US4911912A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Ribosome-inactivating glycoproteins, modified by oxidation of their osidic units and reduction, and in vivo prolonged-action immunotoxins containing such a glycoprotein
Assignee: Elf Sanofi SA
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Filing: 1986-12-15
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Granted: 1990-03-27
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Expires: 2006-12-15
Abstract
Abstract Glycoprotein (GPIR) having the ribosome-inhibiting activity of the native GPIR and having a prolonged-action in vivo which is obtained by oxidation of its osidic units by the action of periodate ions, and simultaneous reduction with cyanoborohydride ions. Said modified glycoprotein may be coupled to an antibody or a fragment thereof in order to form an immunotoxin having a prolonged-action in vivo.
Inventors
- 👤 Pierre Casellas
- 👤 Bernard Bourrie
- 👤 Xavier Canat
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:52
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/06; C07K14/00; C07K14/415; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K47/6819; A61K47/6825; A61K47/6827; C07K1/107; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/863; Y10S530/866
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
87 words
A modified glycoprotein which inactivates ribosomes and having the ribosome-inhibiting activity of the corresponding native glycoprotein which inactivates ribosomes, and an in vivo prolonged-action with respect to the corresponding native glycoprotein which inactivates ribosomes, wherein said modified glycoprotein which inactivates ribosomes is obtained by treatment of a glycoprotein which inactivates ribosomes having a molecular weight from about 20,000 to 30,000 jointly with an aqueous solution of a periodate and an aqueous solution of cyanoborohydride at pH 5 to 7 for a period of 0.2 to 24 hours.
Claim 2
Dependent Claim
87 words
A modified glycoprotein which inactivates ribosomes and having the ribosome-inhibiting activity of the corresponding native glycoprotein which inactivates ribosomes, and an in vivo prolonged-action with respect to the corresponding native glycoprotein which inactivates ribosomes, wherein said modified glycoprotein which inactivates ribosomes is obtained by treatment of a glycoprotein which inactivates ribosomes having a molecular weight from about 20,000 to 30,000 jointly with an aqueous solution of a periodate and an aqueous solution of cyanoborohydride at pH 5 to 7 for a period of 0.2 to 24 hours.
Claim 3
Dependent Claim
29 words
A modified glycoprotein which inactivates ribosomes as claimed in claim 1, wherein the treatment is carried out in the dark at a temperature of from 0° to 15° C.
Claim 4
Dependent Claim
80 words
A process for the preparation of a modified glycoprotein which inactivates ribosomes as claimed in claim 1, wherein a glycoprotein which inhibits ribosomes and has a molecular weight of from about 20,000 to about 30,000 is treated jointly with an aqueous solution of a periodate and an aqueous solution of a cyanoborohydride at a pH of from 5 to 7, at a temperature of 0° to 15° C., in the dark and for a period of 0.2 to 24 hours.
Claim 5
Dependent Claim
26 words
Modified glycoprotein which inactivates ribosomes as claimed in claim 1, wherein at least one of the thiol groups of the GPIR is protected during the treatment.
Claim 6
Dependent Claim
37 words
Modified glycoprotein which inactivates ribosomes as claimed in claim 2, wherein the reaction solution contains between 1 and 10 mg/ml of reactive A chain, 10 to 50 mM alkaline periodate and 10 to 200 mM sodium cyanoborohydride.
Claim 7
Dependent Claim
33 words
Process as claimed in claim 3, wherein the reaction solution contains between 1 and 10 mg/ml of reactive A chain, 10 to 50 mM alkaline periodate and 10 to 200 mM sodium cyanoborohydride.
Claim 8
Dependent Claim
41 words
Process as claimed in claim 6, wherein the glycoprotein which inactivates ribosomes is treated beforehand with a conventional reagent protecting the protecting groups, and said groups SH are released after the treatment by the IO 4 - ions and the cyanoborohydride.
Claim 9
Dependent Claim
35 words
Process as claimed in claim 7, wherein the reagent protecting the groups SH is selected from the 2,2'-dinitro-5,5'-dithio-dibenzoic acid and 3-(2-pyridyldisulfanyl)propionic acid, the deprotection of the SH groups being achieved by the action of 2-mercaptoethanol.
Claim 10
Dependent Claim
27 words
Immunotoxin having a prolonged-action in vivo, resulting from the coupling of an antibody or antibody fragment with a modified glycoprotein which inactivates ribosomes according to claim 1.
Claim 11
Dependent Claim
28 words
Immunotoxin as claimed in claim 9, wherein the coupling between the antibody or antibody fragment and the modified GPIR is carried out by means of a disulfide bridge.
Claim 12
Dependent Claim
29 words
Immunotoxin as claimed in claim 10, wherein the coupling is carried out with a heterobifunctional reagent selected from the N-succinimidyl-3-(2-pyridyldithio)propionate or the 3-(2-pyridyldisulfanyl) propionic acid activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide.
Claim 13
Dependent Claim
14 words
Anti-cancerous pharmaceutical composition containing as active principle, an immunotoxin as claimed in claim 9.
Claim 14
Dependent Claim
26 words
An immunotoxin having a prolonged-action in vivo, resulting from the coupling of an antibody fragment with a modified glycoprotein which inactivates ribosomes according to claim 4.
Claim 15
Dependent Claim
26 words
An immunotoxin having a prolonged-action in vivo, resulting from the coupling of an antibody fragment with a modified glycoprotein which inactivates ribosomes according to claim 2.
Claim 16
Dependent Claim
28 words
An immunotoxin having a prolonged-action in vivo, resulting from the coupling of an antibody or antibody fragment with a modified glycoprotein which inactivates ribosomes according to claim 5.
Claim 17
Dependent Claim
19 words
An immunotoxin as claimed in claim 13 where the coupling is carried out by means of a dissulfide bridge.
Claim 18
Dependent Claim
19 words
An immunotoxin as claimed in claim 14 where the coupling is carried out by means of a disulfide bridge.
Claim 19
Dependent Claim
19 words
An immunotoxin as claimed in claim 15 where the coupling is carried out by means of a disulfide bridge.
Claim 20
Dependent Claim
14 words
A pharmaceutical composition containing as active principal, an immunotoxin as claimed in claim 13.
Claim 21
Dependent Claim
14 words
A pharmaceutical composition containing as active principal, an immunotoxin as claimed in claim 14.
Claim 22
Dependent Claim
14 words
A pharmaceutical composition containing as active principal, an immunotoxin as claimed in claim 15.
Claim 23
Dependent Claim
18 words
A modfified glycoprotein as claimed in claim 1 wherein the modified glycoproteins is the A chain of ricin.
References Cited (Backward Citations)
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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) | 1993-03-26 | 1993-09-25 | 1994-03-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-03-26 | 1997-09-25 | 1998-03-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-03-26 | 2001-09-25 | 2002-03-27 | $7700.00 | Window Closed / Lapsed |