FcRn antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10676526-B2
Application number	US-201615546870-A
Country	US
Kind code	B2
Filing date	Jan 29, 2016
Priority date	Jan 30, 2015
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

The present invention features antibodies that have high binding affinity 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.

First claim

What is claimed is:

1. An isolated antibody that binds to human FcRn, the isolated antibody comprising: (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 isolated antibody is selected from the group consisting of:
(a) an antibody wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4), CDR H2 comprise the amino acid sequence SIGSSGAQTRYADS (SEQ ID NO: 7), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11);
(b) an antibody wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence DYAMG (SEQ ID NO: 5), CDR H2 comprise the amino acid sequence SIGASGSQTRYADS (SEQ ID NO: 8), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11);
(c) an antibody wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence NYAMG (SEQ ID NO: 6), CDR H2 comprise the amino acid sequence SIGASGAQTRYADS (SEQ ID NO: 9), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11);
(d) an antibody wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4), CDR H2 comprise the amino acid sequence SIGASGGQTRYADS (SEQ ID NO: 10), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11); and
(e) an antibody wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4), CDR H2 comprise the amino acid sequence SIGASGSQTRYADS (SEQ ID NO: 8) and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11).

2. The isolated antibody of claim 1 , wherein the antibody binds human FcRn with a K D of less than or equal to that of an antibody having a light chain comprising the amino acid sequence of SEQ ID NO: 19 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 23.

3. The isolated antibody of claim 1 , wherein
CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1),
CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2),
CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3),
CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4),
CDR H2 comprises the amino acid sequence SIGASGSQTRYADS (SEQ ID NO: 8), and
CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11).

4. The isolated antibody of claim 1 , wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequence SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4), CDR H2 comprise the amino acid sequence SIGSSGAQTRYADS (SEQ ID NO: 7), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11); and the light chain of comprises an amino acid sequence having at least 90% identity to

(SEQ ID NO: 19)

QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMI

YGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYV

FGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVT

HEGSTVEKTVAPTECS.

5. The isolated antibody of claim 1 or claim 4 , wherein CDR L1 comprises the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO: 1), CDR L2 comprises the amino acid sequence GDSERPS (SEQ ID NO: 2), CDR L3 comprises the amino acid sequences SSYAGSGIYV (SEQ ID NO: 3), CDR H1 comprises the amino acid sequence TYAMG (SEQ ID NO: 4), CDR H2 comprise the amino acid sequence SIGASGSQTRYADS (SEQ ID NO: 8), and CDR H3 comprises the amino acid sequence LAIGDSY (SEQ ID NO: 11); and
the heavy chain comprises an amino acid sequence having at least 90% identity to

(SEQ ID NO: 24)

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSS

IGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLA

IGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTL

PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.

6. An isolated antibody that binds to human FcRn selected from the group consisting of:
(a) an antibody comprising a light chain comprising the amino acid sequence

(SEQ ID NO: 19)

QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMI

YGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYV

FGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVT

Assignees

• Momenta Pharmaceuticals Inc

Inventors

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

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/283 Primary

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

• A61K2039/505

  comprising antibodies · CPC title