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OwnerGeorge Phillip Vlasuk, Patrick Eric Hugo Stanssens +7inventors
InventorsGeorge Phillip Vlasuk, Patrick Eric Hugo Stanssens, Joris Hilda Lieven Messens, Marc Josef Lauwereys, Yves Rene LaRoche, Laurent Stephane Jespers, Yannick Georges Jozef Gansemans, Matthew Moyle, Peter W. Bergum
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Proteins which have activity as anticoagulants and/or serine protease inhibitors and have at least one NAP domain and are described. Certain of these proteins have factor Xa inhibitory activity and others have activity as inhibitors of factor VIIa/TF. These proteins can be isolated from natural sources as nematodes, chemically synthesized or made by recombinant methods using various DNA expression systems.
An isolated protein having anticoagulant activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
An isolated protein having Factor Xa inhibitory activity selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40] and AcaNAP6 [SEQ. ID. NO. 41].
An isolated recombinant cDNA molecule encoding a protein having Factor Xa inhibitory activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
A cDNA molecule encoding a protein having Factor Xa inhibitory activity selected from the group (consisting of proteins having NAP domains substantially the same as AcaNAP5 [SEQ. ID. NO. 40] or AcaNAP6 [SEQ. ID. NO. 41].
A pharmaceutical composition comprising a protein selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40] and AcaNAP6 [SEQ. ID. NO. 41].
A method of inhibiting blood coagulation comprising administering a protein selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40] and AcaNAP6 [SEQ. ID. NO. 41].
An isolated protein having anticoagulant activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
An isolated protein having Factor VIIa/TF inhibitory activity having a NAP domain with cm amino acid sequence that is substantially the same as the NAP domain of AcaNAPc2 [SEQ. ID. NO. 59].
An isolated recombinant cDNA molecule encoding a protein having anticoagulant activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
An isolated cDNA molecule encoding a protein having Factor VIIa/TF inhibitory activity and a NAP domain with an amino acid sequence that is substantially the same as the NAP domain of AcaNAPc2 [SEQ. ID. NO. 59].
A pharmaceutical composition comprising an AcaNAPc2 protein [SEQ. ID. NO. 59].
A method of inhibiting blood coagulation comprising administering an AcaNAPc2 protein [SEQ. ID. NO. 59].
An isolated protein having anticoagulant activity, wherein said protein specifically inhibits the catalytic activity of the fVIIa/TF complex in the presence of fXa or catalytically inactive fXa derivative, and does not specifically inhibit the activity of FVIIa in the absence of TF and does not specifically inhibit prothrombinase.
An isolated recombinant cDNA molecule encoding a protein having anticoagulant activity, wherein said protein specifically inhibits the catalytic activity of the fVIIa/TF complex in the presence of fXa or catalytically inactive fXa derivative, and does not specifically inhibit the activity of FVIIa in the absence of TF and does not specifically inhibit prothrombinase.
An isolated cDNA molecule having a nucleotide sequence substantially the same as AcaNAPc2 [SEQ. ID. NO. 19].
A protein having an amino acid sequence substantially the same as AcaNAPc2 [SEQ. ID. NO. 59].
An isolated protein having serine protease inhibitory activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
An isolated protein having serine protease inhibitory activity and a NAP domain with an amino acid sequence substantially the same as NAP domains selected from the group consisting of HpoNAP5 [SEQ. ID. NO. 60] and NamNAP [SEQ.—ID. NO. 61].
An isolated recombinant cDNA molecule encoding a protein having serine protease inhibitory activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
A cDNA molecule encoding a protein having serine protease inhibitory activity selected from the group consisting proteins having NAP domains substantially the same as of HpoNAP5 [SEQ. ID. NO. 60] and NamNAP [SEQ. ID. NO. 61].
A pharmaceutical composition comprising a protein selected from the group consisting of HpoNAP5 [SEQ. ID. NO. 60] and NamNAP [SEQ. ID. NO. 61].
A method of inhibiting blood coagulation comprising administering a protein selected front the group consisting of HpoNAP5 [SEQ. ID. NO. 60] and NamNAP [SEQ. ID. NO. 61].
