Antibody Molecule For Human GM-CSF Receptor Alpha

Abstract

Binding members for alpha chain of receptor for granulocyte macrophage colony stimulating factor (GM-CSFRα), especially antibody molecules. Use of the binding members in treating inflammatory and autoimmune diseases, e.g. rheumatoid arthritis, asthma, allergic response, multiple sclerosis, myeloid leukaemia and atherosclerosis.

1 - 54 . (canceled) 
     
     
         55 . A method for treating an inflammatory, respiratory, or autoimmune condition or disease in a subject in need thereof, comprising administering an effective amount of an anti-GMCSFRα antibody comprising a heavy chain with three complementarity determining regions (HCDRs) and a framework and a light chain with three complementarity determining regions (LCDRs) and a framework; wherein the set of complementarity determining regions is set forth in:
 SEQ ID NOs: 3, 4, 5, 8, 9, and 10; 
 SEQ ID NOs: 3, 4, 15, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 25, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 35, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 45, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 55, 8, 9, and 60; 
 SEQ ID NOs: 3, 4, 65, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 75, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 85, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 95, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 105, 8, 9, and 20; 
 SEQ ID NOs: 3, 4, 115, 8, 9, and 120; 
 SEQ ID NOs: 3, 4, 125, 8, 9, and 130; 
 SEQ ID NOs: 3, 4, 135, 8, 9, and 140; 
 SEQ ID NOs: 3, 4, 145, 8, 9, and 150; 
 SEQ ID NOs: 3, 4, 155, 8, 9, and 160; 
 SEQ ID NOs: 3, 4, 165, 8, 9, and 170; 
 SEQ ID NOs: 173, 4, 175, 8, 9, and 180; 
 SEQ ID NOs: 3, 4, 185, 8, 9, and 190; or 
 SEQ ID NOs: 3, 4, 195, 8, 9, and 200. 
 
     
     
         56 . The method of  claim 55 , wherein the condition or disease is selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, allergic response, multiple sclerosis, myeloid leukaemia, and artherosclerosis. 
     
     
         57 . The method of  claim 55 , wherein the antibody is in a composition with at least one additional component. 
     
     
         58 . The method of  claim 55 , wherein HCDR1 has the amino acid sequence set forth in SEQ ID NO: 3; HCDR2 has an amino acid sequence set forth in SEQ ID NO: 4; HCDR3 has an amino acid sequence set forth in SEQ ID NO: 55; LCDR1 has an amino acid sequence set forth in SEQ ID NO: 8; LCDR2 has an amino acid sequence set forth in SEQ ID NO: 9; and LCDR3 has an amino acid sequence set forth in SEQ ID NO: 60. 
     
     
         59 . The method of  claim 58 , wherein the condition or disease is selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, allergic response, multiple sclerosis, myeloid leukaemia, and artherosclerosis. 
     
     
         60 . The method of  claim 58 , wherein the antibody comprises a heavy chain with the amino acid sequence set forth in SEQ ID NO: 52. 
     
     
         61 . The method of  claim 58 , wherein the antibody comprises a light chain with the amino acid sequence as set forth in SEQ D NO: 218. 
     
     
         62 . The method of  claim 58 , wherein the antibody comprises a heavy chain with the amino acid sequence set forth in SEQ ID NO: 52 and a light chain with the amino acid sequence as set forth in SEQ D NO: 218. 
     
     
         63 . A method for treating an inflammatory, respiratory, or autoimmune condition or disease in a subject in need thereof, comprising administering an effective amount of an antibody that binds the alpha chain of human Granulocyte Macrophage Colony Stimulating Factor Receptor (GMCSFRα) and inhibits binding of GM-CSF to human GM-CSFR, wherein the antibody comprises:
 a variable heavy chain (VH) domain comprising HCDR1, HCDR2, HCDR3, and a framework and a variable light chain domain comprising LCDR1, LCDR2, LCDR3, and a framework 
 
