US2007142295A1PendingUtilityA1

Thrombopoietic compounds

62
Assignee: AMGEN INCPriority: Oct 23, 1998Filed: Dec 22, 2006Published: Jun 21, 2007
Est. expiryOct 23, 2018(expired)· nominal 20-yr term from priority
Inventors:Chuan-Fa LiuUlrich FeigeJanet C. Cheetham
A61P 7/00A61P 7/04A61P 7/06A61P 43/00C07K 2319/30C07K 7/08C07K 7/06C07K 2319/75C07K 14/524A61K 38/00C07K 2319/00C07K 14/52
62
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Claims

Abstract

The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.

Claims

exact text as granted — not AI-modified
1 . A TMP compound that binds to an mp1 receptor comprising the core structure:  
         X 2 —X 3 —X 4 —X 5 —X 6 —X 7 —X 8 —X 9 —X 10 ,  wherein,    X 2  is selected from the group consisting of Glu, Asp, Lys, and Val;    X 3  is selected from the group consisting of Gly and Ala;    X 4  is Pro;    X 5  is selected from the group consisting of Thr and Ser;    X 6  is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;    X 7  is selected from the group consisting of Arg and Lys;    X 8  is selected from the group consisting of Gln, Asn, and Glu;    X 9  is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;    X 10  is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; and    wherein any of X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , and X 10  is a non-naturally occurring amino acid; and    physiologically acceptable salts thereof.    
     
     
         2 . The TMP of  claim 1  further comprising the structure:  
         X 1 —X 2 —X 3 —X 4 —X 5 —X 6 —X 7 —X 8 —X 9 —X 10 —X 11 —X 12 —X 13 —X 14 ;  wherein,    X 1  is selected from the group consisting of Ile, Ala, Val, Leu, Ser, and Arg;    X 11  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Ser, Thr, Lys, His, and Glu;    X 12  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Gly, Ser, and Gin;    X 13  is selected from the group consisting of Arg, Lys, Thr, Val, Asn, Gln, and Gly;    X 14  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Thr, Arg, Glu, and Gly, and    wherein any of X 11 , X 12 , X 13 , or X 14  is a non-naturally-occurring amino acid.    
     
     
         3 . The TMP of  claim 1 , 
 wherein,    X 2  is selected from the group consisting of Glu, Asp, Lys, Val, and a non-naturally occurring amino acid.    
     
     
         4 . The TMP of  claim 1 , 
 wherein,    X 3  is selected from the group consisting of Gly, Ala, and a non-naturally occurring amino acid.    
     
     
         5 . The TMP of  claim 1 , 
 wherein,    X 4  is Pro or a non-naturally-occurring amino acid;    
     
     
         6 . The TMP of  claim 1 , 
 wherein,    X 5  is selected from the group consisting of Thr, Ser, and a non-naturally occurring amino acid.    
     
     
         7 . The TMP of  claim 1 , 
 wherein,    X 6  is selected from the group consisting of Leu, Ile, Val, Ala, Phe, and a non-naturally occurring amino acid.    
     
     
         8 . The TMP of  claim 1 , 
 wherein,    X 7  is selected from the group consisting of Arg, Lys, and a non-naturally occurring amino acid.    
     
     
         9 . The TMP of  claim 1 , 
 wherein,    X 8  is selected from the group consisting of Gln, Asn, Glu, and a non-naturally occurring amino acid.    
     
     
         10 . The TMP of  claim 1 , 
 wherein,    X 9  is selected from the group consisting of Trp, Tyr, Cys, Ala, Phe, and a non-naturally occurring amino acid.    
     
     
         11 . The TMP of  claim 1 , 
 wherein,    X 10  is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, Lys, and a non-naturally occurring amino acid.    
     
     
         12 . The TMP of  claim 2 , 
 wherein,    X 1  is selected from the group consisting of Ile, Ala, Val, Leu, Ser, Arg, and a non-naturally occurring amino acid.    
     
     
         13 . The TMP of  claim 2 , 
 wherein,    X 11  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Ser, Thr, Lys, His, Glu, and a non-naturally occurring amino acid.    
     
     
         14 . The TMP of  claim 2 , 
 wherein,    X 13  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Gly, Ser, Gln, and a non-naturally occurring amino acid.    
     
     
         15 . The TMP of  claim 2 , 
 wherein,    X 13  is selected from the group consisting of Arg, Lys, Thr, Val, Asn, Gin, Gly, and a non-naturally occurring amino acid.    
     
     
         16 . The TMP of  claim 2 , 
 wherein,    X 14  is selected from the group consisting of Ala, Ile, Val, Leu, Phe, Thr, Arg, Glu, Gly, and a non-naturally occurring amino acid.    
     
     
         17 . The TMP of  claim 1  wherein the core structure  
         X 2 —X 3 —X 4 —X 5 —X 6 —X 7 —X 8 —X 9 —X 10  is:  E-G-P-T-L-R-Q-W-L  and    wherein, optionally, any of X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , and X 10  is substituted with a non-naturally-occurring amino acid.    
     
     
         18 . The TMP of  claim 17  wherein the core structure:  
         X 1 —X 2 —X 3 —X 4 —X 5 —X 6 —X 7 —X 8 —X 9 —X 10 —X 11 —X 12 —X 13 —X 14  is:  I-E-G-P-T-L-R-Q-W-L-A-A-R-A        and    wherein, optionally any of X 1 , X 11 , X 12 , X 13  and X 14  is substituted with a non-naturally-occurring amino acid.    
     
     
         19 . The TMP of  claim 17 , 
 wherein,    X 2  is substituted with a non-naturally-occurring amino acid.    
     
     
         20 . The TMP of  claim 17 , 
 wherein,    X 3  is substituted with a non-naturally-occurring amino acid.    
     
     
         21 . The TMP of  claim 17 , 
 wherein,    X 4  is substituted with a non-naturally-occurring amino acid.    
     
     
         22 . The TMP of  claim 17 , 
 wherein,    X 5  is substituted with a non-naturally-occurring amino acid.    
     
     
         23 . The TMP of  claim 17 , 
 wherein,    X 6  is substituted with a non-naturally-occurring amino acid.    
     
     
         24 . The TM P of  claim 17 , 
 wherein,    X 7  is substituted with a non-naturally-occurring amino acid.    
     
     
         25 . The TMP of  claim 17 , 
 wherein,    X 8  is substituted with a non-naturally-occurring amino acid.    
     
     
         26 . The TMP of  claim 17 , 
 wherein,    X 9  is substituted with a non-naturally-occurring amino acid.    
     
     
         27 . The TMP of  claim 17 , 
 wherein,    X 10  is substituted with a non-naturally-occurring amino acid.    
     
     
         28 . The TMP of  claim 18 , 
 wherein,    X 1  is substituted with a non-naturally-occurring amino acid.    
     
     
         29 . The TMP of  claim 18 , 
 wherein,    X 11  is substituted with a non-naturally-occurring amino acid.    
     
     
         30 . The TMP of  claim 18 , 
 wherein,    X 12  is substituted with a non-naturally-occurring amino acid.    
     
     
         31 . The TMP of  claim 18 , 
 wherein,    X 13  is substituted with a non-naturally-occurring amino acid.    
     
     
         32 . The TMP of  claim 18 , 
 wherein,    X 14  is substituted with a non-naturally-occurring amino acid.

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