US2011124102A1PendingUtilityA1

Rage Fusion Proteins And Methods Of Use

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Assignee: MJALLI ADNAN M MPriority: Aug 3, 2004Filed: Jan 7, 2011Published: May 26, 2011
Est. expiryAug 3, 2024(expired)· nominal 20-yr term from priority
Inventors:Adnan M. M. MjalliYe TianJeffrey C. WebsterRobert Rothlein
A61P 9/10A61P 37/06A61P 7/00A61P 37/02A61P 35/00A61P 9/04A61P 3/10A61P 43/00A61P 29/00A61P 25/00A61P 27/02A61P 25/28A61P 1/00A61P 17/02C07K 14/705A61K 38/00A61P 13/12A61P 19/02A61P 17/06C07K 19/00
55
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Claims

Abstract

Disclosed are RAGE fusion proteins comprising RAGE polypeptide sequences linked to a second, non-RAGE polypeptide. The RAGE fusion protein may utilize a RAGE polypeptide domain comprising a RAGE ligand binding site and an interdomain linker directly linked to an immunoglobulin C H 2 domain. Such fusion proteins may provide specific, high affinity binding to RAGE ligands. Also disclosed is the use of the RAGE fusion proteins as therapeutics for RAGE-mediated pathologies.

Claims

exact text as granted — not AI-modified
1 . A nucleic acid encoding a fusion protein comprising a RAGE polypeptide directly linked to a polypeptide comprising a C H 2 domain of an immunoglobulin or a portion of a C H 2 domain of an immunoglobulin, wherein the RAGE polypeptide comprises a RAGE ligand binding site, and wherein the fusion protein does not include an immunoglobulin Fc hinge region. 
     
     
         2 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises a RAGE interdomain linker linked to a RAGE immunoglobulin domain such that the C-terminal amino acid of the RAGE immunoglobulin domain is linked to the N-terminal amino acid of the RAGE interdomain linker, and the C-terminal amino acid of the RAGE interdomain linker is directly linked to the N-terminal amino acid of the polypeptide comprising the C H 2 domain of the immunoglobulin or the portion of the C H 2 domain of the immunoglobulin. 
     
     
         3 . The nucleic acid of  claim 1 , comprising the nucleic acid sequence as set forth in SEQ ID NO: 30, or the nucleic acid sequence as set forth in SEQ ID NO:  31 . 
     
     
         4 . An expression vector comprising the nucleic acid of  claim 1 . 
     
     
         5 . An expression vector comprising the nucleic acid of  claim 3 . 
     
     
         6 . A cell comprising the nucleic acid of  claim 1 . 
     
     
         7 . The nucleic acid of  claim 1 , wherein the RAGE ligand binding site comprises the amino acid sequence as set forth in SEQ ID NO: 9 or a sequence 90% identical thereto, or the amino acid sequence as set forth in SEQ ID NO: 10 or a sequence 90% identical thereto. 
     
     
         8 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises a RAGE interdomain linker linked to a RAGE immunoglobulin domain. 
     
     
         9 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises a first RAGE immunoglobulin domain and a first RAGE interdomain linker linked to a second RAGE immunoglobulin domain and a second RAGE interdomain linker, such that the N-terminal amino acid of the first interdomain linker is linked to the C-terminal amino acid of the first RAGE immunoglobulin domain, the N-terminal amino acid of the second RAGE immunoglobulin domain is linked to the C-terminal amino acid of the first interdomain linker, the N-terminal amino acid of the second interdomain linker is linked to the C-terminal amino acid of the second RAGE immunoglobulin domain, and the C-terminal amino acid of the second RAGE interdomain linker is directly linked to the N-terminal amino acid of the C H 2 domain of the immunoglobulin or the portion of the C H 2 domain of the immunoglobulin. 
     
     
         10 . The nucleic acid of  claim 1 , wherein the fusion protein comprises the amino acid sequence as set forth in SEQ ID NO: 32, SEQ ID NO: 33 or SEQ ID NO: 34. 
     
     
         11 . The nucleic acid of  claim 9 , wherein the second RAGE interdomain linker directly linked to the C H 2 domain of the immunoglobulin or the portion of the C H 2 domain of the immunoglobulin comprises the amino acid sequence as set forth in SEQ ID NO: 22 or a sequence 90% identical thereto, or the amino acid sequence as set forth in SEQ ID NO: 24, or a sequence 90% identical thereto. 
     
     
         12 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises a single RAGE immunoglobulin domain linked via a RAGE interdomain linker to the N-terminal amino acid of the polypeptide comprising the C H 2 domain of the immunoglobulin or the portion of the C H 2 domain of the immunoglobulin. 
     
     
         13 . The nucleic acid of  claim 1 , encoding a fusion protein comprising the amino acid sequence as set forth in SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. 
     
     
         14 . The nucleic acid of  claim 12 , wherein the RAGE linker is directly linked to the C H 2 domain of the immunoglobulin or the portion of the C H 2 domain of the immunoglobulin and the RAGE linker comprises the amino acid sequence as set forth in SEQ ID NO: 21 or a sequence 90% identical thereto, or the amino acid sequence as set forth in SEQ ID NO: 23 or a sequence 90% identical thereto. 
     
     
         15 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 7 or the amino acid sequence as set forth in SEQ ID NO: 8. 
     
     
         16 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 13 or the amino acid sequence as set forth in SEQ ID NO:14. 
     
     
         17 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 15 or the amino acid sequence as set forth in SEQ ID NO: 16. 
     
     
         18 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 17 or the amino acid sequence as set forth in SEQ ID NO: 18. 
     
     
         19 . The nucleic acid of  claim 1 , wherein the RAGE polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 19 or the amino acid sequence as set forth in SEQ ID NO: 20. 
     
     
         20 . The nucleic acid of  claim 1 , wherein the amino acid sequence of the RAGE polypeptide is as set forth in SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
         21 . The nucleic acid of  claim 1 , wherein the amino acid sequence of the RAGE polypeptide is as set forth in SEQ ID NO: 19 or SEQ ID NO: 20. 
     
     
         22 . The nucleic acid of  claim 1 , wherein the polypeptide is derived from a human IgA, IgD, IgE, IgG or IgM. 
     
     
         23 . The nucleic acid of  claim 1 , wherein the polypeptide is derived from a human IgG. 
     
     
         24 . The nucleic acid of  claim 1 , wherein the polypeptide is derived from a human IgG1. 
     
     
         25 . The nucleic acid of  claim 1 , wherein the polypeptide further comprises a C H 3 domain of the immunoglobulin or a portion thereof. 
     
     
         26 . The nucleic acid of  claim 1 , wherein the amino acid sequence of the polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 38. 
     
     
         27 . The nucleic acid of  claim 1 , wherein the amino acid sequence of the polypeptide is the amino acid sequence as set forth in SEQ ID NO: 38. 
     
     
         28 . The nucleic acid of  claim 1 , wherein the nucleic acid sequence encoding the RAGE polypeptide comprises the nucleic acid sequence as set forth in any one of SEQ ID NOS: 25, 26, 27, 28 or 29. 
     
     
         29 . The nucleic acid of  claim 1 , comprising the nucleic acid sequence set forth in SEQ ID NO: 30. 
     
     
         30 . The nucleic acid of  claim 1 , comprising the nucleic acid sequence set forth in SEQ ID NO: 31. 
     
     
         31 . A host cell comprising the expression vector of  claim 4 . 
     
     
         32 . A host cell comprising the expression vector of  claim 5 .

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