FcRn antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11345751-B2
Application number	US-201716321801-A
Country	US
Kind code	B2
Filing date	Jul 31, 2017
Priority date	Jul 29, 2016
Publication date	May 31, 2022
Grant date	May 31, 2022

Abstract

The present application features antibodies that bind to human neonatal Fc receptor (FcRn). These anti-FcRn antibodies are useful, e.g., to promote clearance of autoantibodies in a subject, to suppress antigen presentation in a subject, to block an immune response, e.g., block an immune complex-based activation of the immune response in a subject, and to treat immunological diseases (e.g., autoimmune diseases) in a subject. These anti-FcRn antibodies are also useful, e.g., to decrease pathogenic antibody transport across the placenta of a pregnant subject, to increase pathogenic antibody catabolism in a pregnant subject, and to treat an antibody-mediated enhancement of viral disease in a fetus or a neonate.

First claim

What is claimed is:

1. A method of treating an alloimmune and/or autoimmune disorder comprising administering an antibody to a pregnant subject, wherein the antibody comprises: (1) a light chain variable region comprising a CDR L1, a CDR L2, and a CDR L3 and (2) a heavy chain variable region comprising a CDR H1, a CDR H2, and a CDR H3, wherein
the CDR L1 comprises a sequence X 1 GTGSDVGSYNX 2 VS (SEQ ID NO: 12),
the CDR L2 comprises a sequence GDX 3 X 4 RPS (SEQ ID NO: 13),
the CDR L3 comprises a sequence X 5 SYX 6 GSGIYV (SEQ ID NO: 14),
the CDR H1 comprises a sequence Z 1 YAMG (SEQ ID NO: 15),
the CDR H2 comprises a sequence Z 7 IGZ 2 SGZ 3 QTZ 4 YADS (SEQ ID NO: 16), and
the CDR H3 comprises a sequence LAZ 5 Z 6 DSY (SEQ ID NO: 17), wherein
X 1 is a polar or hydrophobic amino acid,
X 2 is a hydrophobic amino acid,
X 3 is a polar amino acid,
X 4 is a polar or acidic amino acid,
X 5 is a polar or hydrophobic amino acid,
X 6 is a hydrophobic amino acid,
Z 1 is a polar or acidic amino acid,
Z 2 is a polar or hydrophobic amino acid,
Z 3 is G, S, or A,
Z 4 is a basic amino acid,
Z 5 is a hydrophobic or basic amino acid,
Z 6 is G, S, D, Q, or H, and
Z 7 is S or T.

2. The method of claim 1 , wherein the antibody comprises: (1) a light chain variable region comprising a CDR L1, a CDR L2, and a CDR L3 and (2) a heavy chain variable region comprising a CDR H1, a CDR H2, and a CDR H3, wherein
the CDR L1 comprises the sequence X 1 GTGSDVGSYNLVS (SEQ ID NO: 48) or TGTGSDVGSYNX 2 VS (SEQ ID NO: 49),
the CDR L2 comprises the sequence GDX 3 ERPS (SEQ ID NO: 50) or GDSX 4 RPS (SEQ ID NO: 51),
the CDR L3 comprises the sequence X 5 SYAGSGIYV (SEQ ID NO: 52) or SSYX 6 GSGIYV (SEQ ID NO: 53),
the CDR H1 comprises the sequence of TYAMG (SEQ ID NO: 4), DYAMG (SEQ ID NO: 5), or NYAMG (SEQ ID NO: 6),
the CDR H2 comprises the sequence of SIGASGSQTRYADS (SEQ ID NO: 8), SIGSSGAQTRYADS (SEQ ID NO: 7), SIGASGAQTRYADS (SEQ ID NO: 9), SIGASGGQTRYADS (SEQ ID NO: 10), TIGSSGAQTRYADS (SEQ ID NO: 41), SIGASGSQTRYADS (SEQ ID NO: 42), TIGASGAQTRYADS (SEQ ID NO: 43), or TIGASGGQTRYADS (SEQ ID NO: 46), and
the CDR H3 comprises the sequence LAZ 5 GDSY (SEQ ID NO: 54) or LAIZ 6 DSY (SEQ ID NO: 55).

3. The method of claim 2 , wherein the antibody comprises (1) a light chain variable region comprising a CDR L1, a CDR L2, and a CDR L3 and (2) a heavy chain variable region comprising a CDR H1, a CDR H2, and a CDR H3, wherein
the CDR L1 comprises the sequence TGTGSDVGSYNLVS (SEQ ID NO: 1),
the CDR L2 comprises the sequence GDSERPS (SEQ ID NO: 2),
the CDR L3 comprises the sequence SSYAGSGIYV (SEQ ID NO: 3),
the CDR H1 comprises the sequence TYAMG (SEQ ID NO: 4),
the CDR H2 comprises the sequence SIGSSGAQTRYADS (SEQ ID NO: 7), or TIGSSGAQTRYADS (SEQ ID NO: 41), and

the CDR H3 comprises the sequence LAIGDSY (SEQ ID NO: 11).

4. The method of claim 2 , wherein
the CDR L1 of the isolated antibody comprises the sequence TGTGSDVGSYNLVS (SEQ ID NO: 1),
the CDR L2 of the isolated antibody comprises the sequence GDSERPS (SEQ ID NO: 2),
the CDR L3 of the isolated antibody comprises the sequence SSYAGSGIYV (SEQ ID NO: 3),
the CDR H1 of the isolated antibody comprises the sequence NYAMG (SEQ ID NO: 6),
the CDR H2 of the isolated antibody comprises the sequence SIGASGAQTRYADS (SEQ ID NO: 9) or TIGASGAQTRYADS (SEQ ID NO: 43), and
the CDR H3 of the isolated antibody comprises the sequence LAIGDSY (SEQ ID NO: 11).

5. The method of claim 1 , wherein the light chain comprises an amino acid sequence having at least 90% identity to the sequence:

(SEQ ID NO: 19)

QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGK

APKLMIYGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADY

YCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKY

AASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS.

6. The method of claim 5 , wherein the light chain variable region of the isolated antibody comprises a sequence having at least 95%, 97%, 99%, or 100% identity to the sequence of SEQ ID NO: 19.

7. The method of claim 1 , wherein the heavy chain comprises an amino acid sequence selected from the group consisting of:
a sequence having at least 90% identity to the sequence of

(SEQ ID NO: 20)

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKG

LEWVSSIGSSGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRA

EDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS

GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD

KTHTCPPCPAPELIGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVL

HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPG;

a sequence having at least 90% identity to the sequence of

(SEQ ID NO: 21)

EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKG

LEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRA

EDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSK

Assignees

• Momenta Pharmaceuticals Inc

Inventors

• Ling Leona E
• Roy Sucharita
• Washburn Nathaniel
• Kehry Marilyn
• King David J
• Manning Anthony
• Meador Iii James
• Hillson Jan

Classifications

• C07K16/283 Primary

  against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851) · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title