IP Library › Granted Patent US 12,486,334
Granted Patent B2
US 12,486,334 · App. 17/626,459 · Granted Dec 2, 2025

Chemically controlled monoclonal antibody target engagement

Inventors: Charles S. Craik (San Francisco, CA); Kevan M. Shokat (San Francisco, CA); Ziyang Zhang (San Francisco, CA); Peter J. Rohweder (San Francisco, CA)
Assignee: The Regents of the University of California
C07K16/44A61K39/39558A61K39/39583A61K47/50A61K47/6843A61P35/00C07K16/2809G01N33/574A61K2039/505C07K2317/21C07K2317/24C07K2317/31C07K2317/55C07K2317/565C07K2317/92
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Quick Facts
Patent No.
US 12,486,334
App. No.
17/626,459
Granted
Dec 2, 2025
Kind
B2
Abstract

The present disclosure relates generally to antibodies reactive with tumor-specific neoantigens, as well as neoantigen-binding fragments thereof. The present disclosure also relates to nucleic acids, expression cassettes, and expression vectors encoding the antibodies and neoantigen-binding fragments. The antibodies and neoantigen binding-fragments are useful for diagnosis and treatment of cancer.

Claims (20)

1 . An antibody or antigen binding fragment thereof, comprising:

(a) a light chain variable region comprising a CDRL1 of SEQ ID NO:33, a CDRL2 of SEQ ID NO:34, CDRL3 of SEQ ID NO:35, and a heavy chain variable region comprising a CDRH1 of SEQ ID NO:36, a CDRH2 of SEQ ID NO:37, and a CDRH3 of SEQ ID NO:38;

(b) a light chain variable region comprising a CDRL1 of SEQ ID NO:25, a CDRL2 of SEQ ID NO:26, CDRL3 of SEQ ID NO:27, and a heavy chain variable region comprising a CDRH1 of SEQ ID NO:28, a CDRH2 of SEQ ID NO:29, and a CDRH3 of SEQ ID NO:30;

(c) a light chain variable region comprising a CDRL1 of SEQ ID NO:17, a CDRL2 of SEQ ID NO:18, CDRL3 of SEQ ID NO:19, and a heavy chain variable region comprising a CDRH1 of SEQ ID NO:20, a CDRH2 of SEQ ID NO:21, and a CDRH3 of SEQ ID NO:22;

(d) a light chain variable region comprising a CDRL1 of SEQ ID NO:41, a CDRL2 of SEQ ID NO:42, CDRL3 of SEQ ID NO:43, and a heavy chain variable region comprising a CDRH1 of SEQ ID NO:44, a CDRH2 of SEQ ID NO:45, and a CDRH3 of SEQ ID NO:46; or

(e) a light chain variable region comprising a CDRL1 of SEQ ID NO:49, a CDRL2 of SEQ ID NO:50, CDRL3 of SEQ ID NO:51, and a heavy chain variable region comprising a CDRH1 of SEQ ID NO:52, a CDRH2 of SEQ ID NO:53, and a CDRH3 of SEQ ID NO:54, and

wherein the antibody or antigen binding fragment binds to an antigen comprising the amino acid sequence GAC (1620) GVGKSAL (SEQ ID NO:2) but not the amino acid sequence GACGVGKSAL (SEQ ID NO:1), wherein 1620 is ARS-1620.

2 . The antibody or antigen binding fragment of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:31 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 32.

3 . The antibody or antigen binding fragment of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:23 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24.

4 . The antibody or antigen binding fragment of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:15 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 16.

5 . The antibody or antigen binding fragment of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:39 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 40.

6 . The antibody or antigen binding fragment of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:47 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 48.

7 . The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment is selected from the group consisting of a Fab, F(ab′) 2 , Fv and Sfv.

8 . The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment, is a full-length human immunoglobulin g (IgG) antibody.

9 . An immunoconjugate comprising the antibody or antigen binding fragment of claim 1 and a detectable marker or cytotoxic agent.

10 . The immunoconjugate of claim 9 , wherein the immunoconjugate comprises a detectable marker selected from the group consisting of a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound, and a chemiluminescent compound.

11 . The immunoconjugate of claim 9 , wherein the immunoconjugate comprises a cytotoxic agent selected from the group consisting of an alkylating agent, antimetabolite, mitotic inhibitor, antineoplastic antibiotic, and toxin.

12 . An isolated nucleic acid encoding the antibody or antigen binding fragment of claim 1 .

13 . A method for treating cancer, the method comprising:

