US5800828A
Expired / Lapsed
US
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Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products
Assignee: Brown University Research Foundation Inc
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Filing: 1994-01-10
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Granted: 1998-09-01
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Expires: 2014-01-10
Abstract
Abstract Immunoisolatory vehicles having a core and a surrounding jacket are disclosed, the core having a volume in excess of 1 mu l and at least about 104 living cells capable of secreting a biologically active product or of providing a biological function to a patient, the cells dispersed in a biocompatible matrix formed of a hydrogel or an extracellular matrix component, and the external jacket being permselective, biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biological product or function.
Inventors
- 👤 Keith E. Dionne
- 👤 Dwaine F. Emerich
- 👤 Diane Hoffman
- 👤 Paul R. Sanberg
- 👤 Lisa Christenson
- 👤 Orion D. Hegre
- 👤 David W. Scharp
- 👤 Paul E. Lacy
- 👤 Patrick Aebischer
- 👤 Alfred V. Vasconcellos
- 👤 Michael J. Lysaght
- 👤 Frank T. Gentile
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 08:09
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0087; A61K9/0092; A61K35/00; A61K35/12; A61K35/30; A61K35/37; A61K35/39; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/185; A61K48/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K9/48; A61K9/4816; A61P; A61P15/00; A61P25/00; A61P25/14; A61P25/28; A61P3/00; A61P3/08; A61P3/10; A61P31/00; A61P31/12; A61P31/14; A61P31/18; A61P37/00; A61P37/02; A61P37/06; A61P43/00; A61P5/00; A61P5/24; C; C12; C12N; C12N5/00; C12N5/0012; C12N5/0062; C12N5/06; C12N5/0602; C12N5/0613; C12N5/0614; C12N5/0652; C12N5/0656; C12N5/0676; C12N5/0677; A61K2035/126; A61K2035/128; C12N2510/00; C12N2510/02
Claims Analysis
Total Claims: 46
Claim 1
Independent Claim
142 words
An implantable immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 living cells dispersed in a biocompatible matrix formed of a hydrogel, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket being greater than 5 microns thick and formed from a hydrogel that does not ionically bond to a polymer of opposite charge on the core during formation of the jacket, said jacket being free of said cells projecting, externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.
Claim 2
Dependent Claim
142 words
An implantable immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 living cells dispersed in a biocompatible matrix formed of a hydrogel, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket being greater than 5 microns thick and formed from a hydrogel that does not ionically bond to a polymer of opposite charge on the core during formation of the jacket, said jacket being free of said cells projecting, externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.
Claim 3
Dependent Claim
16 words
The vehicle of claim 1 wherein said core and jacket are formed of the same hydrogel.
Claim 4
Dependent Claim
15 words
The vehicle of claim 2 wherein said hydrogel comprises alginate cross-linked with a multivalent ion.
Claim 5
Dependent Claim
15 words
The vehicle of claim 1 wherein said vehicle has a tether for retrieval after implantation.
Claim 6
Dependent Claim
32 words
The vehicle of claim 1 wherein said cells are selected from the group consisting of insulin-producing cells, adrenal chromaffin cells, antibody-secreting cells, fibroblasts, astrocytes, Beta cell lines, and Chinese hamster ovary cells.
Claim 7
Dependent Claim
14 words
The vehicle of claim 1 wherein the cells are derived from a cell bank.
Claim 8
Dependent Claim
24 words
The vehicle of claim 1 wherein all of the cells are disposed at a distance no greater than about 800 μm from the jacket.
Claim 9
Dependent Claim
101 words
An immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 living cells dispersed in a biocompatible hydrogel matrix, said cells being callable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket comprising a biocompatible thermoplastic, said jacket being immunoisolatory and having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biological product or function.
Claim 10
Dependent Claim
101 words
An immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 living cells dispersed in a biocompatible hydrogel matrix, said cells being callable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket comprising a biocompatible thermoplastic, said jacket being immunoisolatory and having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biological product or function.
Claim 11
Dependent Claim
15 words
The vehicle of claim 8 wherein the core biocompatible matrix is formed of an alginate.
Claim 12
Dependent Claim
32 words
The vehicle of claim 8 wherein said cells are selected from the group consisting of insulin-producing cells, adrenal chromaffin cells, antibody-secreting cells, fibroblasts, astrocytes, Beta cell lines, and Chinese hamster ovary cells.
Claim 13
Dependent Claim
24 words
The vehicle of claim 8 wherein all of the cells are disposed at a distance no greater than about 800 μm from the jacket.
Claim 14
Dependent Claim
13 words
The vehicle of claim 8 wherein said external jacket has a non-spherical shape.
Claim 15
Dependent Claim
112 words
An implantable immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 isolated cells dispersed in biocompatible extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket comprising a thermoplastic or a hydrogel comprising a biocompatible layer greater than 5 microns thick and, said jacket having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.
Claim 16
Dependent Claim
112 words
An implantable immunoisolatory vehicle for providing a biologically active product or function, the vehicle comprising: (a) a core comprising a volume in excess of 1 μl and at least about 10 4 isolated cells dispersed in biocompatible extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function; and (b) an external permselective jacket surrounding said core, said jacket comprising a thermoplastic or a hydrogel comprising a biocompatible layer greater than 5 microns thick and, said jacket having a molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.
