Patent US5563123A successfully refreshed from Google Patents.
US5563123A
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Chimeric proteins
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1995-05-09
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Granted: 1996-10-08
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Expires: 2015-05-09
Abstract
Abstract Chimeric proteins possessing Kunitz-type domain 1 of TFPI-2 and Kunitz-type domain 2 of TFPI are disclosed, as are muteins of TFPI and TFPI-2. Nucleic acid sequences, expression vectors and transformed host cells encoding and capable of producing the disclosed chimeric proteins and muteins are also disclosed. Finally, methods for prevention and treatment of septic shock using the chimeric proteins and muteins are disclosed.
Inventors
- 👤 Michael A. Innis
- 👤 Abla A. Creasey
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 23:51
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/81; C07K14/8107; C07K14/811; C07K14/8114; A; A61; A61P; A61P31/00; A61P31/04; A61P43/00; A61P7/00; A61P7/02; A61P9/00; A61P9/02; A61K; A61K38/00; C07K2319/00
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
64 words
A method of treating thrombosis disorders comprising administering an effective amount of a chimeric protein to a mammal in need of such treatment, said chimeric protein comprising: (a) a Kunitz-type domain 1 of Tissue-Factor Pathway Inhibitor-2 (TFPI-2), and (b) a Kunitz-type domain 2 of Tissue-Factor Pathway Inhibitor (TFPI); or (c) a Kunitz-type domain 1 of TFPI, and (d) a Kunitz-type domain 2 of TFPI-2.
Claim 2
Independent Claim
64 words
A method of treating thrombosis disorders comprising administering an effective amount of a chimeric protein to a mammal in need of such treatment, said chimeric protein comprising: (a) a Kunitz-type domain 1 of Tissue-Factor Pathway Inhibitor-2 (TFPI-2), and (b) a Kunitz-type domain 2 of Tissue-Factor Pathway Inhibitor (TFPI); or (c) a Kunitz-type domain 1 of TFPI, and (d) a Kunitz-type domain 2 of TFPI-2.
Claim 3
Dependent Claim
143 words
The method of claim 1, wherein said chimeric protein is represented by the generic structure: A--(X.sub.1).sub.a --B--(X.sub.2).sub.b --C wherein A and C are independently optional flanking peptides, the flanking peptides containing 0-100 amino acids; wherein B is an optional spacer peptide, the spacer peptide containing 0-25 amino acids; wherein each X 1 is --D--K 1 --E-- where D, E are independently peptides of 0-25 amino acids, where K 1 comprises TFPI Kunitz-type domain 1, or TFPI-2 Kunitz-type domain 1; wherein each X 2 is --F--K 2 --G-- where F, G are independently peptides of 0-25 amino acids, where K 2 comprises TFPI Kunitz-type domain 2, or TFPI-2 Kunitz-type domain 2; wherein a, b are integers from 0-6; wherein A, B, C, D, E, F, G may comprise portions of native TFPI or TFPI-2 sequences; and the molecule is not native TFPI or TFPI-2.
Claim 4
Dependent Claim
15 words
The method of claim 1, wherein A or C comprises Kunitz-type domain 3 of TFPI.
Claim 5
Dependent Claim
15 words
The method of claim 1, wherein A or C comprises Kunitz-type domain 3 of TFPI-2.
Claim 6
Dependent Claim
26 words
The method of claim 2, wherein at least one of said flanking peptides comprises an amino acid sequence that binds one or more cell surface components.
Claim 7
Dependent Claim
14 words
The method of claim 5, wherein said amino acid sequence that binds a glycosaminoglycan.
Claim 8
Dependent Claim
22 words
The method of claim 6, wherein said amino acid sequence that binds a glycosaminoglycan is an amino acid sequence that binds heparin.
Claim 9
Dependent Claim
59 words
The method of claim 7, wherein said amino acid sequence that bonds heparin is a heparin binding domain from a protein, said protein selected form the group consisting of: (a) protease nexin-1; (b) protease nexin-2; (c) antithrombin III; (d) heparin cofactor II; (e) protein C inhibitor; (f) platelet factor 4; (g) bovine pancreatic trypsin inhibitor; and (h) ghilanten-related inhibitors.
