US2004101932A1PendingUtilityA1
Compositions and methods for targeted enzymatic release of cell regulatory compounds
Assignee: MARKER GENE TECHNOLOGIES INCPriority: Jun 30, 1999Filed: Nov 7, 2003Published: May 27, 2004
Est. expiryJun 30, 2019(expired)· nominal 20-yr term from priority
C07H 15/244C07H 15/252C07H 19/06C07H 15/26A61K 48/00C07J 17/005A61K 47/549A61K 47/54C07H 15/203C07H 15/04C12N 15/87C07H 15/24
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Claims
Abstract
Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of targeted delivery of a bioactive compound comprising:
(a) introducing into targeted cells a gene encoding an enzyme; (b) administering an inactive conjugate of the bioactive compound;
wherein the enzyme releases the bioactive compound from conjugation.
2 . The method of claim 1 wherein the enzyme does not naturally occur in the targeted cells in an amount effective to release the bioactive compound from conjugation
3 . The method of claim 1 wherein the enzyme is an hydrolitic enzyme.
4 . The method of claim 1 wherein the enzyme is a marker gene.
5 . The method of claim 1 wherein the enzyme is an active component of lacZ β-galactosidase from the bacteria Escherichia coli.
6 . The method of claim 1 wherein the enzyme is an active component of GUS β-glucuronidase from the bacteria Escherichia coli.
7 . The method of claim 1 wherein the enzyme is an active component of firefly luciferase from Photinus pyralis.
8 . The method of claim 1 wherein the enzyme is an active component of firefly luciferase from Renilla reniformis.
9 . The method of claim 1 wherein the enzyme is an active component of β-lactamase from the bacteria Escherichia coli.
10 . The method of claim 1 wherein the enzyme is an active component of alkaline phosphatase.
11 . The method of claim 1 wherein the bioactive compound is selected from the group consisting of cycloheximide (3-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-O-β-(β-D-galactopyranosyl)ethyl]glutarimide), dexamethasone, 4′-Hydroxymethyl-trimethylpsoralen, chloramphenicol, 5-fluorouridine, tetracycline, doxorubicin, resveratrol, phorbol octanoate acetate, dioctanoyl glycerol, 4-hydroxyphenylretinamide, mitoxantrone, and thymidine.
12 . A method of hindering cell growth comprising:
(a) introducing into targeted cells a gene encoding an enzyme; and (b) administering in an amount effect to hinder growth of the targeted cells an inactive conjugate of a bioactive compound;
wherein the enzyme releases the bioactive compound from conjugation.
13 . The method of claim 12 wherein the targeted cells are the cancer cells.
14 . The method of claim 13 wherein the targeted cells are proximal to the cancer cells.
15 . The method of claim 13 wherein the drug initiates a host immune response to the cancer cells.
16 . The method of claim 13 wherein the cancer cells are present in a mammal.
17 . The method of claim 12 wherein the cells are plant cells.
18 . The method of claim 12 where in the cells are bacterial cells.
19 . The method of claim 12 wherein the enzyme does not naturally occur in the targeted cells in an amount effective to release the bioactive compound from conjugation.
20 . The method of claim 12 wherein the enzyme is an hydrolitic enzyme.
21 . The method of claim 12 wherein the enzyme is a marker gene.
22 . The method of claim 12 wherein the enzyme is an active component of lacZ β-galactosidase from the bacteria Escherichia coli.
23 . The method of claim 12 wherein the enzyme is an active component of GUS β-glucuronidase from the bacteria Escherichia coli.
24 . The method of claim 12 wherein the enzyme is an active component of firefly luciferase from Photinus pyralis.
25 . The method of claim 12 wherein the enzyme is an active component of firefly luciferase from Renilla reniformis.
26 . The method of claim 12 wherein the enzyme is an active component of β-lactamase from the bacteria Escherichia coli.
27 . The method of claim 12 wherein the enzyme is an active component of alkaline phosphatase.
28 . A method of enhancing cell growth comprising:
(a) introducing into the cells a gene encoding an enzyme; and (b) administering a conjugate of a bioactive compound in an amount effect to enhance cell growth an inactive conjugate of a bioactive compound;
wherein the bioactive compound enhances cell growth and the enzyme releases the bioactive compound from conjugation.
29 . The method of claim 28 wherein enhancing cell growth increases the production of a protein in a cell culture.
30 . The method of claim 28 wherein the enzyme does not naturally occur in the targeted cells in an amnount effective to release the bioactive compound from conjugation.
31 . The method of claim 28 wherein the enzyme is an hydrolitic enzyme.
32 . The method of claim 28 wherein the enzyme is a marker gene.
33 . The method of claim 28 wherein the enzyme is an active component of lacZ β-galactosidase from the bacteria Escherichia coli.
34 . The method of claim 28 wherein the enzyme is an active component of GUS β-glucuronidase from the bacteria Escherichia coli.
35 . The method of claim 28 wherein the enzyme is an active component of firefly luciferase from Photinus pyralis.
36 . The method of claim 28 wherein the enzyme is an active component of firefly luciferase from Renilla reniformis.
37 . The method of claim 28 wherein the enzyme is an active component of β-lactamase from the bacteria Escherichia coli.
38 . The method of claim 28 wherein the enzyme is an active component of alkaline phosphatase.
39 . An inactive conjugate of a bioactive compound having the formula
40 . An inactive conjugate of a bioactive compound having the formula.
41 . An inactive conjugate of a bioactive compound having the formula
42 . An inactive conjugate of a bioactive compound having the formula
43 . An inactive conjugate of a bioactive compound having the formula
44 . An inactive conjugate of a bioactive compound having the formula
45 . An inactive conjugate of a bioactive compound having the formula
46 . An inactive conjugate of a bioactive compound having the formula
47 . An inactive conjugate of a bioactive compound having the formula
48 . An inactive conjugate of a bioactive compound having the formula
49 . An inactive conjugate of a bioactive compound having the formula
50 . An inactive conjugate of a bioactive compound having the formula
51 . An inactive conjugate of a bioactive compound having the formula
52 . An inactive conjugate of a bioactive compound havjin the formula
53 . An inactive conjugate of a bioactive compound having the formulaCited by (0)
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