Platelet-activating factor acetylhydrolase
AssigneeICOS Corporation
InventorsLawrence S. Cousens, Christine D. Eberhardt, Patrick Gray, Hai Le Trong, Larry W. Tjoelker, Cheryl L. Wilder
Life of this patent
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Abstract
The present invention provides purified and isolated polynucleotide sequences encoding human plasma platelet-activating factor acetylhydrolase. Also provided are materials and methods for the recombinant production of platelet-activating factor acetylhydrolase products which are expected to be useful in regulating pathological inflammatory events.
Claims12
A method for treating a mammal susceptible to or suffering from a PAF-mediated pathological condition comprising administering a pharmaceutical composition comprising platelet-activating factor acetylhydrolase (PAF-AH) enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF in said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method for treating a mammal susceptible to or suffering from pleurisy comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF of said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method for treating a mammal susceptible to or suffering from asthma comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactive pathological amounts of PAF of said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method for treating a mammal susceptible to or suffering from rhinitis comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF in said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method for treating a mammal susceptible to or suffering from necrotizing enterocolitis comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF in said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method for treating a mammal susceptible to or suffering from acute respiratory distress syndrome comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF in said mammal, wherein said PAF-AH enzyme comprises the mature human animo acid sequence of SEQ ID NO:
- 8 or comprises a polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being produced by growing a host cell transformed or transfected with a DNA and isolating said PAF-AH enzyme from said host cell or the medium of its growth, said DNA being selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from a PAF-mediated pathological condition comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from pleurisy comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from asthma comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from rhinitis comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from necrotizing enterocolitis comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
A method of treating a mammal susceptible to or suffering from acute respiratory distress syndrome comprising administering a pharmaceutical composition comprising PAF-AH enzyme to said mammal in an amount sufficient to supplement endogenous PAF-AH activity and to inactivate pathological amounts of PAF, wherein said PAF-AH enzyme comprises the mature human amino acid sequence of SEQ ID NO:
- 8 or comprises a PAF-AH polypeptide fragment, variant or variant fragment that hydrolyzes .sup.3 H-acetate from PAF, said PAF-AH enzyme being encoded by a DNA selected from the group consisting of (a) a DNA comprising the sequence set out in SEQ ID NO:
- 7, and (b) a DNA which hybridizes under stringent conditions to the non-coding strand of (a).
Dependencies are inferred from the claim text.