US 12,441,786 B2
Bispecific antibodies for use in treatment of NLRC4-GOF inflammasomapathy
Guido Junge, Basel (CH); Michael Kiffe, Efringen-Kirchen (DE); Jiri Kovarik, Zurich (CH); Richard Stein, Weil am Rhein (DE); and Frank Waldron-Lynch, Brookline, MA (US)
Assigned to NOVARTIS AG, Basel (CH)
Filed by NOVARTIS AG, Basel (CH)
Filed on Nov. 16, 2021, as Appl. No. 17/455,192.
Claims priority of provisional application 63/237,473, filed on Aug. 26, 2021.
Claims priority of provisional application 63/115,473, filed on Nov. 18, 2020.
Prior Publication US 2022/0177569 A1, Jun. 9, 2022
Int. Cl. A61K 39/00 (2006.01); A61K 45/06 (2006.01); A61P 37/00 (2006.01); C07K 16/24 (2006.01); C07K 16/28 (2006.01); C07K 16/46 (2006.01)
CPC C07K 16/245 (2013.01) [A61K 45/06 (2013.01); A61P 37/00 (2018.01); C07K 16/2875 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01)] 6 Claims
 
1. A method for the treatment or prevention of an NLRC4 inflammasomopathy in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a bispecific antibody, wherein the antibody comprises
a. a first part which is an immunoglobulin with a first variable light chain of (VL1) and a first variable heavy chain (VH1), that binds specifically to a IL1β, and a first constant heavy chain (CH1) with a hetero-dimerization modification, and
b. a second part which is an immunoglobulin with a second variable light chain (VL2) and a second variable heavy chain (VH2), that binds specifically to IL-18 and a second constant heavy chain (CH2) with a hetero-dimerization modification which is complementary to the hetero-dimerization modification of the first constant heavy chain, wherein the method comprises administering the bispecific antibody intravenously at a dose of about 10 mg/kg, and wherein
i. the first immunoglobulin VH1 domain of the bispecific antibody comprises the amino acid sequence SEQ ID NO: 85,
ii. the first immunoglobulin VL1 domain of the bispecific antibody comprises the amino acid sequence SEQ ID NO: 101,
iii. the second immunoglobulin VH2 domain of the bispecific antibody comprises the amino acid sequence SEQ ID NO: 53, and
iv. the second immunoglobulin VL2 domain of the bispecific antibody comprises the amino acid sequence SEQ ID NO: 69.