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US 2019/0241678 A1Published application
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
Life of this patent
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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.
Claims22
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;
- and
- d) said first target protein is BAFF and said second target protein is IL-23A or said first target protein is IL-23A and said second target protein is BAFF,
- and wherein:
- (i) said VL1 comprises SEQ ID NO:2, said VH1 comprises SEQ ID NO:1, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (ii) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:2 and said VH2 comprises SEQ ID NO:1;
- or
- (iii) said VL1 comprises SEQ ID NO:89, said VH1 comprises SEQ ID NO:88, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (iv) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:89 and said VH2 comprises SEQ ID NO:88;
- or
- (v) said VL1 comprises SEQ ID NO:91, said VH1 comprises SEQ ID NO:90, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (vi) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:91 and said VH2 comprises SEQ ID NO:90.
24 more elements
2-16. (canceled)
18-32. (canceled)
A nucleic acid comprising a nucleotide sequence encoding a polypeptide as follows:
- one 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;
- and
- d) said first target protein is BAFF and said second target protein is IL-23A or said first target protein is IL-23A and said second target protein is BAFF, and
- wherein:
- (i) said VL1 comprises SEQ ID NO:2, said VH1 comprises SEQ ID NO:1, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (ii) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:2 and said VH2 comprises SEQ ID NO:1;
- or
- (iii) said VL1 comprises SEQ ID NO:89, said VH1 comprises SEQ ID NO:88, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (iv) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:89 and said VH2 comprises SEQ ID NO:88;
- or
- (v) said VL1 comprises SEQ ID NO:91, said VH1 comprises SEQ ID NO:90, said VL2 comprises SEQ ID NO:4 and said VH2 comprises SEQ ID NO:3;
- or
- (vi) said VL1 comprises SEQ ID NO:4, said VH1 comprises SEQ ID NO:3, said VL2 comprises SEQ ID NO:91 and said VH2 comprises SEQ ID NO:90.
25 more elements
(canceled)
39-40. (canceled)
Dependencies are inferred from the claim text.