US5789189A
Expired / Lapsed
US
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Inhibition of cyst formation by cytoskeletal specific drugs
Assignee: University of California
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Filing: 1993-09-24
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Granted: 1998-08-04
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Expires: 2013-09-24
Abstract
Abstract PCT No. PCT/US93/09124 Sec. 371 Date May 22, 1995 Sec. 102(e) Date May 22, 1995 PCT Filed Sep. 24, 1993 PCT Pub. No. WO94/08041 PCT Pub. Date Apr. 14, 1994The invention provides a method of producing a culture of polycystic kidney cells which form cysts in vitro. A cell culture of polycystic kidney cells is also provided. A method for screening an agent in vitro to determine the effectiveness of the agent in treating polycystic kidney disease is disclosed. Further, a method of treating a mammal having polycystic kidney disease by administering a pharmaceutical composition is provided.
Inventors
- 👤 David D. L. Woo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 07:06
CPC Classifications
C; C12; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/0684; C12N5/0686; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5008; C12N2503/00; C12N2503/02; G01N2500/00
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
64 words
A method of producing a culture of polycystic kidney cells which form cysts in vitro, comprising: preparing a suspension of polycystic kidney cells that form cysts in vivo in a medium suitable for the maintenance of said cells; and culturing said cells on a solid phase which substantially prevents the formation of a layer of said cells on the surface of said solid phase.
Claim 2
Independent Claim
64 words
A method of producing a culture of polycystic kidney cells which form cysts in vitro, comprising: preparing a suspension of polycystic kidney cells that form cysts in vivo in a medium suitable for the maintenance of said cells; and culturing said cells on a solid phase which substantially prevents the formation of a layer of said cells on the surface of said solid phase.
Claim 3
Dependent Claim
25 words
The method of claim 1, wherein said solid phase is coated with a material which substantially prevents the growth of a layer of said cells.
Claim 4
Dependent Claim
10 words
The method of claim 2, wherein said material is agarose.
Claim 5
Dependent Claim
38 words
A cell culture of polycystic kidney cells, wherein said cells are suspended in a medium suitable for the maintenance of said cells in culture, and wherein said cells form cysts in vitro without induction by a cyst-inducing agent.
Claim 6
Dependent Claim
38 words
A cell culture of polycystic kidney cells, wherein said cells are suspended in a medium suitable for the maintenance of said cells in culture, and wherein said cells form cysts in vitro without induction by a cyst-inducing agent.
Claim 7
Dependent Claim
19 words
The cell culture of claim 4, wherein the apical surfaces of said cells face the lumens of said cysts.
Claim 8
Dependent Claim
14 words
The cell culture of claim 4, wherein said cells are of distal nephron origin.
Claim 9
Dependent Claim
19 words
The cell culture of claim 4, wherein said cells are capable of forming cysts within 24 hours of culture.
Claim 10
Dependent Claim
18 words
The cell culture of claim 4, wherein said cells have DNA synthesis capabilities that are greater than normal.
Claim 11
Dependent Claim
32 words
The cell culture of claim 4, wherein cysts formed by said cells have an outer cell layer from about 1 to 5 cells thick, and about 10 to 50 cells in circumference.
Claim 12
Dependent Claim
18 words
The cell culture of claim 4, wherein cysts formed by said cells have an abnormally thickened basement membrane.
Claim 13
Dependent Claim
23 words
The cell culture of claim 4, wherein cells line said cysts and the cells lining said cysts have prominent interdigitating cell processes therebetween.
Claim 14
Dependent Claim
17 words
The cell culture of claim 4, wherein said cells have short sparse microvilli on the anti-luminal surface.
Claim 15
Dependent Claim
65 words
The cell culture of claim 4, wherein said cells have been produced by a method comprising: preparing a suspension of said cells that form cysts in vivo in a medium suitable for the maintenance of said cells; and culturing the suspension of cells on a solid phase which substantially prevents the formation of a monolayer of said cells on the surface of said solid phase.
Claim 16
Dependent Claim
26 words
The cell culture of claim 13, wherein said solid phase is coated with a material which substantially prevents the growth of a layer of said cells.
