Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease

• US 7,829,086 B2
• Filed: 03/06/2007
• Issued: 11/09/2010
• Est. Priority Date: 03/06/2006
• Status: Expired due to Fees

• Current Assignee: Medimmune LLC (Astrazeneca PLC), Aeres Biomedical, Ltd. (Lifearc)
• Original Assignee: Medimmune LLC (Astrazeneca PLC), Aeres Biomedical, Ltd. (Lifearc)
• Inventors: Williams, David G., Jones, Tarran, Hilbert, David M.
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US11/715,308
• Publication Number:
  US 20070258981A1
• Time in Patent Office: 1,344 Days
• Field of Search: 424/133.1, 530/388.1, 530/138.1
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/465 with additional modified FR-residues
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention provides chimeric and humanized versions of anti-CD22 mouse monoclonal antibody, HB22.7. The anti-CD22 antibodies of the invention comprise four human or humanized framework regions of the immunoglobulin heavy chain variable region (“VH”) and four human or humanized framework regions of the immunoglobulin light chain variable region (“VK”). The invention further comprises heavy and/or light chain FW regions that contain one or more backmutations in which a human FW residue is exchanged for the corresponding residue present in the parental mouse heavy or light chain. Human or humanized VH framework regions of antibodies of the invention may comprise one or more of the following residues: a valine (V) at position 24 of framework region 1, a glycine (G) at position 49 of framework region 2, and an asparagine (N) at position 73 of framework region 3, numbered according to Kabat. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD22 antigen and that preferably mediate human ADCC, CDC, and/or apoptosis for: the treatment of B cell diseases and disorders in human subjects, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.

Claims

1. A monoclonal humanized anti-CD22 antibody comprising a heavy chain and a light chain, wherein the heavy chain variable region (“

VH”

) comprises three complementarity determining regions, VH CDR1, VH CDR2, and VH CDR3, and four framework regions, VH FW1, VH FW2, VH FW3, and VH FW4, in the order VH FW1-VH CDR1-VH FW2-VH CDR2-VH FW3-VH CDR3-VH FW4;

wherein VH CDR1 comprises the amino acid sequence DYGVN (SEQ ID NO;

62), VH CDR2 comprises the amino acid sequence IIWGDGRTDYNSALKS (SEQ ID NO;

63), and VH CDR3 comprises the amino acid sequence APGNRAMEY (SEQ ID NO;

64);

wherein the light chain variable region (“

VK”

) comprises three complementarity determining regions, VK CDR1, VK CDR2, and VK CDR3, wherein VK CDR1 comprises the amino acid sequence KASQSVTNDVA (SEQ ID NO;

65), VK CDR2 comprises the amino acid sequence YASNRYT (SEQ ID NO;

66), and VK CDR3 comprises the amino acid sequence QQDYRSPWT (SEQ ID NO;

67), and

wherein VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTFS (SEQ ID NO;

81).

2. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:

84).

3. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:

86).

4. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW4 comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO:

88).

5. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:

84), VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO;

86), and VH FW4 comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO;

88).

6. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVG (SEQ ID NO:

85).

7. The monoclonal humanized anti-CD22 antibody of claim 6, wherein VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:

86).

8. The monoclonal humanized anti-CD22 antibody of claim 1, wherein VH FW3 comprises the amino acid sequence RLTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:

87).

9. The monoclonal humanized anti-CD22 antibody of claim 8, wherein VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO:

84).

10. The monoclonal humanized anti-CD22 antibody of claim 5,

wherein the VK comprises four framework regions, VK FW1, VK FW2, VK FW3, and VK FW4, in the order VK FW1-VK CDR1-VK FW2-VK CDR2-VK FW3-VK CDR3-VK FW4;

wherein VK FW1 comprises the amino acid sequence DIVMTQSPSSESASVGDRVTITC (SEQ ID NO;

117), VK FW2 comprises the amino acid sequence WYQQKPGKAPKLLIY (SEQ ID NO;

118), VK FW3 comprises the amino acid sequence GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO;

119) and VK FW4 comprises the amino acid sequence FGGGTKVEIKRT (SEQ ID NO;

127).

