US2003022352A1PendingUtilityA1

Human ADAMTS-1 protein, gene encoding the same, pharmaceutical composition, and method for immunologically analyzing human ADAMTS-1 protein

46
Priority: Jun 3, 1997Filed: Mar 15, 2002Published: Jan 30, 2003
Est. expiryJun 3, 2017(expired)· nominal 20-yr term from priority
A61K 38/00G01N 33/6872C07K 14/47A23L 33/17
46
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Claims

Abstract

A human ADAMTS-1 protein, a gene encoding the same, a pharmaceutical composition containing the protein as an active ingredient, and a method for immunologically analyzing the human ADAMTS-1 protein are disclosed. The protein can decrease the number of leukocytes and platelets, and at the same time, increase the number of erythrocytes.

Claims

exact text as granted — not AI-modified
1 . A protein characterized by containing an amino acid sequence of SEQ ID NO: 1:  
       
         
           
                 
                 
               
                     
                 
                   Met Asp Ile Cys Arg Ile Arg Leu Arg Lys Lys Arg Phe Val Ser Ser 
                     
                 
                     
                 
                   Pro Arg Tyr Val Glu Thr Met Leu Val Ala Asp Gln Ser Met Ala Glu 
                 
                     
                 
                   Phe His Gly Ser Gly Leu Lys His Tyr Leu Leu Thr Leu Phe Ser Val 
                 
                     
                 
                   Ala Ala Arg Leu Tyr Lys His Pro Ser Ile Arg Asn Ser Val Ser Leu 
                 
                     
                 
                   Val Val Val Lys Ile Leu Val Ile His Asp Glu Gln Lys Gly Pro Glu 
                 
                     
                 
                   Val Thr Ser Asn Ala Ala Leu Thr Leu Arg Asn Phe Cys Asn Trp Gln 
                 
                     
                 
                   Lys Gln His Asn Pro Pro Ser Asp Arg Asp Ala Glu His Tyr Asp Thr 
                 
                     
                 
                   Ala Ile Leu Phe Thr Arg Gln Asp Leu Cys Gly Ser Gln Thr Cys Asp 
                 
                     
                 
                   Thr Leu Gly Met Ala Asp Val Gly Thr Val Cys Asp Pro Ser Arg Ser 
                 
                     
                 
                   Cys Ser Val Ile Glu Asp Asp Gly Leu Gln Ala Ala Phe Thr Thr Ala 
                 
                     
                 
                   His Glu Leu Gly His Val Phe Asn Met Pro His Asp Asp Ala Lys Gln 
                 
                     
                 
                   Cys Ala Ser Leu Asn Gly Val Asn Gln Asp Ser His Met Met Ala Ser 
                 
                     
                 
                   Met Leu Ser Asn Leu Asp His Ser Gln Pro Trp Ser Pro Cys Ser Ala 
                 
                     
                 
                   Tyr Met Ile Thr Ser Phe Leu Asp Asn Gly His Gly Glu Cys Leu Met 
                 
                     
                 
                   Asp Lys Pro Gln Asn Pro Ile Gln Leu Pro Gly Asp Leu Pro Gly Thr 
                 
                     
                 
                   Leu Tyr Asp Ala Asn Arg Gln Cys Gln Phe Thr Phe Gly Glu Asp Ser 
                 
                     
                 
                   Lys His Cys Pro Asp Ala Ala Ser Thr Cys Ser Thr Leu Trp Gys Thr 
                 
                     
                 
                   Gly Thr Ser Gly Gly Val Leu Val Cys Gln Thr Lys His Phe Pro Trp 
                 
                     
                 
                   Ala Asp Gly Thr Ser Cys Gly Glu Gly Lys Trp Cys Ile Asn Gly Lys 
                 
                     
                 
                   Cys Val Asn Lys Thr Asp Arg Lys His Phe Asp Thr Pro Phe His Gly 
                 
                     
                 
                   Ser Trp Gly Pro Trp Gly Pro Trp Gly Asp Cys Ser Arg Thr Cys Gly 
                 
                     
                 
                   Gly Gly Val Gln Tyr Thr Met Arg Glu Cys Asp Asn Pro Val Pro Lys 
                 
                     
                 
                   Asn Gly Gly Lys Tyr Cys Glu Gly Lys Arg Val Arg Tyr Arg Ser Cys 
                 
                     
                 
                   Asn Leu Glu Asp Cys Pro Asp Asn Asn Gly Lys Thr Phe Arg Glu Glu 
                 
                     
                 
                   Gln Cys Glu Ala His Asn Glu Phe Ser Lys Ala Ser Phe Gly Ser Gly 
                 
                     
                 
