US4634762A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Conjugates of anticoagulant and protein
Assignee: Cordis Europa NV
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Filing: 1985-03-26
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Granted: 1987-01-06
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Expires: 2005-03-26
Abstract
Abstract Conjugates are provided which are covalently bonded conjugates of an anticoagulant and protein that are prepared in the presence of a coupling agent that forms amide linkages between the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These conjugates are useful for enhancing the blood compatibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra-corporeal medical device.
Inventors
- 👤 Jan Feijen
- 👤 Wilhelmus E. Hennink
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 11:42
CPC Classifications
C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0075; A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0011; C08H; C08H1/00
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
144 words
A process for the preparation of a conjugate for coating the surface of a medical device to enhance the blood compatibility of the surface, the conjugate being of an anticoagulant and a protein, wherein the process includes coupling said anticoagulant to said protein in the presence of a coupling agent and wherein the improvement comprises providing an anticoagulant-protein conjugate that is covalently bonded by using a coupling agent that is an amide bond forming agent to form an amide linkage between said anticoagulant and said protein, said providing step includes selecting a heparinous material as the anticoagulant and selecting the protein of the protein-anticoagulant conjugate to be a water soluble protein that is non-crosslinked when coated onto the surface of the medical device in order to provide a non-crosslinked protein moiety biocompatible surface spacer between said anticoagulant and the surface of the medical device.
Claim 2
Dependent Claim
144 words
A process for the preparation of a conjugate for coating the surface of a medical device to enhance the blood compatibility of the surface, the conjugate being of an anticoagulant and a protein, wherein the process includes coupling said anticoagulant to said protein in the presence of a coupling agent and wherein the improvement comprises providing an anticoagulant-protein conjugate that is covalently bonded by using a coupling agent that is an amide bond forming agent to form an amide linkage between said anticoagulant and said protein, said providing step includes selecting a heparinous material as the anticoagulant and selecting the protein of the protein-anticoagulant conjugate to be a water soluble protein that is non-crosslinked when coated onto the surface of the medical device in order to provide a non-crosslinked protein moiety biocompatible surface spacer between said anticoagulant and the surface of the medical device.
Claim 3
Dependent Claim
21 words
The process according to claim 1, wherein the process is carried out at a pH value of not less than 5.0.
Claim 4
Dependent Claim
19 words
The process according to claim 1, wherein said amide bond forming agent is 1-ethyl-3-dimethylaminopropyl carbodiimide or a homolog thereof.
Claim 5
Dependent Claim
19 words
The process according to claim 1, wherein said amide bond forming agent is N-hydroxy succinimide or a homolog thereof.
Claim 6
Dependent Claim
18 words
The process according to claim 1, wherein said amide bond forming agent is N-ethyl-5-phenyl-isoxazolium-3-sulfonate or a homolog thereof.
Claim 7
Dependent Claim
13 words
The process according to claim 1, wherein said water soluble protein is albumin.
Claim 8
Dependent Claim
29 words
The process according to claim 1, wherein said conjugate is a conjugate of heparinous material and a water soluble human protein, and wherein 1-ethyl-3-dimethylaminopropyl carbodiimide is the coupling agent.
Claim 9
Dependent Claim
14 words
The process according to claim 7, wherein said water soluble human protein is albumin.
Claim 10
Dependent Claim
79 words
The process according to claim 7, wherein said process includes dissolving said heparinous material and said protein in water to form a solution, adjusting the pH of the solution to a value not greater than 5.5; adding an aqueous solution of said 1-ethyl-3-dimethylaminopropyl carbodiimide to said solution, said adding step being in incremental batches while maintaining the pH value at not greater than 5.5; agitating the solution while said coupling is proceeding; and recovering the heparinous material protein conjugate.
Claim 11
Dependent Claim
16 words
The process according to claim 9, wherein the pH value is between about 5.0 and 5.5.
Claim 12
Dependent Claim
31 words
The process according to claim 1, further including adjusting the mol ratio of said anticoagulant added during the process with respect to the weight of said protein added during the process.
Claim 13
Dependent Claim
41 words
The process according to claim 1, further including adjusting the mol ratio of said heparin to said protein by varying the weight of heparinous material added during the process with respect to the weight of said protein added during the process.
Claim 14
Dependent Claim
41 words
The process according to claim 1, further including adjusting the mol ratio of said heparinous material to said protein by varying the weight of heparin added to the solution with respect to the weight of said protein added to the solution.
Claim 15
Dependent Claim
31 words
The process according to claim 1, further including adding an aldehyde to crosslink said protein of the anticoagulant-protein conjugate after the conjugate is coated onto the surface of the medical device.
Claim 16
Dependent Claim
11 words
The process according to claim 14, wherein said aldehyde is glutaraldehyde.
Claim 17
Dependent Claim
32 words
The process according to claim 1, further including adding an aldehyde to crosslink said protein of the heparinous material-protein conjugate after the conjugate is coated onto the surface of the medical device.
Claim 18
Dependent Claim
19 words
The process according to claim 16, wherein said aldehyde is glutaraldehyde and said water soluble human protein is albumin.
Claim 19
Dependent Claim
99 words
A conjugate for coating a surface of a medical device to enhance blood compatibility of the surface, said conjugate comprising a water soluble protein moiety and an anticoagulant moiety, which protein moiety and anticoagulant moiety are covalently bonded through an amide linkage by an amide bond forming agent, said protein of the protein-anticoagulant conjugate being a water soluble protein that is non-crosslinked when coated onto the surface of the medical device in order to provide a non-crosslinked protein moiety biocompatible surface spacer between said anticoagulant and the surface of the medical device, and said anticoagulant moiety is heparinous material.
Claim 20
Dependent Claim
99 words
A conjugate for coating a surface of a medical device to enhance blood compatibility of the surface, said conjugate comprising a water soluble protein moiety and an anticoagulant moiety, which protein moiety and anticoagulant moiety are covalently bonded through an amide linkage by an amide bond forming agent, said protein of the protein-anticoagulant conjugate being a water soluble protein that is non-crosslinked when coated onto the surface of the medical device in order to provide a non-crosslinked protein moiety biocompatible surface spacer between said anticoagulant and the surface of the medical device, and said anticoagulant moiety is heparinous material.
Claim 21
Dependent Claim
11 words
The conjugate of claim 18, wherein said protein moiety is albumin.
Claim 22
Dependent Claim
18 words
the conjugate of claim 18, wherein said amide bond forming agent is 1-ethyl-3-dimethylaminopropyl carbodiimide or a homolog thereof.
Claim 23
Dependent Claim
18 words
The conjugate of claim 18, wherein said amide bond forming agent is N-hydroxy succinimide or a homolog thereof.
Claim 24
Dependent Claim
17 words
The conjugate of claim 18, wherein said amide bond forming agent is N-ethyl-5-phenyl-isoxazolium-3-sulfonate or a homolog thereof.
Claim 25
Dependent Claim
30 words
The conjugate of claim 18, wherein said anticoagulant moiety and said protein moiety are present in the conjugate at a mol ratio of no greater than 3 to 1, respectively.
Claim 26
Dependent Claim
23 words
The conjugate of claim 18, wherein the protein moiety of the conjugate is crosslinked after coating onto the surface of the medical device.
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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) | 1990-01-05 | 1990-07-07 | 1991-01-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-01-05 | 1994-07-07 | 1995-01-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-01-05 | 1998-07-07 | 1999-01-06 | $7700.00 | Window Closed / Lapsed |