An isolated protein having anticoagulant activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
An isolated protein having anticoagulant activity selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40], AcaNAP6 [SEQ. ID. NO. 41], AcaNAP48 [SEQ. ID. NO. 42], AcaNAP23 [SEQ. ID. NO. 43], AcaNAP24 [SEQ. ID. NO. 44], AcaNAP25 [SEQ. ID. NO. 45], AcaNAP44 [SEQ. ID. NO. 46], AcaNAP31 [SEQ. ID. NO. 47], AceNAP4 [SEQ. ID. NO. 62], AcaNAP45 [SEQ. ID. NO. 63], AcaNAP47 [SEQ. ID. NO;
An isolated recombinant cDNA molecule encoding a protein having anticoagulant activity and having one or more NAP domains, wherein each NAP domain includes the sequence:
A cDNA molecule encoding a protein having anticoagulant activity selected from the group) consisting of cDNAs substantially the same as cDNAs coding for AcaNAP5 [SEQ. ID. NO. 3], AcaNAP6 [SEQ. ID. NO. 5], AcaNAP48 [SEQ. ID. NO. 38], AcaNAP23 [SEQ. ID. NO. 31], AcaNAP24 [SEQ. ID. NO. 32], AcaNAP25 [SEQ. ID. NO. 33], AcaNAP44 [SEQ. ID. NO. 35], AcaNAP31 [SEQ. ID. NO. 34], AceNAP4 [SEQ. ID. NO. 9], AcaNAP45 [SEQ. ID. NO. 36], AcaNAP47 [SEQ. ID. NO. 37], AduNAP7 [SEQ. ID. NO. 13], AduNAP4 [SEQ. ID. NO. 12], AceNAP5 [SEQ. ID. NO. 10], and AceNAP7 [SEQ. ID. NO. 11].
A pharmaceutical composition comprising a protein having a NAP domain substantially the same as a NAP domain selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40], AcaNAP6 [SEQ. ID. NO. 41], AcaNAP48 [SEQ. ID. NO. 42], AcaNAP23 [SEQ. ID. NO. 43], AcaNAP24 [SEQ. ID. NO. 44], AcaNAP25 [SEQ. ID. NO. 45], AcaNAP44 [SEQ. ID. NO. 46], AcaNAP31 [SEQ. ID. NO. 47], AceNAP4 [SEQ. ID. NOS. 48 or 49], AcaNAP45 [SEQ. ID. NOS. 50 or 53], AcaNAP47 [SEQ. ID. NOS. 51 or 54], AduNAP7 [SEQ. ID. NO. 52 or 56], AduNAP4 [SEQ. ID. NO. 55], AceNAP5 [SEQ. ID. NO. 57], and AceNAP7 [SEQ. ID. NO. 58].
A method of inhibiting blood coagulation comprising administering a protein having a NAP domain substantially the same as NAP domains selected from the group consisting of AcaNAP5 [SEQ. ID. NO. 40], AcaNAP6 [SEQ. ID. NO. 41], AcaNAP48 [SEQ. ID. NO. 42], AcaNAP23 [SEQ. ID. NO. 43], AcaNAP24 [SEQ. ID. NO. 44], AcaNAP25 [SEQ. ID. NO. 45], AcaNAP44 [SEQ. ID. NO. 46], AcaNAP31 [SEQ. ID. NO. 47], AceNAP4 [SEQ. ID. NOS. 48 and 49], AcaNAP45 [SEQ. ID. NOS. 50 and 53], AcaNAP47 [SEQ. ID. NOS. 51 and 54], AduNAP7 [SEQ. ID. NOS. 52 and 56], AduNAP4 [SEQ. ID. NO. 55], AceNAP5 [SEQ. ID. NO. 57], and AceNAP7 [SEQ. ID. NO. 58].
A protein having two NAP domains, wherein said protein is selected from the group consisting of AceNAP4 [SEQ. ID. NO. 62], AcaNAP45 [SEQ. ID. NO. 63], AcaNAP47 [SEQ. ID. NO. 64], and AduNAP7 [SEQ. ID. NO. 65].
An oligonucleotide comprising a nucleotide sequence selected from
Dependencies are inferred from the claim text.