CPC C07K 16/468 (2013.01) [C07K 16/241 (2013.01); C07K 16/244 (2013.01); C07K 16/2875 (2013.01); C12N 5/10 (2013.01); C12N 15/63 (2013.01); A61K 39/39558 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/524 (2013.01); C07K 2317/53 (2013.01); C07K 2317/56 (2013.01); C07K 2317/60 (2013.01); C07K 2317/62 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C12N 15/00 (2013.01); C12P 21/00 (2013.01)] | 20 Claims |
1. A method of suppressing an inflammatory response in in a subject in need thereof comprising administering a compound comprising a first polypeptide and a second polypeptide, wherein:
(A) said first polypeptide comprises:
(i) a light chain variable domain of a first immunoglobulin (VL1) specific for a first target protein;
(ii) a heavy chain variable domain of a second immunoglobulin (VH2) specific for a second target protein; and
(iii) a hinge region, a heavy chain constant region 2 (CH2) and a heavy chain constant region 3 (CH3); and
(B) said second polypeptide comprises:
(i) a light chain variable domain of the second immunoglobulin (VL2) specific for said second target protein;
(ii) a heavy chain variable domain of the first immunoglobulin (VH1) specific for said first target protein; wherein:
a) said VL1 and VH1 associate to form a binding site that binds said first target protein;
b) said VL2 and VH2 associate to form a binding site that binds said second target protein;
c) said heavy chain constant region 2 (CH2) comprises a tyrosine at position 252, a threonine at position 254 and a glutamic acid a position 256, numbered according to the EU index as in Kabat for the CH2 of a conventional antibody; and
d) said first target protein is B-cell activating factor (“BAFF”) and said second target protein is Interleukin-23A (“IL-23A”); or
e) said first target protein is IL-23A and said second target protein is BAFF, and
wherein:
(i) said VL1 comprises the amino acid sequence of SEQ ID NO:2, said VH1 comprises the amino acid sequence of SEQ ID NO:1, said VL2 comprises the amino acid sequence of SEQ ID NO:4 and said VH2 comprises the amino acid sequence of SEQ ID NO:3; or
(ii) said VL1 comprises the amino acid sequence of SEQ ID NO:4, said VH1 comprises the amino acid sequence of SEQ ID NO:3, said VL2 comprises the amino acid sequence of SEQ ID NO:2 and said VH2 comprises the amino acid sequence of SEQ ID NO:1; or
(iii) said VL1 comprises the amino acid sequence of SEQ ID NO:89, said VH1 comprises the amino acid sequence of SEQ ID NO:88, said VL2 comprises the amino acid sequence of SEQ ID NO:4 and said VH2 comprises the amino acid sequence of SEQ ID NO:3; or
(iv) said VL1 comprises the amino acid sequence of SEQ ID NO:4, said VH1 comprises the amino acid sequence of SEQ ID NO:3, said VL2 comprises the amino acid sequence of SEQ ID NO:89 and said VH2 comprises the amino acid sequence of SEQ ID NO:88; or
(v) said VL1 comprises the amino acid sequence of SEQ ID NO:91, said VH1 comprises the amino acid sequence of SEQ ID NO:90, said VL2 comprises the amino acid sequence of SEQ ID NO:4 and said VH2 comprises the amino acid sequence of SEQ ID NO:3; or
(vi) said VL1 comprises the amino acid sequence of SEQ ID NO:4, said VH1 comprises the amino acid sequence of SEQ ID NO:3, said VL2 comprises the amino acid sequence of SEQ ID NO:91 and said VH2 comprises the amino acid sequence of SEQ ID NO:90.
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