Stabilized human Igg4 antibodies
AssigneeKyowa Hakko Kirin Co., Ltd.
InventorsNobuaki Takahashi, Hideaki Yoshida
Life of this patent
Estimating the term…
Abstract
A highly stable mutant of human IgG4 antibody is provided. Such antibody is an antibody in which the CH3 domain of human IgG4 is substituted with the CH3 domain of human IgG1 and which exhibits inhibited aggregate formation, an antibody in which the CH3 and CH2 domains of human IgG4 are substituted with the CH3 and CH2 domains of human IgG1, respectively, or an antibody in which arginine at position 409 indicated in the EU index proposed by Kabat et al. of human IgG4 is substituted with lysine and which exhibits inhibited aggregate formation.
Claims14
An antibody, wherein arginine at position 409 according to the EU index as in Kabat in a heavy chain constant region of human IgG4, is substituted with lysine, threonine, methionine, or leucine,
- and wherein in said antibody, serine at position 228 and/or leucine at position 235 according to the EU index as in Kabat in the heavy chain constant region, are substituted with proline and/or glutamic acid, respectively.
A method for inhibiting antibody aggregation comprising substituting arginine at position 409 according to the EU index as in Kabat in a heavy chain constant region of human IgG4, with lysine, threonine, methionine, or leucine.
A method for producing an antibody, comprising the steps:
- producing an expression vector having genes encoding the heavy chain and the light chain of an antibody in which arginine at position 409 according to the EU index as in Kabat in a heavy chain constant region of human IgG4, is substituted with lysine, threonine, methionine or leucine;
- introducing the expression vector into a host;
- culturing the host;
- and
- obtaining the antibody from the culture product.
A method for producing an antibody, comprising the steps:
- producing an expression vector having a heavy chain nucleic acid sequence represented by SEQ ID NO:
- 47 and a light chain nucleic acid sequence represented by SEQ ID NO:
- 45;
- introducing the expression vector into a host;
- culturing the host;
- and
- obtaining the antibody from the culture product.
An antibody, wherein arginine at position 409 according to the EU index as in Kabat in a heavy chain constant region of human IgG4, is substituted with lysine, threonine, methionine or leucine, wherein aggregation of the antibody is decreased at a low pH condition,
- and wherein in said antibody, serine at position 228 and/or leucine at position 235 according to the EU index as in Kabat in the heavy chain constant region, are substituted with proline and/or glutamic acid, respectively.
Dependencies are inferred from the claim text.