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US5270192A Expired / Lapsed US ⏱️ 0.0 years remaining

Biological artificial liver

Assignee: Monsanto Co
•
Filing: 1991-02-07
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Granted: 1993-12-14
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Expires: 2011-02-07
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Abstract

Abstract Disclosed is a hepatocyte bioreactor or bioartificial liver which comprises a containment vessel having a perfusion inlet and a perfusion outlet; a matrix within the containment vessel so as to entrap hepatocyte aggregates within the containment vessel while allowing perfusion of the matrix. The invention is useful as an artificial liver.

Inventors

  • 👤 Albert Pak-Hung Li
  • 👤 Timothy D. Whitehead
  • 👤 Dale J. Beck
  • 👤 George E. Barker

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 21:55
CPC Classifications
C; C12; C12M; C12M29/00; C12M29/10; A; A61; A61M; A61M1/00; A61M1/34; A61M1/3472; A61M1/3486; A61M1/3489; A61M1/36; A61M1/3601; A61M1/3603; C12M25/00; C12M25/16; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/067; C12N5/0671; A61M2202/00; A61M2202/04; A61M2202/0413; A61M2202/0415

Claims Analysis

Total Claims: 28
Claim 1
Independent Claim 83 words
A hepatocyte bioreactor, which comprises: a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; and a plurality of hepatocyte aggregates entrapped within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact.
Claim 2
Dependent Claim 83 words
A hepatocyte bioreactor, which comprises: a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; and a plurality of hepatocyte aggregates entrapped within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact.
Claim 3
Dependent Claim 12 words
The hepatocyte bioreaction of claim 1 wherein said hepatocyte aggregates are spheroids.
Claim 4
Dependent Claim 12 words
The hepatocyte bioreactor of claim 1 wherein said matrix is glass beads.
Claim 5
Dependent Claim 16 words
The hepatocyte bioreactor of claim 1 wherein said hepatocyte aggregates are essentially free of connective tissue.
Claim 6
Dependent Claim 24 words
The hepatocyte bioreactor of claim 1 wherein said matrix has a hepatocytes density of at least about 3.00×10 6 cells per ml of matrix.
Claim 7
Independent Claim 91 words
A method for making a bioreactor, which comprises the steps of: providing a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; providing a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; and entrapping a plurality of hepatocyte aggregates within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact.
Claim 8
Independent Claim 91 words
A method for making a bioreactor, which comprises the steps of: providing a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; providing a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; and entrapping a plurality of hepatocyte aggregates within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact.
Claim 9
Dependent Claim 17 words
The method for making a bioreactor as recited in claim 6 wherein said hepatocyte aggregates are spheroids.
Claim 10
Dependent Claim 16 words
The method for making a hepatocyte bioreactor of claim 6 wherein said matrix is glass beads.
Claim 11
Dependent Claim 20 words
The method for making a hepatocyte bioreactor of claim 6 wherein said hepatocyte aggregates are essentially free of connective tissue.
Claim 12
Dependent Claim 28 words
The method for making a heptocyte bioreactor of claim 6 wherein said matrix has a hepatocytes density of at least about 3.00×10 6 cells per ml of matrix.
Claim 13
Dependent Claim 24 words
The method for making a hepatocyte bioreactor of claim 6 wherein said hepatocyte aggregates are formed by perfusion of said hepatocytes through said matrix.
Claim 14
Independent Claim 107 words
A method for using a hepatocyte bioreactor, which comprises the steps of: providing a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; providing a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; entrapping a plurality of hepatocyte aggregates within said containment vessel wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact; and causing medium to be perfused through said inlet, said containment vessel and said outlet.
Claim 15
Independent Claim 107 words
A method for using a hepatocyte bioreactor, which comprises the steps of: providing a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; providing a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress, said matrix being in fluid communication with said inlet and said outlet; entrapping a plurality of hepatocyte aggregates within said containment vessel wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact; and causing medium to be perfused through said inlet, said containment vessel and said outlet.
Claim 16
Dependent Claim 20 words
The method of using a hepatocyte bioreactor as recited in claim 12 wherein said plurality of hepatocyte aggregates are spheroids.
Claim 17
Dependent Claim 24 words
The method of using a hepatocyte bioreactor of claim 12 wherein said hepatocyte aggregates are formed by perfusion of said hepatocytes through said matrix.
Claim 18
Dependent Claim 17 words
The method of using a hepatocyte bioreactor as recited in claim 12 wherein said medium contains metabolites.
Claim 19
Dependent Claim 12 words
The hepatocyte bioreactor of claim 12 wherein said matrix is glass beads.
Claim 20
Dependent Claim 22 words
The method of using a hepatocyte bioreactor as recited in claim 12 wherein said hepatocyte aggregates are essentially free of connective tissue.
Claim 21
Dependent Claim 30 words
The method of using a hepatocyte bioreactor as recited in claim 12 wherein said matrix has a hepatocytes density of at least about 3.00×10 6 cells per ml of matrix.
Claim 22
Dependent Claim 170 words
A hepatocyte bioreactor liver assist system for treating a mammal in need of liver assistance, which comprises; means for extracting blood from the mammal in need of liver assistance; means for separating the blood of the mammal which is to be treated into cellular and non-cellular components; a hepatocyte bioreactor comprising; a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress; said matrix being in fluid communication with said inlet and aid outlet; and a plurality of hepatocyte aggregates entrapped within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact; means causing said noncellular blood components of the mammal which is to be treated to be perfused through said inlet, said matrix and said outlet; and means to return said treated noncellular blood components and cellular blood components to said mammal.
Claim 23
Dependent Claim 170 words
A hepatocyte bioreactor liver assist system for treating a mammal in need of liver assistance, which comprises; means for extracting blood from the mammal in need of liver assistance; means for separating the blood of the mammal which is to be treated into cellular and non-cellular components; a hepatocyte bioreactor comprising; a containment vessel having an inlet which allows hepatocytes or aggregates thereof to ingress into said containment vessel and an outlet which allows hepatocytes or aggregates thereof to egress; a matrix within said containment vessel into which said hepatocytes or aggregates thereof can ingress; said matrix being in fluid communication with said inlet and aid outlet; and a plurality of hepatocyte aggregates entrapped within said matrix wherein said hepatocyte aggregates are interconnected within said matrix by cell-cell contact; means causing said noncellular blood components of the mammal which is to be treated to be perfused through said inlet, said matrix and said outlet; and means to return said treated noncellular blood components and cellular blood components to said mammal.
Claim 24
Dependent Claim 30 words
The hepatocyte bioreactor liver assist system of claim 19 further comprising a means for maintaining a flow rate of medium through the hepatocyte bioreactor which is independent of the mammal.
Claim 25
Dependent Claim 15 words
The hepatocyte bioreactor liver assist system of claim 19 wherein said hepatocyte aggregates are spheroids.
Claim 26
Dependent Claim 15 words
The hepatocyte bioreactor liver assist system of claim 19 wherein said matrix is glass beads.
Claim 27
Dependent Claim 19 words
The hepatocyte bioreactor liver assist system of claim 19 wherein said hepatocyte aggregates are essentially free of connective tissue.
Claim 28
Dependent Claim 27 words
The hepatocyte bioreactor liver assist system of claim 19 wherein said matrix has a hepatocytes density of at least about 3.00×10 6 cells per ml of matrix.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1996-12-13 1997-06-14 1997-12-14 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2000-12-13 2001-06-14 2001-12-14 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2004-12-13 2005-06-14 2005-12-14 $7700.00 Window Closed / Lapsed

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