US5057313A
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Diagnostic and therapeutic antibody conjugates
Assignee: Center for Molecular Medicine and Immunology
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Filing: 1987-02-25
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Granted: 1991-10-15
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Expires: 2007-02-25
Abstract
Abstract The present invention relates to conjugates of diagnostic or therapeutic principles, such as drugs, toxins, chelators, boron compounds and detectable labels, to an antibody, in which the diagnostic or therapeutic principle is first loaded onto a polymer carrier such as an aminodextran or a polypeptide of at least 50 amino acids in length, and this intermediate is in turn site-specifically conjugated to a targeting antibody such as an antitumor antibody. The resultant conjugate substantially retains the immunoreactivity of the antibody, and targets the diagnostic or therapeutic principle to a target tissue or organ where the diagnostic or therapeutic effect is realized.
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 20:47
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/08; A61K49/10; A61K49/12; A61K49/126; A61K49/128; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6883; A61K49/085; A61K49/14; A61K49/16; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K2123/00
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
72 words
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.
Claim 2
Dependent Claim
72 words
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.
Claim 3
Dependent Claim
13 words
The antibody conjugate of claim 1, wherein said antibody is a monoclonal antibody.
Claim 4
Dependent Claim
24 words
The antibody conjugate of claim 1, wherein said polymer carrier is an aminodextran or a polypeptide of at least 50 amino acids in length.
Claim 5
Dependent Claim
13 words
The antibody conjugate of claim 1, wherein said antibody is an anti-cancer antibody.
Claim 6
Dependent Claim
33 words
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.
Claim 7
Dependent Claim
25 words
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.
Claim 8
Dependent Claim
23 words
The antibody conjugate of claim 1, wherein said antibody specifically binds to a target of a specific type of normal organ or tissue.
Claim 9
Dependent Claim
13 words
The antibody conjugate of claim 1, wherein said polymer carrier is an aminodextran.
Claim 10
Dependent Claim
17 words
The antibody conjugate of claim 8, wherein said aminodextran is a condensation product of dextran and 1,3-diamino-2-hydroxypropane.
Claim 11
Dependent Claim
15 words
The antibody conjugate of claim 8, wherein said aminodextran has about 50-150 amino groups thereon.
Claim 12
Dependent Claim
22 words
The antibody conjugate of claim 1, wherein said polymer carrier is a polypeptide chain of at least 50 amino acids in length.
Claim 13
Dependent Claim
21 words
The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a cytotoxic agent.
Claim 14
Dependent Claim
14 words
The antibody conjugate of claim 12, wherein said cytotoxic agent is an anti-cancer drug.
Claim 15
Dependent Claim
26 words
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.
Claim 16
Dependent Claim
13 words
The antibody conjugate of claim 12, wherein said cytotoxic agent is a toxin.
Claim 17
Dependent Claim
19 words
The antibody conjugate of claim 15, wherein said toxin is ricin or the A-chain thereof or pokeweed antiviral protein.
Claim 18
Dependent Claim
20 words
The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of an antibiotic.
Claim 19
Dependent Claim
16 words
The antibody conjugate of claim 17, wherein said antibiotic is an antiviral, antifungal or antimicrobial drug.
Claim 20
Dependent Claim
15 words
The antibody conjugate of claim 17, wherein said antibiotic is an antineoplastic mitomycin or actinomycin.
Claim 21
Dependent Claim
21 words
The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a boron addend.
Claim 22
Dependent Claim
13 words
The antibody conjugate of claim 17, wherein said boron addend comprises a carborane.
Claim 23
Dependent Claim
20 words
The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a chelator.
Claim 24
Dependent Claim
15 words
The antibody conjugate of claim 22, wherein said chelator is a chelator for a radiometal.
Claim 25
Dependent Claim
19 words
The antibody conjugate of claim 22, wherein said chelator is a chelator for a magnetic resonance enhancing metal ion.
Claim 26
Dependent Claim
30 words
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.
Claim 27
Dependent Claim
21 words
The antibody conjugate of claim 1, wherein said polymer carrier is loaded with a plurality of molecules of a detectable label.
Claim 28
Dependent Claim
20 words
The antibody conjugate of claim 26, wherein said label is an enzyme, a fluorescent compound or an electron transfer agent.
Claim 29
Independent Claim
69 words
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.
Claim 30
Independent Claim
69 words
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.
Claim 31
Dependent Claim
49 words
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.
Claim 32
Dependent Claim
59 words
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.
Claim 33
Dependent Claim
34 words
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.
Claim 34
Dependent Claim
29 words
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.
References Cited (Backward Citations)
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