Antibodies to FeRn and uses thereof
View Patent ↗This disclosure provides, inter alia, proteins that bind to FcRn, e.g., immunoglobulins that inhibit FcRn with high affinity and selectivity. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.
1. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising:
administering to the subject in need thereof an effective amount of an antibody that binds human FcRn thereby treating the autoimmune disorder, wherein the antibody comprises a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, and wherein: the HC comprises:
a HC CDR1 comprising an amino acid sequence EYAMG (SEQ ID NO: 144) or VYAMG (SEQ ID NO:156),
a HC CDR2 comprising an amino acid sequence SIGSSGGQTKYADSVKG (SEQ ID NO:145), or SIGSSGGPTKYADSVKG (SEQ ID NO:157), and
a HC CDR3 comprising an amino acid sequence LSTGELY (SEQ ID NO:146), LSIRELV (SEQ ID NO:158), LSIVDSY (SEQ ID NO:164), LSLGDSY (SEQ ID NO:170), or LAIGDSY (SEQ ID NO: 176); and
the LC comprises:
a LC CDR1 comprising an amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO:141),
a LC CDR2 comprising an amino acid sequence GDSQRPS (SEQ ID NO:142), and
a LC CDR3 comprising an amino acid sequence CSYAGSGIYV (SEQ ID NO: 143).
2. The method of claim 1 , wherein the HC comprises a HC CDR1 comprising the amino acid sequence EYAMG (SEQ ID NO:144), a HC CDR2 comprising the amino acid sequence SIGSSGGQTKYADSVKG (SEQ ID NO: 145), and a HC CDR3 comprising the amino acid sequence LAIGDSY (SEQ ID NO: 176).
3. The method of claim 1 , wherein the HC comprises a HC CDR1 comprising the amino acid sequence VYAMG (SEQ ID NO:156), a HC CDR2 comprising the amino acid sequence SIGSSGGPTKYADSVKG (SEQ ID NO: 157), and a HC CDR3 comprising the amino acid sequence LSIVDSY (SEQ ID NO: 164).
4. The method of claim 1 , wherein the HC comprises, a HC CDR1 comprising the amino acid sequence EYAMG (SEQ ID NO:144), a HC CDR2 comprising the amino acid sequence SIGSSGGQTKYADSVKG (SEQ ID NO:145), and a HC CDR3 comprising the amino acid sequence LSTGELY (SEQ ID NO: 146).
5. The method of claim 1 , wherein the HC comprises: (i) a HC CDR1 of EYAMG (SEQ ID NO:144), a HC CDR2 of SIGSSGGQTKYADSVKG (SEQ ID NO:145), and a HC CDR3 of LSTGELY (SEQ ID NO:146); (ii) a HC CDR1 of VYAMG (SEQ ID NO:156), a HC CDR2 of SIGSSGGPTKYADSVKG (SEQ ID NO:157), and a HC CDR3 of LSIRELV (SEQ ID NO:158); (iii) a HC CDR1 of VYAMG (SEQ ID NO:156), a HC CDR2 of SIGSSGGPTKYADSVKG (SEQ ID NO:157), and a HC CDR3 of LSIVDSY (SEQ ID NO:164); (iv) a HC CDR1 of EYAMG (SEQ ID NO: 144), a HC CDR2 of SIGSSGGQTKYADSVKG (SEQ ID NO:145), and a HC CDR3 of LSLGDSY (SEQ ID NO:170); or (v) a HC CDR1 of EYAMG (SEQ ID NO: 144), a HC CDR2 of SIGSSGGQTKYADSVKG (SEQ ID NO:145), and a HC CDR3 of LAIGDSY (SEQ ID NO:176).
6. The method of claim 1 , wherein the autoimmune disorder is a disorder selected from the group consisting of: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Myasthenia Gravis (MG), Graves Disease, Idiopathic Thrombocytopenia Purpura (ITP), Guillain-Barre Syndrome, autoimmune myocarditis, Membrane Glomerulonephritis, diabetes mellitus, Type I diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune thyroiditis, gastritis, Celiac Disease, Vitiligo, Hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathies, experimental autoimmune encephalomyelitis, immune neutropenia, sarcoidosis, polymyositis, polyarteritis, cutaneous vasculitis, pemphigus , pemphigoid, Goodpasture's syndrome, Kawasaki's disease, systemic sclerosis, anti-phospholipid syndrome, and Sjogren's syndrome.