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US4906452A
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Trichothecene conjugates and methods of use
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1988-04-28
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Granted: 1990-03-06
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Expires: 2008-04-28
Abstract
Abstract Conjugates of trichothecenes and agents that bind to a defined population of cells are disclosed. Preferred are conjugates of trichothecene molecules with polyclonal or monoclonal antibodies or fragments thereof that recognize antigens that are present only on tumor cells or are augmented in their expression on tumor cells as compared to normal tissues. Trichothecene molecules are coupled to the agent through non-covalent and covalent linkages, such as peptide bonds, disulfide bonds, thioester bonds, or thioether bonds. Methods for reducing intoxification in a recipient of a trichothecene and an agent and for producing a trichothecene conjugate with improved solubility are also disclosed.
Inventors
- 👤 Gowsala Sivam
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 09:23
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/335; A61K31/35; A61K31/365; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K47/6831; A61P; A61P35/00; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
56 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, wherein said trichothecene is selected from the group consisting of myrotoxin A, myrotoxin B, myrotoxin C, myrotoxin D, mytoxin A, mytoxin B, mytoxin C, roritoxin A, roritoxin B, roritoxin C and roritoxin D.
Claim 2
Dependent Claim
56 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, wherein said trichothecene is selected from the group consisting of myrotoxin A, myrotoxin B, myrotoxin C, myrotoxin D, mytoxin A, mytoxin B, mytoxin C, roritoxin A, roritoxin B, roritoxin C and roritoxin D.
Claim 3
Dependent Claim
59 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said trichothecene comprises the formula: ##STR43## wherein: R 1 is H, OH, or O--C--CH 3 R 2 is H, OH, O--C--CH 3 , or OCOCH 2 CH(CH 3 ) 2 ; and R' is: ##STR44##
Claim 4
Dependent Claim
59 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said trichothecene comprises the formula: ##STR43## wherein: R 1 is H, OH, or O--C--CH 3 R 2 is H, OH, O--C--CH 3 , or OCOCH 2 CH(CH 3 ) 2 ; and R' is: ##STR44##
Claim 5
Dependent Claim
57 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said trichothecene and said antibody or antibody fragment are coupled through a covalent linkage formed between a trichothecene/poly-L-lysine complex and one or more sulfhydryl or carboxyl groups of the antibody or antibody fragment.
Claim 6
Dependent Claim
57 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said trichothecene and said antibody or antibody fragment are coupled through a covalent linkage formed between a trichothecene/poly-L-lysine complex and one or more sulfhydryl or carboxyl groups of the antibody or antibody fragment.
Claim 7
Independent Claim
47 words
A method for producing a trichothecene conjugate with improved solubility, comprising: glycosylating a trichothecene to form a glycosylated trichothecene; and conjugating said glycosylated trichothecene to an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, thereby forming said trichothecene conjugate.
Claim 8
Independent Claim
47 words
A method for producing a trichothecene conjugate with improved solubility, comprising: glycosylating a trichothecene to form a glycosylated trichothecene; and conjugating said glycosylated trichothecene to an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, thereby forming said trichothecene conjugate.
Claim 9
Dependent Claim
31 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said conjugate is rendered soluble by glycosylation.
Claim 10
Dependent Claim
31 words
A conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells wherein said conjugate is rendered soluble by glycosylation.
Claim 11
Independent Claim
64 words
A method for reducing intoxification in a recipient of a conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, comprising: administering to the recipient the conjugate of a trichothecene and an antibody or antibody fragment; and administering to the recipient monoclonal or polyclonal antibodies that inhibit the toxicity of released trichothecene.
Claim 12
Independent Claim
64 words
A method for reducing intoxification in a recipient of a conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, comprising: administering to the recipient the conjugate of a trichothecene and an antibody or antibody fragment; and administering to the recipient monoclonal or polyclonal antibodies that inhibit the toxicity of released trichothecene.
Claim 13
Independent Claim
66 words
A method for reducing intoxification in a recipient of a conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, comprising: administering to the recipient the conjugate of a trichothecene and an antibody or antibody fragment; and administering to the recipient activated charcoal and an oral cathartic, thereby reducing gastrointestinal levels of free trichothecene.
Claim 14
Independent Claim
66 words
A method for reducing intoxification in a recipient of a conjugate of a trichothecene and an antibody or antibody fragment that is capable of specifically binding to a defined population of cells, comprising: administering to the recipient the conjugate of a trichothecene and an antibody or antibody fragment; and administering to the recipient activated charcoal and an oral cathartic, thereby reducing gastrointestinal levels of free trichothecene.
References Cited (Backward Citations)
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