Dimeric protein with triple mutations
AssigneeGenmab B.V.
InventorsRob N. DE JONG, Frank BEURSKENS, Paul PARREN, Aran Frank LABRIJN, Janine SCHUURMAN, Arjen VLUG, Sandra VERPLOEGEN
Life of this patent
Estimating the term…
Abstract
The present invention relates to dimeric proteins comprising amino acids at three different positions which are different from those present in a human IgG1. Six of said dimeric proteins are capable of forming a hexameric structure in solution.
Claims21
1-83. (canceled)
A hexamer comprising six non-covalently associated dimeric proteins, wherein each dimeric protein comprises a first and a second polypeptide, each polypeptide comprising at least CH2 and CH3 regions of an immunoglobulin heavy chain, wherein in said first and/or second polypeptide, the amino acids at the positions corresponding to E345 and E430 in a human IgG1 heavy chain are not E, and the amino acid in at least one position corresponding to a position selected from the group consisting of S440, Y436, D/E356, T359, E382, N434, Q438, I253, and S254 in a human IgG1 heavy chain is Y, K, R or W;
- not Y;
- not D or E;
- not T;
- not E;
- not N;
- not Q;
- not I;
- and not S, respectively, and wherein the numbering is according to the EU Index as set forth in Kabat.
A method of increasing oligomerization in solution and/or an effector function of a dimeric protein comprising a first and second polypeptide, each comprising at least CH2 and CH3 regions of an immunoglobulin heavy chain, the method comprising introducing into said first and/or second polypeptide amino acid substitutions in at least the positions corresponding to E345 and E430 in a human IgG1 heavy chain, and in a position corresponding to a position selected from the group consisting of S440, Y436, D/E356, T359, E382, N434, Q438, I253, and S254 in a human IgG1 heavy chain.
A method for treating a bacterial, viral or parasitic infection, for imaging of at least a part of the body of human or other mammal, or for modulating clearance of a target molecule from the body of a human or other mammal, comprising administering a dimeric protein to the human or other mammal,
- wherein the dimeric protein comprises a first and a second polypeptide, each polypeptide comprising at least CH2 and CH3 regions of an immunoglobulin heavy chain, wherein in said first and/or second polypeptide, the amino acids at the positions corresponding to E345 and E430 in a human IgG1 heavy chain are not E, and the amino acid in at least one position corresponding to a position selected from the group consisting of S440, Y436, D/E356, T359, E382, N434, Q438, I253 and S254 in a human IgG1 heavy chain is Y, K, R or W;
- not Y;
- not D or E;
- not T;
- not E;
- not N;
- not Q;
- not I;
- and not S, for each position, respectively, and wherein the numbering is according to the EU Index as set forth in Kabat.
A method for preventing or treating cancer, auto-immune diseases, organ transplant rejections, or C1q depletion in the humoral system, comprising administering to a subject in need thereof a dimeric protein,
- wherein the dimeric protein comprises a first and a second polypeptide, each polypeptide comprising at least CH2 and CH3 regions of an immunoglobulin heavy chain, wherein in said first and/or second polypeptide, the amino acids at the positions corresponding to E345 and E430 in a human IgG1 heavy chain are not E, and the amino acid in at least one position corresponding to a position selected from the group consisting of S440, Y436, D/E356, T359, E382, N434, Q438, I253 and S254 in a human IgG1 heavy chain is Y, K, R or W;
- not Y;
- not D or E;
- not T;
- not E;
- not N;
- not Q;
- not I;
- and not S, for each position, respectively, and wherein the numbering is according to the EU Index as set forth in Kabat.
Dependencies are inferred from the claim text.