Anti-vla-4 antibodies

Abstract

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.