Patent US2796533A successfully refreshed from Google Patents.
US4409331A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Preparation of substances with encapsulated cells
Assignee: Abbott Biotech Inc
•
Filing: 1982-04-28
•
Granted: 1983-10-11
•
Expires: 2002-04-28
Abstract
Abstract Disclosed is a system and process for producing substances produced in cells such as antibodies and biological response modifiers. Cells which produce the substance of interest are encapsulated within semipermeable membranes having an upper limit of permeability sufficient to allow traverse of ions, amino acids and other cell nutrients and then suspended in a culture medium. Serum components or other high molecular weight materials needed for ongoing viability and normal in vitro metabolism of certain types of cells may be included within the intracapsular volume and may be excluded from the extracapsular medium by limiting the permeability of the membranes. The substance of interest collects either in the intracapsular volume or the extracapsular medium, depending on the degree of permeability of the membranes and on the molecular weight of the substance.
Inventors
- 👤 Franklin Lim
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:34
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5036; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/5031; A61K9/5073; B; B01; B01J; B01J13/00; B01J13/02; B01J13/06; B01J13/14; C; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/575; C07K14/62; C12; C12M; C12M25/00; C12M25/16; C12N; C12N11/00; C12N11/02; C12N11/04; C12N5/00; C12N5/0012; A61K35/00; A61K35/12; A61K2035/126; A61K2035/128; A61K38/00; C12N2510/00; C12N2510/02; C12N2533/00; C12N2533/30; C12N2533/32; C12N2533/70; C12N2533/74; Y; Y10; Y10S; Y10S424/00; Y10S424/07; Y10S623/00; Y10S623/915
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
118 words
A process for producing a substance which is produced by living cells, said process comprising the steps of: A. encapsulating said cells within semipermeable membranes having a selected upper limit of permeability, said encapsulating being effected by forming said semipermeable membranes by reacting cationic groups on polymer chains having a molecular weight greater than about 3000 with anionic groups on a polysaccharide gel encapsulating said cells to crosslink surface layers of said polysaccharide gel to form said semipermeable membranes; B. suspending said encapsulated cells in an aqueous culture medium; C. allowing said cells to undergo metabolism in vitro and to produce said substance; and D. harvesting said substance either from said aqueous medium or from within said membranes.
Claim 2
Dependent Claim
118 words
A process for producing a substance which is produced by living cells, said process comprising the steps of: A. encapsulating said cells within semipermeable membranes having a selected upper limit of permeability, said encapsulating being effected by forming said semipermeable membranes by reacting cationic groups on polymer chains having a molecular weight greater than about 3000 with anionic groups on a polysaccharide gel encapsulating said cells to crosslink surface layers of said polysaccharide gel to form said semipermeable membranes; B. suspending said encapsulated cells in an aqueous culture medium; C. allowing said cells to undergo metabolism in vitro and to produce said substance; and D. harvesting said substance either from said aqueous medium or from within said membranes.
Claim 3
Dependent Claim
11 words
The process of claim 1 wherein said cells comprise hybridoma cells.
Claim 4
Dependent Claim
106 words
The process of claim 1 wherein said encapsulation step (A) is effected by the steps of: (1) suspending the cells in an aqueous medium physiologically compatible therewith and containing a water-soluble gum having plural anionic moieties; (2) forming the suspension into droplets containing the cells; (3) subjecting the droplets to a solution of multivalent, physiologically compatible cations to gel the droplets to form discrete, shape-retaining, water-insoluble temporary capsules as said polysaccharide gel encapsulating said cells; and (4) cross-linking surface layers of said temporary capsules to produce semipermeable membranes about said gelled droplets by subjecting them to said polymer containing cationic groups reactive with said anionic groups.
Claim 5
Dependent Claim
20 words
The process of claim 3 comprising the additional step of resolubilizing the gel within the membrane produced in step (4).
Claim 6
Dependent Claim
41 words
The process of claim 1 wherein said substance has a molecular weight below said selected upper permeability limit, said process comprising the step of allowing the substance to diffuse through said membranes into said aqueous medium and harvesting said substance therefrom.
Claim 7
Dependent Claim
33 words
The process of claim 1 or 5 wherein said cells are encapsulated together with a complete cell culture medium sufficient to maintain said cells and to allow biosynthesis of said substance in vitro.
Claim 8
Dependent Claim
35 words
The process of claim 1 or 5 wherein the aqueous medium used in step (B) is a complete cell culture medium sufficient to maintain said cells and to allow biosynthesis of said substance in vitro.
Claim 9
Dependent Claim
51 words
The process of claim 6 wherein a component having a molecular weight in excess of the upper permeability limit of said membranes is needed by said cells in order to allow in vitro biosynthesis of said substance, said process comprising the additional step of encapsulating said component together with said cells.
Claim 10
Dependent Claim
13 words
The process of claim 1 or 5 wherein said cells are mammalian cells.
