US 11,884,744 B2
Compound targeting IL-23A and B-cell activating factor (BAFF) and uses thereof
Sanjaya Singh, Sandy Hook, CT (US); Qi Pan, Chappaqua, NY (US); Rachel Rebecca Barrett, Bethel, CT (US); Leslie S. Johnson, Damestoen, MD (US); Pankaj Gupta, Scarsdale, NY (US); Sarah Low, Carmel, NY (US); and Haixia Wu, Danbury, CT (US)
Assigned to Boehringer Ingelheim International GmbH, Ingelheim Am Rhein (DK); and MacroGenics, Inc., Rockville, MD (US)
Filed by Boehringer Ingelheim International GmbH, Ingelheim Am Rhein (DK); and MacroGenics, Inc., Rockville, MD (US)
Filed on Oct. 22, 2020, as Appl. No. 17/076,894.
Application 17/076,894 is a division of application No. 16/278,216, filed on Feb. 18, 2019, granted, now 10,844,138.
Application 16/278,216 is a division of application No. 15/215,690, filed on Jul. 21, 2016, granted, now 10,280,231, issued on May 7, 2019.
Claims priority of provisional application 62/355,302, filed on Jun. 27, 2016.
Claims priority of provisional application 62/201,067, filed on Aug. 4, 2015.
Claims priority of provisional application 62/196,170, filed on Jul. 23, 2015.
Prior Publication US 2021/0107998 A1, Apr. 15, 2021
Int. Cl. A61K 39/395 (2006.01); C07K 16/46 (2006.01); C07K 16/28 (2006.01); C12N 15/63 (2006.01); C12N 5/10 (2006.01); C07K 16/24 (2006.01); C12P 21/00 (2006.01); C12N 15/00 (2006.01); A61K 39/00 (2006.01)
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.