                   Pro Ala Val Glu Trp Ile Pro Lys Tyr Ala Gly Val Ser Pro Lys Asp 
                 
                     
                 
                   Arg Cys Lys Leu Ile Cys Gln Ala Lys Gly Ile Gly Tyr Phe Phe Val 
                 
                     
                 
                   Leu Gln Pro Lys Val Val Asp Gly Thr Pro Cys Ser Pro Asp Ser Thr 
                 
                     
                 
                   Ser Val Cys Val Gln Gly Gln Cys Val Lys Ala Gly Cys Asp Arg Ile 
                 
                     
                 
                   Ile Asp Ser Lys Lys Lys Phe Asp Lys Cys Gly Val Cys Gly Gly Asn 
                 
                     
                 
                   Gly Ser Thr Cys Lys Lys Ile Ser Gly Ser Val Thr Ser Ala Lys Pro 
                 
                     
                 
                   Gly Tyr His Asp Ile Val Thr Ile Pro Thr Gly Ala Thr Asn Ile Glu 
                 
                     
                 
                   Val Lys Gln Arg Asn Gln Arg Gly Ser Arg Asn Asn Gly Ser Phe Leu 
                 
                     
                 
                   Ala Ile Lys Ala Ala Asp Gly Thr Tyr Ile Leu Asn Gly Asp Tyr Thr 
                 
                     
                 
                   Leu Ser Thr Leu Glu Gln Asp Ile Met Tyr Lys Gly Val Val Leu Arg 
                 
                     
                 
                   Tyr Ser Gly Ser Ser Ala Ala Leu Glu Arg Ile Arg Ser Phe Ser Pro 
                 
                     
                 
                   Leu Lys Glu Pro Leu Thr Ile Gln Val Leu Thr Val Gly Asn Ala Leu 
                 
                     
                 
                   Arg Pro Lys Ile Lys Tyr Thr Tyr Phe Val Lys Lys Lys Lys Glu Ser 
                 
                     
                 
                   Phe Asn Ala Ile Pro Thr Phe Ser Ala Trp Val Ile Glu Glu Trp Gly 
                 
                     
                 
                   Glu Cys Ser Lys Ser Cys Glu Leu Gly Trp Gln Arg Arg Leu Val Glu 
                 
                     
                 
                   Cys Arg Asp Ile Asn Gly Gln Pro Ala Ser Glu Cys Ala Lys Glu Val 
                 
                     
                 
                   Lys Pro Ala Ser Thr Arg Pro Cys Ala Asp His Pro Cys Pro Gln Trp 
                 
                     
                 
                   Gln Leu Gly Glu Trp Ser Ser Cys Ser Lys Thr Cys Gly Lys Gly Tyr 
                 
                     
                 
                   Lys Lys Arg Ser Leu Lys Cys Leu Ser His Asp Gly Gly Val Leu Ser 
                 
                     
                 
                   His Glu Ser Cys Asp Pro Leu Lys Lys Pro Lys His Phe Ile Asp Phe 
                 
                     
                 
                   Cys Thr Leu Thr Gln Cys Ser. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . A variation functionally equivalent to a protein containing an amino acid sequence of SEQ ID NO: 1.  
     
     
         3 . A protein characterized by containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, except for a mouse ADAMTS-1 protein.  
     
     
         4 . A gene characterized by encoding said protein according to any one of claims  1  to 3.  
     
     
         5 . A gene containing a base sequence of SEQ ID NO: 2:  
       
         
           
                 
                 
               
                     
                 
                   ATG GAT ATC TGC AGA ATT CGG CTT AGG AAG AAG CGA TTT GTG TCC AGC 
                     
                 
                     
                 
                   CCC CGT TAT GTG GAA ACC ATG CTT GTG GCA GAC CAG TCG ATG GCA GAA 
                 
                     
                 
                   TTC CAC GGC AGT GGT CTA AAG CAT TAC CTT CTC ACG TTG TTT TCG GTG 
                 
                     
                 
                   GCA GCC AGA TTG TAC AAA CAC CCC AGC ATT CGT AAT TCA GTT AGC CTG 
                 
                     
                 
                   GTG GTG GTG AAG ATC TTG GTC ATC CAC GAT GAA CAG AAG GGG CCG GAA 
                 
                     
                 
                   GTG ACC TCC AAT GCT GCC CTC ACT CTG CGG AAC TTT TGC AAC TGG CAG 
                 
                     
                 
                   AAG CAG CAC AAC CCA CCC AGT GAC CGG GAT GCA GAG CAC TAT GAC ACA 
                 
                     
                 