       (i) wherein the VH domain comprises:
 (a) an amino acid sequence as set forth in SEQ NO: 52; or 
 (b) a variant VH domain comprising an amino acid sequence as set forth in SEQ ID NO: 52 with less than 10 amino acid alterations selected from:
 S at Kabat residue 117 of the VH framework; 
 I at Kabat residue 34 of HCDR1; 
 E at Kabat residue 54 of HCDR2 
 I at Kabat residue 57 of HCDR2; 
 I, L, V, A, or M at Kabat residue 94 of the VH framework; 
 V, N, A, or L at Kabat residue 95 of HCDR3; 
 S at Kabat residue 97 of HCDR3; 
 S, F, H, P, T, or W at Kabat residue 99 of HCDR3; and 
 A, T, P, S, V, or H at Kabat residue 100B of HCDR3; and 
 
 
       (ii) wherein the VL domain comprises:
 (a) an amino acid sequence as set forth in SEQ ID NO: 57 or SEQ ID NO: 218; or 
 (b) a variant VL domain comprising an amino acid sequence as set forth in SEQ ID NO: 57 or SEQ ID NO: 218 with less than 10 amino acid alterations selected from:
 S at Kabat residue 27A of LCDR1; 
 N at Kabat residue 27B of LCDR1 
 I at Kabat residue 27C of LCDR1; 
 D at Kabat residue 32 of LCDR1; 
 N at Kabat residue 51 of LCDR1 
 N at Kabat residue 52 of LCDR2 
 N at Kabat residue 53 of LCDR2; 
 S, T, or M at Kabat residue 90 of LCDR3; 
 D, E, Q, S, M, or T at Kabat residue 92 of LCDR3; and 
 S, P, I, or V at Kabat residue 96 of LCDR3, 
 
 
       provided that the functionality of the antibody is preserved. 
     
     
         64 . The method of  claim 63 , wherein the antibody is in a composition with at least one additional component. 
     
     
         65 . The method of treating of  claim 63 , wherein the condition or disease is selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, allergic response, multiple sclerosis, myeloid leukaemia, and artherosclerosis. 
     
     
         66 . A method for treating an inflammatory, respiratory, or autoimmune condition or disease in a subject in need thereof, comprising administering an effective amount of an antibody that binds GMCSFRα and inhibits binding of GM-CSF to human GM-CSFR, wherein the antibody comprises:
 a VH domain of SEQ ID NO: 2 and a VL domain of SEQ ID NO: 208; 
 a VH domain of SEQ ID NO: 12 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 32 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 42 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 52 and a VL domain of SEQ ID NO: 218; 
 a VH domain of SEQ ID NO: 62 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 72 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 82 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 92 and a VL domain of SEQ ID NO: 210; 
 a VH domain of SEQ ID NO: 102 and a VL domain of SEQ ID NO: 228; 
 a VH domain of SEQ ID NO: 22 and a VL domain of SEQ ID NO: 230; 
 a VH domain of SEQ ID NO: 22 and a VL domain of SEQ ID NO: 232; 
 a VH domain of SEQ ID NO: 132 and a VL domain of SEQ ID NO: 234; 
 a VH domain of SEQ ID NO: 142 and a VL domain of SEQ ID NO: 236; 
 a VH domain of SEQ ID NO: 152 and a VL domain of SEQ ID NO: 238; 
 a VH domain of SEQ ID NO: 152 and a VL domain of SEQ ID NO: 240; 
 a VH domain of SEQ ID NO: 172 and a VL domain of SEQ ID NO: 242; 
 a VH domain of SEQ ID NO: 182 and a VL domain of SEQ ID NO: 244; 
 a VH domain of SEQ ID NO: 192 and a VL domain of SEQ ID NO: 246. 
 
     
     
         67 . The method of treating of  claim 66 , wherein the antibody is in a composition with at least one additional component. 
     
     
         68 . The method of treating of  claim 62 , wherein the condition or disease is selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, allergic response, multiple sclerosis, myeloid leukaemia, and artherosclerosis.