US4699784A
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Tumoricidal methotrexate-antibody conjugate
Assignee: Center for Molecular Medicine and Immunology
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Filing: 1986-02-25
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Granted: 1987-10-13
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Expires: 2006-02-25
Abstract
Abstract A conjugate of methotrexate to an antibody is prepared by loading methotrexate onto an aminodextran, then specifically conjugating the polymer carrier to the carbohydrate portion of an antitumor antibody, using a reduced Schiff base linkage. The conjugate is useful for tumor targeted therapy.
Inventors
- 👤 Lisa B. Shih
- 👤 Frederick J. Primus
- 👤 Milton D. Goldenberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:31
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/08; A61K49/10; A61K49/14; A61K49/16; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6883; A61K49/085; A61K49/12; A61K49/126; A61K49/128; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K2123/00; Y; Y10; Y10S; Y10S530/00; Y10S530/808; Y10S530/809
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
43 words
An antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
Claim 2
Dependent Claim
43 words
An antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
Claim 3
Dependent Claim
26 words
The antibody conjugate of claim 1, wherein said anti-cancer antibody specifically binds to an antigen produced by or associated with a lung, breast or epidermoid tumor.
Claim 4
Dependent Claim
12 words
The antibody conjugate of claim 2, wherein said antigen is carcinoembryonic antigen.
Claim 5
Dependent Claim
13 words
The antibody conjugate of claim 3, wherein said antibody is a monoclonal antibody.
Claim 6
Dependent Claim
15 words
The antibody conjugate of claim 1, wherein said aminodextran has about 50-150 amino groups thereon.
Claim 7
Dependent Claim
17 words
The antibody conjugate of claim 5, wherein said aminodextran is a condensation product of dextran and 1,3-diamino-2-hydroxypropane.
Claim 8
Dependent Claim
16 words
The antibody conjugate of claim 5, wherein said conjugate has about 25-50 methotrexate molecules per aminodextran.
Claim 9
Dependent Claim
15 words
The antibody conjugate of claim 5, wherein said conjugate has 1-3 methotrexate-aminodextran moieties per antibody.
Claim 10
Independent Claim
82 words
A method of preparing a methotrexate-aminodextran-antibody conjugate wherein the methotrexate is linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a Reduced Schiff base linkage, comprising the steps of: (a) reacting an aminodextran containing about 25-40 methotrexate molecules linked thereto with an anti-cancer antibody having an oxidized carbohydrate portion; and (b) reductively stabilizing the resultant Schiff base adduct.
Claim 11
Independent Claim
82 words
A method of preparing a methotrexate-aminodextran-antibody conjugate wherein the methotrexate is linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a Reduced Schiff base linkage, comprising the steps of: (a) reacting an aminodextran containing about 25-40 methotrexate molecules linked thereto with an anti-cancer antibody having an oxidized carbohydrate portion; and (b) reductively stabilizing the resultant Schiff base adduct.
Claim 12
Dependent Claim
21 words
The method of claim 9, wherein said methotrexate-loaded aminodextran used in step (a) is produced by reacting carboxylactivated methotrexate with aminodextran.
Claim 13
Dependent Claim
16 words
The method of claim 9, wherein said aminodextran is a condensation product of dextran and 1,3-diamino-2-hydroxypropane.
Claim 14
Independent Claim
63 words
A method of tumor therapy, comprising administering to an animal or human having a tumor a therapeutically effective amount of an antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
Claim 15
Independent Claim
63 words
A method of tumor therapy, comprising administering to an animal or human having a tumor a therapeutically effective amount of an antibody conjugate, comprising methotrexate linked through one of its carboxyl groups to an aminodextran polymer, which in turn is linked through at least one of its amino groups to the carbohydrate portion of an anti-cancer antibody by a reduced Schiff base linkage.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-10-12 | 1991-04-13 | 1991-10-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-10-12 | 1995-04-13 | 1995-10-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-10-12 | 1999-04-13 | 1999-10-13 | $7700.00 | Window Closed / Lapsed |