US4764368A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Acid-cleavable compound
Assignee: Dana Farber Cancer Institute Inc
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Filing: 1986-09-17
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Granted: 1988-08-16
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Expires: 2006-09-17
Abstract
Abstract Heterobifunctional reagents that are cleavable under mildly acidic conditions are disclosed. The reagents include an acid cleavable cyclohexene-1,2,-dicarboxylic acid monoamide group. Also disclosed are methods of making the cross-linkers, as well as methods of using the cross-linkers, e.g., to deliver a biologically active substance across the membranes of selected cells in a heterogeneous cell population; once inside the cell the active substance is released, intact, by the transient, mild acidity of certain cell structures. Finally, a method of characterizing complex multi-chain protein structures is disclosed.
Inventors
- 👤 Walter A. Blattler
- 👤 John M. Lambert
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:06
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/44; C07D207/444; C07D207/448; C07D207/452; C07D405/00; C07D405/02; C07D405/12
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
65 words
A compound having the formula: ##STR5## where X is an amino-group containing substance whose amino nitrogen forms an amide link with the carbonyl group of the cyclohexene-1, 2,dicarboxylic acid function; R 1 , R 2 , and R 3 are independently selected from hydrogen, alkyl, or phenyl groups; and F comprises an organic macromolecule function from which the amino-group containing substance is to be released.
Claim 2
Dependent Claim
65 words
A compound having the formula: ##STR5## where X is an amino-group containing substance whose amino nitrogen forms an amide link with the carbonyl group of the cyclohexene-1, 2,dicarboxylic acid function; R 1 , R 2 , and R 3 are independently selected from hydrogen, alkyl, or phenyl groups; and F comprises an organic macromolecule function from which the amino-group containing substance is to be released.
Claim 3
Dependent Claim
11 words
The compound of claim 1 wherein X comprises a polypeptide residue.
Claim 4
Dependent Claim
14 words
The compound of claim 2 wherein the polypeptide is a drug or an enzyme.
Claim 5
Dependent Claim
13 words
The compound of claim 1 wherein X is a residue of a cytotoxin.
Claim 6
Dependent Claim
18 words
The compound of claim 4 wherein X is a residue of a cytotoxin that inactivates cellular protein synthesis.
Claim 7
Dependent Claim
22 words
The compound of claim 4 wherein X is a residue of pokeweed antiviral protein, ricin A-chain, abrin A-chain, modeccin A-chain or gelonin.
Claim 8
Dependent Claim
21 words
The compound of claim 1 wherein F comprises a polymeric carrier, an antibody, or a binding partner for a cell-surface receptor.
Claim 9
Dependent Claim
15 words
The compound of claim 1 wherein F is ##STR6## and A comprises the organic macromolecule.
Claim 10
Dependent Claim
21 words
The compound of claim 8 wherein A is selected from: (a) polymeric carriers; (b) N-alkyl maleimido-linked polypeptides; and (c) thioether-linked polypeptides.
Claim 11
Dependent Claim
18 words
The compound of claim 1 wherein R 1 , R 2 , and R 3 are each --H.
Claim 12
Dependent Claim
22 words
The compound of claim 7 wherein F comprises an antibody that is specific for a cell surface receptor of said cell type.
Claim 13
Dependent Claim
15 words
The compound of claim 7 wherein F comprises an antibody to a T-cell surface antigen.
Claim 14
Dependent Claim
16 words
The compound of claim 12 wherein said T-cell surface antigen is T3, T4, T11, or T12.
Claim 15
Dependent Claim
16 words
The compound of claim 7 wherein F comprises an antibody to a tumor associated surface antigen.
Claim 16
Dependent Claim
10 words
The compound of claim 7 wherein F comprises J5 antibody.
Claim 17
Dependent Claim
48 words
The compound of claim 7 wherein F comprises a binding partner for said cell receptor of cells of a desired cell type, said compound selectively binding to cells of said cell type, being internalized by said cells by cytosis, and being cleaved in acidified organelles of said cells.
Claim 18
Dependent Claim
71 words
The compound ##STR7## where: (a) R 1 , R 2 , R 3 are independently selected from hydrogen, alkyl, or phenyl groups; (b) T is selected from --OH, ##STR8## where Z is an N-alkyl maleimido group, I--CH 2 -- or Br--CH 2 --; and (c) U and V are independently selected from --OH, and OR 4 (R 4 being a benzyl group or an alkyl group of C 5 or less).
Claim 19
Dependent Claim
71 words
The compound ##STR7## where: (a) R 1 , R 2 , R 3 are independently selected from hydrogen, alkyl, or phenyl groups; (b) T is selected from --OH, ##STR8## where Z is an N-alkyl maleimido group, I--CH 2 -- or Br--CH 2 --; and (c) U and V are independently selected from --OH, and OR 4 (R 4 being a benzyl group or an alkyl group of C 5 or less).
Claim 20
Dependent Claim
18 words
The compound of claim 17 wherein R 1 , R 2 , and R 3 are each --H.
Claim 21
Dependent Claim
55 words
A method of using the compound of claim 16 comprising providing said compound, and administering said compound to a heterogeneous cell population comprising said cell type and other cells, said compound selectively binding to and being internalized by said cell type, and being cleaved in an organelle of said cell type responsible for protein synthesis.
Claim 22
Dependent Claim
60 words
A method of making the compound of claim 8 comprising the steps: (a) providing one of the following reagents, ##STR9## where: X is defined in claim 1, r=1-5, R 1 , R 2 , R 3 are defined as in claim 8, R 5 is --CH 2 I or --CH 2 Br; (b) reacting said reagent with a functionalized antibody.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-08-16 | 1992-02-15 | 1992-08-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-08-16 | 1996-02-15 | 1996-08-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-08-16 | 2000-02-15 | 2000-08-16 | $7700.00 | Window Closed / Lapsed |