CPC C07K 16/2866 (2013.01) [A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); C07K 2317/21 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/55 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] | 14 Claims |
1. A nucleic acid encoding a protein comprising an antigen binding site of an antibody, wherein the antigen-binding site binds to human granulocyte-colony stimulating factor receptor (hG-CSFR) and neutralizes granulocyte-colony stimulating factor (G-CSF) signaling, and wherein the antigen-binding site comprises:
(i) a heavy chain variable region (VH) comprising:
a. a complementarity determining region (CDR1) comprising a sequence set forth in SEQ ID NO: 6,
b. a CDR2 comprising a sequence set forth in SEQ ID NO: 7, and
c. a CDR3 comprising a sequence set forth in LGELGX1X2X3X4, wherein:
X1 is selected from the group consisting of tryptophan, glutamine, methionine, serine, phenylalanine, glutamic acid and histidine;
X2 is an amino acid selected from the group consisting of phenylalanine, tyrosine, methionine, serine, glycine and isoleucine;
X3 is an amino acid selected from the group consisting of aspartic acid, methionine, glutamine, serine, leucine, valine, arginine and histidine; and
X4 is any amino acid or an amino acid selected from the group consisting of proline, glutamic acid, alanine, leucine, phenylalanine, tyrosine, threonine, asparagine, aspartic acid, serine, glycine, arginine, and lysine; and
(ii) a light chain variable region (VL) comprising:
a. a CDR1 comprising a sequence set forth in SEQ ID NO: 9,
b. a CDR2 comprising a sequence set forth in SEQ ID NO: 10, and
c. a CDR3 comprising a sequence set forth in X1X2X3X4X5X6X7X8X9, wherein:
X1 is an amino acid selected from the group consisting of glutamine, glutamic acid, histidine, alanine and serine;
X2 is an amino acid selected from the group consisting of glutamine, valine, phenylalanine, asparagine and glutamic acid;
X3 is an amino acid selected from the group consisting of serine and glycine;
X4 is an amino acid selected from the group consisting of tryptophan, methionine, phenylalanine, tyrosine, isoleucine and leucine;
X5 is an amino acid selected from the group consisting of glutamic acid, methionine, glutamine, tryptophan, serine, valine, asparagine, glycine, alanine, arginine, histidine, tyrosine, lysine and threonine;
X6 is an amino acid selected from the group consisting of tyrosine, methionine, isoleucine and threonine;
X7 is an amino acid selected from the group consisting of proline, alanine, histidine, glycine and lysine;
X8 is an amino acid selected from the group consisting of leucine, glutamine, methionine, alanine, phenylalanine, isoleucine, lysine, histidine and glycine; and
X9 is an amino acid selected from the group consisting of threonine, phenylalanine, tyrosine, methionine, lysine, serine, histidine, proline, tryptophan, isoleucine, glutamine, glycine and valine.
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