11. The monoclonal humanized anti-CD22 antibody of claim 5,

wherein the VK comprises four framework regions, VK FW1, VK FW2, VK FW3, and VK FW4, in the order VK FW1-VK CDR1-VK FW2-VK CDR2-VK FW3-VK CDR3-VK FW4;

wherein VK FW1 comprises the amino acid sequence DIVMTQSPSSESASVGDRVTITC (SEQ ID NO;

117), VK FW2 comprises the amino acid sequence WYQQKPGKAPKLLIY (SEQ ID NO;

118), VK FW3 comprises the amino acid sequence GVPDRFSGSGYGTDFTLTISSLQPEDFATYFC (SEQ ID NO;

126) and VK FW4 comprises the amino acid sequence FGGGTKVEIKRT (SEQ ID NO;

127).

12. A pharmaceutical composition comprising a monoclonal humanized anti-CD22 antibody of claim 10, in a pharmaceutically acceptable carrier.

13. The pharmaceutical composition of claim 12, wherein the monoclonal humanized anti-CD22 antibody is of the IgG1, IgG2, IgG3, or IgG4 human isotype.

14. A pharmaceutical composition comprising the monoclonal humanized anti-CD22 antibody of claim 11, in a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14, wherein the monoclonal humanized anti-CD22 antibody is of the IgG1, IgG2, IgG3, or IgG4 human isotype.

16. A monoclonal humanized anti-CD22 antibody comprising a heavy chain and a light chain, wherein the VH comprises three complementarity determining regions, VH CDR1, VH CDR2, and VH CDR3, and four framework regions, VH FW1, VH FW2, VH FW3, and VH FW4, in the order VH FW1-VH CDR1-VH FW2-VH CDR2-VH FW3-VH CDR3-VH FW4;

wherein VH CDR1 comprises the amino acid sequence DYGVN (SEQ ID NO;

62), VH CDR2 comprises the amino acid sequence IIWGDGRTDYNSALKS (SEQ ID NO;

63), and VH CDR3 comprises the amino acid sequence APGNRAMEY (SEQ ID NO;

64);

wherein the VK comprises three complementarity determining regions, VK CDR1, VK CDR2, and VK CDR3, wherein VK CDR1 comprises the amino acid sequence KASQSVTNDVA (SEQ ID NO;

65), VK CDR2 comprises the amino acid sequence YASNRYT (SEQ ID NO;

66), and VK CDR3 comprises the amino acid sequence QQDYRSPWT (SEQ ID NO;

6′

7), and

wherein VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO;

83), and VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVT (SEQ ID NO;

84).

20. The monoclonal humanized anti-CD22 antibody of claim 16 or 18, wherein VH FW3 comprises the amino acid RLTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO:

87).

22. The monoclonal humanized anti-CD22 antibody of claim 20, wherein VH FW4 comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO:

88).

24. The monoclonal humanized anti-CD22 antibody of claim 22,

wherein the VK comprises four framework regions, VK FW1, VK FW2, VK FW3, and VK FW4, in the order VK FW1-VK CDR1-VK FW2-VK CDR2-VK FW3-VK CDR3-VK FW4;

wherein VK FW1 comprises the amino acid sequence DIVMTQSPSSLSASVGDRVTITC (SEQ ID NO;

117), VK FW2 comprises the amino acid sequence WYQQKPGKAPKLLIY (SEQ ID NO;

118), VK FW3 comprises the amino acid sequence GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO;

119) or GVPDRFSGSGYGTDFTLTISSLQPEDFATYFC (SEQ ID NO;

126), and VK FW4 comprises the amino acid sequence FGGGTKVEIKRT (SEQ ID NO;

127).