                   GCA ATT CTT TTC ACC AGA CAG GAC TTG TGT GGG TCC CAG ACA TGT GAT 
                 
                     
                 
                   ACT CTT GGG ATG GCT GAT GTT GGA ACT GTG TGT GAT CCG AGC AGA AGC 
                 
                     
                 
                   TGC TCC GTC ATA GAA GAT GAT GGT TTA CAA GCT GCC TTC ACC ACA GCC 
                 
                     
                 
                   CAT GAA TTA GGC CAC GTG TTT AAC ATG CCA CAT GAT GAT GCA AAG CAG 
                 
                     
                 
                   TGT GCC AGC CTT AAT GGT GTG AAC CAG GAT TCC CAC ATG ATG GCG TCA 
                 
                     
                 
                   ATG CTT TCC AAC CTG GAC CAC AGC CAG CCT TGG TCT CCT TGC AGT GCC 
                 
                     
                 
                   TAC ATG ATT ACA TCA TTT CTG GAT AAT GGT CAT GGG GAA TGT TTG ATG 
                 
                     
                 
                   GAC AAG CCT CAG AAT CCC ATA CAG CTC CCA GGC GAT CTC CCT GGC ACC 
                 
                     
                 
                   TTG TAC GAT GCC AAC CGG CAG TGC CAG TTT ACA TTT GGG GAG GAC TCC 
                 
                     
                 
                   AAA CAC TGC CCC GAT GCA GCC AGC ACA TGT AGC ACC TTG TGG TGT ACC 
                 
                     
                 
                   GGC ACC TCT GGT GGG GTG CTG GTG TGT CAA ACC AAA CAC TTC CCG TGG 
                 
                     
                 
                   GCG GAT GGC ACC AGC TGT GGA GAA GGG AAA TGG TGT ATC AAC GGC AAG 
                 
                     
                 
                   TCT GTG AAC AAA ACC GAC AGG AAG CAT TTT GAT ACG CCT TTT CAT GGA 
                 
                     
                 
                   AGC TGG GGA CCA TGG GGA CCG TGG GGA GAC TGT TCG AGA ACG TGC GGT 
                 
                     
                 
                   GGA GGA GTC CAG TAC ACG ATG AGG GAA TGT GAC AAC CCA GTC CCA AAG 
                 
                     
                 
                   AAT GGA GGG AAG TAC TGT GAA GGC AAA CGA GTG CGC TAC AGA TCC TGT 
                 
                     
                 
                   AAC CTT GAG GAC TGT CCA GAC AAT AAT GGA AAA ACC TTT AGA GAG GAA 
                 
                     
                 
                   CAA TGT GAA GCA CAC AAC GAG TTT TCA AAA GCT TCC TTT GGG AGT GGG 
                 
                     
                 
                   CCT GCG GTG GAA TGG ATT CCC AAG TAC GCT GGC GTC TCA CCA AAG GAC 
                 
                     
                 
                   AGG TGC AAG CTC ATC TGC CAA GCC AAA GGC ATT GGC TAC TTC TTC GTT 
                 
                     
                 
                   TTG CAG CCC AAG GTT GTT GAT GGT ACT CCA TGT AGC CCA GAT TCC ACC 
                 
                     
                 
                   TCT GTC TGT GTG CAA GGA CAG TGT GTA AAA GCT GGT TGT GAT CGC ATC 
                 
                     
                 
                   ATA GAC TCC AAA AAG AAG TTT GAT AAA TGT GGT GTT TGC GGG GGA AAT 
                 
                     
                 
                   GGA TCT ACT TGT AAA AAA ATA TCA GGA TCA GTT ACT AGT GCA AAA CCT 
                 
                     
                 
                   GGA TAT CAT GAT ATC GTC ACA ATT CCA ACT GGA GCC ACC AAC ATC GAA 
                 
                     
                 
                   GTG AAA CAG CGG AAC CAG AGG GGA TCC AGG AAC AAT GGC AGC TTT CTT 
                 
                     
                 
                   GCC ATC AAA GCT GCT GAT GGC ACA TAT ATT CTT ATT GGT GAC TAC ACT 
                 
                     
                 
                   TTG TCC ACC TTA GAG CAA GAC ATT ATG TAC AAA GGT GTT GTC TTG AGG 
                 
                     
                 
                   TAC AGC GGC TCC TCT GCG GCA TTG GAA AGA ATT CGC AGC TTT AGC CCT 
                 
                     
                 
                   CTC AAA GAG CCC TTG ACC ATC CAG GTT CTT ACT GTG GGC AAT GCC CTT 
                 
                     
                 
