FC RECEPTOR BINDING PROTEINS
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 - 96 : (canceled)
97 : A method for reducing the binding of IgG to FcRn in an individual comprising:
providing an antibody or a fragment thereof which binds to human FcRn, is generated against the heavy chain of human FcRn or a fragment thereof, is a non-competitive inhibitor of IgG binding to human FcRn and does not bind β2-microglobulin; and
administering the antibody or the fragment thereof to an individual in an amount sufficient to reduce the binding of IgG to FcRn in the individual.
98 - 110 : (canceled)
111 : The method of claim 97 , wherein the individual has an autoimmune or alloimmune disease.
112 : The method of claim 97 , wherein the individual is an organ transplant recipient.
113 : The method of claim 97 , wherein the individual has been administered a therapeutic antibody.
114 : The method of claim 97 , wherein the autoimmune disease is immune thrombocytopenia.
115 : The method of claim 97 , wherein the autoimmune disease is immune pemphigus.
116 : The method of claim 97 , wherein the individual is a human.
117 : The method of claim 97 , wherein the antibody is administered at a dosage of 1 mg/kg to 2 g/kg.
118 : The method of claim 97 , wherein the antibody is administered at a dosage of 1 mg/kg to 200 mg/kg.
119 : The method of claim 97 , 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 the amino acid sequence EYAMG (SEQ ID NO:144) or VYAMG (SEQ ID NO:156),
a HC CDR2 comprising the amino acid sequence SIGSSGGQTKYADSVKG (SEQ ID NO:145) or SIGSSGGPTKYADSVKG (SEQ ID NO:157), and
a HC CDR3 comprising the 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 the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO:141),
a LC CDR2 comprising the amino acid sequence GDSQRPS (SEQ ID NO:142), and
a LC CDR3 comprising the amino acid sequence CSYAGSGIYV (SEQ ID NO:143).