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 .
Receipt is acknowledged of IDS filed on 05/12/2023, 02/18/2025 and 02/13/2026.
Claims 1-3, 5-8, 10-12 and 15-25 are pending.
Claims 4, 9, 13, 14, and 26-28 are cancelled.
Claims 15 and 22-25 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I and Species A-E in the reply filed on 02/06/2026 is acknowledged.
Claim Objections
Claim 21 objected to because of the following informalities: The structures listed in claim 21 are blurry. Clearer images are required. 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 19 and 21 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.
Claim 19, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 19 recites the broad recitation “chelator”, and the claim also recites "(e.g. 1,4,7,10- tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA))" which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 21 has the following structure:
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. The variables s, n, and o are not defined. It is unclear what those variables represent. It is unclear what the “/” in “ABM/Targeting Motifs” represents or if multiple motifs are required or not.
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.
Claims 1, 2, 5, 7, 10-12, 16 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ODEGARD (WO 2020/056008 A1).
Regarding claim 1, ODEGARD teaches a prodrug (paragraph 0348) that targets tumors (page 4, paragraph 0029) comprising:
a targeting moiety, such as an antigen binding domain that binds to PSMA (claim 111), which read son a targeting moiety that specifically binds to an extracellular antigen,
an enzyme cleavable linker (paragraph 0257), and
a first innate immune system activator, such as a TLR7 agonist (claim 39).
Wherein the first linker covalently links the targeting moiety to the innate immune activator (page 79, paragraph 0257).
Regarding claim 2, ODEGARD teaches that the binding domain binds to PSMA (claim 111).
Regarding claim 5, ODEGARD teaches the linker can be cleaved by a lysosomal enzyme, such as cathepsin (page 113, paragraph 0372).
Regarding claim 7, ODEGARD teaches that there is a spacer linker between the targeting moiety and the first linker (page 114, paragraph 0376).
Regarding claims 10-12, ODEGARD teaches a first innate immune system activator, such as a TLR7 agonist (claim 39), such as Imiquimod (page 36, paragraph 1).
Regarding claim 16, ODEGARD teaches adding a radioactive isotope, such as 18F (page 105, paragraph 0340), which applicants specification defines as a radiolabel moiety (page15, paragraph 0085).
Regarding claim 20, ODEGARD teaches an additional linker attached to an immune-stimulatory compound is present in the prodrug conjugate (page 149, paragraph 0428 and formula I).
Claim 21 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by BERKMAN (WO 2014/143736).
Regarding claim 21, BERKMAN teaches the following prodrug:
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(page 72).
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.
Claims 1-3, 5, 7, 10-12, 16, 17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over ODEGARD (WO 2020/056008 A1) in view of MOON (Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. EJNMMI Radiopharmacy and Chemistry. July 2020.).
ODEGARD teaches Applicant’s invention as discussed above. ODEGARD further teaches that an antigen binding domain that binds to PSMA can instead be an antigen binding domain that binds to FAP (page 258, claim 69).
Regarding claims 3, 17 and 19, ODEGAR does not teach using a specific FAP inhibitor, such as FAPI-04 or attaching the radiolabel to a chelator, such as DOTA.
Regarding claim 3, MOON teaches a prodrug that targets tumors that uses FAPI-04 (page 3, paragraph 2) which had improved imaging parameters and high tumor uptake.
Regarding claims 17 and 19, MOON teaches incorporating a 68Ga radioisotope into DOTA (abstract) which showed low accumulation in normal tissues, rapid clearance from the blood via kidneys and bladder and high tumor uptake (page 3, paragraph 2).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate FAPI-04. The person of ordinary skill in the art would have been motivated to make those modifications, because FAPI-04 is s specific form of the FAP inhibitor taught by ODEGAR and it showed improved imaging parameters and high tumor uptake, and reasonably would have expected success because the references are in the same field of endeavor, such as prodrugs that are used to target tumors.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a 68Ga radioisotope into DOTA. The person of ordinary skill in the art would have been motivated to make those modifications, because it showed low accumulation in normal tissues, rapid clearance from the blood via kidneys and bladder and high tumor uptake, and reasonably would have expected success because the references are in the same field of endeavor, such as prodrugs that are used to target tumors.