                   CGA CCT AAA ATT AAA TAC ACC TAC TTC GTA AAG AAG AAG AAG GAA TCT 
                 
                     
                 
                   TTC AAT GCT ATC CCC ACT TTT TCA GCA TGG GTC ATT GAA GAG TGG GGC 
                 
                     
                 
                   GAA TGT TCT AAG TCA TGT GAA TTG GGT TGG CAG AGA AGA CTG GTA GAA 
                 
                     
                 
                   TGC CGA GAC ATT AAT GGA CAG CCT GCT TCC GAG TGT GCA AAG GAA GTG 
                 
                     
                 
                   AAG CCA GCC AGC ACC AGA CCT TGT GCA GAC CAT CCC TGC CCC CAG TGG 
                 
                     
                 
                   CAG CTG GGG GAG TGG TCA TCA TGT TCT AAG ACC TGT GGG AAG GGT TAC 
                 
                     
                 
                   AAA AAA AGA AGC TTG AAG TGT CTG TCC CAT GAT GGA GGG GTG TTA TCT 
                 
                     
                 
                   CAT GAG AGC TGT GAT CCT TTA AAG AAA CCT AAA CAT TTC ATA GAC TTT 
                 
                     
                 
                   TGC ACA CTG ACA CAG TGC AGT TAA. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . A vector characterized by containing said gene according to  claim 4  or  5 .  
     
     
         7 . A transformant characterized by being transformed by said vector according to  claim 6 .  
     
     
         8 . A pharmaceutical composition characterized by comprising 
 (1) a protein containing an amino acid sequence of SEQ ID NO: 1,    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, and a pharmaceutically or veterinarily acceptable carrier.    
     
     
         9 . The pharmaceutical composition according to  claim 8 , for reducing leukocytes.  
     
     
         10 . The pharmaceutical composition according to  claim 8 , for reducing platelets.  
     
     
         11 . The pharmaceutical composition according to  claim 8 , for increasing erythrocytes.  
     
     
         12 . A food characterized by comprising 
 (1) a protein containing an amino acid sequence of SEQ ID NO:    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, and a food additive.    
     
     
         13 . A food additive characterized by comprising 
 (1) a protein containing an amino acid sequence of SEQ ID NO: 1,    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain.    
     
     
         14 . An immunologically reactive substance characterized by being reactive specifically to said protein according to any one of  claims 1  to  3 .  
     
     
         15 . A method for immunologically analyzing a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1, characterized in that a sample is brought into contact with an immunologically reactive substance which is reactive specifically to said human ADAMTS-1 protein, and a complex of said human ADAMTS-1 protein and said immunologically reactive substance is detected.  
     
     
         16 . A method for extracorporeally detecting an immunological state, characterized by analyzing a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1 in a sample.  
     
     
         17 . A method for immunologically analyzing an mRNA of a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1, characterized in that a sample is brought into contact with a polynucleotide containing a base sequence complementary to that of said mRNA of said human ADAMTS-1 protein, and a complex of said mRNA of said human ADAMTS-1 protein and said gene is detected.  
     
     
         18 . A method for extracorporeally detecting an immunological state, characterized by analyzing an mRNA of a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1 in a sample.  
     
     
         19 . An agent for analyzing an immunological state, characterized by containing an immunologically reactive substance capable of immunologically reacting a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1.  
     
     
         20 . An agent for analyzing an immunological state, characterized by containing a polynucleotide containing a base sequence complementary to that of an mRNA of a human ADAMTS-1 protein containing an amino acid sequence of SEQ ID NO: 1.  
     
     
         21 . A method for reducing leukocytes, comprising administering to a subject in need thereof, 
 (1) a protein containing an amino acid sequence of SEQ ID NO: 1,    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, in an amount effective therefor.    
     
     
         22 . A method for reducing platelets, comprising administering to a subject in need thereof, 
 (1) a protein containing an amino acid sequence of SEQ ID NO:    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, in an amount effective therefor.    
     
     
         23 . A method for increasing erythrocytes, comprising administering to a subject in need thereof, 
 (1) a protein containing an amino acid sequence of SEQ ID NO:    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, in an amount effective therefor.    
     
     
         24 . Use of 
 (1) a protein containing an amino acid sequence of SEQ ID NO: 1,    (2) a variation functionally equivalent to said protein containing said amino acid sequence of SEQ ID NO: 1, or    (3) a protein containing a matrix metalloproteinase domain, a disintegrin domain, and a thrombospondin domain, for preparing a pharmaceutical composition.

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