US 12,583,922 B2Granted

Bispecific antibodies targeting CD47 and PD-L1 and methods of use thereof

AssigneeNovImmune S.A.

InventorsXavier Chauchet, Krzysztof Masternak, Limin Shang, Elise Penarrieta, Walter Ferlin

Life of this patent

Estimating the term…

Abstract

This disclosure provides bispecific antibodies that specifically bind to CD47 and Programmed Death-Ligand 1 (PD-L1). The disclosure further relates to methods of making the bispecific antibodies and nucleic acids encoding the antibodies. The disclosure further relates to therapeutic methods for use of the bispecific antibodies in the treatment of a condition associated with malignant cells expressing CD47 and/or PD-L1.

Claims27

Dependent claims

A bispecific antibody comprising:

i) a heavy chain comprising
a heavy chain complementarity determining region 1 (CDRH1) comprising an amino acid sequence of SEQ ID NO:
1;
a heavy chain complementarity determining region 2 (CDRH2) comprising an amino acid sequence of SEQ ID NO:
2;
and
a heavy chain complementarity determining region 3 (CDRH3) comprising an amino acid sequence of SEQ ID NO:
3;
ii) a first light chain comprising
a light chain complementarity determining region 1 (CDRL1) comprising an amino acid sequence of SEQ ID NO:
89;
a light chain complementarity determining region 2 (CDRL2) comprising an amino acid sequence of Ala-Ala-Ser;
and
a light chain complementarity determining region 3 (CDRL3) comprising an amino acid sequence of SEQ ID NO:
96;
and
iii) a second light chain comprising:
a) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
20;
or
b) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
21;
or
c) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
22;
or
d) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
23;
or
e) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
24;
or
f) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
25;
or
g) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
h) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
98;
or
i) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
11;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
j) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
12;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
k) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
13;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
l) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
27;
or
m) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
28;
or
n) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
101;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
o) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
102;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
p) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
103;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
and
wherein the bispecific antibody comprises a first antigen binding region comprising i) and ii) that specifically binds to CD47 and a second antigen binding region comprising i) and iii) that specifically binds to Programmed Death-ligand 1 (PD-L1).

127 more elements

A method of treating a PD-L1+ or CD47+ solid tumor, killing a PD-L1+ or CD47+ tumor cell, or reducing the proliferation of a PD-L1+ or CD47+ tumor cell, comprising contacting the cell with a bispecific antibody comprising:

(i) a first antigen binding region comprising a heavy chain and a light chain, wherein the first antigen binding region binds CD47 and comprises:
(a) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
89;
a CDRL2 comprising an amino acid sequence of Ala-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
96;
and
(ii) a second antigen binding region comprising a heavy chain and a light chain, wherein the second antigen binding region binds PD-L1 and comprises:
(a) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
103;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
(b) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
19;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
28;
(c) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
102;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
(d) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
11;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
(e) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
24;
or
(f) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
12;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26.

86 more elements

An antibody comprising:

i) a heavy chain comprising:
a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
and
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
and
ii) light chain comprising:
a) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
20;
or
b) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
21;
or
c) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
22;
or
d) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
23;
or
e) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
24;
or
f) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
25;
or
g) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
h) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
98;
or
i) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
11;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
j) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
12;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
k) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
13;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
l) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
27;
or
m) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
28;
or
n) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
101;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
o) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
102;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
p) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
103;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
and
wherein the antibody specifically binds to Programmed Death-ligand 1 (PD-L1).

120 more elements

A method of treating a PD-L1+ solid tumor, killing a PD-L1+ tumor cell, or reducing the proliferation of a PD-L1+ tumor cell, comprising contacting the cell with an antibody comprising:

an antigen binding region comprising a heavy chain and a light chain, wherein the antigen binding region binds PD-L1 and comprises:
(a) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
103;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
18;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
(b) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
102;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
18;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
c) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
11;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
18;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
(d) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
19;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
28;
(e) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
16;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
24;
or
(f) a CDRH1 comprising an amino acid sequence of SEQ ID NO:
1;
a CDRH2 comprising an amino acid sequence of SEQ ID NO:
2;
a CDRH3 comprising an amino acid sequence of SEQ ID NO:
3;
a CDRL1 comprising an amino acid sequence of SEQ ID NO:
12;
a CDRL2 comprising an amino acid sequence of SEQ ID NO:
19;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26.

77 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/701,570Filed 22 Mar 2022 · us provisional application
Priority: 22 Mar 2021
Published: US 2022/0315654 A16 Oct 2022
Granted: 24 Mar 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily
C07K 16/2827
Against the immunoglobulin superfamily: against B7 molecules, e.g. CD80, CD86
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61P 35/00
Antineoplastic agents

Family

Application63/164,237Us provisional application · filed 22 Mar 2021
Application63/317,892Us provisional application · filed 8 Mar 2022
US 2022/0315654 A1Pre-grant publication · published 6 Oct 2022
US 12,583,922 B2This patent

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

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Abstract

A bispecific antibody comprising:

i) a heavy chain comprising
a heavy chain complementarity determining region 1 (CDRH1) comprising an amino acid sequence of SEQ ID NO:
1;
a heavy chain complementarity determining region 2 (CDRH2) comprising an amino acid sequence of SEQ ID NO:
2;
and
a heavy chain complementarity determining region 3 (CDRH3) comprising an amino acid sequence of SEQ ID NO:
3;
ii) a first light chain comprising
a light chain complementarity determining region 1 (CDRL1) comprising an amino acid sequence of SEQ ID NO:
89;
a light chain complementarity determining region 2 (CDRL2) comprising an amino acid sequence of Ala-Ala-Ser;
and
a light chain complementarity determining region 3 (CDRL3) comprising an amino acid sequence of SEQ ID NO:
96;
and
iii) a second light chain comprising:
a) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
20;
or
b) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
21;
or
c) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
8;
a CDRL2 comprising an amino acid sequence of Ala-Thr-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
22;
or
d) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
23;
or
e) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
24;
or
f) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
9;
a CDRL2 comprising an amino acid sequence of Phe-Gly-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
25;
or
g) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
h) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
10;
a CDRL2 comprising an amino acid sequence of His-Asp-Asn;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
98;
or
i) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
11;
a CDRL2 comprising an amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
97;
or
j) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
12;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
k) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
13;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
26;
or
l) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
27;
or
m) a CDRL1 comprising an amino acid sequence of SEQ ID NO:
14;
a CDRL2 comprising an amino acid sequence of Phe-Ala-Ser;
and
a CDRL3 comprising an amino acid sequence of SEQ ID NO:
28;
or
n) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
101;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
o) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
102;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
or
p) a CDRL1 comprising the amino acid sequence of SEQ ID NO:
103;
a CDRL2 comprising the amino acid sequence of His-Asp-Thr;
and
a CDRL3 comprising the amino acid sequence of SEQ ID NO:
97;
and
wherein the bispecific antibody comprises a first antigen binding region comprising i) and ii) that specifically binds to CD47 and a second antigen binding region comprising i) and iii) that specifically binds to Programmed Death-ligand 1 (PD-L1).

127 more elements

Facts

Application

17/701,570Filed 22 Mar 2022 · us provisional application

Priority

22 Mar 2021

Published

US 2022/0315654 A16 Oct 2022

Granted

24 Mar 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily
C07K 16/2827
Against the immunoglobulin superfamily: against B7 molecules, e.g. CD80, CD86
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61P 35/00
Antineoplastic agents