Claim 10
Dependent Claim
69 words
The method of claim 7, wherein said amino acid sequence that binds heparin is a heparin-binding domain selected form the group consisting of: (a) SEQ ID NO: 10; (b) SEQ ID NO: 11; (c) SEQ ID NO: 12; (d) SEQ ID NO: 13; (e) SEQ ID NO: 14; (f) SEQ ID NO: 15; (g) SEQ ID NO: 16; (h) SEQ ID NO: 17; and (i) SEQ ID NO: 18.
Claim 11
Dependent Claim
19 words
The method of claim 5, wherein said flanking peptides comprise the C-terminal tail of TFPI (SEQ ID NO: 7).
Claim 12
Dependent Claim
19 words
The method of claim 5, wherein said flanking peptides comprise the C-terminal tail of TFPI-2 (SEQ ID NO: 8).
Claim 13
Dependent Claim
33 words
The method of claim 2, wherein each K 1 is Kunitz-type domain 1 of TFPI-2, each K 2 is Kunitz-type domain 2 of TFPI, and a and b are integers greater than 1.
Claim 14
Dependent Claim
123 words
The method of claim 1, wherein said chimeric proteins is represent by the generic structure: A--(X.sub.1 --B--X.sub.2).sub.n --C wherein A and C are independently optional flanking peptides, the flanking peptides containing 0-100 amino acids; wherein B is an optional spacer peptide, the spacer peptide containing 0-25 amino acids; wherein each X 1 is --D--K 1 --E-- where D, E are independently peptides of 0-25 amino acids, where K 1 is TFPI Kunitz-type domain 1 of TFPI or TFPI-2; wherein each X 2 is --F--K 2 --G-- where F, G are independently peptides of 0-25 amino acids, where K 2 is Kunitz-type domain 2 of TFPI or TFPI-2, wherein n is an integer from 1-10; and the molecule is not native TFPI or TFPI-2.
Claim 15
Dependent Claim
15 words
The method of claim 13, wherein A or C comprises Kunitz-type domain 3 of TFPI.
Claim 16
Dependent Claim
15 words
The method of claim 13, wherein A or C comprises Kunitz-type domain 3 of TFPI-2.
Claim 17
Dependent Claim
26 words
The method of claim 13, wherein at least one of said flanking peptides comprises an amino acid sequence that binds one or more cell surface components.
Claim 18
Dependent Claim
14 words
The method of claim 16, wherein said amino acid sequence that binds a glycosaminoglycan.
Claim 19
Dependent Claim
22 words
The method of claim 17, wherein said amino acid sequence that binds a glycosaminoglycan is an amino acid sequence that binds heparin.
Claim 20
Dependent Claim
59 words
The method of claim 18, wherein said amino acid sequence that binds heparin is a heparin binding domain from a protein, said protein selected form the group consisting of: (a) protease nexin-1; (b) protease nexin-2; (c) antithrombin III; (d) heparin cofactor II; (e) protein C inhibitor; (f) platelet factor 4; (g) bovine pancreatic trypsin inhibitor; and (h) ghilanten-related inhibitors.
Claim 21
Dependent Claim
69 words
The method of claim 18, wherein said amino acid sequence that binds heparin is a heparin-binding domain selected form the group consisting of: (a) SEQ ID NO: 10; (b) SEQ ID NO: 11; (c) SEQ ID NO: 12; (d) SEQ ID NO: 13; (e) SEQ ID NO: 14; (f) SEQ ID NO: 15; (g) SEQ ID NO: 16; (h) SEQ ID NO: 17; and (i) SEQ ID NO: 18.
Claim 22
Dependent Claim
19 words
The method of claim 16, wherein said flanking peptides comprise the C-terminal tail of TFPI (SEQ ID NO: 7).
Claim 23
Dependent Claim
19 words
The method of claim 16, wherein said flanking peptides comprise the C-terminal tail of TFPI-2 (SEQ ID NO: 8).
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