Albumin fusion proteins

Abstract

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

1 . An albumin fusion protein comprising an exendin-4 polypeptide fused to an albumin polypeptide, wherein said exendin-4 polypeptide is selected from: 
 (a) a full-length exendin-4;    (b) a mature exendin-4;    (c) a fragment of exendin-4, wherein said fragment has exendin-4 activity;    (d) a polypeptide consisting of an amino acid sequence at least 90% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (e) a polypeptide consisting of an amino acid sequence at least 95% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (f) a polypeptide consisting of an amino acid sequence at least 99% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (g) a polypeptide comprising amino acids 1 to 87 of SEQ ID NO:635;    (h) a polypeptide comprising amino acids 48 to 86 of SEQ ID NO:635; and wherein said albumin polypeptide is selected from:    (i) a full-length albumin;    (ii) a mature albumin;    (iii) a fragment of albumin, wherein said fragment of albumin has the ability to prolong the serum half-life of the exendin-4 polypeptide;    (iv) a polypeptide consisting of an amino acid sequence at least 95% identical to albumin, wherein said polypeptide has the ability to prolong the serum half-life of the exendin-4 polypeptide;    (v) amino acids 1 to 585 of SEQ ID NO:1038; and    (vi) amino acids 1 to 387 of SEQ ID NO: 1038.    
     
     
         2 . The albumin fusion protein of  claim 1 , produced from a host cell comprising an albumin fusion construct which expresses said albumin fusion protein, wherein said albumin fusion construct is selected from: 
 (a) 2469; and    (b) 2470.    
     
     
         3 . The albumin fusion protein of  claim 1 , wherein said albumin fusion protein comprises an amino acid sequence selected from: 
 (a) amino acids 25 to 648 of SEQ ID NO:419; and    (b) amino acids 25 to 648 of SEQ ID NO:420.    
     
     
         4 . The albumin fusion protein of  claim 1 , wherein said exendin-4 polypeptide is fused to the N-terminus, the C-terminus, or both the N-terminus and C-terminus of said albumin polypeptide.  
     
     
         5 . The albumin fusion protein of  claim 1 , which is expressed in a host cell.  
     
     
         6 . The albumin fusion protein of  claim 5 , wherein said host cell is a yeast, mammalian, or bacterial cell.  
     
     
         7 . A nucleic acid molecule comprising a first polynucleotide and a second polynucleotide, wherein said first polynucleotide encodes an exendin-4 polypeptide selected from: 
 (a) a full-length exendin-4;    (b) a mature exendin-4;    (c) a fragment of exendin-4, wherein said fragment has exendin-4 activity;    (d) a polypeptide consisting of an amino acid sequence at least 90% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (e) a polypeptide consisting of an amino acid sequence at least 95% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (f) a polypeptide consisting of an amino acid sequence at least 99% identical to exendin-4, wherein said polypeptide has exendin-4 activity;    (g) a polypeptide comprising amino acids 1 to 87 of SEQ ID NO:635;    (h) a polypeptide comprising amino acids 48 to 86 of SEQ ID NO:635; and wherein said second polynucleotide encodes an albumin polypeptide selected from:    (i) a full-length albumin;    (ii) a mature albumin;    (iii) a fragment of albumin, wherein said fragment of albumin has the ability to prolong the serum half-life of the exendin-4 polypeptide;    (iv) a polypeptide consisting of an amino acid sequence at least 95% identical to albumin, wherein said polypeptide has the ability to prolong the serum half-life of the exendin-4 polypeptide;    (v) amino acids 1 to 585 of SEQ ID NO:1038; and    (vi) amino acids 1 to 387 of SEQ ID NO:1038.    
     
     
         8 . An albumin fusion construct comprising the nucleic acid molecule of  claim 7 , which upon expression in a host cell produces an albumin fusion protein comprising exendin-4 fused to human albumin or a human albumin fragment or variant, wherein said albumin fusion construct is selected from: 
 (a) 2469; and    (b) 2470.    
     
     
         9 . A vector comprising the nucleic acid molecule of  claim 7 .  
     
     
         10 . An isolated host cell comprising the nucleic acid molecule of  claim 7 .  
     
     
         11 . An isolated host cell comprising the vector of  claim 9 .  
     
     
         12 . An isolated host cell comprising the albumin fusion construct of  claim 8 .  
     
     
         13 . A method for producing a fusion protein, comprising: 
 (a) culturing the host cell of  claim 10  under conditions suitable to produce the fusion protein encoded by said polynucleotide; and    (b) recovering said fusion protein.    
     
     
         14 . A method for producing a fusion protein, comprising: 
 (a) culturing the host cell of  claim 11  under conditions suitable to produce the fusion protein encoded by said vector; and    (b) recovering said fusion protein.    
     
     
         15 . A method for producing a fusion protein, comprising: 
 (a) culturing the host cell of  claim 12  under conditions suitable to produce the fusion protein encoded by said albumin fusion construct; and    (b) recovering said fusion protein.    
     
     
         16 . A method of treating a disease or disorder in a patient comprising the step of administering an effective amount of the albumin fusion protein of  claim 1 .  
     
     
         17 . The method of  claim 16 , wherein the disease or disorder is selected from: hyperglycemia, diabetes, diabetes insipidus, diabetes mellitus, type 1 diabetes, type 2 diabetes, insulin resistance, insulin deficiency, hyperlipidemia, hyperketonemia, non-insulin dependent diabetes mellitus (NIDDM), insulin-dependent diabetes mellitus (IDDM), obesity, heart disease, infections, retinopathy, ulcers, metabolic disorders, immune disorders, vascular disorders, suppression of body weight, suppression of appetite, and syndrome X.  
     
     
         18 . The method of  claim 17 , wherein the disease or disorder is diabetes.  
     
     
         19 . The method of  claim 17 , wherein the disease or disorder is obesity or of losing weight in a patient.  
     
     
         20 . A method of stimulating insulin synthesis and release, enhancing adipose, muscle or liver tissue sensitivity towards insulin uptake, stimulating glucose uptake, slowing digestive process, or blocking the secretion of glucagon in a patient, comprising administering to said patient an albumin fusion protein of  claim 1.