US5399665A
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Biodegradable polymers for cell transplantation
Assignee: Boston Children's Hospital
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Filing: 1992-11-05
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Granted: 1995-03-21
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Expires: 2012-11-05
Abstract
Abstract Polymers more suitable for use in organ transplantation are formed by coupling biologically active moieties to the free amino groups of polymers formed by incorporation of α amino acids into polymers formed of alpha hydroxy acids such as lactic acids. In the preferred embodiment, the peptides are coupled to the free amino groups.
Inventors
- 👤 Denise Barrera
- 👤 Robert S. Langer
- 👤 Peter T. Lansbury, Jr.
- 👤 Joseph P. Vacanti
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 14:08
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/54; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/593; A61K47/62; A61K47/64; A61K47/645; A61L27/14; A61L27/18; A61L27/36; A61L27/38; A61L27/3804; C; C07; C07K; C07K14/00; C07K14/001; C08; C08G; C08G63/00; C08G63/68; C08G63/685; C08G63/6852; C12; C12N; C12N5/00; C12N5/0068; A61L2300/00; A61L2300/20; A61L2300/25; A61L2300/60; A61L2300/602; A61L2300/604; A61L2300/64; C12N2533/00; C12N2533/30; C12N2533/40; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/812; Y10S530/815
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
89 words
a biodegradable, biocompatible polymer formed by polymerizing a morpholinedione, wherein the morpholinedione is a dimer of (i) an α-hydroxy acid of the formula R, R'--COH--CO--OH wherein R and R' are independently H or a linear or branched alkyl; and (ii) an α-amino acid of the formula R", R"'--CNH 2 --CO--OH wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole.
Claim 2
Dependent Claim
89 words
a biodegradable, biocompatible polymer formed by polymerizing a morpholinedione, wherein the morpholinedione is a dimer of (i) an α-hydroxy acid of the formula R, R'--COH--CO--OH wherein R and R' are independently H or a linear or branched alkyl; and (ii) an α-amino acid of the formula R", R"'--CNH 2 --CO--OH wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole.
Claim 3
Dependent Claim
25 words
The polymer of claim 1 wherein the α-hydroxy acids are selected from the group consisting of lactic acid, glycolic acid, hydroxybutyric acid, and valeric acid.
Claim 4
Dependent Claim
12 words
The polymer of claim 1 wherein the amino acid is N-e-protected lysine.
Claim 5
Dependent Claim
28 words
The polymer of claim 1 wherein biologically active moieties are coupled to free carboxylic acids, amino groups, sulfide groups, guanidino, imidazole or hydroxyl groups on the amino acids.
Claim 6
Dependent Claim
23 words
The polymer of claim 4 wherein the biologically active moieties are selected from the group consisting of GRGDY, YIGSR and other RGD peptides.
Claim 7
Dependent Claim
97 words
A process for making a biocompatible, biodegradable polymer comprising: (A) forming a morpholinedione by chemically coupling (i) an α-amino acid of the formula R", R"'--CNH 2 --CO--OH, wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole; and (ii) an α-hydroxy acid of the formula R,R'--COH--CO--OH, wherein R and R' are independently H or a linear or branched alkyl; and (B) polymerizing the morpholinedione with a Lewis acid.
Claim 8
Dependent Claim
97 words
A process for making a biocompatible, biodegradable polymer comprising: (A) forming a morpholinedione by chemically coupling (i) an α-amino acid of the formula R", R"'--CNH 2 --CO--OH, wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole; and (ii) an α-hydroxy acid of the formula R,R'--COH--CO--OH, wherein R and R' are independently H or a linear or branched alkyl; and (B) polymerizing the morpholinedione with a Lewis acid.
Claim 9
Dependent Claim
25 words
The process of claim 6 wherein the α-hydroxy acids are selected from the group consisting of lactic acid, glycolic acid, hydroxybutyric acid, and valeric acid.
Claim 10
Dependent Claim
12 words
The process of claim 1 wherein the amino acid is N-e-protected lysine.
Claim 11
Dependent Claim
28 words
The process of claim 1 further comprising coupling biologically active moieties to free carboxylic acids, amino groups, sulfide groups, guanidino, imidazole or hydroxyl groups on the amino acids.
Claim 12
Dependent Claim
23 words
The process of claim 9 wherein the biologically active moleties are selected from the group consisting of GRGDY, YIGSR and other RGD peptides.
Claim 13
Dependent Claim
17 words
The process of claim 9 further comprising forming the polymer into a matrix for seeding with cells.
Claim 14
Dependent Claim
12 words
The process of claim 11 further comprising seeding the matrix with cells.
Claim 15
Independent Claim
108 words
A method for implanting cells into an animal comprising (A) forming a matrix of a biocompatible, biodegradable polymer formed by polymerizing a morpholinedione wherein the morpholinedione is a dimer of (i) an α-hydroxy acid of the formula R,R'--COH--CO--OH, wherein R and R' are independently H or a linear or branched alkyl; and (ii) an α-amino acid of the formula R",R"'--CNH 2 --CO--OH, wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole, and (B) seeding the matrix with cells.
Claim 16
Independent Claim
108 words
A method for implanting cells into an animal comprising (A) forming a matrix of a biocompatible, biodegradable polymer formed by polymerizing a morpholinedione wherein the morpholinedione is a dimer of (i) an α-hydroxy acid of the formula R,R'--COH--CO--OH, wherein R and R' are independently H or a linear or branched alkyl; and (ii) an α-amino acid of the formula R",R"'--CNH 2 --CO--OH, wherein R" and R"' are independently H or a linear or branched alkyl; a protected primary or secondary amino group; a protected ester; a protected hydroxyl; a protected sulfide; a protected amide; a protected guanidino; or a protected imidazole, and (B) seeding the matrix with cells.
Claim 17
Dependent Claim
43 words
The method of claim 13 further comprising deprotecting protected amino, ester, hydroxyl, sulfide, amide, guanidino or imidazole groups on the polymer, and coupling biologically active moieties to free carboxylic acid, amino groups, sulfide groups, guanidino, imidazole or hydroxyl groups on the amino acids.
Claim 18
Dependent Claim
21 words
The process of claim 13 wherein the α-hydroxy acids are selected from the group consisting of lactic acid and glycolic acid.
Claim 19
Dependent Claim
11 words
The process of claim 13 wherein the amino acid is lysine.
Claim 20
Dependent Claim
23 words
The process of claim 13 wherein the biologically active moieties are selected from the group consisting of GRGDY, YIGSR and other RGD peptides.
Claim 21
Dependent Claim
31 words
The process of claim 13 wherein the cells are selected from the group consisting of hepatocytes, pancreatic cells, intestinal cells, uroendothelial cells, skin cells, muscle cells, nerve cells, and bone cells.
Claim 22
Dependent Claim
13 words
The process of claim 13 further comprising implanting the matrix seeded with cells.
Claim 23
Dependent Claim
17 words
The biocompatible biodegradable polymer of claim 1 further comprising biologically active moieties chemically coupled to the polymer.
Claim 24
Dependent Claim
13 words
The polymer of claim 20 wherein the biologically active moieties are attachment peptides.
Claim 25
Dependent Claim
15 words
The polymer of claim 1 wherein the protecting groups on the α-amino acid are deprotected.
Claim 26
Dependent Claim
15 words
The method of claim 6 further comprising deprotecting the protecting groups on the α-amino acid.
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