Anti-human ROR1 antibodies

Patent metadata

Field	Value
Publication number	US-9316646-B2
Application number	US-201013265582-A
Country	US
Kind code	B2
Filing date	Apr 23, 2010
Priority date	Apr 23, 2009
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The invention relates to antibodies having specificity for human ROR1, compositions thereof, and methods for using such antibodies, including in the diagnosis and treatment of disorders associated with aberrant ROR1 expression.

First claim

The invention claimed is:

1. An antibody having specificity for the extracellular domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1), comprising complementarity determining regions (CDRs) with the following sequences: SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 13, and SEQ ID NO: 15.

2. The antibody of claim 1 , wherein the antibody comprises:
(a) a heavy chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1; and
(b) a light chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2.

3. The antibody of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 1.

4. The antibody of claim 2 , wherein the heavy chain variable domain has a sequence comprises the amino acid sequence of SEQ ID NO: 1 with a glycine to cysteine substitution at position 44.

5. The antibody of claim 2 , wherein the light chain variable domain consists of the amino acid sequence of SEQ ID NO: 2.

6. The antibody of claim 2 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 2 with a glycine to cysteine substitution at position 100.

7. The antibody of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 1 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 2.

8. The antibody of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 1 with a glycine to cysteine substitution at position 44, and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 2 with a glycine to cysteine substitution at position 100.

9. The antibody of claim 1 , wherein the antibody is selected from the group consisting of IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, IgM, F(ab)2, Fv, scFv, IgGΔCH2, F(ab′)2, scFv2CH3, F(ab), VL, VH, scFv4, scFv3, scFv2, dsFv, Fv, scFv-Fc, (scFv)2, a non-depleting IgG, a diabody, and a bivalent antibody.

10. The antibody of claim 9 , wherein the antibody is an IgG selected from the group consisting of IgG1, IgG2, IgG3, IgG4, and synthetic IgG.

11. The antibody of claim 9 , wherein the antibody is a Fab.

12. The antibody of claim 9 , wherein the antibody is a dsFv.

13. The antibody of claim 1 , wherein the antibody is conjugated to a synthetic molecule.

14. The antibody of claim 13 , wherein the antibody is a T-body and the synthetic molecule comprises a transmembrane region and an intracellular T-cell receptor (TCR) signaling domain.

15. The antibody of claim 13 , wherein the synthetic molecule is a label.

16. The antibody of claim 13 , wherein the synthetic molecule is a cytotoxic agent or a therapeutic radioisotope.

17. A pharmaceutical composition comprising a therapeutically effective amount of an antibody of claim 2 and a pharmaceutically acceptable carrier.

18. A kit comprising the antibody of claim 2 .

19. The kit of claim 18 , further comprising one or more immunoassay buffers.

20. The kit of claim 18 , wherein the antibody is conjugated to a label.

21. A pharmaceutical composition comprising a therapeutically effective amount of an antibody of claim 1 and a pharmaceutically acceptable carrier.

22. A kit comprising the antibody of claim 1 .

23. A conjugate comprising the antibody of claim 2 and a cytotoxic agent.

24. The conjugate of claim 23 , wherein the cytotoxic agent is Pseudomonas exotoxin A (PE38).

25. A conjugate comprising the antibody of claim 1 and a cytotoxic agent.

26. The conjugate of claim 25 , wherein the cytotoxic agent is Pseudomonas exotoxin A (PE38).

27. The antibody of claim 2 , wherein the antibody has specificity for one or more antigens in addition to ROR1.

28. The antibody of claim 27 , wherein the one or more antigens is a tumor antigen.

29. The antibody of claim 27 , wherein the one or more antigens is an antigen that promotes activation or targeting of cytotoxic effector cells.

30. The antibody of claim 1 , wherein the antibody has specificity for one or more antigens in addition to ROR1.

31. The antibody of claim 30 , wherein the one or more antigens is a tumor antigen.

32. The antibody of claim 30 , wherein the one or more antigens is an antigen that promotes activation or targeting of cytotoxic effector cells.

Assignees

• Rader Christoph
• Baskar Sivasubramanian
• Us Health

Inventors

• Rader Christoph
• Baskar Sivasubramanian

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• G01N33/5759 Primary

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K2039/505

  comprising antibodies · CPC title