Claim 17
Dependent Claim
11 words
The cell culture of claim 14, wherein said material is agarose.
Claim 18
Independent Claim
145 words
A method of screening an agent in vitro in order to determine its effectiveness of the agent in treating polycystic kidney disease comprising: forming a suspension of polycystic kidney cells which form cysts in vivo in a medium comprising an agent to be tested for its ability to inhibit cyst formation; culturing said cells in said medium on a solid phase without formation of a layer of said cells on the surface of said solid phase; detecting the extent to which said cells form cysts; comparing the result from detecting the extent of cyst formation with the extent of cyst formation when if said cells were cultured in a medium without said agent; and identifying said agent as effective in training a cystic disorder if the detected extent of cyst formation is less than the extent of cyst formation in the medium without said agent.
Claim 19
Independent Claim
145 words
A method of screening an agent in vitro in order to determine its effectiveness of the agent in treating polycystic kidney disease comprising: forming a suspension of polycystic kidney cells which form cysts in vivo in a medium comprising an agent to be tested for its ability to inhibit cyst formation; culturing said cells in said medium on a solid phase without formation of a layer of said cells on the surface of said solid phase; detecting the extent to which said cells form cysts; comparing the result from detecting the extent of cyst formation with the extent of cyst formation when if said cells were cultured in a medium without said agent; and identifying said agent as effective in training a cystic disorder if the detected extent of cyst formation is less than the extent of cyst formation in the medium without said agent.
Claim 20
Dependent Claim
21 words
The method of claim 16, wherein said agent is a compound that interferes with the normal metabolism of a cytoskeletal component.
Claim 21
Dependent Claim
24 words
The method of claim 16, wherein said agent is a compound that inhibits the delivery of membrane proteins to the membrane of said cells.
Claim 22
Dependent Claim
24 words
The method of claim 17, wherein said agent is one of the following: cytochalasin-B, cytochalasin-D, phalloidin or a derivative of any of the foregoing.
Claim 23
Independent Claim
49 words
A method of treating a mammal having polycystic kidney disease, comprising: administering to the mammal having polycystic kidney disease a pharmacologically effective anti-cystic amount of an agent that interferes with the normal functioning of a cytoskeletal component, said agent being administered in a pharmacologically acceptable carrier, excipient or diluent.
Claim 24
Independent Claim
49 words
A method of treating a mammal having polycystic kidney disease, comprising: administering to the mammal having polycystic kidney disease a pharmacologically effective anti-cystic amount of an agent that interferes with the normal functioning of a cytoskeletal component, said agent being administered in a pharmacologically acceptable carrier, excipient or diluent.
Claim 25
Dependent Claim
12 words
The method of claim 20, wherein said drug is specific for microtubules.
Claim 26
Dependent Claim
13 words
The method of claim 20, wherein said drug is specific for actin microfilaments.
Claim 27
Dependent Claim
28 words
The method of claim 21, wherein said drug is selected from the group consisting of: colchicine, nocodazole, vincristine, vinblastine, griseofulvin and a derivative of any of the foregoing.
Claim 28
Dependent Claim
27 words
The method of claim 22, wherein said drug is selected from the group consisting of: cytochalasin-B, cytochalasin-D, phalloidin, phallacidin and a derivative of any of the foregoing.
Claim 29
Independent Claim
55 words
A method of treating a mammal having polycystic kidney disease, comprising: administering to the mammal having polycystic kidney disease a pharmacologically effective anti-cystic amount of an agent that inhibits the delivery of membrane proteins to the membrane of a cell of said mammal, said agent being administered in a pharmacologically acceptable carrier, excipient or diluent.
Claim 30
Independent Claim
55 words
A method of treating a mammal having polycystic kidney disease, comprising: administering to the mammal having polycystic kidney disease a pharmacologically effective anti-cystic amount of an agent that inhibits the delivery of membrane proteins to the membrane of a cell of said mammal, said agent being administered in a pharmacologically acceptable carrier, excipient or diluent.
Claim 31
Dependent Claim
11 words
The method of claim 25, wherein said agent comprises brefeldin A.
Claim 32
Dependent Claim
14 words
The method of claim 21, wherein said drug is taxol or a derivative thereof.
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