17. A monoclonal humanized anti-CD22 antibody comprising a heavy chain and a light chain, wherein the VH comprises three complementarity determining regions, VH CDR1, VH CDR2, and VH CDR3, and four framework regions, VH FW1, VH FW2, VH FW3, and VH FW4, in the order VH FW1-VH CDR1-VH FW2-VH CDR2-VH FW3-VH CDR3-VH FW4;

wherein VH CDR1 comprises the amino acid sequence DYGVN (SEQ ID NO;

62), VH CDR2 comprises the amino acid sequence IIWGDGRTDYNSALKS (SEQ ID NO;

63), and VH CDR3 comprises the amino acid sequence APGNRAMEY (SEQ ID NO;

64);

wherein the VK comprises three complementarity determining regions, VK CDR1, VK CDR2, and VK CDR3, wherein VK CDR1 comprises the amino acid sequence KASQSVTNDVA (SEQ ID NO;

65), VK CDR2 comprises the amino acid sequence YASNRYT (SEQ ID NO;

66), and VK CDR3 comprises the amino acid sequence QQDYRSPWT (SEQ ID NO;

67), and

wherein VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLS (SEQ ID NO;

83), and VH FW3 comprises the amino acid sequence RFTVSRNNSNNTLSLQMNSLTTEDTAVYYCVR (SEQ ID NO;

86).

19. The monoclonal humanized anti-CD22 antibody of claim 17 or 18, wherein VH FW2 comprises the amino acid sequence WIRQAPGKGLEWVG (SEQ ID NO:

85).

21. The monoclonal humanized anti-CD22 antibody of claim 19, wherein VH FW4 comprises the amino acid sequence WGQGVLVTVS (SEQ ID NO:

88).

23. The monoclonal humanized anti-CD22 antibody of claim 21,

wherein the VK comprises four framework regions, VK FW1, VK FW2, VK FW3, and VK FW4, in the order VK FW1-VK CDR1-VK FW2-VK CDR2-VK FW3-VK CDR3-VK FW4;

wherein VK FW1 comprises the amino acid sequence DIVMTQSPSSLSASVGDRVTITC (SEQ ID NO;

117), VK FW2 comprises the amino acid sequence WYQQKPGKAPKLLIY (SEQ ID NO;

118), VK FW3 comprises the amino acid sequence GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO;

119) or GVPDRFSGSGYGTDFTLTISSLQPEDFATYFC (SEQ ID NO;

126), and VK FW4 comprises the amino acid sequence FGGGTKVEIKRT (SEQ ID NO;

127).

18. A monoclonal humanized anti-CD22 antibody comprising a heavy chain and a light chain, wherein the VH comprises three complementarity determining regions, VH CDR1, VH CDR2, and VH CDR3, and four framework regions, VH FW1, VH FW2, VH FW3, and VH FW4, in the order VH FW1-VH CDR1-VH FW2-VH CDR2-VH FW3-VH CDR3-VH FW4;

wherein VH CDR1 comprises the amino acid sequence DYGVN (SEQ ID NO;

62), VH CDR2 comprises the amino acid sequence IIWGDGRTDYNSALKS (SEQ ID NO;

63), and VH CDR3 comprises the amino acid sequence APGNRAMEY (SEQ ID NO;

64);

wherein the VK comprises three complementarity determining regions, VK CDR1, VK CDR2, and VK CDR3, wherein VK CDR1 comprises the amino acid sequence KASQSVTNDVA (SEQ ID NO;

65), VK CDR2 comprises the amino acid sequence YASNRYT (SEQ ID NO;

66), and VK CDR3 comprises the amino acid sequence QQDYRSPWT (SEQ ID NO;

67), and

wherein VH FW1 comprises the amino acid sequence QVQLEESGGGVVRPGRSLRLSCAASGFTLD (SEQ ID NO;

82).