Antibodies binding to ILT4

Patent metadata

Field	Value
Publication number	US-12435136-B2
Application number	US-202217845742-A
Country	US
Kind code	B2
Filing date	Jun 21, 2022
Priority date	Jul 9, 2018
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

The present application relates to antibodies specifically binding to immunoglobulin-like transcript 4 (ILT4), which is also known as LILRB2, LIR2, MIR10, and CD85d, and corresponding nucleic acids, host cells, compositions, and uses. In some embodiments, the antibodies bind specifically to human ILT4, but do not significantly bind to ILT2, ILT3, or ILT5, or to other members of the LILRA or LILRB families.

First claim

The invention claimed is:

1. A nucleic acid comprising a polynucleotide sequence that encodes an antibody that specifically binds to human ILT4 (hILT4), the antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region (VH) comprising VH complementary determining region 1 (CDR1), CDR2 and CDR3 comprising the amino acid sequences of SEQ ID Nos: 155, 156, and 157, respectively, and wherein the light chain comprises a light chain variable region (VL) comprising VL CDR1, CDR2 and CDR3 comprising the amino acid sequences of SEQ ID Nos: 158, 159, and 160, respectively.

2. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein:
a. the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 71 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
b. the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 74 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
c. the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 75 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
d. the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 78 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70; or
e. the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 80 and the VL comprises an amino acid sequence that 3 is at least 90% identical to the amino acid sequence of SEQ ID NO: 70.

3. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein:
a. the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
b. the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
c. the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70;
d. the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 78 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70; or
e. the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 80 and the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 70.

4. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein:
a. the VH comprises the amino acid sequence of SEQ ID NO: 71;
b. the VH comprises the amino acid sequence of SEQ ID NO: 74;
c. the VH comprises the amino acid sequence of SEQ ID NO: 75;
d. the VH comprises the amino acid sequence of SEQ ID NO: 78; or
e. the VH comprises the amino acid sequence of SEQ ID NO: 80.

5. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VL comprises the amino acid sequence of SEQ ID NO: 70.

6. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein:
a. the VH comprises the amino acid sequence of SEQ ID NO: 71 and the VL comprises the amino acid sequence of SEQ ID NO: 70;
b. the VH comprises the amino acid sequence of SEQ ID NO: 74 and the VL comprises the amino acid sequence of SEQ ID NO: 70;
c. the VH comprises the amino acid sequence of SEQ ID NO: 75 and the VL comprises the amino acid sequence of SEQ ID NO: 70;
d. the VH comprises the amino acid sequence of SEQ ID NO: 78 and the VL comprises the amino acid sequence of SEQ ID NO: 70; or
e. the VH comprises the amino acid sequence of SEQ ID NO: 80 and the VL comprises the amino acid sequence of SEQ ID NO: 70.

7. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an IgG antibody.

8. The nucleic acid of claim 7 , wherein the polynucleotide sequence encodes an IgG1, IgG2 or IgG4 antibody.

9. The nucleic acid of claim 8 , wherein the polynucleotide sequence encodes a human IgG4 antibody comprising an S228P substitution (EU numbering).

10. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain lacks a C-terminal lysine residue.

11. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes a full length antibody, and wherein the heavy chain comprises or does not comprise a C-terminal lysine residue.

12. The nucleic acid of claim 4 , wherein the polynucleotide sequence encodes an antibody comprising a heavy chain constant region comprising the amino acid sequence of any one of 13 SEQ ID Nos: 98, 100, 102, 103, 104 or 179.

13. The nucleic acid of claim 12 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region comprises the amino acid sequence of any one of SEQ ID Nos: 100, 102, 103, 104 or 179 and further comprises a C-terminal lysine residue.

14. The nucleic acid of claim 12 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 100.

15. The nucleic acid of claim 14 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region further comprises a C-terminal lysine residue.

16. The nucleic acid of claim 6 , wherein the polynucleotide sequence encodes an antibody comprising a heavy chain constant region comprising the amino acid sequence of any one of SEQ ID Nos: 98, 100, 102, 103, 104 or 179.

17. The nucleic acid of claim 16 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region comprises the amino acid sequence of any one of SEQ ID Nos: 100, 102, 103, 104 or 179 and further comprises a C-terminal lysine residue.

18. The nucleic acid of claim 16 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 100.

19. The nucleic acid of claim 18 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain constant region further comprises a C-terminal lysine residue.

20. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 13.

21. The nucleic acid of claim 20 , wherein the polynucleotide sequence encodes an antibody wherein the heavy chain further comprises a C-terminal lysine residue.

22. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the light chain comprises the amino acid sequence of SEQ ID NO: 11.

23. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody

Assignees

• Five Prime Therapeutics Inc
• Bristol Myers Squibb Co

Inventors

• Schebye Xiao Min
• Chen Diana Yuhui
• Rankin Andrew
• Deng Xiaodi
• Toth Joseph
• Liang Linda
• Han Michelle Minhua
• BEE Christine
• Truong Hong-An
• Selby Mark J
• Lonberg Nils
• Chen Guodong
• Huang Richard Y
• Deyanova Ekaterina G
• Korman Alan J

Classifications

• G01N33/577

  involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)} · CPC title

• G01N33/563

  involving antibody fragments · CPC title

• C07K2317/92

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

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/71

  Decreased effector function due to an Fc-modification · CPC title