Patent US4598064A successfully refreshed from Google Patents.
US4598064A
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Alpha-alpha cross-linked hemoglobins
Assignee: University of Iowa Research Foundation
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Filing: 1984-06-27
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Granted: 1986-07-01
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Expires: 2004-06-27
Abstract
Abstract Blood substitute and blood plasma expanders comprising alpha-alpha cross-linked stroma-free hemoglobin, which is substantially free of hemoglobin derivatives modified at other sites. The hemoglobin composition is intramolecularly cross-linked between Lys 99 Alpha 1 and Lys 99 Alpha 2 .
Inventors
- 👤 Joseph A. Walder
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 12:00
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/795; C07K14/805; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
57 words
A pharmaceutical composition for use as a blood substitute and blood plasma expander comprising a therapeutically effective amount of Lys 99 Alpha 1 to Lys 99 Alpha 2 intramolecularly cross-linked, stroma-free hemoglobin, substantially free of hemoglobin modified at other sites, soluble in aqueous and physiological fluids and capable of reversibly binding oxygen, and a pharmaceutically acceptable carrier.
Claim 2
Dependent Claim
57 words
A pharmaceutical composition for use as a blood substitute and blood plasma expander comprising a therapeutically effective amount of Lys 99 Alpha 1 to Lys 99 Alpha 2 intramolecularly cross-linked, stroma-free hemoglobin, substantially free of hemoglobin modified at other sites, soluble in aqueous and physiological fluids and capable of reversibly binding oxygen, and a pharmaceutically acceptable carrier.
Claim 3
Dependent Claim
16 words
The composition of claim 1 wherein said alpha-alpha cross-link is with an amino group-specific cross-linking agent.
Claim 4
Dependent Claim
13 words
The composition of claim 2 wherein said cross-linking agent is an acylating agent.
Claim 5
Dependent Claim
14 words
The composition of claim 3 wherein said cross-linking agent is a diester cross-linking agent.
Claim 6
Dependent Claim
15 words
The composition of claim 6 wherein said cross-linking agent is a phenyl ester cross-linking agent.
Claim 7
Dependent Claim
12 words
The composition of claim 7 wherein said cross-linking agent is bis(3,5-dibromosalicyl) fumarate.
Claim 8
Dependent Claim
23 words
The composition of claim 1 wherein the carrier is liquid and the composition contains from about 1% to about 10% of said hemoglobin.
Claim 9
Dependent Claim
25 words
The composition of claim 1 wherein said hemoglobin is also modified with a second reagent introducing a negatively charged group at the 2,3-diphosphoglycerate binding site.
Claim 10
Dependent Claim
11 words
The composition of claim 8 wherein said reagent is mono(3,5-dibromosalicyl) fumarate.
Claim 11
Independent Claim
71 words
A method of replacing or increasing the circulating blood volume or increasing oxygen delivery to tissues in man or animal species comprising: transfusing into the blood circulatory system a blood volume expander which consists essentially of Lys 99 Alpha 1 to Lys 99 Alpha 2 intramolecularly cross-linked, stroma-free hemoglobin which is substantially free of hemoglobin derivatives modified at other sites, having a molecular weight of about 64,000 in an isotonic solution.
Claim 12
Independent Claim
71 words
A method of replacing or increasing the circulating blood volume or increasing oxygen delivery to tissues in man or animal species comprising: transfusing into the blood circulatory system a blood volume expander which consists essentially of Lys 99 Alpha 1 to Lys 99 Alpha 2 intramolecularly cross-linked, stroma-free hemoglobin which is substantially free of hemoglobin derivatives modified at other sites, having a molecular weight of about 64,000 in an isotonic solution.
Claim 13
Dependent Claim
21 words
The method of claim 10 wherein the hemoglobin is also modified with a negatively charged group at the 2,3-diphosphoglycerate binding site.
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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) | 1989-06-30 | 1989-12-30 | 1990-07-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-06-30 | 1993-12-30 | 1994-07-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-06-30 | 1997-12-30 | 1998-07-01 | $7700.00 | Window Closed / Lapsed |