Anti-GM-CSF antibodies and uses thereof
Provided are anti-GM-CSF antibodies or fragments thereof including humanized antibodies and fragments. Also provided are uses of the antibodies and fragments for therapeutic, diagnostic and prognostic purposes. Therapeutic uses of the antibodies and fragments, for example include the treatment of inflammatory and autoimmune diseases and disorders.
1. An antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof has specificity to a human granulocyte macrophage colony-stimulating factor (GM-CSF) protein and comprises a heavy chain variable region (VH) complementarity determining region (CDR) 1 (CDR1) comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25, a light chain variable region (VL) CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28.
2. The antibody or antigen-binding fragment thereof of claim 1 , further comprising a heavy chain constant region, a light chain constant region, an Fc region, or the combination thereof.
3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof is humanized.
4. The antibody or antigen-binding fragment thereof of claim 3 , comprising a heavy chain variable region comprising one or more amino acid residues selected from the group consisting of:
(a) Glu at position 1,
(b) Arg at position 84,
(c) Tyr at position 27,
(d) Ile at position 28,
(e) Ile at position 48,
(f) Thr at position 68,
(g) Leu at position 70, or
(h) Thr at position 30, according to Kabat numbering and with reference to SEQ ID NO:29, and combinations thereof.
5. The antibody or antigen-binding fragment thereof of claim 3 , comprising a light chain variable region comprising one or more amino acid residues selected from the group consisting of:
(a) Val at position 48,
(b) Asp at position 57,
(d) Gln at position 70, or
(d) Ser at position 43, according to Kabat numbering and with reference to SEQ ID NO: 36, and combinations thereof.
6. The antibody or antigen-binding fragment thereof of claim 1 , comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 30-35.
7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34 or 35.
8. The antibody or antigen-binding fragment thereof of claim 1 , comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 37-41.
9. The antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 38 or 39.
10. The antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 38, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 35 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 39.
11. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or fragment thereof is a bispecific antibody or single chain variable fragment.
12. A composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
13. An isolated cell comprising one or more polynucleotides encoding the antibody or antigen-binding fragment thereof of claim 1 .
14. A method of detecting expression of GM-CSF in a sample, comprising contacting the sample with the antibody or antigen-binding fragment thereof of claim 1 under conditions for the antibody or fragment thereof to bind to the GM-CSF, and detecting the binding which indicates expression of GM-CSF in the sample.