Claim 11
Dependent Claim
21 words
The process of claim 1 or 5 comprising the additional step of allowing said cells to undergo mitosis within said capsule.
Claim 12
Dependent Claim
17 words
The process of claim 1 or 5 wherein said cells are cells which have been genetically modified.
Claim 13
Dependent Claim
26 words
The process of claim 1 or 5 wherein during said encapsulation step (A), spheroidal microcapsules having a diameter from about 0.4 to 1.0 mm are produced.
Claim 14
Dependent Claim
34 words
The process of claim 1 or 5 wherein the substance harvested in step (E) is selected from the group consisting of insulin, glucagon, prolactin, somatostatin, thyroxin, steroid hormones, pituitary hormones, interferons, FSH, and PTH.
Claim 15
Dependent Claim
26 words
The process of claim 1 or 5 wherein the substance harvested in step (E) is selected from the group consisting of hormones, interferons, lymphokines, and antibodies.
Claim 16
Dependent Claim
67 words
The process of claim 1 or 5 wherein the cells encapsulated in step (A) require contact with a component having a molecular weight in excess of the upper permeability limit of said membranes in order to maintain production of said substance, said component being encapsulated together with said cells in step (A) and the aqueous culture medium used in step (B) being substantially free of said component.
Claim 17
Dependent Claim
18 words
The process of claim 1 wherein said selected upper limit of permeability is below about 1.5×10 5 daltons.
Claim 18
Dependent Claim
38 words
The process of claim 1 wherein said cells comprise hybridoma cells, said substance comprises monoclonal antibodies having a molecular weight in excess of said selected upper limit of permeability, and said antibodies are harvested from within said membranes.
Claim 19
Independent Claim
151 words
A system for producing a substance which is produced by living cells comprising viable cells encapsulated within semipermeable membranes and suspended in an aqueous culture medium for said cells, the semipermeable membranes of said encapsulated viable cells having an upper limit of permeability sufficient to allow traverse of nutrients required by said cells, said semipermeable membranes comprising a polysaccharide gel having plural anionic groups cross-linked with a polymer having a molecular weight greater than about 3000 and having plural cationic groups, said semipermeable membranes encapsulating suspended viable, healthy, physiologically active cells disposed in a medium which includes all components (A) needed to maintain viability of said cells and which components are of a size in excess of the upper permeability limit of said membranes, said aqueous culture medium comprising all components (B) needed to maintain viability of said cells having a molecular weight below the upper permeability limit of said membranes.
Claim 20
Independent Claim
151 words
A system for producing a substance which is produced by living cells comprising viable cells encapsulated within semipermeable membranes and suspended in an aqueous culture medium for said cells, the semipermeable membranes of said encapsulated viable cells having an upper limit of permeability sufficient to allow traverse of nutrients required by said cells, said semipermeable membranes comprising a polysaccharide gel having plural anionic groups cross-linked with a polymer having a molecular weight greater than about 3000 and having plural cationic groups, said semipermeable membranes encapsulating suspended viable, healthy, physiologically active cells disposed in a medium which includes all components (A) needed to maintain viability of said cells and which components are of a size in excess of the upper permeability limit of said membranes, said aqueous culture medium comprising all components (B) needed to maintain viability of said cells having a molecular weight below the upper permeability limit of said membranes.
Claim 21
Dependent Claim
12 words
The system of claim 18 wherein said components (A) comprise serum components.
Claim 22
Dependent Claim
11 words
The system of claim 18 wherein said cells comprise mammalian cells.
Claim 23
Dependent Claim
10 words
The system of claim 18 wherein said cells comprise microorganisms.
Claim 24
Dependent Claim
12 words
The system of claim 18 wherein said cells comprise genetically modified cells.
Claim 25
Dependent Claim
11 words
The system of claim 18 wherein said cells comprise hybridoma cells.
Claim 26
Dependent Claim
28 words
The system of claim 18 wherein said cells comprise cells capable of producing in vitro a substance selected from the group consisting of hormones, interferons, lymphokines, and antibodies.
Claim 27
Dependent Claim
36 words
The system of claim 18 wherein said cells comprise cells capable of producing in vitro a substance selected from the group consisting of insulin, glycogen, growth hormones, pituitary hormones, steroid hormones, prolactin, somatostatin, PTH, and FSH.
References Cited (Backward Citations)
FR1600988A
Cited
US3522346A
Cited
US3827565A
Cited
US3733205A
Cited
US3725113A
Cited
US3730841A
Cited
US3860490A
Cited
GB1422854A
Cited
GB1525665A
Cited
GB1506112A
Cited
GB1545545A
Cited
US4138292A
Cited
GB1520217A
Cited
GB1553190A
Cited
GB1556584A
Cited
DE2835875C2
Cited
GB2046271B
Cited
US4251387A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-10-10 | 1987-04-11 | 1987-10-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-10-10 | 1991-04-11 | 1991-10-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-10-10 | 1995-04-11 | 1995-10-11 | $7700.00 | Window Closed / Lapsed |