Claim 17
Dependent Claim
15 words
The vehicle of claim 13 wherein the core biocompatible matrix is formed of a hydrogel.
Claim 18
Dependent Claim
15 words
The vehicle of claim 13 wherein the molecular weight cutoff is above about 100 kD.
Claim 19
Dependent Claim
22 words
The vehicle of claim 13 wherein said cells are aggregated into a diffusional aggregate form adapted for increased packing per unit volume.
Claim 20
Dependent Claim
25 words
The vehicle of claim 13 wherein said cells are selected from the group consisting of pancreatic islets, adrenal chromaffin cells and insulin secreting cell lines.
Claim 21
Dependent Claim
30 words
The vehicle of claim 1, 8, or 13 said cells are capable of secreting a biologically active product selected from the group consisting of growth factor, trophic factor, or both.
Claim 22
Dependent Claim
12 words
The vehicle of claim 18 wherein said cells secrete nerve growth factor.
Claim 23
Dependent Claim
17 words
The vehicle of claim 1, 8, or 13 wherein said cells comprise cells from a cell bank.
Claim 24
Dependent Claim
15 words
The vehicle of claim 1, 8, or 13 wherein said vehicle is a flat sheet.
Claim 25
Dependent Claim
19 words
The vehicle of claim 1, 8, or 13 wherein said external jacket is in substantially flat or tubular form.
Claim 26
Dependent Claim
18 words
The vehicle of claim 1, 12, or 21 wherein said cells are derived from a pathogen free animal.
Claim 27
Dependent Claim
22 words
The vehicle of claim 1, 8, or 13 wherein the jacket has a molecular weight cutoff in excess of about 100 kD.
Claim 28
Dependent Claim
17 words
The vehicle of claim 1, 8, or 13 wherein said cells are allogeneic or syngeneic upon implantation.
Claim 29
Dependent Claim
13 words
The vehicle of claim 1, 8 or 13 wherein said cells secrete antibodies.
Claim 30
Dependent Claim
19 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is an analgesic or pain-reducing substance.
Claim 31
Dependent Claim
37 words
The vehicle of claim 1 or 8 wherein the core is selected from the group consisting of alginate, collagen, laminin-containing hydrogels, agarose, cellulose, methylcellulose, block copolymer of ethylene-vinylalcohol, sodium polystyrene sulfonate, vinyl-methyl-tribenzyl ammonium chloride, phosphazene, and polyvinylalcohol.
Claim 32
Dependent Claim
24 words
The vehicle of claim 13 wherein the core is selected from the group consisting of collagen, laminin, glycoaminoglycans, proteoglycans, fibronectin, elastin, and mixtures thereof.
Claim 33
Dependent Claim
25 words
The vehicle of claim 8 or 13 wherein the jacket is selected from the group consisting of polyacrylonitrile-polyvinylchloride, polyacrylonitrile, polymethylmethacrylate, polyvinyldifluoride, polyolefins, polysulfones and celluloses.
Claim 34
Dependent Claim
17 words
The vehicle of claims 8 or 13 wherein the jacket further comprises a hydrophilic or hydrophobic additive.
Claim 35
Dependent Claim
27 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is selected from the group consisting of enkephalins, catecholamines, opioid peptides, and mixtures thereof.
Claim 36
Dependent Claim
31 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is selected from the group consisting of antibodies, enzymes, trophic factors, growth factors, hormones and biological response modifiers.
Claim 37
Dependent Claim
15 words
The vehicle of claim 33 wherein the biologically active product is a cytokine or lymphokine.
Claim 38
Dependent Claim
16 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is a neurotransmitter.
Claim 39
Dependent Claim
26 words
The vehicle of claim 35 wherein the neurotransmitter selected from the group consisting of dopamine, L-dopa, gamma aminobutyric acid, serotonin, acetylcholine, noradrenaline, epinephrine and glutamic acid.
Claim 40
Dependent Claim
15 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is dopamine.
Claim 41
Dependent Claim
48 words
The vehicle of claim 1, 8 or 13 wherein the biologically active product is selected from the group consisting of nerve growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, brain-derived neurotrophic factor, glial-derived neurotrophic factor, neurotrophin-3, platelet derived growth factor, epidermal growth factor, neurotensin and Substance P.
Claim 42
Dependent Claim
25 words
The vehicle of claims 1, 8, or 13 wherein the biologically active product is insulin, parathyroid hormone, interleukin 3, erythropoietin, albumin, transferrin or Factor VIII.
Claim 43
Dependent Claim
19 words
The vehicle of claims 1, 8, or 13 wherein accessory cells are coisolated with the cells in the core.
Claim 44
Dependent Claim
15 words
The vehicle of claim 1, 8 or 13, wherein the cells are adrenal chromaffin cells.
Claim 45
Dependent Claim
20 words
The vehicle of any one of claims 1, 8 or 13, wherein the molecular weight cutoff is between 50-2000 kD.
Claim 46
Dependent Claim
19 words
The vehicle of claim 1, 8 or 13 wherein said jacket is between about 10 and 200 microns thick.
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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) | 2001-08-31 | 2002-03-02 | 2002-09-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-08-31 | 2006-03-02 | 2006-09-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-08-31 | 2010-03-02 | 2010-09-01 | $7700.00 | Window Closed / Lapsed |