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US5882881A Expired / Lapsed US ⏱️ 0.0 years remaining

Inhibition of cyst formation by cytoskeletal specific drugs

Assignee: University of California, San Diego
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Filing: 1998-01-09
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Granted: 1999-03-16
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Expires: 2018-01-09
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Abstract

Abstract The 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 2026-10-29 17:31
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: 36
Claim 1
Independent Claim 60 words
A method of producing a culture of cells which form cysts in vitro, comprising: preparing a suspension of 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 60 words
A method of producing a culture of cells which form cysts in vitro, comprising: preparing a suspension of 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 35 words
A culture of 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 35 words
A culture of 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 18 words
The culture of claim 4, wherein the apical surfaces of said cells face the lumens of said cysts.
Claim 8
Dependent Claim 13 words
The culture of claim 4, wherein said cells are of distal nephron origin.
Claim 9
Dependent Claim 18 words
The culture of claim 4, wherein said cells are capable of forming cysts within 24 hours of culture.
Claim 10
Dependent Claim 17 words
The culture of claim 4, wherein said cells have DNA synthesis capabilities that are greater than normal.
Claim 11
Dependent Claim 32 words
The culture of claim 4, wherein cysts formed by a said cell have an outer cell layer from about 1 to 5 cells thick, and about 10 to 50 cells in circumference.
Claim 12
Dependent Claim 17 words
The culture of claim 4, wherein cysts formed by said cells have an abnormally thickened basement membrane.
Claim 13
Dependent Claim 22 words
The 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 16 words
The culture of claim 4, wherein said cells have short sparse microvilli on the anti-luminal surface.
Claim 15
Dependent Claim 64 words
The 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 25 words
The 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 10 words
The culture of claim 14, wherein said material is agarose.
Claim 18
Independent Claim 142 words
A method of screening an agent in vitro in order to determine the effectiveness of the agent in treating a cystic disorder, comprising: forming a suspension of 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 form detecting the extent of cyst formation with the extent of cyst formation when said cells were cultured in a medium without said agent; and identifying said agent as effective in treating 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 142 words
A method of screening an agent in vitro in order to determine the effectiveness of the agent in treating a cystic disorder, comprising: forming a suspension of 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 form detecting the extent of cyst formation with the extent of cyst formation when said cells were cultured in a medium without said agent; and identifying said agent as effective in treating 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 25 words
The method of claim 17, wherein said agent is one of the following: taxol, cytochalasin-B, cytochalasin-D, phalloidin or a derivative of any of the foregoing.
Claim 23
Independent Claim 44 words
A method of treating a mammal having a cystic disease, comprising: administering to the mammal a pharmacologically effective anti-cystic amount of an agent that interferes with the normal functioning of a cytoskeletal component, said agent being administered in pharmacologically acceptable carrier, excipient or diluent.
Claim 24
Independent Claim 44 words
A method of treating a mammal having a cystic disease, comprising: administering to the mammal a pharmacologically effective anti-cystic amount of an agent that interferes with the normal functioning of a cytoskeletal component, said agent being administered in 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 ground consisting of: taxol, colchicine, nocodazole, vincristine, vinblastine, griseofulvin and 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 51 words
A method of treating a mammal having a cystic disease, comprising: administering to the mammal 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 51 words
A method of treating a mammal having a cystic disease, comprising: administering to the mammal 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 25, wherein said drug is taxol or a derivative thereof.
Claim 33
Dependent Claim 22 words
A pharmaceutical composition useful for inhibiting cyst formation in a mammal, comprising: a cyst-inhibiting amount of taxol; and dimethylsulfoxide as a carrier.
Claim 34
Dependent Claim 22 words
A pharmaceutical composition useful for inhibiting cyst formation in a mammal, comprising: a cyst-inhibiting amount of taxol; and dimethylsulfoxide as a carrier.
Claim 35
Dependent Claim 21 words
The pharmaceutical composition of claim 28, wherein the cyst-inhibiting amount of taxol is an amount ranging from 0.01 to 500 mg.
Claim 36
Dependent Claim 37 words
The pharmaceutical composition of claim 28, wherein the mammal has a body surface area, and wherein the cyst-inhibiting amount of taxol is an amount corresponding to from 10 to 250 mg/m 2 of said body surface area.

References Cited (Backward Citations)

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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 2002-03-15 2002-09-14 2003-03-16 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2006-03-15 2006-09-14 2007-03-16 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2010-03-15 2010-09-14 2011-03-16 $7700.00 Window Closed / Lapsed

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