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US 11,884,744 B2Granted
Compound targeting IL-23A and B-cell activating factor (BAFF) and uses thereof
AssigneesBoehringer Ingelheim International GmbH, MacroGenics, Inc.
InventorsSanjaya Singh, Qi Pan, Rachel Rebecca Barrett, Leslie S. Johnson, Pankaj Gupta, Sarah Low, Haixia Wu
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Abstract
The disclosure relates to compounds specific for IL23A and BAFF, compositions comprising the compounds, and methods of use thereof. Nucleic acids, cells, and methods of production related to the compounds and compositions are also disclosed.
Claims20
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.
26 more elements
Dependencies are inferred from the claim text.