Cd131 binding proteins and uses thereof
AssigneeCSL Limited
InventorsCatherine OWCZAREK, Con PANOUSIS, Nicholas WILSON, Matthew HARDY, Kirsten EDWARDS, Veronika RAYZMAN
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Abstract
The present disclosure provides a CD131-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain binds to or specifically binds to CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF), and uses thereof.
Claims28
A CD131-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain:
- (a) binds to or specifically binds to CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF), and wherein the CD131-binding protein inhibits GM-CSF-induced proliferation of TF-1 erythroleukemic cells with an IC50 of at least 700 nM;
- or
- (b) binds to or specifically binds to an epitope within site 2 of CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF);
- or
- (c) binds to an epitope formed upon dimerization of two CD131 polypeptides, or
- (d) binds to residues within domain 1 of a CD131 polypeptide and residues within domain 4 of another CD131 polypeptide;
- or
- (e) binds to or specifically binds to CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF),
- wherein the CD131-binding protein binds to one or more or all of the following mutant polypeptide(s):
- (i) a mutant polypeptide comprising the sequence set forth in SEQ ID NO 119;
- (ii) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 123;
- (iii) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 124;
- (iv) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 135;
- (v) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 131;
- (vi) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 136;
- (vii) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 137;
- (viii) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 139;
- and
- (ix) a mutant polypeptide comprising the sequence set forth in SEQ ID NO:
- 145,
- at a level that is reduced compared to the level of binding of the CD131-binding protein to a polypeptide comprising the sequence set forth in SEQ ID NO:
- 192;
- or
- (f) binds to or specifically binds to CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF),
- wherein the CD131-binding protein competitively inhibits binding of antibody 9A2 comprising a light chain variable region (VL) comprising the sequence set forth in SEQ ID NO:
- 5 and a heavy chain variable region (VH) comprising the sequence set forth in SEQ ID NO:
- 20.
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-26. (canceled)
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A method for depleting or reducing eosinophils, and/or treating eosinophilia in a subject, comprising neutralizing signaling by interleukin (IL) 3, IL-5, and granulocyte-macrophage colony stimulating factor (GM-CSF) in the subject.
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Dependencies are inferred from the claim text.