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US5182111A
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In vivo delivery of active factors by co-cultured cell implants
Assignee: BROWN UNIVERSITY RESEARCH FOUNDATION A Corp OF RI
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Filing: 1991-06-28
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Granted: 1993-01-26
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Expires: 2011-06-28
Abstract
Abstract Methods and devices are disclosed for the delivery of an active factor from an implanted co-culture of an active factor-secreting cell obtained from a first source and an augmentary substance-secreting cell obtained from a second source different from the first source, to a target region in a subject. The co-culture is maintained within a biocompatible, semipermeable membrane in which the augmentary substance secreted by the augmentary substance-producing cells stimulates the active factor-producing cells to secrete active factor. The semipermeable membrane permits the diffusion of the active factor therethrough while excluding detrimental agents present in the extenral environment from gaining access to the co-culture.
Inventors
- 👤 Patrick Aebischer
- 👤 Shelley R. Winn
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 23:20
CPC Classifications
A; A61; A61F; A61F2/00; A61F2/02; A61F2/022; A61K; A61K35/00; A61K35/12; A61K35/22; A61K35/30; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/185; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K9/0085; A61K9/0087; A61K9/0092; A61M; A61M31/00; A61M31/002; B; B01; B01J; B01J13/00; B01J13/02; C; C12; C12N; C12N11/00; C12N11/02; C12N11/04; C12N5/00; C12N5/0012; C12N5/06; C12N5/0602; C12N5/0613; C12N5/0614; C12N5/0618; C12N5/0619; C12N5/0676; C12P; C12P1/00; A61M2210/00; A61M2210/06; A61M2210/0687; A61M2210/0693; C12N2533/00; C12N2533/30; C12N2533/70; C12N2533/74
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
143 words
A cell culture device for implantation within a subject for the delivery of an active factor to said subject, said device comprising: a semipermeable membrane permitting the diffusion of an active factor therethrough, while excluding agents present at the site of implantation which are detrimental to cells; at least one specific active factor-secreting cell disposed within the membrane, said active factor-secreting cell being isolated from a first tissue or cell line; and at least one specific augmentary substance-producing cell disposed within said membrane, said augmentary substance being a molecule which induces the active factor-producing cell to produce active factor, said augmentary substance-secreting cell being isolated from a second tissue or cell line different from said first tissue or cell line, and secreting an augmentary substance that is different from said active factor and that stimulates aid active factor-producing cell to secrete active factor.
Claim 2
Dependent Claim
143 words
A cell culture device for implantation within a subject for the delivery of an active factor to said subject, said device comprising: a semipermeable membrane permitting the diffusion of an active factor therethrough, while excluding agents present at the site of implantation which are detrimental to cells; at least one specific active factor-secreting cell disposed within the membrane, said active factor-secreting cell being isolated from a first tissue or cell line; and at least one specific augmentary substance-producing cell disposed within said membrane, said augmentary substance being a molecule which induces the active factor-producing cell to produce active factor, said augmentary substance-secreting cell being isolated from a second tissue or cell line different from said first tissue or cell line, and secreting an augmentary substance that is different from said active factor and that stimulates aid active factor-producing cell to secrete active factor.
Claim 3
Dependent Claim
23 words
The device of claim 1 wherein said semipermeable membrane is permeable to solutes having a molecular weight of up to about 150,000 daltons.
Claim 4
Dependent Claim
41 words
The device of claim 1 wherein said semipermeable membrane comprises a material selected from the group consisting of polyvinylchloride, polyvinylidene fluoride, polyurethane isocyanates, polyalginate, cellulose acetate, cellulose nitrate, polysulfone, polystyrene, polyurethane, polyvinyl alcohols, polyacrylonitrile, polyamides, polymethylmethacrylate, polyethylene oxide, and mixtures thereof.
Claim 5
Dependent Claim
17 words
The device of claim 1 wherein said active factor-producing cell or said augmentary substance-producing cell is allospecific.
Claim 6
Dependent Claim
17 words
The device of claim 1 wherein said active factor-producing cell or said augmentary substance-producing cell is xenospecific.
Claim 7
Dependent Claim
33 words
The device of claim 1 wherein said active factor-producing cell or said augmentary substance-producing cell or said augmentary substance-producing cell has been genetically engineered to produce said active factor or said augmentary substance.
Claim 8
Dependent Claim
33 words
The device of claim 1 wherein said active factor-producing cell is a cell which produces an active factor selected from the group consisting of a neurotransmitter, neuromodulator, growth factor, trophic factor, and hormone.
Claim 9
Dependent Claim
48 words
The device of claim 1 wherein said active factor is dopamine, and said active factor-secreting cell is isolated from a tissue or culture selected from the group consisting of adrenal medulla tissue, chromaffin cells, ventral mesencephalic embryonic tissue, neuroblastoid tissue, and a cell genetically engineered to produce dopamine.
Claim 10
Dependent Claim
46 words
The device of claim 1 wherein said augmentary substance-producing cell produced an augmentary substance selected from the group consisting of nerve growth factor (NGF), epidermal growth factor (EGF), brain derived neutrophic factor (BDNF), neurotrophin-3 (NT-3), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and combinations thereof.
Claim 11
Dependent Claim
31 words
The device of claim 1 further comprising a retrievable, nonresorbable, and biocompatible guide wire attached to said semipermeable membrane, so as to enable the removal of said device from said subject.
Claim 12
Dependent Claim
23 words
The device of claim 1 wherein said semipermeable membrane is tubular, having at least one end with a removable and reattachable cap element.
Claim 13
Dependent Claim
50 words
The device of claim 1 wherein said active factor-secreting cell and said augmentary substance-producing cell are disposed within said semipermeable membrane in a removable fashion, said membrane being tubular, having at least one end with a removable and reattachable cap element, so as to enable extraction of said cells therein.
Claim 14
Dependent Claim
40 words
The device of claim 1 wherein said active factor is a neurotransmitter selected from the group consisting of dopamine, norepinephrine, epinephrine, acetylcholine, enkephalins, dynorphin, substance P, gamma aminobutyric acid, glutamic acid, agonists, precursors, analogs, and fragments thereof having neurotransmitter activity.
Claim 15
Dependent Claim
11 words
The device of claim 13 wherein said neurotransmitter precursor is L-dopa.
Claim 16
Dependent Claim
11 words
The device of claim 13 wherein said neurotransmitter analog is bromocriptine.
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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) | 1996-01-26 | 1996-07-27 | 1997-01-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-01-26 | 2000-07-27 | 2001-01-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-01-26 | 2004-07-27 | 2005-01-26 | $7700.00 | Window Closed / Lapsed |