Antibody specific for CD22 and methods of use thereof
View Patent ↗The present disclosure provides antibodies specific for an epitope present on CD22. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.
1. An antibody that specifically binds an epitope in CD22, wherein the antibody comprises:
a) an immunoglobulin heavy chain comprising a VH region having the amino acid sequence EVQLVESGGGLVKPGGSLX 1 LSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTTYYPD TVKGRFTISRDNAKNX 2 LYLQMX 3 SLRAEDTAMYYCARHSGYGSSYGVLFAYWGQGTLVTVSS (SEQ ID NO:1), where X 1 is K or R; X 2 is S or T; and X 3 is N or S; and
b) an immunoglobulin light chain.
2. The antibody of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLLIYYTSILHSGVPSRFSGS GSGTDYTLTISSLQQEDFATYFCQQGNTLPWTFGGGTKVEIK (SEQ ID NO:7; VK1).
3. The antibody of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLLIYYTSILHSGVPSRFSGS GSGTDYTLTISSLQPEDFATYFCQQGNTLPWTFGGGTKVEIK (SEQ ID NO:8; VK2).
4. The antibody of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence DIQMTQSPSSVSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSILHSGVPSRFSGS GSGTDYTLTISSLQPEDFATYFCQQGNTLPWTFGGGTKVEIK (SEQ ID NO:9; VK4).
5. An antibody that specifically binds an epitope in CD22, wherein the antibody comprises:
a) an immunoglobulin light chain comprising the amino acid sequence DIQMTQSPSSX 1 SASVGDRVTITCRASQDISNYLNWYQQKPGKAX 2 KLLIYYTSILHSGVPSRFSG SGSGTDYTLTISSLQX 3 EDFATYFCQQGNTLPWTFGGGTKVEIK (SEQ ID NO:2), where X 1 is L (Leu) or V (Val); X 2 is V or P; and X 3 is Q or P; and
b) an immunoglobulin heavy chain.
6. The antibody of claim 5 , wherein the immunoglobulin heavy chain comprises an amino acid sequence selected from:
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNTLYLQMSSLRAEDTAMYYCARHSGYGSSYGVLFAYWGQ GTLVTVSS (SEQ ID NO:3; VH3);
EVQLVESGGGLVKPGGSLRLSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMYYCARHSGYGSSYGVLFAYWGQ GTLVTVSS (SEQ ID NO:4; VH4);
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCARHSGYGSSYGVLFAYWGQ GTLVTVSS (SEQ ID NO:5; VH5); and
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMYYCARHSGYGSSYGVLFAYWGQGTLVT VSS (SEQ ID NO:6; VH6).
7. The antibody of claim 1 , wherein the light chain region and the heavy chain region are present in separate polypeptides.
8. The antibody of claim 1 , wherein the light chain region and the heavy chain region are present in a single polypeptide.
9. The antibody of claim 1 , wherein the antibody binds the epitope with an affinity of from about 10 7 M −1 to about 10 12 M −1.
10. The antibody of claim 1 , wherein the heavy chain region is of the isotype IgG1, IgG2, IgG3, or IgG4.
11. The antibody of claim 1 , wherein the antibody is detectably labeled.
12. The antibody of claim 1 , wherein the antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′.
13. The antibody of claim 1 , wherein the antibody comprises a covalently linked non-peptide synthetic polymer.
14. The antibody of claim 1 , wherein the synthetic polymer is poly(ethylene glycol) polymer.
15. The antibody of claim 1 , wherein the antibody comprises a covalently linked lipid or fatty acid moiety.
16. The antibody of claim 1 , wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.
17. The antibody of claim 1 , wherein the antibody comprises a contrast agent.
18. The antibody of claim 1 , wherein the antibody comprises an affinity domain.
19. The antibody of claim 1 , wherein the antibody is immobilized on a solid support.
20. The antibody of claim 1 , wherein the antibody is a single chain Fv (scFv) antibody.
21. The antibody of claim 20 , wherein the scFv is multimerized.
22. The antibody of claim 1 , wherein the antibody comprises a covalently linked cytotoxin.
23. The antibody of claim 1 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif.
24. The antibody of claim 1 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif, and wherein the sulfatase motif is modified to comprise a 2-formylglycine (FG 1 y) moiety.
25. The antibody of claim 24 , wherein the antibody comprises a heterologous moiety covalently linked to the antibody via the FG 1 y moiety.
26. The antibody of claim 25 , wherein the heterologous moiety is selected from a drug, a toxin, a detectable label, a water-soluble polymer, and a synthetic peptide.
27. A recombinant expression vector comprising a nucleotide sequence encoding the antibody of claim 1 , wherein the nucleotide sequence is operably linked to a transcriptional control element that is active in a eukaryotic cell.
28. A pharmaceutical composition comprising:
a) the antibody of claim 1 ; and
b) a pharmaceutically acceptable carrier.
29. The pharmaceutical composition of claim 28 , wherein the antibody is encapsulated in a liposome.
30. A method of treating B cell malignancy in a subject, the method comprising:
administering to a subject having cancer an effective amount of the pharmaceutical composition of claim 28 .