US5089274A
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US
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Use of bactericidal/permeability increasing protein or biologically active analogs thereof to treat endotoxin-related disorders
Assignee: Incyte Corp
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Filing: 1990-01-22
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Granted: 1992-02-18
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Expires: 2010-01-22
Abstract
Abstract The present invention provides a method of inhibiting lipopolysaccharide (LPS)-mediated stimulation of cells. This method comprises contacting the cells, in the presence of a cell-stimulating amount of lipopolysaccharide, with Bactericidal/Permeability Increasing Protein (BPI) in an amount effective to inhibit cell stimulation.
Inventors
- 👤 Marian N. Marra
- 👤 Randal W. Scott
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 11:50
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61P; A61P29/00; A61P31/00; A61P31/04; A61P7/00; A61P7/06; C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; C07K14/4701; C07K14/4742; C07K14/52; A61K; A61K38/00; F; F02; F02B; F02B75/00; F02B75/02; F02B2075/022; F02B2075/027; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/829
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
31 words
A method of inhibiting the pyrogenic activity of an endotoxin which comprises contacting the endotoxin with an amount of Bactericidal/Permeability Increasing Protein effective to inhibit the pyrogenic activity of the endotoxin.
Claim 2
Independent Claim
31 words
A method of inhibiting the pyrogenic activity of an endotoxin which comprises contacting the endotoxin with an amount of Bactericidal/Permeability Increasing Protein effective to inhibit the pyrogenic activity of the endotoxin.
Claim 3
Independent Claim
36 words
A method of inhibiting lipopolysaccharide-mediated tumor necrosis factor production by human mononuclear cells which comprises contacting LPS with Bactericidal/Permeability Increasing Protein in an amount effective to inhibit lipopolysaccharide-mediated tumor necrosis factor production by the mononuclear cells.
Claim 4
Independent Claim
36 words
A method of inhibiting lipopolysaccharide-mediated tumor necrosis factor production by human mononuclear cells which comprises contacting LPS with Bactericidal/Permeability Increasing Protein in an amount effective to inhibit lipopolysaccharide-mediated tumor necrosis factor production by the mononuclear cells.
Claim 5
Independent Claim
46 words
A method of inhibiting endotoxin-mediated stimulation of neutrophils or mononuclear cells which comprises contacting endotoxin-associated lipopolysaccharide (LPS) with a purified, endotoxin-free human Bactericidal/Permeability Increasing Protein (BPI) under conditions such that the BPI binds to endotoxin-associated LPS and thereby inhibits endotoxin-mediated stimulation of neutrophils or mononuclear cells.
Claim 6
Independent Claim
46 words
A method of inhibiting endotoxin-mediated stimulation of neutrophils or mononuclear cells which comprises contacting endotoxin-associated lipopolysaccharide (LPS) with a purified, endotoxin-free human Bactericidal/Permeability Increasing Protein (BPI) under conditions such that the BPI binds to endotoxin-associated LPS and thereby inhibits endotoxin-mediated stimulation of neutrophils or mononuclear cells.
Claim 7
Independent Claim
77 words
A method of treating a subject suffering from a disorder selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and thereby inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby treat the subject.
Claim 8
Independent Claim
77 words
A method of treating a subject suffering from a disorder selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and thereby inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby treat the subject.
Claim 9
Dependent Claim
13 words
A method of claim 4, wherein the disorder is endotoxin-related, disseminated intravascular coagulation.
Claim 10
Dependent Claim
11 words
A method of claim 4, wherein the disorder is endotoxin-related anemia.
Claim 11
Dependent Claim
11 words
A method of claim 4, wherein the disorder is endotoxin-related leukopenia.
Claim 12
Dependent Claim
11 words
A method of claim 4, wherein the disorder is endotoxin-related thrombocytopenia.
Claim 13
Dependent Claim
14 words
A method of claim 4, wherein the disorder is endotoxin-related adult respiratory distress syndrome.
Claim 14
Dependent Claim
12 words
A method of claim 4, wherein the disorder is endotoxin-related renal failure.
