Rage protein derivatives
The present invention is drawn to fusion proteins comprising a Receptor for Advanced Glycation Endproducts (RAGE) and an immunoglobulin element. The invention also encompasses methods of treating a condition characterized by activation of an inflammatory cytokine cascade comprising administering such fusion proteins. The invention is also drawn to nucleic acids encoding the fusion proteins, as well as vectors and cells comprising such nucleic acids.
1 . A method of treating a condition characterized by activation of an inflammatory cytokine cascade in a subject, comprising administering to said subject a fusion protein, wherein
said fusion protein comprises at least a first and a second polypeptide;
wherein:
said first polypeptide consists of a fragment of a Receptor for Advanced Glycation End Product (RAGE) extracellular domain, wherein said fragment consists of amino acid residue 1 to amino acid residue 305 of SEQ ID NO: 2; and
said second polypeptide comprises an immunoglobulin element, wherein said immunoglobulin element comprises from about amino acid residue 101 to about amino acid residue 329 of SEQ ID NO: 4.
2 . The method of claim 1 , wherein said immunoglobulin element comprises an Fc domain.
3 . The method of claim 1 , wherein said immunoglobulin element comprises an immunoglobulin heavy chain.
4 . The method of claim 1 , wherein said immunoglobulin element comprises a C H 1 domain and a Fc domain.
5 . A method of treating a condition characterized by activation of an inflammatory cytokine cascade in a subject, comprising administering to said subject an effective amount of a pharmaceutical composition comprising:
a pharmaceutically-acceptable excipient; and
a fusion protein, wherein said fusion protein comprises at least a first and a second polypeptide; wherein:
said first polypeptide consists of a fragment of a Receptor for Advanced Glycation End Product (RAGE) extracellular domain, wherein said fragment consists of amino acid residue 1 to amino acid residue 305 of SEQ ID NO: 2; and
said second polypeptide comprises an immunoglobulin element, wherein said immunoglobulin element comprises from about amino acid residue 101 to about amino acid residue 329 of SEQ ID NO: 4.
6 . The method of claim 5 , wherein said immunoglobulin element comprises an Fc domain.
7 . The method of claim 5 , wherein said immunoglobulin element comprises an immunoglobulin heavy chain.
8 . The method of claim 5 , wherein said immunoglobulin element comprises a C H 1 domain and a Fc domain.
9 . The method of claim 5 , wherein said pharmaceutical composition further comprises an antibody or antigen-binding fragment thereof that binds to an HMGB1 polypeptide or an antigenic fragment of said HMGB1 polypeptide.
10 . A method of treating a condition characterized by activation of an inflammatory cytokine cascade in a subject, comprising administering to said subject a fusion protein, wherein said fusion protein comprises the amino acid sequence depicted in SEQ ID NO: 6.
11 . A method of treating a condition characterized by activation of an inflammatory cytokine cascade in a subject, comprising administering to said subject an effective amount of a pharmaceutical composition comprising a pharmaceutically-acceptable excipient and fusion protein, wherein said fusion protein comprises the amino acid sequence depicted in SEQ ID NO: 6.
12 . The method of claim 11 , wherein said pharmaceutical composition further comprises an antibody or antigen-binding fragment thereof that binds to an HMGB1 polypeptide or an antigenic fragment of said HMGB1 polypeptide.