imaging cancer and detecting radiation from the compound and methods of treating cancer overexpressing PSMA (pgs. 127-128).
Babich et al. do not teach compounds of formulas (IV) and (V) containing the claimed linker fragment
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or
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and a sarc domain that is
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optionally further chelating 64Cu or 67Cu or a composition thereof further comprising a pharmaceutically acceptable carrier. Babich et al. do not exemplify a compound wherein the BBD is
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. Babich et al. do not disclose a method comprising administering an effective amount of a compound of claim 15 for imaging or treating a cancer
Donnelly et al. teach nitrogen containing macrocyclic conjugates as radiopharmaceuticals (see title). Donnelly et al. teach compounds that contain a molecular recognition moiety and coordinated to a suitable radionuclide. The coordinated compounds are useful in areas of radiotherapy and diagnostic imaging (see abstract). The caged compounds form remarkably stable complexes with metals such as Cu2+ and have fast complexation kinetics even at low concentrations of metal at ambient temperatures (see pg. 2). Donnelly et al. teach antibodies (pg. 3). Donnelly et al. teach 64Cu and 67Cu (pg. 17). Donnelly et al. teach the sarcophagine
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(R22=Me; pg. 29). Donnelly et al. teach molecular recognition moieties such as octreotate (pg. 34).
Berkman et al. teach albumin-binding PSMA inhibitors (see title). Berkman et al. teach imaging diagnostics and therapeutics for prostate cancer that capitalize of the potency and specific affinity of small-molecule inhibitors to PSMA (0005]). Berkman et al. teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier ([0011]). Berkman et al. teach the triazole linking groups
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and
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(see [0046], [0047]). Berkman et al. teach dibenzocyclooctyne (pgs. 10, 43). Berkman et al. teach the compounds
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and
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([00102]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compounds of Babich et al. (e.g., RPS-063) by substituting the triazole linker fragment with a linker fragment represented by
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or
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that attaches to a -NH- on the TTD as taught by Berkman et al. because linker fragments would have been expected to equivalent linker fragments formed by chemoselective cycloaddition reaction by advantageous strain promoted azide alkyne cycloaddition using a dibenzocyclooctyne. 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 Babich et al. by further substituting the DOTA-Bz-SCN chelator of RPS063 with a Sarc chelator such as
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to arrive at the claimed sarcophagine containing domain wherein L3=-C3 alylene-NR25C(O)-C3 alkylene-C(O)-, R22=Me and R25=H and so that the sarc optionally chelates 64Cu or 67Cu and then optionally add an effective amount of one of those compounds to a pharmaceutically acceptable carrier to form a pharmaceutical composition as taught by Babich et al. and Donnelly et al. because it would have been expected to advantageously enable remarkably fast and stable radiocopper complex and compositions suitable for imaging and treating prostate cancer. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Babich et al. because further substituting the BBD domain with
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as taught by Babich et al. because that substituting would have been expected to provide an equivalent BBD domain suitable for binding to albumin. Stereoisomers are prima facie obvious. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Babich et al. by further administering an effective amount of the obvious sarc containing derivatives chelating 64/67Cu to a subject for PET imaging or treating a prostate cancer and optionally PET image the subject as taught by Babich et al., Donnelly et al. and Berkman et al. because the administering would have been expected to advantageously enable in vivo imaging and therapy of cancer using remarkably stable radiocopper complexes.
Claim(s) 1-5, 7-10, 12, 14-18, and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Babich et al. (WO 2018/187631 A1; published 11 Oct. 2018), in view of Donnelly et al. (WO 2010/063069 A1; published 10 Jun. 2010) and Berkman et al. (WO 2018/098390 A1; published 31 May 2018), in further view of Zeglis et al. (US 2016/0331852 A1; published 17 Nov. 2016).
Babich et al. teach as discussed above.
Babich et al. do not further teach a tumor targeting domain that comprises trastuzumab or bevacizimab.
Donnelly et al. teach as discussed above.
Berkman et al. teach as discussed above.
