Heterodimeric antibodies that bind CD3 and CD38

Patent metadata

Field	Value
Publication number	US-10526417-B2
Application number	US-201514952786-A
Country	US
Kind code	B2
Filing date	Nov 25, 2015
Priority date	Nov 26, 2014
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

Abstract

The present invention is directed to heterodimeric antibodies that bind CD3 and CD38.

First claim

What is claimed is:

1. A heterodimeric anti-CD3 and anti-CD38 antibody comprising
a) a first monomer comprising:
i) a first Fc domain;
ii) an anti-CD3 scFv comprising a scFv variable light domain, an scFv linker and a scFv variable heavy domain; wherein said scFv variable light domain comprises a vlCDR1 having SEQ ID NO:15, a vlCDR2 having SEQ ID NO:16 and a vlCDR3 having SEQ ID NO:17, and said scFv variable heavy domain comprises a vhCDR1 having SEQ ID NO:11, a vhCDR2 having SEQ ID NO:12 and a vhCDR3 having SEQ ID NO:13,

wherein said scFv is covalently attached to the N-terminus of said Fc domain using a domain linker;
b) a second monomer comprising a heavy chain comprising:
i) a heavy variable domain; and
ii) a heavy constant domain comprising a second Fc domain; and

c) a light chain comprising a variable light domain and a constant light domain;
wherein said variable light domain comprises a vlCDR1 comprising the sequence RASQNVDTWVA (SEQ ID NO:69), a vlCDR2 comprising the sequence SASYRYS (SEQ ID NO:70) and a vlCDR3 comprising the sequence QQYDSYPLT (SEQ ID NO:71), and said variable heavy domain comprises a vhCDR1 comprising the sequence RSWMN (SEQ ID NO:65), a vhCDR2 comprising the sequence EINPDSSTINYATSVKG (SEQ ID NO:66) and a vhCDR3 comprising the sequence YGNWFPY (SEQ ID NO:67);
and wherein said (b)(i) heavy variable domain and said (c) variable light domain bind CD38.

2. The heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 wherein said variable light domain has the sequence DIVMTQSPSSLSASVGDRVTITCRASQNVDTWVAWYQQKPGQSPKALIYSASYRYSGVPD RFTGSGSGTDFTLTISSLQPEDFATYFCQQYDSYPLTFGGGTKLEIK (SEQ ID NO:68) and said variable heavy domain has the sequence EVQLVESGGGLVQPGGSLRLSCAASGFDFSRSWMNWVRQAPGKGLEWVSEINPDSSTIN YATSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGNWFPYWGQGTLVTVSS (SEQ ID NO:64).

3. The heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 , wherein said scFv linker is a charged linker.

4. The heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 , wherein said scFv has a polypeptide sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:45, and SEQ ID NO:54.

5. A nucleic acid composition encoding the heterodimeric antibody of claim 1 , said composition comprising:
a) a first nucleic acid encoding said first monomer;
b) a second nucleic acid encoding said second monomer; and
c) a third nucleic acid encoding said light chain.

6. An expression vector composition comprising:
a) an expression vector comprising a nucleic acid encoding a first monomer of claim 1 ;
b) an expression vector comprising a nucleic acid encoding said second monomer of claim 1 ; and
c) an expression vector comprising a nucleic acid encoding said light chain of claim 1 .

7. A host cell comprising the nucleic acid composition of claim 5 .

8. A host cell comprising the expression vector composition of claim 6 .

9. A method of making a heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 comprising culturing the host cell of claim 7 under conditions wherein said antibody is expressed, and recovering said antibody.

10. A method of making a heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 comprising culturing the host cell of claim 8 under conditions wherein said antibody is expressed, and recovering said antibody.

11. A method of treating cancer comprising administering heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 to a patient in need thereof.

12. The heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 wherein said scFv variable light domain has the sequence SEQ ID NO:14 and said scFv variable heavy domain has the sequence SEQ ID NO:10.

13. The heterodimeric anti-CD3 and anti-CD38 antibody of claim 1 wherein said scFv has the sequence SEQ ID NO:18.

14. A heterodimeric anti-CD3 and anti-CD38 antibody comprising a) a first monomer comprising SEQ ID NO:109; b) a second monomer comprising SEQ ID NO:104; and c) a light chain comprising SEQ ID NO:111.

15. A nucleic acid composition encoding the heterodimeric antibody of claim 1 , said composition comprising:
a) a first nucleic acid encoding SEQ ID NO: 109;
b) a second nucleic acid encoding SEQ ID NO: 104; and
c) a third nucleic acid encoding SEQ ID NO: 111.

Assignees

• Xencor Inc

Inventors

• Bernett Matthew J
• Moore Gregory
• Desjarlais John
• Chu Seung
• Rashid Rumana
• Muchhal Umesh

Classifications

• A61P35/02

  specific for leukemia · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/524

  CH2 domain · CPC title

• C07K2317/526

  CH3 domain · CPC title

• C07K2317/522

  CH1 domain · CPC title