Fc receptor binding proteins
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. An isolated antibody comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the antibody binds to human FcRn; 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).
2. The isolated antibody 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 isolated antibody 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 isolated antibody 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. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
6. The isolated antibody 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).