US 2026/0226173 A1 · COMPOSITIONS INCLUDING ANTI-WT-1 ANTIBODIES & ANTIGEN BINDING FRAGMENTS AND USES THEREOF

Abstract

The present technology relates generally to compositions that specifically recognize and bind to a WT-1 peptide complexed with a major histocompatibility antigen (e.g., HL A-A*02). The compositions of the present technology are useful in methods for treating WT-1-associated diseases (e.g., cancers) in a subject in need thereof.

Claims120

Dependent claims

An anti-WTMC (WT1/major histocompatibility class I protein complex) construct comprising an antibody moiety that specifically binds to a complex comprising WT1 peptide (WT1-RMF) and a major histocompatibility (MHC) class I protein, wherein the WT1-RMF comprises the amino acid sequence of RMFPNAPYL (SEQ ID NO:

113), and wherein the antibody moiety specifically recognizes amino acid residues FPNA (SEQ ID NO:
349) of SEQ ID NO:
113t optionally
wherein the MHC class I protein is ILA-A*02:01, or wherein the antibody moiety comprises:
(i) a VH comprising a HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
1, 7, 13, 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, or 79, or a variant thereof comprising up to about 3 amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs:
2, 8, 14, 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, or 80, or a variant thereof comprising up to about 3 amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs:
3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75 or 81, or a variant thereof comprising up to about 3 amino acid substitutions;
and
(ii) a VL comprising a LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, or 82;
or a variant thereof comprising up to about 3 amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs:
5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, or 83, or a variant thereof comprising about 2 amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs:
6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 or 84, or a variant thereof comprising up to about 3 amino acid substitutions;
or wherein the antibody moiety comprises:
(iii) a VH comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
1, 7, 13, 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, or 79, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs:
2, 8, 14, 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, or 80, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs:
3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75 or 81;
and
(iv) a VL comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, or 82, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs:
5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, or 83, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs:
6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 71, 78 or 84.

21 more elements

An anti-WTMC construct comprising an antibody moiety that comprises:

(i) a heavy chain immunoglobulin variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
85, and a light chain immunoglobulin variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
86;
or
(ii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
87, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
88;
or
(iii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
89, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
90;
or
(iv) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
91, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
92;
or
(v) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
93, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
94;
or
(vi) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
95, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
96;
or
(vii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
97, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
98;
or
(viii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
99, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
100;
or
(ix) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
101, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
102;
or
(x) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
103, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
104;
or
(xi) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
105, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
106;
or
(xii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
107, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
108;
or
(xiii) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
109, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
110;
or
(xiv) a VH comprising a HC-CDR1 sequence, a HC-CDR2 sequence, and a HC-CDR3 sequence of the VH sequence of SEQ ID NO:
111, and a VL comprising a LC-CDR1 sequence, a LC-CDR2 sequence, and a LC-CDR3 sequence of the VL sequence SEQ ID NO:
112;
optionally wherein the construct specifically binds to a complex comprising WT1-RMF and an MHC class I protein, wherein the WT1-RMF comprises the amino acid sequence of SEQ ID NO:
113, or wherein the MHC class I protein is HLA-A*02:01.

54 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/153,961Filed 5 Feb 2024

Priority

6 Feb 2023

Published

6 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification38 codes

C07K 16/2833
Against the immunoglobulin superfamily: against MHC-molecules, e.g. HLA-molecules
C07K 16/3038
From tumour cells: kidney, bladder
A61K 35/17
Blood; Artificial blood: lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
A61K 38/00
Medicinal preparations containing peptides

Compositions including anti-wt-1 antibodies & antigen binding fragments and uses thereof

Life of this patent

Abstract

Claims120

Compositions including anti-wt-1 antibodies & antigen binding fragments and uses thereof

Life of this patent

Abstract

Claims120