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