Constructs targeting histone H3 peptide/MHC complexes and uses thereof

Patent metadata

Field	Value
Publication number	US-11274157-B2
Application number	US-201816477509-A
Country	US
Kind code	B2
Filing date	Jan 11, 2018
Priority date	Jan 12, 2017
Publication date	Mar 15, 2022
Grant date	Mar 15, 2022

Abstract

The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising a histone H3 peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

First claim

What is claimed is:

1. An isolated anti-HMC construct comprising an antibody moiety that specifically binds to a complex comprising a histone H3 peptide and a major histocompatibility (MHC) class I protein (“HMC”); wherein:
the histone H3 peptide is the peptide set forth in SEQ ID NO: 7;
the MEW is HLA-A02; and
the antibody moiety comprises:
i) a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising the amino acid sequence of SEQ ID NO: 99, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising the amino acid sequence of SEQ ID NO: 129, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 139, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 148; or
ii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 118; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 129, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 140, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 149; or
iii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 119; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 130, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 140, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 148; or
iv) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 130, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 140, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 148; or
v) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 100, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 121; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 131, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 141, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 150; or
vi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 101, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 110, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 122; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 132, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 142, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 151; or
vii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 102, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 111, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 133, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 143, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 152; or
viii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 103, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 112, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 124; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 134, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 144, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 153; or
ix) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 104, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 113, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 125; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 135, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 145, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 154; or
x) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 105, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 114, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 136, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 155; or
xi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 106, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 115, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 127; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 137, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 145, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 156; or
xii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 107, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 116, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 128; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 138, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 147, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 157.

2. The isolated anti-HMC construct of claim 1 wherein the antibody moiety comprises:
a) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 75, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 87 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 87; or
b) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 76, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 88 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 88; or
c) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 77, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 89; or
d) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 78, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 90 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 90; or
e) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 79, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 91; or
f) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 80, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 92 or a variant thereof having at least 95% sequence identity to SEQ ID NO: 92; or
g) a heavy chain variable domain comprising the amino acid sequence of SEQ ID

Assignees

• Eureka Therapeutics Inc

Inventors

• Chan Vivien Wai-Fan
• Liu Hong
• Nakano Yoko
• Xu Yiyang

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• A61K40/42

  Cancer antigens · CPC title

• A61K40/32

  T-cell receptors [TCR] · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title