ANTI-VLA-4 ANTIBODIES
This invention relates to alpha-4 binding antibodies, and fragments thereof.
1 . A recombinant antibody molecule, or an α4-binding fragment thereof, comprising a variable light chain framework comprising an acceptor sequence from IGKV4-1 and a variable heavy chain framework comprising an acceptor sequence from IGHV1-f and having heavy and light chain CDRs derived from murine antibody HP1/2 or from murine antibody 21.6.
2 . A recombinant antibody molecule, or an α4-binding fragment thereof, capable of binding α4, comprising a variable light chain framework comprising an acceptor sequence from germline engineered AAH70335.1 (SEQ ID NO:15) and a variable heavy chain framework comprising an acceptor sequence from IGHV1-f.
3 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 1 , further comprising CDRs derived from murine antibody HP1/2.
4 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 1 , further comprising CDRs derived from murine antibody 21.6.
5 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 1 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.
6 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 1 , wherein the light chain variable region comprises the sequence of SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10.
7 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 2 , wherein the light chain variable region comprises the sequence of SEQ ID NO:11.
8 . The antibody of claim 1 , wherein the antibody binds VLA-4.
9 . A vector comprising DNA encoding an antibody heavy chain, or an α4-binding fragment thereof, comprising the sequences of SEQ ID NOs:3, 4, or 5.
10 . A vector comprising DNA encoding an antibody light chain, or an α4-binding fragment thereof, comprising SEQ ID NOs:8, 9, 10, or 11.
11 . A method of making a recombinant anti-α4 antibody, or an α4-binding fragment thereof, comprising
(a) providing a host cell comprising (i) a DNA sequence encoding an antibody heavy chain, or an α4-binding fragment thereof, wherein the DNA sequence comprises the sequence of SEQ ID NOs:3, 4, or 5, and (ii) a DNA sequence encoding an antibody light chain, or an α4-binding fragment thereof, wherein the DNA sequence comprises the sequence of SEQ ID NOs:8, 9, 10, or 11, and
(b) culturing the cell to produce the recombinant anti-α4 antibody molecule or α4 binding fragment thereof.
12 . A method of treating a patient comprising administering to said patient the composition of claim 1 .
13 . The method of claim 12 , wherein the patient has a cancer.
14 . The method of claim 13 , wherein the patient has a solid tumor, a hematological malignancy, a multiple myeloma or acute myelogenous leukemia (AML).
15 . (canceled)
16 . (canceled)
17 . The method of claim 12 , wherein the patient has an inflammatory disorder, multiple sclerosis, asthma, rheumatoid arthritis, diabetes, optic neuritis, Crohn's disease, an acute disorder, a spinal cord injury or traumatic brain injury.
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . The method of claim 12 , wherein the composition is administered as a regimen.
22 . The method of claim 12 , further comprising administering to the patient a second therapeutic agent.
23 . The method of claim 22 , wherein the second therapeutic agent is a thrombolytic agent, a chemotherapeutic agent, a neuroprotective agent, an anti-inflammatory agent, a steroid, a cytokine, or a growth factor.
24 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 2 , further comprising CDRs derived from murine antibody HP1/2.
25 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 2 , further comprising CDRs derived from murine antibody 21.6.
26 . The recombinant antibody molecule, or α4-binding fragment thereof, of claim 2 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.
27 . The antibody of claim 2 , wherein the antibody binds VLA-4.
28 . A method of treating a patient comprising administering to said patient the composition of claim 2 .
29 . The method of claim 28 , wherein the patient has a cancer.
30 . The method of claim 29 , wherein the patient has a solid tumor, a hematological malignancy, a multiple myeloma or acute myelogenous leukemia (AML).
31 . The method of claim 28 , wherein the patient has an inflammatory disorder, multiple sclerosis, asthma, rheumatoid arthritis, diabetes, optic neuritis, Crohn's disease, an acute disorder, a spinal cord injury or traumatic brain injury.
32 . The method of claim 28 , wherein the composition is administered as a regimen.
33 . The method of claim 28 , further comprising administering to the patient a second therapeutic agent.
34 . The method of claim 33 , wherein the second therapeutic agent is a thrombolytic agent, a chemotherapeutic agent, a neuroprotective agent, an anti-inflammatory agent, a steroid, a cytokine, or a growth factor.