US4640835A
Expired / Lapsed
US
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Plasminogen activator derivatives
Assignee: Nippon Chemiphar Co Ltd
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Filing: 1983-10-28
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Granted: 1987-02-03
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Expires: 2003-10-28
Abstract
Abstract Derivatives of a nonimmunogenic plasminogen activator which comprises at least one polyalkylene glycol group chemically bonded with at least one coupling agent to amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight of about 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof. The plasminogen activator derivatives have an extended circulating life in the mammalian bloodstream and also inhibit the formation of thrombus in the same.
Inventors
- 👤 Kimihiro Shimizu
- 👤 Tsuguji Nakahara
- 👤 Taketoshi Kinoshita
- 👤 Jun Takatsuka
- 👤 Michiko Igarashi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:58
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6456; C12N9/6462; C12N9/96; C12Y; C12Y304/00; C12Y304/21; C12Y304/21073; A61K38/00
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
64 words
A derivative of a nonimmunogenic human plasminogen activator, comprising at least one polyalkylene glycol chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 2
Dependent Claim
64 words
A derivative of a nonimmunogenic human plasminogen activator, comprising at least one polyalkylene glycol chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 3
Dependent Claim
13 words
The derivative as claimed in claim 1, wherein said plasminogen activator is urokinase.
Claim 4
Dependent Claim
57 words
The derivative as claimed in claim 1, wherein said polyalkylene glycol is selected from the group consisting of an unsubstituted polyethylene glycol, a polyethylene glycol substituted with one or more alkyl, alkoxy or alkanoyl groups, an unsubstituted polypropylene glycol, or a polypropylene glycol substituted with one or more alkyl, alkoxy or alkanoyl groups, or a mixture thereof.
Claim 5
Dependent Claim
19 words
The derivative as claimed in claims 1 or 3, wherein said polyalkylene glycol is a polyethylene glycol monoalkyl ether.
Claim 6
Dependent Claim
17 words
The derivative as claimed in claims 1 or 3, wherein said polyalkylene glycol is a polypropylene glycol.
Claim 7
Dependent Claim
20 words
The derivative as claimed in claim 1, wherein said polyalkylene glycol has a molecular weight in the range of 500-10,000.
Claim 8
Dependent Claim
15 words
The derivative as claimed in claim 1, wherein said coupling agent is a cyanuric halide.
Claim 9
Dependent Claim
17 words
Monomethyl ether polyethylene glycol-4,6-dichloro-1,3,5-triazine-modified urokinase, whose polyethylene glycol moiety has an average molecular weight of about 5,000.
Claim 10
Dependent Claim
17 words
Monomethyl ether polyethylene glycol-4,6-dichloro-1,3,5-triazine-modified urokinase, whose polyethylene glycol moiety has an average molecular weight of about 5,000.
Claim 11
Dependent Claim
15 words
Polypropylene glycol-4-chloro-6-hydroxy-1,3,5-triazine-modified urokinase, whose polypropylene glycol moiety has an average molecular weight of about 4,000.
Claim 12
Dependent Claim
15 words
Polypropylene glycol-4-chloro-6-hydroxy-1,3,5-triazine-modified urokinase, whose polypropylene glycol moiety has an average molecular weight of about 4,000.
Claim 13
Dependent Claim
66 words
A process for preparing a derivative of a nonimmunogenic human plasminogen activator, which comprises reacting a coupled product of at least one polyalkylene glycol and at least one coupling agent with a plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 14
Dependent Claim
66 words
A process for preparing a derivative of a nonimmunogenic human plasminogen activator, which comprises reacting a coupled product of at least one polyalkylene glycol and at least one coupling agent with a plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 15
Dependent Claim
13 words
The process as claimed in claim 10, wherein said plasminogen activator is urokinase.
Claim 16
Dependent Claim
30 words
The process as claimed in claim 10, wherein said coupled product and said plasminogen activator are reacted under such conditions that the latter activator does not lose its physiological activity.
Claim 17
Dependent Claim
17 words
A thrombolytic agent comprising a derivative of a non-immunogenic human plasminogen activator as claimed in claim 1.
Claim 18
Dependent Claim
51 words
The process as claimed in claim 12, wherein said conditions comprise reacting said coupled product and said plasminogen activator at a temperature in the range of 0° C. to room temperature at a pH in the range of 2 to 10, whereby said plasminogen activator does not lose its physiological activity.
Claim 19
Independent Claim
58 words
A method of extending the circulating life of a human plasminogen activator in a mammalian bloodstream which comprises chemically modifying said plasminogen activator by bonding at least one polyalkylene glycol moiety having a molecular weight of between about 200 and 20,000, thereto by means of a coupling agent to the amino acid side chains of said plasminogen activator.
Claim 20
Independent Claim
58 words
A method of extending the circulating life of a human plasminogen activator in a mammalian bloodstream which comprises chemically modifying said plasminogen activator by bonding at least one polyalkylene glycol moiety having a molecular weight of between about 200 and 20,000, thereto by means of a coupling agent to the amino acid side chains of said plasminogen activator.
Claim 21
Dependent Claim
11 words
The method of claim 15, wherein said plasminogen activator is urokinase.
Claim 22
Dependent Claim
13 words
The method of claim 15, wherein said mammalian bloodstream is a human bloodstream.
Claim 23
Dependent Claim
15 words
The method of claim 15, wherein said polyalkylene glycol moiety is a methoxypolyethylene glycol moiety.
Claim 24
Dependent Claim
16 words
The method of claim 18, wherein said methoxypolyethylene glycol has a molecular weight of about 5,000.
Claim 25
Independent Claim
84 words
A method of inhibiting the formation of thrombus in a mammalian bloodstream which comprises administering to said mammals an effective amount of a nonimmunogenic human plasminogen activator comprising at least one polyalkylene glycol moiety chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 26
Independent Claim
84 words
A method of inhibiting the formation of thrombus in a mammalian bloodstream which comprises administering to said mammals an effective amount of a nonimmunogenic human plasminogen activator comprising at least one polyalkylene glycol moiety chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Claim 27
Dependent Claim
11 words
The method of claim 20, wherein said plasminogen activator is urokinase.
Claim 28
Dependent Claim
14 words
The method of claim 20, wherein said mammalian blood stream is a human bloodstream.
Claim 29
Dependent Claim
15 words
The method of claim 20, wherein said polyalkylene glycol moiety is a methoxypolyethylene glycol moiety.
Claim 30
Dependent Claim
16 words
The method of claim 23, wherein said methoxypolyethylene glycol has a molecular weight of about 5,000.
References Cited (Backward Citations)
US4179337A
Cited
US4349630A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 7.5 Years (Year 8) | 1994-02-02 | 1994-08-04 | 1995-02-03 | $3760.00 | Window Closed / Lapsed |
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