Claims 1-3, 5-7, 10-12, 16, 17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over ODEGARD (WO 2020/056008 A1) and MOON (Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. EJNMMI Radiopharmacy and Chemistry. July 2020.) in view of POREBA (Protease-activated prodrugs: strategies, challenges, and future directions. The FEBS Journal. Jan 2020.).
ODEGARD and MOON teach Applicant’s invention as discussed above. ODEGARD further teaches that the enzyme cleavable linker can be a valine-citrulline peptide.
Regarding claim 6, ODEGARD and MOON do not teach wherein the enzyme-cleavable linker is an alanine-alanine-asparagine legumain linker.
Regarding claim 6, POREBA teaches an alanine-alanine-asparagine legumain enzyme cleavable linker (figure 3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate an alanine-alanine-asparagine legumain linker. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because an alanine-alanine-asparagine legumain linker and a valine-citrulline peptide linker are functional equivalents of enzyme cleavable linkers commonly used in the pharmaceutical industry for prodrugs.
Claims 1-3, 5-8, 10-12, 16, 17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over ODEGARD (WO 2020/056008 A1), MOON (Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. EJNMMI Radiopharmacy and Chemistry. July 2020.) and POREBA (Protease-activated prodrugs: strategies, challenges, and future directions. The FEBS Journal. Jan 2020.) in view of ZURICH (WO 2016/181304).
ODEGARD, MOON and POREBA teach Applicant’s invention as discussed above. ODEGARD further teaches using a spacer linker between the targeting moiety and the first linker (page 114, paragraph 0376), such as bifunctional para-aminobenzyl alcohol group (PABA) (page 114 paragraph 0377). ODEGARD further teaches that polyethylene glycol (PEG) can be included in the linkers.
Regarding claim 8, ODEGARD, MOON and POREBA do not teach using a N-hydroxysuccinimide (NHS)-PEG-Alkyne spacer linker.
Regarding claim 8, ZURICH teaches using compound for targeting that uses a NHS-PEG-Alkyne spacer linker (page 53, paragraph 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a NHS-PEG-Alkyne spacer. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because a NHS-PEG-Alkyne spacer and a PABA spacer are functional equivalents of spacers commonly used in the pharmaceutical industry for targeting compounds. Furthermore, ODEGARD teaches that polyethylene glycol (PEG) can be included in the linkers.
Claims 1-3, 5-8, 10-12, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over ODEGARD (WO 2020/056008 A1), MOON (Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. EJNMMI Radiopharmacy and Chemistry. July 2020.), POREBA (Protease-activated prodrugs: strategies, challenges, and future directions. The FEBS Journal. Jan 2020.) and ZURICH (WO 2016/181304) in view of KOSTIKOV (Synthesis of [18F]SiFB: a prosthetic group for direct protein radiolabeling for application in positron emission tomography. Protocol. 2012.).
ODEGARD, MOON, POREBA and ZURICH teach Applicant’s invention as discussed above.
Regarding claim 18, ODEGARD, MOON, POREBA and ZURICH do not teach adding the radiolabel with a prosthetic group, such as a benzoate moiety.
Regarding claim 18, KOSTIKOV teaches using a prosthetic group with a radioisotope for labeling, such as N-Succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB) (abstract), which is a benzoate moiety.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate (18)F]SiFB. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because (18)F]SiFB and 68Ga into DOTA are functional equivalents of radiolabels commonly used in the pharmaceutical industry for drugs and ODEGARD teaches using 18F.
Allowable Subject Matter
Structures 1-13 in claim 21 are free of the prior art.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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