US 12,703,746 B2Granted

Anti-TCR delta variable 1 antibodies

AssigneeAdaptate Biotherapeutics Ltd.

InventorsMihriban Tuna, Oxana Polyakova, Mark Uden, Robert Good, Joshua Freedman, Shefali Bhumbra, Natalie Mount, Aoife McGinley, Dan Foxler

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Abstract

The present invention provides high-affinity anti-TCR delta variable 1 (anti-Vδ1) antibodies and antibody fragments thereof. The present invention also provides compositions and pharmaceutical compositions comprising such antibodies, and method of making such antibodies. The present invention also provides methods of treatment and medical uses involving the antibodies.

Claims21

Dependent claims

An anti-TCR delta variable 1 (anti-Vδ1) antibody or antigen-binding fragment thereof comprising:

a) a variable heavy chain complementarity determining region 1 (VHCDR1), a variable heavy chain complementarity determining region 2 (VHCDR2) and a variable heavy chain complementarity determining region 3 (VHCDR3) comprising the amino acid sequences of SEQ ID NO:
51, 53 and 55, respectively, and a variable light chain complementarity determining region 1 (VLCDR1), a variable light chain complementarity determining region 2 (VLCDR2) and a variable light chain complementarity determining region 3 (VLCDR3) comprising the amino acid sequences of SEQ ID NO:
79, 80 and 82, respectively;
b) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 56, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 83, respectively;
c) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 57, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 84, respectively;
d) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 58, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 85, respectively;
e) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 59, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 86, respectively;
f) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 60, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 87, respectively;
g) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 61, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 88, respectively;
h) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 62, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 89, respectively;
i) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 63, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 90, respectively;
j) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 64, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 91, respectively;
k) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 65, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 92, respectively;
l) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 66, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 93, respectively;
m) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 67, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 94, respectively;
n) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 69, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 96, respectively;
o) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 70, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 97, respectively;
p) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 71, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs:
79, 80 and 98, respectively;
q) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 72, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 99, respectively;
r) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 73, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 100, respectively;
s) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 74, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 101, respectively;
t) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 75, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 102, respectively;
u) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 76, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 103, respectively;
V a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 77, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 104, respectively;
or
w) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 78, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 105, respectively.

67 more elements

An anti-TCR delta variable 1 (anti-Vδ1) antibody or antigen-binding fragment thereof comprising:

a heavy chain variable region (VH) comprising:
a VHCDR1 comprising an amino acid sequence of SEQ ID NO:
130;
a VHCDR2 comprising an amino acid sequence of:
SEQ ID NO:
131;
and
a VHCDR3 comprising an amino acid sequence of any one of:
SEQ ID NO:
133 to 143;
and
a light chain variable region (VL) comprising:
a VLCDR1 comprising an amino acid sequence of SEQ ID NO:
144;
a VLCDR2 comprising an amino acid sequence of SEQ ID NO:
145;
and
a VLCDR3 comprising an amino acid sequence of any one of:
SEQ ID NO:
147 to 157.

17 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/674,129Filed 17 Feb 2022
Priority: GB 210222417 Feb 2021
Published: US 2023/0028110 A126 Jan 2023
Granted: 11 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07K 16/2809
Against the immunoglobulin superfamily: against the T-cell receptor -CD3 complex
A61P 35/00
Antineoplastic agents
C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily

Family

US 2023/0028110 A1Pre-grant publication · published 26 Jan 2023
US 12,703,746 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

An anti-TCR delta variable 1 (anti-Vδ1) antibody or antigen-binding fragment thereof comprising:

a) a variable heavy chain complementarity determining region 1 (VHCDR1), a variable heavy chain complementarity determining region 2 (VHCDR2) and a variable heavy chain complementarity determining region 3 (VHCDR3) comprising the amino acid sequences of SEQ ID NO:
51, 53 and 55, respectively, and a variable light chain complementarity determining region 1 (VLCDR1), a variable light chain complementarity determining region 2 (VLCDR2) and a variable light chain complementarity determining region 3 (VLCDR3) comprising the amino acid sequences of SEQ ID NO:
79, 80 and 82, respectively;
b) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 56, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 83, respectively;
c) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 57, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 84, respectively;
d) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 58, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 85, respectively;
e) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 59, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 86, respectively;
f) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 60, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 87, respectively;
g) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 61, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 88, respectively;
h) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 62, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 89, respectively;
i) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 63, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 90, respectively;
j) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 64, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 91, respectively;
k) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 65, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 92, respectively;
l) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 66, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 93, respectively;
m) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 67, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 94, respectively;
n) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 69, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 96, respectively;
o) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 70, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 97, respectively;
p) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 71, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs:
79, 80 and 98, respectively;
q) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 72, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 99, respectively;
r) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 73, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 100, respectively;
s) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
52, 53 and 74, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 101, respectively;
t) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 75, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 102, respectively;
u) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 76, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 103, respectively;
V a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 77, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 104, respectively;
or
w) a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO:
51, 53 and 78, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NO:
79, 80 and 105, respectively.

67 more elements

Facts

Application

17/674,129Filed 17 Feb 2022

Priority

GB 210222417 Feb 2021

Published

US 2023/0028110 A126 Jan 2023

Granted

11 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07K 16/2809
Against the immunoglobulin superfamily: against the T-cell receptor -CD3 complex
A61P 35/00
Antineoplastic agents
C07K 16/18
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material from animals or humans
C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily