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. A composition comprising (i) 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 LSCAASGFAFSIYDMSWVRQAPGKGLEWVAYISSGGGTT YYPDTVKGRFTISRDNAKNX 2 LYLQMX 3 SLRAEDTAMYYCARHSGYGSSYGVLFAYWG QGTLVTVSS (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; and
(ii) a carrier.
2. The composition of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence
(SEQ ID NO: 7; VK1)
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLL
IYYTSILHSGVPSRFSGSGSGTDYTLTISSLQQEDFATYFCQQGNTL
PWTFGGGTKVEIK.
3. The composition of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence
(SEQ ID NO: 8; VK2)
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAVKLL
IYYTSILHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQGNTL
PWTFGGGTKVEIK.
4. The composition of claim 1 , wherein the immunoglobulin light chain comprises the amino acid sequence
(SEQ ID NO: 9; VK4)
DIQMTQSPSSVSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLL
IYYTSILHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQGNTL
PWTFGGGTKVEIK.
5. A composition comprising (i) 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 KLLIYYTSILHSGVP SRFSGSGSGTDYTLTISSLQX 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; and
(ii) a carrier.
6. The composition of claim 5 , wherein the immunoglobulin heavy chain comprises an amino acid sequence selected from:
(SEQ ID NO: 3; VH3)
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEW
VAYISSGGGTTYYPDTVKGRFTISRDNAKNTLYLQMSSLRAEDTAMY
YCARHSGYGSSYGVLFAYWGQGTLVTVSS;
(SEQ ID NO: 4; VH4)
EVQLVESGGGLVKPGGSLRLSCAASGFAFSIYDMSWVRQAPGKGLEW
VAYISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMY
YCARHSGYGSSYGVLFAYWGQGTLVTVSS;
(SEQ ID NO: 5; VH5)
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEW
VAYISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMNSLRAEDTAMY
YCARHSGYGSSYGVLFAYWGQGTLVTVSS;
and
(SEQ ID NO: 6; VH6)
EVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQAPGKGLEW
VAYISSGGGTTYYPDTVKGRFTISRDNAKNSLYLQMSSLRAEDTAMY
YCARHSGYGSSYGVLFAYWGQGTLVTVSS.
7. The composition of claim 5 , wherein the light chain region and the heavy chain region are present in separate polypeptides.
8. The composition of claim 5 , wherein the light chain region and the heavy chain region are present in a single polypeptide.
9. The composition of claim 5 , wherein the antibody binds the epitope with an affinity of from about 10 7 M −1 to about 10 12 M −1 .
10. The composition of claim 5 , wherein the heavy chain region is of the isotype IgG1, IgG2, IgG3, or IgG4.
11. The composition of claim 5 , wherein the antibody is detectably labeled.
12. The composition of claim 5 , wherein the antibody is a F v , scF v , F ab , F( ab′ ) 2 , or F ab′ .
13. The composition of claim 5 , wherein the antibody comprises a covalently linked non-peptide synthetic polymer.
14. The composition of claim 13 , wherein the synthetic polymer is poly(ethylene glycol) polymer.
15. The composition of claim 5 , wherein the antibody comprises a covalently linked lipid or fatty acid moiety.
16. The composition of claim 5 , wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.
17. The composition of claim 5 , wherein the antibody comprises a contrast agent.
18. The composition of claim 5 , wherein the antibody comprises an affinity domain.
19. The composition of claim 5 , wherein the antibody is immobilized on a solid support.
20. The composition of claim 5 , wherein the antibody is a single chain F v (scF v ) antibody.
21. The composition of claim 20 , wherein the scF v is multimerized.
22. The composition of claim 5 , wherein the antibody comprises a covalently linked cytotoxin.
23. The composition of claim 5 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif.
24. The composition of claim 5 , 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 (FGly) moiety.
25. The composition of claim 24 , wherein the antibody comprises a heterologous moiety covalently linked to the antibody via the FGly moiety.
26. The composition 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 pharmaceutical composition comprising:
a) an effective amount of the composition of claim 1 ; and
b) a pharmaceutically acceptable carrier.
28. The pharmaceutical composition of claim 27 , wherein the antibody is encapsulated in a liposome.
29. A pharmaceutical composition comprising:
a) the composition of claim 5 ; and
b) a pharmaceutically acceptable carrier.
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 29 .