CD131 binding proteins

Patent metadata

Field	Value
Publication number	US-10894834-B2
Application number	US-201615779252-A
Country	US
Kind code	B2
Filing date	Nov 25, 2016
Priority date	Nov 27, 2015
Publication date	Jan 19, 2021
Grant date	Jan 19, 2021

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.

First claim

The invention claimed is:

1. 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 wherein the antigen binding domain comprises:
(i) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 64 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 5; or
(ii) a V H comprising the sequence set forth in SEQ ID NO: 64 and a V L comprising the sequence set forth in SEQ ID NO: 5.

2. The CD131-binding protein of claim 1 , which has one or more of the following activities:
(i) reduces or inhibits activation of isolated human neutrophils by GM-CSF as determined by reducing or inhibiting GM-CSF-induced increase in neutrophil cell size;
(ii) reduces or inhibits IL-3-induced IL-8 secretion by human basophils;
(iii) reduces IL-3-mediated survival or plasmacytoid dendritic cells (pDCs);
(iv) reduces activation of human peripheral blood eosinophils by IL-5 as determined by assessing change in forward scatter assessed by flow cytometry;
(v) reduces survival of human peripheral blood eosinophils in the presence of IL-5 and/or GM-CSF and/or IL-3;
(vi) reduces IL-3-induced tumor necrosis factor (TNF) a release from human mast cells;
(vii) reduces IL-3-induced IL-13 release from human mast cells;
(viii) reduces potentiation of IgE-mediated IL-8 release from human mast cells by IL-3 and/or IL-5 and/or GM-CSF; or
(ix) reduces formation of colony forming units-granulocytes-macrophages (CFU-GM) by CD34+ human bone marrow cells cultured in the presence of stem cell factor (SCF), GM-CSF, IL-3 and IL-5.

3. The CD131-binding protein of claim 1 , wherein if the V H and V L are in a single polypeptide chain, the protein is:
(i) a single chain Fv fragment (scFv);
(ii) a dimeric scFv (di-scFv);
(iii) one of (i) or (ii) linked to a constant region of an antibody, Fc or a heavy chain constant domain (C H ) 2 and/or C H 3; or
(iv) one of (i) or (ii) linked to a protein that binds to an immune effector cell, or if the V H and V L are in separate polypeptide chains the protein is:
(i) a diabody;
(ii) a triabody;
(iii) a tetrabody;
(iv) a Fab;
(v) a F(ab′) 2 ;
(vi) a Fv;
(vii) one of (i) to (vi) linked to a constant region of an antibody, Fc or a heavy chain constant domain (C H ) 2 and/or C H 3;
(viii) one of (i) to (vi) linked to a protein that binds to an immune effector cell; or
(ix) an antibody.

4. The CD131-binding protein of claim 1 , which is conjugated to another compound.

5. A composition comprising the CD131-binding protein of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Csl Ltd

Inventors

• Owczarek Catherine
• Panousis Kosta
• Wilson Nicholas
• Hardy Matthew
• Edwards Kirsten
• Rayzman Veronika

Classifications

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• G01N33/577

  involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)} · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title