administering to a patient with cancer an effective amount of the antibody or antigen binding fragment of claim 1 , wherein the patient has received or is receiving an effective amount of ARS-1620.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 19, 2024
From: CRAIK, CHARLES S.; SHOKAT, KEVAN M.; ZHANG, ZIYANG; ROHWEDER, PETER J.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 066186/0024 →
Continuity (2)
Provisional Application 62873505 · Jul 12, 2019
Related Publication 20220289866A1 · Sep 15, 2022
References Cited (41)
US 11207394B2 · Wang et al. · 2021 [cited by applicant]
US 20180153975A1 · Fritsch et al. · 2018 [cited by applicant]
US 20190307868A1 · Rooney · 2019 [cited by examiner]
WO WO2016172722A1 · 2016 [cited by applicant]
WO WO2017173321A1 · 2017 [cited by applicant]
WO WO2018144955A1 · 2018 [cited by applicant]
Awad et al., (2021). “Acquired Resistance to KRASG12C Inhibition in Cancer,” N Engl J Med, 384:2382-2393. [cited by applicant]
Canon et al., (2019). “The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity,” Nature, 575:217-223, 21 pages. [cited by applicant]
Chandran et al., (2022). “Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA,” Nat Med, 28:946-957, 28 pages. [cited by applicant]
Engelhard et al., (2006). “Post-translational modifications of naturally processed MHC-binding epitopes,” Current Opinion in Immunology, 18:92-97. [cited by applicant]
Fakih et al., (2019). “Abstract 3003: Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors,” J Clin Oncol… [cited by applicant]
FDA, (2021). “Highlights of Prescribing Information: Lumakras™ (sotorasib) tablets,” available online at <https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214665s009lbl.pdf>, 15 pages. [cited by applicant]
Hattori et al., (2023). “Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy,” Cancer Discovery, 13:132-145. [cited by applicant]
Koga et al., (2021). “KRAS Secondary Mutations That Confer Acquired Resistance to Kras G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From In Vitro Experiments,” J Thorac Oncol, 16(8):1321… [cited by applicant]
Mallevaey et al., (2011). “A Molecular Basis for NKT Cell Recognition of CD1d-Self-Antigen,” Immunity, 34:315-326. [cited by applicant]
Pellicci et al., (2011). “Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors,” Nat Immunol, 12:827-833, 17 pages. [cited by applicant]
Pramanick et al., (2013). “Excipient Selection in Parenteral Formulation Development,” Pharma Times, 45:65-77. [cited by applicant]
Ramarathinam et al., (2018). “Employing proteomics in the study of antigen presentation: an update,” Expert Review of Proteomics, 15:637-645, 19 pages. [cited by applicant]
Reynisson et al., (2020). “NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data,” Nucleic Acids Research, 48:… [cited by applicant]
Rohweder, (Mar. 6, 2023). “Tumor-specific therapies targeting antigen presentation and misregulated proteolysis,” Doctoral Dissertation submitted Aug. 15, 2022, University of California, San Francisco, 133 pages+1 page … [cited by applicant]
Rullo et al., (2016). “Re-engineering the Immune Responpse to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor,” Angewandte Chemie Intemational Edition, 55:3642-3646. [cited by applicant]
Szeto et al., (2020). “TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers,” Int J Mol Sci, 22:68, 26 pages. [cited by applicant]
Tanaka et al., (2021). “Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS-MAPK Reactivation,” Cancer Discov, 11(8):1913-1922. [cited by applicant]
Wang et al., (2019). “Direct detection and quantification of neoantigens,” Cancer Immunology Research, 7(11):1748-1754. [cited by applicant]
Chang et al., (2016). “Opportunities and challenges for TCR mimic antibodies in cancer therapy,” Expert Opin Biol Ther, 16:979-987, 18 pages. [cited by applicant]
Dao et al., (2013). “Targeting the Intracellular WTI Oncogene Product with a Therapeutic Human Antibody,” Science Translational Medicine, 5(176):90-100, 26 pages. [cited by applicant]
Dao et al., (2015). “Therapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1,” Nature Biotechnology, 33:1079-1086, 21 pages. [cited by applicant]
Duriseti et al., (2010). “Antagonistic anti-urokinase plasminogen activator receptor (uPAR) antibodies significantly inhibit uPAR-mediated cellular signaling and migration,” J Biol Chem, 285:26878-26888. [cited by applicant]
Erkes et al., (2014). “Hapten-induced contact hypersensitivity, autoimmune reactions, and tumor regression: plausibility of mediating antitumor immunity,” J Immunol Res, 2014:175265, 28 pages. [cited by applicant]
Extended European Search Report and Written Opinion received for European Patent Application No. 20840331.1 mailed on Jul. 4, 2023, 11 pages. [cited by applicant]
Hansen et al., (2018). “An internally controlled quantitative target occupancy assay for covalent inhibitors,” Scientific Reports, 8:14312, 7 pages. [cited by applicant]
International Search Report and Written Opinion received for International Patent Application No. PCT/US2020/041710 mailed on Oct. 26, 2020, 13 pages. [cited by applicant]
Janes et al., (2018). “Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor,” Cell, 172:578-589. [cited by applicant]
Martin et al., (1994). “T Cell Recognition of Haptens, a Molecular View,” Int Arch Allergy Immunol, 104:10-16. [cited by applicant]
Padovan et al., (1997). “Penicilloyl peptides are recognized as T cell antigenic determinants in penicillin allergy,” Eur J Immunol, 27:1303-1307. [cited by applicant]
Rock et al., (2016). “Present Yourself! By MHC Class I and MHC Class II Molecules,” Trends in Immunology, 37(11):724-737, 24 pages. [cited by applicant]
Sharma et al., (2016). “Recent advances in T-cell engineering for use in immunotherapy,” F1000 Research, 5(F1000 Faculty Rev):2344, 12 pages. [cited by applicant]
Skora et al., (2015). “Generation of MANAbodies specific to HLA-restricted epitopes encoded by somatically mutated genes,” Proc. Natl. Acad. Sci. USA, 112(32):9967-9972. [cited by applicant]
Tran et al., (2016). “T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer,” New England Journal of Medicine, 375:2255-2262. [cited by applicant]
Visscher et al., (2016). “Covalent targeting of acquired cysteines in cancer,” Current Opinion in Chemical Biology, 30:61-67. [cited by applicant]
Zhang et al., (2022). “A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy,” Cancer Cell, 40(9):1060-1069, 18 pages. [cited by applicant]