US4744981A
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Trichothecene antibody conjugates
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1985-10-17
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Granted: 1988-05-17
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Expires: 2005-10-17
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. A method for inhibiting the growth and metabolism of antigen-positive cells is also disclosed.
Inventors
- 👤 Gowsala Pavanasasivam
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 16:59
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: 23
Claim 1
Independent Claim
27 words
A conjugate of a trichothecene and an antibody or antibody fragment, said antibody or antibody fragment being capable of specifically binding to a defined population of cells.
Claim 2
Dependent Claim
27 words
A conjugate of a trichothecene and an antibody or antibody fragment, said antibody or antibody fragment being capable of specifically binding to a defined population of cells.
Claim 3
Dependent Claim
13 words
The conjugate of claim 1 wherein said trichothecene has a central sesquiterpenoid structure.
Claim 4
Dependent Claim
13 words
The conjugate of claim 2 wherein said trichothecene has an additional macrocyclic ring.
Claim 5
Dependent Claim
22 words
The conjugate of claim 2 wherein said trichothecene is selected from the group consisting of trichodermol, verrucarol, trichodermin, anguidine, and T-2 toxin.
Claim 6
Dependent Claim
40 words
The conjugate of claim 3 wherein said trichothecene is selected from the group consisting of verrucarin A, verrucarin B, verrucarin J, 2'-dehydroverrucarin A, roridin A, roridin D, roridin E, roridin H, satratoxin F, satratoxin G, satratoxin H, vertisporin, and baccharins.
Claim 7
Dependent Claim
10 words
The conjugate of claim 1 wherein the trichothecene is verrucarol.
Claim 8
Dependent Claim
11 words
The conjugate of claim 1 wherein the trichothecene is verrucarin A.
Claim 9
Dependent Claim
41 words
The conjugate of claim 1 wherein said trichothecene mycotoxin comprises the formula: ##STR28## wherein: R 1 is H, OH, or ##STR29## R 2 is H, OH, ##STR30## R 3 is H, OH, or ##STR31## R 4 is H, OH, ═O, ##STR32##
Claim 10
Dependent Claim
12 words
The conjugate of claim 8 wherein R 4 comprises an epoxide group.
Claim 11
Dependent Claim
37 words
The conjugate of claim 1 wherein said trichothecene comprises the formula: ##STR33## wherein: R 1 is OH, or ##STR34## R 2 is H, OH, ##STR35## or OCOCH 2 CH(CH 3 ) 2 ; and R' is: ##STR36##
Claim 12
Dependent Claim
11 words
The conjugate of claim 1 wherein said antibody comprises monoclonal antibodies.
Claim 13
Dependent Claim
18 words
The conjugate of claim 11 wherein the monoclonal antibodies are of human or other warm blooded animal origin.
Claim 14
Dependent Claim
11 words
The conjugate of claim 1 wherein said antibody comprises polyclonal antibodies.
Claim 15
Dependent Claim
14 words
The conjugate of claim 1 wherein said defined population of cells comprises tumor cells.
Claim 16
Dependent Claim
16 words
The conjugate of claim 1 wherein said defined population of cells comprises cells bearing tumor-associated antigens.
Claim 17
Dependent Claim
20 words
The conjugate of claim 1 wherein said trichothecene and said antibody or antibody fragment are coupled through a covalent linkage.
Claim 18
Dependent Claim
29 words
The conjugate of claim 16 wherein the covalent linkage is formed between a trichothecene hemisuccinate carboxylic acid and one or more amino groups of the antibody or antibody fragment.
Claim 19
Dependent Claim
30 words
The conjugate of claim 16 wherein said covalent linkage is formed between a trichothecene hemisuccinate N-hydroxy succinimidate ester and one or more amino groups of the antibody or antibody fragment.
Claim 20
Dependent Claim
26 words
The conjugate of claim 16 wherein said covalent linkage is formed between trichothecene/poly-L-lysine complexes and one or more amino groups of the antibody or antibody fragment.
Claim 21
Dependent Claim
18 words
The conjugate of claim 16 wherein said covalent linkage is a disulfide bond, thioester bond, or thioether bond.
Claim 22
Independent Claim
31 words
A method for inhibiting antigen positive cells, comprising: exposing the antigen positive cells to a conjugate of a trichothecene and an antibody or antibody fragment specific for said antigen positive cells.
Claim 23
Independent Claim
31 words
A method for inhibiting antigen positive cells, comprising: exposing the antigen positive cells to a conjugate of a trichothecene and an antibody or antibody fragment specific for said antigen positive cells.
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) | 1991-05-17 | 1991-11-16 | 1992-05-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-17 | 1995-11-16 | 1996-05-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-17 | 1999-11-16 | 2000-05-17 | $7700.00 | Window Closed / Lapsed |