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US4957735A
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Target-sensitive immunoliposomes- preparation and characterization
Assignee: BIOWHITTAKER, INC. A CORP. OF DELAWARE
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Filing: 1987-02-09
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Granted: 1990-09-18
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Expires: 2007-02-09
Abstract
Abstract Novel target-sensitive immunoliposomes were prepared and characterized. In this invention, target specific binding of antibody-coated liposomes was sufficient to induce bilayer destabilization, resulting in a site-specific release of liposome contents. Unilamellar liposomes were prepared by using a small quantity of palmitoyl IgG (pIgG) to stabilize the bilayer phase of the unsaturated phosphatidylethanol amine (PE) which by itself does not form stable liposomes. A mouse monoclonal IgG antibody to the glycoprotein D (gD) of Herpes Simplex Virus (HSV) and dioleoyl PE were used in one preferred embodiment. In another preferred embodiment, potentially cytotoxic antiviral drugs were entrapped in target sensitive (TS) immunoliposomes and delivered to HSV infected cells. Potency was as much as 1000 times superior to the free drug and cytotoxicity was decreased by as much as 3000 fold.
Inventors
- 👤 Leaf Huang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-10 01:06
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/58; G01N33/585; G01N33/586; Y; Y10; Y10S; Y10S424/00; Y10S424/812; Y10S436/00; Y10S436/829
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
45 words
Target sensitive immunoliposomes consisting essentially of phosphatidylethanolamine and a stabilizing amount of fatty acid (C 12 to C 24 ) derivatized antibody, said antibody having an affinity for the target cell surface which immunoliposomes release their entrapped contents upon binding to a target cell surface.
Claim 2
Dependent Claim
45 words
Target sensitive immunoliposomes consisting essentially of phosphatidylethanolamine and a stabilizing amount of fatty acid (C 12 to C 24 ) derivatized antibody, said antibody having an affinity for the target cell surface which immunoliposomes release their entrapped contents upon binding to a target cell surface.
Claim 3
Dependent Claim
22 words
The target sensitive immunoliposomes of claim 1, wherein the phosphatidylethanolamine is selected from the group consisting of dioleoyl phosphatidylethanolamine and transphosphotidylated phosphtidylethanolamine.
Claim 4
Dependent Claim
16 words
The target sensitive immunoliposomes of claim 1, wherein the fatty acid is a palmitic acid derivative.
Claim 5
Dependent Claim
12 words
The target sensitive immunoliposomes of claim 1, wherein the antibody is IgG.
Claim 6
Dependent Claim
14 words
The target sensitive immunoliposomes of claim 1, wherein the antibody is a monoclonal antibody.
Claim 7
Dependent Claim
21 words
The target sensitive immunoliposome of claim 5, wherein the monoclonal antibody recognizes the glycoprotein D of the Herpes Simplex Virus (HSV).
Claim 8
Dependent Claim
18 words
The target sensitive immunoliposomes of claim 1, wherein the entrapped contents consist essentially of a pharmaceutically acceptable drug.
Claim 9
Dependent Claim
28 words
The target sensitive immunoliposomes of claim 7, wherein the pharmaceutically acceptable drug is selected from the group consisting of cytotoxic and antiviral drugs of the nucleoside analog family.
Claim 10
Dependent Claim
27 words
The target sensitive immunoliposomes of claim 8, wherein the cyclotoxic and antiviral drugs are selected from the group consisting of fluorodeoxy uridine, iododeoxyuridine, acyclovir and cytosine arabinoside.
Claim 11
Dependent Claim
13 words
The target sensitive immunoliposomes of claim 7, in a form suitable for injection.
Claim 12
Dependent Claim
14 words
The target sensitive immunoliposomes of claim 7, in a form suitable for ophthalmic application.
Claim 13
Dependent Claim
14 words
The target sensitive immunoliposomes of claim 7, in a form suitable for topical applications.
Claim 14
Dependent Claim
26 words
The target sensitive immunoliposomes of claim 1, further consisting essentially of palmitoyl IgG and phosphaticlethanolamine in a molar ratio of not less than 2.5×10 -4 .
Claim 15
Dependent Claim
19 words
The target sensitive immunoliposomes of claim 10, wherein the minimal coupling stoichimetry of palmitic acid to antibody is 2.2.
Claim 16
Independent Claim
82 words
A method of delivering therapeutic agents to the surface of cells in need of such treatment comprising the steps of: (a) forming target sensitive immunoliposomes from phosphatidylethanolamine and a stabilizing amount of fatty acid (C 12 to C 24 ) derivatized antibody, said antibody having an affinity for the target cell surface; (b) entrapping one or more therapeutic agents within the immunoliposomes of step (a); and (c) administering the immunoliposomes prepared in step (b) to a patient in need of such treatment.
Claim 17
Independent Claim
82 words
A method of delivering therapeutic agents to the surface of cells in need of such treatment comprising the steps of: (a) forming target sensitive immunoliposomes from phosphatidylethanolamine and a stabilizing amount of fatty acid (C 12 to C 24 ) derivatized antibody, said antibody having an affinity for the target cell surface; (b) entrapping one or more therapeutic agents within the immunoliposomes of step (a); and (c) administering the immunoliposomes prepared in step (b) to a patient in need of such treatment.
Claim 18
Dependent Claim
20 words
The method of claim 15, wherein the phosphatidylethanolamine is selected from the group consisting of dioleoyl phosphatidylethanolamine and transphosphotidylated phosphatidylethanolamine.
Claim 19
Dependent Claim
14 words
The method of claim 15, wherein the fatty acid is a palmitic acid derivative.
Claim 20
Dependent Claim
10 words
The method of claim 15, wherein the antibodys is IgG.
Claim 21
Dependent Claim
12 words
The method of claim 15, wherein the antibody is a monoclonal antibody.
Claim 22
Dependent Claim
18 words
The method of claim 19, wherein the monoclonal recognizes the glycoprotein D of the Herpes Simplex Virus (HSV).
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1993-09-17 | 1994-03-19 | 1994-09-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-09-17 | 1998-03-19 | 1998-09-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-09-17 | 2002-03-19 | 2002-09-18 | $7700.00 | Window Closed / Lapsed |