Modified fusion molecules for treatment of allergic disease

Abstract

The present invention comprises a fusion molecule comprising a Fcε fragment sequence including functionally active CH2, CH3 and CH4 domains of the constant region of an IgE heavy chain (CHε2-CHε3-CHε4 sequence) linked at its C-terminus to the N-terminus of a second polypeptide including functionally active hinge, CH2 and CH3 domains of the constant region of an IgG 1 heavy chain (γhinge-CHγ2-CH-γ3 sequence), pharmaceutical compositions comprising the fusion molecule and methods of treatment using the fusion molecule.

1 - 21 . (canceled) 
     
     
         22 . A method for the prevention or treatment of symptoms resulting from a type I hypersensitivity reaction in a subject, comprising administering to the subject a fusion molecule comprising a Fcε fragment functionally connected at its carboxy terminus to an Fcγ1 fragment. 
     
     
         23 . The method of  claim 22  wherein the type I hypersensitivity reaction is an anaphylactic response. 
     
     
         24 . The method of  claim 22  wherein the fusion molecule is administered to the subject prior to the subject receiving immunotherapy. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 22  wherein the Fcγ1 fragment of the fusion molecule comprises an amino acid sequence having at least about 90% identity to the hinge-CH2-CH3 domain amino acid sequence of SEQ ID NO: 3 or at least about 90% identity to the CH1-hinge-CH2-C3 domain amino acid sequence of SEQ ID NO: 2. 
     
     
         27 . The method of  claim 22  wherein the Fcγ1 fragment comprises an amino acid sequence having at least about 95% identity, to the hinge-CH2-C3 domain amino acid sequence of SEQ ID NO: 3 or at least about 95% identity to the CH1-hinge-CH2-C3 domain amino acid sequence of SEQ ID NO: 2. 
     
     
         28 . The method of  claim 22  wherein the Fcγ1 fragment comprises an amino acid sequence having at least about 98% identity, to the hinge-CH2-CH3 domain amino acid sequence of SEQ ID NO: 3 or at least about 98% identity to the CH1-hinge-CH2-CH3 domain amino acid sequence of SEQ ID NO: 2. 
     
     
         29 . The method of  claim 22  wherein the Fcγ1 fragment comprises a least part of the CH2 and CH3 domains of a native human IgG 1  constant region. 
     
     
         30 . The method of  claim 22  wherein the Fcγ1 fragment comprises at least part of the hinge, CH2 and CH3 domains of a native human IgG 1  heavy chain constant region in the absence of a functional CH1 region. 
     
     
         31 . The method of  claim 22  wherein the Fcγ1 fragment comprises an amino acid sequence encoded by a nucleic acid hybridizing under stringent conditions to the complement of the IgG heavy chain constant region nucleotide sequence of SEQ ID NO: 1. 
     
     
         32 . The method of  claim 22  wherein the Fcε fragment comprises an amino acid sequence having at least about 90% identity to the CH2-CH3-CH4 domain amino acid sequence of SEQ ID NO: 6. 
     
     
         33 . The method of  claim 22  wherein the Fcε fragment comprises an amino acid sequence having at least about 95% identity, to the CH2-CH3-CH4 domain amino acid sequence of SEQ ID NO: 6. 
     
     
         34 . The method of  claim 22  wherein the Fcε fragment comprises an amino acid sequence having at least about 98% identity, to the CH2-CH33-CH4 domain amino acid sequence of SEQ ID NO: 6. 
     
     
         35 . The method of  claim 22  wherein the Fcε fragment comprises a least part of the CH2-CH3-CH4 domains of a native human IgE constant region. 
     
     
         36 . The method of  claim 22  wherein the Fcε fragment comprises at least part of the CH2-CH3-CH4 domains of a native human IgE heavy chain constant region, in the absence of a functional CH1 region. 
     
     
         37 . The method of  claim 22  wherein the Fcε fragment comprises an amino acid sequence encoded by a nucleic acid hybridizing under stringent conditions to the complement of the IgE heavy chain constant region nucleotide sequence of SEQ ID NO: 4. 
     
     
         38 . A method for the prevention or treatment of symptoms resulting from a type I hypersensitivity reaction in a subject, comprising administering a fusion molecule comprising the polypeptide sequence CHε2-CHε3-CHε4-γhinge-CH-γ2-CH-γ3. 
     
     
         39 . The method of  claim 38  wherein the sequence comprises the sequence of SEQ ID NO: 19. 
     
     
         40 . The method of  claim 22  wherein the Fcε and the Fcγ1 polypeptide sequences are functionally connected via a linker.