Zeglis et al. teach radioligands for pre-targeted PET imaging and methods of their therapeutic use (see title). Zeglis et al. teach Tz/TCO base pre-targeted strategies using a 64Cu-sarcophagine based tetrazine radioligand for pre-targeted PET imaging. The imaging strategies enable PET imaging of cancer ([0015]). Zeglis et al. teach that in certain embodiments the targeting moiety is an antibody selected as trastuzumab or bevacizumab ([0039]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Babich et al. by further substituting the PSMA tumor targeting domain with a trastuzumab or bevacizumab tumor targeting domain as taught Zeglis et al. because the substituting would have been expected to enable targeting HER-2 or VEGF expressing cancer.
Claim(s) 1-3, 7-10, 12, 14-18, 23-24, and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Babich et al. (WO 2018/187631 A1; published 11 Oct. 2018), in view of Donnelly et al. (WO 2010/063069 A1; published 10 Jun. 2010) and Berkman et al. (WO 2018/098390 A1; published 31 May 2018), in further view of Maeke et al. (WO 2009/109332 A1; published 11 Sep. 2009; see attached 892).
Babich et al. teach as discussed above.
Babich et al. do not further teach the compounds
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and
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Donnelly et al. teach as discussed above.
Berkman et al. teach as discussed above.
Maeke et al. teach bombesin analog peptide antagonist conjugates (see title). Maeke et al. teach that preferred spacers comprising 4-amino-l-carboxymethylpiperidine and PEG1-14 (pg. 18), Maeke et al. teach DOTA-PEG4-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-TΦ-Ala-Val-Gly-His-LeuΨ(CHOH-CH2)-(CH2)2-CH3 (pg. 52). Maeke et al. teach the compound
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(pg. 69).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Babich et al. by further substituting the PSMA peptide with an octreotate peptide or bombesin peptide having a -PEGn-4-amino-1-carboxymethyl-piperidine- spacer fragment attached to the D-Phe moiety and so that the L1 is -O(CH2CH2O)2-CH2CH2C(O)- and L2 is -(CH2CH2O)7-CH2CH2C(O)- to arrive at the above two claimed species as taught by Babich et al., Donnelly et al. and Maeke et al. because those substitutions would have been expected to provide equivalent conjugates advantageously suitable for targeting ssrt2 and GRPR associated cancers.
Applicants’ Arguments
Applicants assert that no credible reason has been established for a POSITA to select the particular pieces in the particular necessary locations on the compound of Babich to arrive at the claimed compounds. The combination of references fails to guide a POSITA to select the particular pieces necessary and incorporate those particular pieces in the particular necessary locations on a compound of Babich required to arrive at the claimed compounds. A POSITA would have to engage in trial and error to substitute numerous locations on the several compound disclosed in Babich before arriving at the claimed compound.
Applicants’ arguments filed 12 Aug. 2026 have been fully considered but they are not persuasive. The compounds of Babich differ from the claimed compounds at two different locations: (1) the triazole location, and (2) chelator location. Regarding the motivation to substitute the triazole fragment of the RPS-063 compound in Babich with the claimed linker fragment, the prior art of Berkman teaches that the claimed linker fragments of formulas (IV) and (V), advantageously derived by strained promoted cycloaddition reaction of a DBCO derivative and an azide, are compatible with PSMA receptor conjugates. A person of ordinary skill in the art would have had reason and motivation to substitute the triazole linker fragment of the RPS-063 with the claimed linker fragments in order to an equivalent conjugate suitable to targeting PSMA receptors and in order to gain the advantage of chemoselective strained promoted cycloaddition conjugation.
Regarding the motivation to substitution the chelator moiety of Babich with the claimed sarcophagine containing domain, Babich itself teaches chelator substitution. Donnelly teaches that the claimed sarcophagine containing domain rapidly and stably complexes the theranostic pair 64/67Cu. 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 further modify the exemplified compound RPS-063 of Babich by substituting the DOTA chelator moiety with the claimed sarcophagine containing domain because that substitution would have been expected to advantageously enable rapid and very stable complexes of the theranostic pair to further enable in vivo imaging and therapy of cancers.
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
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