Displacers of IgE-FceRI

A multi-specific construct comprising

• a. a first single domain antibody (sdAb) able to displace bound IgE from FcϵRI,
• b. a second sdAb that binds to IgE,
• c. a moiety that links the first and second sdAb,
• wherein
• the first and second sdAb bind non-identical epitopes of IgE, and
• the multi-specific construct can displace bound IgE from the IgE high-affinity receptor (FcϵRI) with improved displacement activity compared to the first or second sdAb,
• wherein the moiety that links the first and second sdAb comprises
• an Fc region from an IgG antibody or from an Fc region comprising a mutation that induces heterodimerisation, and the first sdAb and second sdAb are fused or coupled covalently to the C-terminal end of a first Fc region polypeptide and a second Fc region polypeptide, respectively,
• wherein the first sdAb comprises a first CDR1, CDR2, and CDR3 binding regions each comprising or consisting of an amino acid sequence in the amino acid sequence set forth in SEQ ID NO:
• 1, wherein the amino acid sequence of the first CDR1, CDR2, and CDR3 binding regions are determined according to a single numbering scheme, wherein said numbering scheme is either Kabat, Chothia, IMTG or Aho numbering scheme, and
• the second sdAb comprises a second CDR1, CDR2, and CDR3 binding regions each comprising or consisting of an amino acid sequence in the amino acid sequence set forth in SEQ ID NO:
• 9 or 25, wherein the amino acid sequence of the second CDR1, CDR2, and CDR3 binding regions are determined according to a single numbering scheme, wherein said numbering scheme is either Kabat, Chothia, IMTG or Aho numbering scheme.