CD131 binding proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-11840573-B2
Application number	US-202016953499-A
Country	US
Kind code	B2
Filing date	Nov 20, 2020
Priority date	Nov 27, 2015
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

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 a heavy chain variable region (V H ) comprising the sequence set forth in SEQ ID NO: 193 and a light chain variable region (V L ) comprising the sequence set forth in SEQ ID NO: 5.

2. The CD131-binding protein of claim 1 , wherein the K D of the CD131-binding protein comprises a polypeptide comprising the sequence set forth in SEQ ID NO: 194 is about 100 nM or less, when the polypeptide is immobilized on a solid surface and the K D is determined by surface plasmon resonance.

3. 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 or prevents IL-3-mediated survival or plasmacytoid dendritic cells (pDCs);
(iv) reduces or prevents activation of human peripheral blood eosinophils by IL-5 as determined by assessing change in forward scatter assessed by flow cytometry;
(v) reduces or prevents survival of human peripheral blood eosinophils in the presence of IL-5 and/or GM-CSF and/or IL-3;
(vi) reduces or prevents IL-3-induced tumor necrosis factor (TNF) a release from human mast cells;
(vii) reduces or prevents IL-3-induced IL-13 release from human mast cells;
(viii) reduces or prevents 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 or prevents 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.

4. 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.

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

6. A nucleic acid encoding the CD131-binding protein of claim 1 .

7. An expression construct comprising the nucleic acid of claim 6 .

8. An isolated or recombinant cell comprising the expression construct of claim 7 .

9. An isolated or recombinant cell expressing the CD131-binding protein of claim 1 .

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

11. 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: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 5;
(ii) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 5;
(iii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 6;
(iv) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 6;
(v) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 7;
(vi) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 7;
(vii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 8;
(viii) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 8;
(ix) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 9;
(x) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 9;
(xi) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 10;
(xii) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 10;
(xiii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 11;
(xiv) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 11;
(xv) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 12;
(xvi) a V H comprising the sequence set forth in SEQ ID NO: 20 and the V L comprising a sequence set forth in SEQ ID NO: 12;
(xvii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 13;
(xviii) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 13;
(xix) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 14;
(xx) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 14;
(xxi) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 15;
(xxii) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 15;
(xxiii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 16;
(xxiv) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 16;
(xxv) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 17;
(xxvi) a V H comprising the sequence set forth in SEQ ID NO: 20 and a V L comprising the sequence set forth in SEQ ID NO: 17;
(xxvii) a V H comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 20 and a V L comprising CDRs 1, 2 and 3 of the sequence set forth in SEQ ID NO: 18;
(xxviii) a V H comprising the sequence set forth in SEQ ID NO:

Assignees

• Csl Ltd

Inventors

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

Classifications

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• G01N33/68

  involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title