Claim 15
Independent Claim
46 words
A method of treating a subject suffering from endotoxin-related shock which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits endotoxin-related shock so as to thereby treat the subject.
Claim 16
Independent Claim
46 words
A method of treating a subject suffering from endotoxin-related shock which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits endotoxin-related shock so as to thereby treat the subject.
Claim 17
Independent Claim
86 words
A method of reducing the symptoms associated with a disorder which comprises administering to a subject in need thereof purified, endotoxin-free Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby reduce the symptoms associated with the disorder, the disorder being selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related leukopenia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure.
Claim 18
Independent Claim
86 words
A method of reducing the symptoms associated with a disorder which comprises administering to a subject in need thereof purified, endotoxin-free Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby reduce the symptoms associated with the disorder, the disorder being selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related leukopenia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure.
Claim 19
Dependent Claim
11 words
A method of claim 12, wherein the disorder is endotoxin-related shock.
Claim 20
Dependent Claim
13 words
A method of claim 12, wherein the disorder is endotoxin-related, disseminated intravascular coagulation.
Claim 21
Dependent Claim
11 words
A method of claim 12, wherein the disorder is endotoxin-related anemia.
Claim 22
Dependent Claim
11 words
A method of claim 12, wherein the disorder is endotoxin-related leukopenia.
Claim 23
Dependent Claim
11 words
A method of claim 12, wherein the disorder is endotoxin-related thrombocytopenia.
Claim 24
Dependent Claim
14 words
A method of claim 12, wherein the disorder is endotoxin-related adult respiratory distress syndrome.
Claim 25
Dependent Claim
12 words
A method of claim 12, wherein the disorder is endotoxin-related renal failure.
Claim 26
Independent Claim
81 words
A method of recovering a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein having enhanced activity to inhibit endotoxin-mediated stimulation of neutrophils and mononuclear cells which comprises: a) obtaining a sample containing Bactericidal/Permeability Increasing Protein; b) subjecting the sample so obtained to chromatography so as to obtain the endotoxin-free, human Bactericidal/Permeability Increasing Protein separate from other substances present in the sample; and c) recovering the purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein having enhanced activity to inhibit endotoxin-mediated stimulation of neutrophils and mononuclear cells.
Claim 27
Independent Claim
81 words
A method of recovering a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein having enhanced activity to inhibit endotoxin-mediated stimulation of neutrophils and mononuclear cells which comprises: a) obtaining a sample containing Bactericidal/Permeability Increasing Protein; b) subjecting the sample so obtained to chromatography so as to obtain the endotoxin-free, human Bactericidal/Permeability Increasing Protein separate from other substances present in the sample; and c) recovering the purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein having enhanced activity to inhibit endotoxin-mediated stimulation of neutrophils and mononuclear cells.
Claim 28
Dependent Claim
13 words
A method of claim 20, wherein the Bactericidal/Permeability Increasing Protein comprises native BPI.
Claim 29
Dependent Claim
18 words
A method of claim 20, wherein the Bactericidal/Permeability Increasing Protein comprises a biologically active polypeptide analog of BPI.
Claim 30
Dependent Claim
35 words
A method of claim 22, wherein the biologically active polypeptide analog of BPI comprises a polypeptide which has a molecular weight of about 25 kD and corresponds to the N-terminal amino acid sequence of BPI.
Claim 31
Dependent Claim
22 words
A method of claim 3, wherein the Bactericidal/Permeability Increasing Protein comprises recombinant Bactericidal/Permeability Increasing Protein or a biologically active polypeptide analog thereof.
Claim 32
Dependent Claim
37 words
A method of claim 24, wherein the biologically active polypeptide analog of Bactercidal/Permeability Increasing Protein comprises a polypeptide which has a molecular weight of about 25 kD and corresponds to the N-terminal amino acid sequence of BPI.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-02-17 | 1995-08-19 | 1996-02-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-02-17 | 1999-08-19 | 2000-02-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-02-17 | 2003-08-19 | 2004-02-18 | $7700.00 | Window Closed / Lapsed |