Antibodies and FC fusion protein modifications with enhanced persistence or pharmacokinetic stability in vivo and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10457719-B2
Application number	US-67849408-A
Country	US
Kind code	B2
Filing date	Sep 17, 2008
Priority date	Sep 18, 2007
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

In certain embodiments, this present invention provides antibodies and Fc fusion proteins with enhanced pharmacokinetics, such as biotinylated antibodies or biotinylated Fc fusion polypeptides.

First claim

We claim:

1. A method of increasing the half-life of an IgG (immunoglobulin G) antibody in blood circulation in a human subject in need thereof, comprising the steps of:
(i) providing an IgG (immunoglobulin G) antibody preparation, said IgG antibody comprising a human Fc domain and said preparation comprising a biotinylated IgG antibody, wherein said IgG antibody is conjugated to biotin at a molar ratio of 2-10 biotin molecules per IgG antibody molecule;
(ii) administering to a human subject said IgG antibody preparation comprising an effective amount of said biotinylated IgG antibody, wherein said biotinylated IgG antibody binds to human FcRn via the constant region of said human Fc domain on said biotinylated IgG antibody to increase the half-life of said biotinylated IgG antibody in vivo, and
(iii) maintaining said biotinylated IgG antibody in blood circulation over a period of days in said human subject,
wherein said IgG antibody is covalently conjugated to biotin via a lysine amino acid residue at position 288 and/or 326, numbering according to EU index of Kabat, and wherein said biotin molecule is covalently conjugated to a solvent exposed lysine within the human Fc domain sequence selected from the group consisting of:

FNWYVDGVEVHNAKTKPR,
(SEQ ID NO: 1)

FKWYVDGVEVHNAKTKPR,
(SEQ ID NO: 2)

and

VSNKALPAPIEK.
(SEQ ID NO: 3)

2. The method of claim 1 , wherein said IgG antibody is a monoclonal antibody.

3. The method of claim 1 , wherein said IgG antibody is a humanized IgG antibody.

Assignees

• Roopenian Derry
• Christianson Gregory
• Jackson Lab

Inventors

• Roopenian Derry
• Christianson Gregory

Classifications

• A61K47/557

  the modifying agent being biotin · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/72

  Increased effector function due to an Fc-modification · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title