CD40 binding protein

Abstract

The present invention provides binding proteins that bind to and are agonists of CD40. In certain embodiments, the present invention provides agonistic anti-CD40 antibodies. Also provided are bispecific conjugates comprising the binding proteins and complexes comprising the bispecific conjugates noncovalently linked to tag constructs comprising antigens for antigen delivery to immune cells. Medical uses of the binding proteins, conjugates, and complexes of the present invention are also provided.

Claims

[Claim 1] A binding protein that specifically binds to CD40, wherein the binding protein is a CD40 agonist and includes an antigen-binding domain obtained from an antibody or an antigen-binding domain derived from an antibody, and the binding domain includes a heavy chain variable domain and a light chain variable domain, each of which includes three complementarity-determining domains (CDRs), VLCDR1 has the sequence described in SEQ ID NO: 1, VLCDR2 has the sequence described in SEQ ID NO: 2, VLCDR3 has the sequence described in SEQ ID NO:3, VHCDR1 has the sequence described in SEQ ID NO: 4, VHCDR2 has the sequence described in SEQ ID NO: 5, and VHCDR3 has the sequence described in SEQ ID NO:

6. Binding protein. [Claim 2] The binding protein according to claim 1, wherein the binding protein binds to human CD40 and is an agonist of human CD40. [Claim 3] The binding protein according to claim 1 or 2, wherein the binding protein is a monoclonal antibody, an antibody fragment, or an scFv. [Claim 4] The binding protein according to claim 3, wherein the antibody, the antibody fragment, or the scFv comprises a sequence derived from human germline immunoglobulin. [Claim 5] The antibody fragment is Fab or F(ab') ２ The binding protein according to claim 3 or 4, which is an antibody fragment. [Claim 6] The light chain variable domain comprises the amino acid sequence described in SEQ ID NO: 7, or an amino acid sequence having at least 90% sequence identity thereto. The heavy chain variable domain comprises the amino acid sequence described in SEQ ID NO: 8, or an amino acid sequence having at least 90% sequence identity thereto. The CDR sequence of the amino acid sequence having at least 90% sequence identity is unchanged from the VLCDR1, VLCDR2, and VLCDR3 sequences described in SEQ ID NO: 1-3, and the VHCDR1, VHCDR2, and VHCDR3 sequences described in SEQ ID NO: 4-6. The binding protein according to any one of claims 3 to 5. [Claim 7] The binding protein according to any one of claims 3 to 6, wherein the binding protein is an IgG2 isotype monoclonal antibody. [Claim 8] The antibody comprises a light chain containing the amino acid sequence described in SEQ ID NO: 9, or an amino acid sequence having at least 90% sequence identity thereto, A heavy chain comprising the amino acid sequence described in SEQ ID NO: 10, or an amino acid sequence having at least 90% sequence identity thereto, Includes, The CDR sequence of the amino acid sequence having at least 90% sequence identity is unchanged from the VLCDR1, VLCDR2, and VLCDR3 sequences described in SEQ ID NO: 1-3, and the VHCDR1, VHCDR2, and VHCDR3 sequences described in SEQ ID NO: 4-6. The binding protein according to claim 7. [Claim 9] (i) at least one first binding protein according to any one of claims 1 to 8, (ii) At least one second binding protein containing an antibody binding domain and binding to the peptide moiety, A bispecific conjugate including, The first binding protein and the second binding protein are covalently bonded. Bispecific conjugate. [Claim 10] The bispecific conjugate according to claim 9, wherein the first binding protein is a monoclonal antibody and the second binding protein is scFv. [Claim 11] The bispecific conjugate according to claim 10, wherein the monoclonal antibody is of the IgG2 isotype. [Claim 12] The aforementioned scFv is, (i) C of the antibody Ｈ 3 domains, or (ii) C of the antibody Ｌ domain, A bispecific conjugate according to claim 10 or 11, which is covalently bonded to the other. [Claim 13] The bispecific conjugate comprises one monoclonal antibody and two scFvs, (i) One scFv is the C of each heavy chain of the antibody. Ｈ It is connected to three domains, or (ii) One scFv is the C of each light chain of the antibody. Ｌ Bound to the domain, The bispecific conjugate according to claim 12. [Claim 14] The bispecific conjugate according to any one of claims 9 to 13, wherein the peptide portion has a non-human amino acid sequence. [Claim 15] The peptide portion is (i) Microorganisms, or (ii) Bacterial toxins, or (iii) Tetanus toxin A bispecific conjugate according to claim 14, having the derived amino acid sequence. [Claim 16] The bispecific conjugate according to claim 15, wherein the peptide portion includes an amino acid sequence described in any one of SEQ ID NO: 11-16 or 42-46, or an amino acid sequence having up to two amino acid substitutions relative to any one of SEQ ID NO: 11-16 or 42-46. [Claim 17] A complex comprising a bispecific conjugate according to any one of claims 9 to 16 and a tag construct, wherein the tag construct comprises a peptide moiety according to any one of claims 9 or 14 to 16 covalently bound to an antigen, A complex in which the peptide portion of the tag construct is non-covalently bonded to the second binding protein of the bispecific conjugate. [Claim 18] The complex according to claim 17, wherein the antigen is a cancer antigen. [Claim 19] The complex according to claim 18, wherein the cancer antigen is a neoantigen, a tumor-associated antigen, or an antigen derived from an oncovirus. [Claim 20] The complex according to claim 17, wherein the antigen is derived from a pathogen. [Claim 21] (i) The binding protein according to any one of claims 1 to 8, (ii) A double-specific conjugate according to any one of claims 9 to 16, or (iii) The composite according to any one of claims 17 to 20, and, A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier or excipient. [Claim 22] A kit comprising a bispecific conjugate according to any one of claims 9 to 16 and a tag construct according to any one of claims 17 to 20. [Claim 23] A binding protein according to any one of claims 1 to 8, a bispecific conjugate according to any one of claims 9 to 16, a complex according to any one of claims 17 to 20, a composition according to claim 21, or a kit according to claim 22, for use in therapeutic purposes. [Claim 24] A binding protein according to any one of claims 1 to 8, a bispecific conjugate according to any one of claims 9 to 16, a complex according to any one of claims 17 to 20, a composition according to claim 21, or a kit according to claim 22, for use in the treatment or prevention of cancer or infectious diseases. [Claim 25] Use of a binding protein according to any one of claims 1 to 8, a bispecific conjugate according to any one of claims 9 to 16, or a complex according to any one of claims 17 to 20 in the manufacture of a drug for the treatment or prevention of cancer or infectious disease.

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