Dimeric protein with triple mutations

The dimeric protein of any one of the preceding claims, wherein, for one or both polypeptides, the amino acid at the position corresponding to E430 is selected from the group consisting of G, S, T, F, H, A, C, D, I, K, L, M, N, P, Q, R, V, W and Y, such as from the group consisting of G, S, T, F and H.

The dimeric protein of any one of the preceding claims, wherein said first and/or second polypeptide further comprises a region capable of covalent binding between said first and second polypeptide.

The dimeric protein of any one of the preceding claims, wherein said first and/or said second polypeptide further comprises a hinge region of an immunoglobulin heavy chain.

The dimeric protein of any one of the preceding claims, wherein the isotype of the immunoglobulin heavy chain is selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE and IgM.

The dimeric protein of any one of the preceding claims, wherein the immunoglobulin heavy chain is of primate or murine origin, such as human.

The dimeric protein of any one of the preceding claims, wherein at least one of the polypeptides comprises a binding region that specifically binds to a target.

The dimeric protein of any one of the preceding claims, wherein at least one of the polypeptides comprises an immunoglobulin heavy chain variable region.

The dimeric protein of any one of the preceding claims, which is an antibody.

The dimeric protein of any one of the preceding claims, wherein in said first and/or second polypeptide the amino acid in the position corresponding to K439 is not K.

The dimeric protein according to any of the preceding claims, wherein in said first and/or second polypeptide the amino acid in the position corresponding to S440 is K or R.

The dimeric protein of any one of the preceding claims, wherein in said first and/or second polypeptide the amino acid residue in the position corresponding to K447 is D or E.

The dimeric protein of any one of the preceding claims, wherein in said first and/or second polypeptide the amino acid in the position corresponding to Q386 is K.

The dimeric protein of any one of the preceding claims, comprising a drug, toxin, radiolabel, radioopaque agent, paramagnetic agent, fluorescent agent, phosphorescent agent, ultrasound enhancing agent or polyethyleneglycol (PEG), optionally conjugated to at least one of the polypeptides via a linker.

The dimeric protein of any one of the preceding claims, which is a homodimer.

The dimeric protein of any one of the preceding claims, which is predominantly in oligomeric form, such as hexameric form, in a phosphate buffer at a pH of about 6.8.

An oligomer comprising at least two non-covalently associated dimeric proteins, each according to any one of the preceding claims.

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, E430 and in 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.

The dimeric protein, oligomer, hexamer, composition or kit-of-parts according to any one of claims 1 to 63, 76, 77 and 79, for use in the treatment of a disease, such as a bacterial, viral or parasitic infection, autoimmune disease, cancer, inflammation, and/or reducing the risk for septic shock caused by a bacterial infection.

The dimeric protein, oligomer, hexamer, composition or kit-of-parts of any one of claims 1 to 63, 76, 77 and 79, wherein the dimeric protein comprises a binding region specifically binding to a lipopolysaccharide (LPS), a lipooligosaccharide (LOS), a delta endotoxin, Botulinum toxin, Corynebacterium diphtheriae exotoxin, a bacterial superantigen, a heat-stable enterotoxin, cytolysin, a channel-forming toxin, an enzymatically active toxin, or a mycotoxin.