DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claim 1 is 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 111(a) filing and a continuation of international application No. PCT/US22/39601 filed on 5 Aug. 2022 and claims benefit under 35 USC 119(e) to US provisional application No. 63/230,439 filed on 6 Aug. 2021.
Information Disclosure Statement
An information disclosure statements (IDS) has not been filed for this application.
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Si et al. (Cancer Biotherapy and Radiopharmaceuticals; published 2019; see attached 892).
Regarding claim 1, Si et al. disclose the compounds
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(pg. 553) that bind to EGFR having and intracellular protein domain (pg. 551). The Michael acceptor side chain of irreversible inhibitors at 6-position forms a covalent bond with the sulfhydryl group of Cys-773 of EGFR (pg. 552). The compound bound specifically to HCC 827 cells harboring an activating mutation in the EGFR gene.
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 is/are rejected under 35 U.S.C. 103 as being unpatentable over Planken et al. (J. Med. Chem.; published 2017; see attached 892)., in view of Si et al. (Cancer Biotherapy and Radiopharmaceuticals; published 2019; see attached 892).
Planken et al. teach discovery of PF-06747775 through structure-based design: a high affinity irreversible inhibitor targeting oncogenic EGFR mutants with selectivity over wild-type EGFR (see title). Planken et al. teach the compound 1
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having low nanomolar potency against both EGFR T790M-resistant mutants, excellent selectivity for drug resistant mutants over WT EGFR and in vitro and in vivo ADME characteristics well suited for in vitro efficacy studies (Fig. 1, pg. 3003). Planken et al. teach chemical probes P_1
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and P_21
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(see Fig. 10) compared to that of a chemical probe P_AQ a quinazoline based covalent second generation pan ERBB2 inhibitor, which contains a Michael acceptor acrylamide (pg. 3013). (P_1 and P_21 on a conjugate comprising a targeting ligand wherein the targeting ligand selectively binds to an intracellular protein wherein the intracellular protein is mutated and a linker.) Planken et al. teach compounds 17 , 19 and 21 (tables 4 and 6). The tert-butyl afforded the highest selectivity margin (pgs. 3010-3011). Addition of methyl, methoxy, or ethyl all improved kinase selectivity (pg. 3009). Compound 21 has potency against both common T790M EGFR double mutants and single activating mutants Del and L858R while retaining selectivity over EGFR wild type (pg. 3016).
Planken et al. do not expressly teach a conjugate further comprising a metal chelator.
Si et al. teach as discussed above. Si et al. teach evaluation of EGFR-TK expression with a 99mTc-labeled complex bearing a quinazoline pharmacophore (see title). Si et al. teach that considering widespread application, in this study, a aniloquinazoline derivative was conjugated with a bifunctional chelator and then labeled with 99mTc to establish a novel SPECT imaging probe (pg. 556). The whole-body noninvasive imaging based on probes specific for activated status of EGFR kinase could provide information of EGFR expression of the tumor lesions for forecasting treatment response before initiating the EGFR inhibitor-based therapy. The results demonstrate the feasibility of using complex13 as a SPECT tracer for screening EGFR TKIs sensitive patients (pg. 557).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify compounds of Planken et al. (P_1 and P_21) by connecting a chelator moiety to a linker attached to the pyrazolyl N as taught by Planken et al. and Si et al. because the a chelator attached to the linker would have been expected to advantageously enable whole body SPECT or PET imaging of mutated EGFR with high selectivity over WT EGFR enabling the in vivo detection of cancer and the forecasting of treatment response.
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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 8-12, 19, 35, 38, 40, 42, 69, 75, 81, 88, 94, 96, and 108 of copending Application No. 18/434,621 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because those claims claim a conjugate comprising a targeting ligand wherein the targeting ligand covalently binds to an intracellular protein wherein the intracellular protein is mutated; a linker and a metal chelator. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, 22, 24, 43-45, 47, 50-54, 57-58, 60, 63-64, 71, and 74 of copending Application No. 18/431,646 in view of Si et al. (Cancer Biotherapy and Radiopharmaceuticals; published 2019; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1, 18, 22, 24, 43-45, 47, 50-54, 57-58, 60, 63-64, 71, and 74 of copending Application No. 18/431,646 claim a radiopharmaceutical conjugate comprising a targeting ligand that covalently binds to an intracellular KRAS protein wherein the intracellular KRAS protein is mutated and wherein the conjugate comprises a linker and a radionuclide such as
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.
Claims 1, 18, 22, 24, 43-45, 47, 50-54, 57-58, 60, 63-64, 71, and 74 of copending Application No. 18/431,646 do not claim the instant conjugate comprising a chelator.
Si 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, 18, 22, 24, 43-45, 47, 50-54, 57-58, 60, 63-64, 71, and 74 of copending Application No. 18/431,646 so that a chelated radionuclide replaces the radioiodine radionuclide as taught by Si et al. because the chelated radionuclide would have been expected to advantageously enable widespread SPECT imaging or PET imaging of disease associated intracellular proteins wherein the intracellular proteins are mutated.
Technical Background Material
Jain et al. (Bioorg. Med. Chem. Lett.; published 2017; see attached 892) is being made of record; however, it is not being used in a rejection because it is cumulative.
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
Prosecution Insights