US 8,506,960 B2 · 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.

Claims15

Dependent claims

An isolated binding member for human GM-CSFRα, wherein the binding member binds the extracellular domain of human GM-CSFRα with an affinity (Kd) of 5 nM or less in a surface plasmon resonance assay, inhibits binding of GM-CSF to GM-CSFRα, and comprises a human or humanised antibody molecule that competes for binding the extracellular domain of human GM-CSFRα with an antibody molecule having a VH domain amino acid sequence SEQ ID NO:

52 and a VL domain amino acid sequence SEQ ID NO:
57.

An isolated binding member for human GM-CSFRα, wherein the binding member inhibits binding of GM-CSF to GM-CSFRα and wherein the binding member comprises an antibody molecule comprising an antibody VH domain comprising a set of complementarity determining regions HCDR1, HCDR2 and HCDR3 and a framework, and an antibody VL domain comprising a set of complementarity determining regions LCDR1, LCDR2 and LCDR3 and a framework, wherein the set of complementarity determining regions comprises:

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.

38 more elements

An isolated binding member for human GM-CSFRα, wherein the binding member comprises an antibody molecule which inhibits binding of GM-CSF to GM-CSFRα, wherein the binding member binds at least one residue of Tyr-Leu-Asp-Phe-Gln at positions 226 to 230 of human GM-CSFRα, as shown in SEQ ID NO:

206, wherein the binding member binds to human GM-CSFRα, extra-cellular domain with an affinity (KD) of 5 nM or less in a surface plasmon resonance assay, and wherein the binding member comprises an antibody VH domain comprising a set of complementarity determining regions HCDR1, HCDR2 and HCDR3 and a framework, and an antibody VL domain comprising a set of complementarity determining regions LCDR1, LCDR2 and LCDR3 and a framework, wherein the set of complementarity determining regions comprises:
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.

39 more elements

An isolated antibody molecule which binds the alpha chain of human Granulocyte/Macrophage Colony Stimulating Factor Receptor (GM-CSFRα) and inhibits binding of GM-CSF to human GM-CSFRα, wherein the antibody molecule comprises:

(i) a VH domain comprising a set of VH complementarity determining regions (CDRs):
CDR1, CDR2 and CDR3 and a framework, wherein the VH domain comprises:
(a) VH domain amino acid sequence SEQ ID NO:
52 or
(b) a variant of VH domain amino acid sequence SEQ ID NO:
52 with less than 10 amino acid alterations,
and wherein the VH domain comprises:
S at Kabat residue H17 of the VH framework;
I at Kabat residue H34 of VH CDR1;
E at Kabat residue H54 of VH CDR2;
I at Kabat residue H57 of VH CDR2;
I, L, V, A or M at Kabat residue H94 of the VH framework;
V, N, A or L at Kabat residue H95 of VH CDR3;
S at Kabat residue H97 of VH CDR3;
S, F, H, P, T or W at Kabat residue H99 of VH CDR3;
and
A, T, P, S, V or H at Kabat residue H100B of VH CDR3;
and
(ii) a VL domain comprising a set of VL CDRs:
CDR1, CDR2 and CDR3 and a framework, wherein the VL domain comprises:
(a) VL domain amino acid sequence SEQ ID NO:
57 or 218;
or
(b) a variant of VL domain amino acid sequence SEQ ID NO:
57 or 218 with less than 10 amino acid alterations,
and wherein the VL domain comprises:
S at Kabat residue 27A of VL CDR1;
N at Kabat residue 27B of VL CDR1;
I at Kabat residue 27C of VL CDR1;
D at Kabat residue 32of VL CDR1;
N at Kabat residue 51 of VL CDR1;
N at Kabat residue 52 of VL CDR2;
K at Kabat residue 53 of VL CDR2;
S, T or M at Kabat residue L90 of VL CDR3;
D, E, Q, S, M or T at Kabat residue L92 of VL CDR3;
and
S, P, I or V at Kabat residue L96 of VL CDR3 provided that the functionality of the antibody molecule is preserved.

34 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/294,616Filed 27 Mar 2007 · us provisional application

Priority

27 Mar 2006

Published

US 2009/0130093 A121 May 2009

Granted

13 Aug 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07K 16/2866
Against receptors, cell surface antigens or cell surface determinants: against receptors for cytokines, lymphokines, interferons
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/00
Drugs for disorders of the respiratory system
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics

Abstract

Claims15

Dependent claims

52 and a VL domain amino acid sequence SEQ ID NO:
57.

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.

38 more elements

206, wherein the binding member binds to human GM-CSFRα, extra-cellular domain with an affinity (KD) of 5 nM or less in a surface plasmon resonance assay, and wherein the binding member comprises an antibody VH domain comprising a set of complementarity determining regions HCDR1, HCDR2 and HCDR3 and a framework, and an antibody VL domain comprising a set of complementarity determining regions LCDR1, LCDR2 and LCDR3 and a framework, wherein the set of complementarity determining regions comprises:
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.

39 more elements

(i) a VH domain comprising a set of VH complementarity determining regions (CDRs):
CDR1, CDR2 and CDR3 and a framework, wherein the VH domain comprises:
(a) VH domain amino acid sequence SEQ ID NO:
52 or
(b) a variant of VH domain amino acid sequence SEQ ID NO:
52 with less than 10 amino acid alterations,
and wherein the VH domain comprises:
S at Kabat residue H17 of the VH framework;
I at Kabat residue H34 of VH CDR1;
E at Kabat residue H54 of VH CDR2;
I at Kabat residue H57 of VH CDR2;
I, L, V, A or M at Kabat residue H94 of the VH framework;
V, N, A or L at Kabat residue H95 of VH CDR3;
S at Kabat residue H97 of VH CDR3;
S, F, H, P, T or W at Kabat residue H99 of VH CDR3;
and
A, T, P, S, V or H at Kabat residue H100B of VH CDR3;
and
(ii) a VL domain comprising a set of VL CDRs:
CDR1, CDR2 and CDR3 and a framework, wherein the VL domain comprises:
(a) VL domain amino acid sequence SEQ ID NO:
57 or 218;
or
(b) a variant of VL domain amino acid sequence SEQ ID NO:
57 or 218 with less than 10 amino acid alterations,
and wherein the VL domain comprises:
S at Kabat residue 27A of VL CDR1;
N at Kabat residue 27B of VL CDR1;
I at Kabat residue 27C of VL CDR1;
D at Kabat residue 32of VL CDR1;
N at Kabat residue 51 of VL CDR1;
N at Kabat residue 52 of VL CDR2;
K at Kabat residue 53 of VL CDR2;
S, T or M at Kabat residue L90 of VL CDR3;
D, E, Q, S, M or T at Kabat residue L92 of VL CDR3;
and
S, P, I or V at Kabat residue L96 of VL CDR3 provided that the functionality of the antibody molecule is preserved.

34 more elements

Dependencies are inferred from the claim text.

Antibody molecule for human GM-CSF receptor alpha

Life of this patent

Abstract

Claims15

Antibody molecule for human GM-CSF receptor alpha

Life of this patent

Abstract

Claims15