Claims
- 1. A soluble antibody conjugate, comprising a plurality of drug, toxin, chelator, boron addend or detectable label molecules covalently bound to a polymer carrier having at least one remaining free amine group, to form a loaded carrier, said loaded carrier in turn being covalently bound through said at least one amine group to the carbohydrate portion of an antibody by a reduced Schiff base linkage; wherein said conjugate is soluble in human serum.
- 2. The antibody conjugate of claim 1, wherein said antibody is a monoclonal antibody.
- 3. The antibody conjugate of claim 1, wherein said polymer carrier is an aminodextran or a polypeptide of at least 50 amino acids in length.
- 4. The antibody conjugate of claim 1, wherein said antibody is an anti-cancer antibody.
- 5. The antibody conjugate of claim 4, wherein said anti-cancer antibody specifically binds to an antigen produced by or associated with a lung, breast, colorectal, liver, pancreatic, urogenital, stomach, kidney, lymphoid or epidermoid cancer.
- 6. The antibody conjugate of claim 1, wherein said antibody specifically binds to an antigen produced by or associated with a non-cancerous infectious or inflammatory lesion.
- 7. The antibody conjugate of claim 1, wherein said antibody specifically binds to a target of a specific type of normal organ or tissue.
- 8. The antibody conjugate of claim 1, wherein said polymer carrier is an aminodextran.
- 9. The antibody conjugate of claim 8, wherein said aminodextran is a condensation product of dextran and 1,3-diamino-2-hydroxypropane.
- 10. The antibody conjugate of claim 8, wherein said aminodextran has about 50-150 amino groups thereon.
- 11. The antibody conjugate of claim 1, wherein said polymer carrier is a polypeptide chain of at least 50 amino acids in length.
- 12. The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a cytotoxic agent.
- 13. The antibody conjugate of claim 12, wherein said cytotoxic agent is an anti-cancer drug.
- 14. The antibody conjugate of claim 13, wherein said anti-cancer drug is methotrexate, 5-fluorouracil, cycloheximide, daunomycin, doxorubicin, chlorambucil, trenimon, phenylenediamine mustard, adriamycin, bleomycin, cytosine arabinoside or cyclophosphamide.
- 15. The antibody conjugate of claim 12, wherein said cytotoxic agent is a toxin.
- 16. The antibody conjugate of claim 15, wherein said toxin is ricin or the A-chain thereof or pokeweed antiviral protein.
- 17. The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of an antibiotic.
- 18. The antibody conjugate of claim 17, wherein said antibiotic is an antiviral, antifungal or antimicrobial drug.
- 19. The antibody conjugate of claim 17, wherein said antibiotic is an antineoplastic mitomycin or actinomycin.
- 20. The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a boron addend.
- 21. The antibody conjugate of claim 17, wherein said boron addend comprises a carborane.
- 22. The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a chelator.
- 23. The antibody conjugate of claim 22, wherein said chelator is a chelator for a radiometal.
- 24. The antibody conjugate of claim 22, wherein said chelator is a chelator for a magnetic resonance enhancing metal ion.
- 25. The antibody conjugate of claim 22, wherein said chelator comprises: (a) an ethylenediaminetetraacetic acid or diethylenetriaminepentaacetic acid mostly; (b) deferoxamine; or (c) a bisthiosemicarbazone of a 1,2- or 1,3-dicarbonyl compound.
- 26. The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a detectable label.
- 27. The antibody conjugate of claim 26, wherein said label is an enzyme, a fluorescent compound or an electron transfer agent.
- 28. A method of preparing a soluble antibody conjugate, comprising the steps of:
- (a) reacting a polymer carrier, to which are covalently bound a plurality of drug, toxin, chelator, boron addend or detectable label molecules, said carrier having at least one remaining free amine group, with an antibody having an oxidized carbohydrate portion; and
- (b) reductively stabilizing the resultant Schiff base adduct;
- wherein said conjugate is soluble in human serum.
- 29. In a scintigraphic imaging agent composition, comprising: (a) a radiolabeled antibody which specifically binds to an antigen produced by or associated with a cancer or other pathological lesion; and (b) a sterile, pharmaceutically acceptable injection vehicle,
- the improvement wherein said radiolabeled antibody is the antibody conjugate of claim 23.
- 30. In a magnetic resonance imaging agent composition, comprising: (a) an antibody labeled with a magnetic resonance enhancing metal ion, wherein said antibody specifically binds to an antigen produced by or associated with a cancer or other pathological lesion; and (b) a sterile, pharmaceutically acceptable injection vehicle,
- the improvement wherein said labeled antibody is the antibody conjugate of claim 24.
- 31. A therapeutic composition for treatment of humans, comprising: (a) the antibody conjugate of any of claims 4, 6, 7, 12, 13, 15, 17, 22, and 23; and (b) a sterile, pharmaceutically acceptable injection vehicle.
- 32. A diagnostic composition for immunoassay or immunohistology, comprising the antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a detectable label.
CROSS REFERENCE TO RELATED APPLICATION
This application is the U.S. national phase application of PCT Application No. PCT/US/00406, filed Feb. 25, 1987, and designating the United States, and is a continuation-in-part of copending application U.S. Ser. No. 833,204, filed Feb. 25, 1986, and now issued as U.S. Pat. No. 4,699,784.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US87/00406 |
2/25/1987 |
|
|
8/23/1988 |
8/23/1988 |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4671958 |
Rodwell et al. |
Jun 1987 |
|
4699784 |
Shih et al. |
Oct 1987 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
1079268 |
Jun 1980 |
CAX |
0088695 |
Sep 1983 |
EPX |
Non-Patent Literature Citations (2)
Entry |
Gilman et al. eds. Goodman and Gilman's The Pharmacological Basis of Theraputics 7th ed. MacMillan Pub. Co., N.Y.; pp. 1281-1283 and 1288-1289. |
Ghose et al. (1983) Methods Enzymol 93: pp. 280-333. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
833204 |
Feb 1986 |
|