US2003022352A1PendingUtilityA1
Human ADAMTS-1 protein, gene encoding the same, pharmaceutical composition, and method for immunologically analyzing human ADAMTS-1 protein
Priority: Jun 3, 1997Filed: Mar 15, 2002Published: Jan 30, 2003
Est. expiryJun 3, 2017(expired)· nominal 20-yr term from priority
Inventors:Kunitaka HiroseEiji InoguchiMichinori HakozakiKeiko IshiokaYukako IshidaKouji MatsushimaKouji Kuno
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-modified1 . 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.Cited by (0)
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