Bispecific and monospecific antibodies using novel anti-PD-1 sequences

Patent metadata

Field	Value
Publication number	US-11312770-B2
Application number	US-201816184895-A
Country	US
Kind code	B2
Filing date	Nov 8, 2018
Priority date	Nov 8, 2017
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

The present invention is directed to bispecific, heterodimeric checkpoint antibodies.

First claim

What is claimed is:

1. A method for treating cancer comprising administering to a patient in need thereof:
a) a heterodimeric bispecific antibody that binds CTLA-4 and LAG-3; and
b) an anti-PD-1 antibody,

wherein said heterodimeric bispecific antibody comprises:
i) a first monomer comprising
A) a single chain Fv domain (scFv) that binds human CTLA-4, wherein said scFv domain comprises:

1) a first variable heavy domain (VH1);
2) a scFv linker; and
3) a first variable light domain (VL1); and
B) a first variant Fc domain;

ii) a second monomer comprising a VH2-CH1-hinge-CH2-CH3 heavy chain, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second variant Fc domain; and
c) a light chain comprising a second variable light domain (VL2) and a constant light domain (CL);

wherein said VH2 and said VL2 bind LAG-3, wherein said VH1 comprises a vhCDR1 comprising the amino acid sequence of SEQ ID NO:35616, a vhCDR2 comprising the amino acid sequence SEQ ID NO:35617 and a vhCDR3 comprising the amino acid sequence of SEQ ID NO:35618, said VL1 comprises a vlCDR1 comprising the amino acid sequence of SEQ ID NO:35619, a vlCDR2 comprising the amino acid sequence SEQ ID NO:35620 and a v1CDR3 comprising the amino acid sequence of SEQ ID NO:35621, and wherein said VH2 comprises a vhCDR1 comprising the amino acid sequence of SEQ ID NO:35609, a vhCDR2 comprising the amino acid sequence SEQ ID NO:35610 and a vhCDR3 comprising the amino acid sequence of SEQ ID NO:35611, said VL2 comprises a vlCDR1 comprising the amino acid sequence of SEQ ID NO:35624, a vlCDR2 comprising the amino acid sequence SEQ ID NO:35625 and a vlCDR3 comprising the amino acid sequence of SEQ ID NO:35626.

2. A method according to claim 1 , wherein said VH1 comprises SEQ ID NO:35613, VL1 comprises SEQ ID NO:35614, VH2 comprises SEQ ID NO:35608 and VL2 has SEQ ID NO:35623.

3. A method for treating cancer comprising administering to a patient in need thereof:
a) a heterodimeric bispecific antibody that binds CTLA-4 and LAG-3; and
b) an anti-PD-1 antibody,

wherein said heterodimeric bispecific antibody comprises:
i) a first monomer comprising
A) a single chain Fv domain (scFv) that binds human CTLA-4, wherein said scFv domain comprises:

1) a first variable heavy domain (VH1);
2) a scFv linker; and
3) a first variable light domain (VL1); and
B) a first variant Fc domain;

ii) a second monomer comprising a VH2-CH1-hinge-CH2-CH3 heavy chain, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second variant Fc domain; and
c) a light chain comprising a second variable light domain (VL2) and a constant light domain (CL);

wherein said VH2 and said VL2 bind LAG-3,
wherein said first monomer comprises SEQ ID NO:35612, said second monomer comprises SEQ ID NO:35607 and said light chain comprises SEQ ID NO:35622.

4. A method for treating cancer comprising administering to a patient in need thereof:
a) a heterodimeric bispecific antibody comprising:
i) a first monomer comprising SEQ ID NO:35612;
ii) a second monomer comprising SEQ ID NO:35607; and
iii) a light chain comprising SEQ ID NO:35622; and

b) an anti-PD-1 antibody.

Assignees

• Xencor Inc

Inventors

• Bernett Matthew
• Moore Gregory
• Desjarlais John
• Hedvat Michael
• Bonzon Christine
• Nisthal Alex
• Muchhal Umesh

Classifications

• C07K2317/31

  multispecific · CPC title

• A61K39/39541 Primary

  against normal tissues, cells · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• A61P35/00

  Antineoplastic agents · CPC title