US4568544A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration and a method
Assignee: Asahi Kasei Corp
•
Filing: 1985-02-26
•
Granted: 1986-02-04
•
Expires: 2005-02-26
Abstract
Abstract An aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration which comprises an aqueous medium and, dissolved therein, a high purity tissue plasminogen activator and at least one dissolution aid selected from the group consisting of lysine, ornithine and salts thereof, and a method for increasing a solubility of a high purity tissue plasminogen activator in an aqueous medium comprising adding said at least one dissolution aid to an aqueous solution of a high purity tissue plasminogen activator. The present aqueous solution contains a high purity tissue plasminogen activator dissolved therein at an increased concentration and the activity of the tissue plasminogen activator can be maintained during handling and storage of the aqueous solution. Therefore, not only can be easily and efficiently performed the treatment of a tissue plasminogen activator in each purification step but also can be stored safely, stably an aqueous tissue plasminogen activator solution as a final product.
Inventors
- 👤 Akio Hasegawa
- 👤 Shuhei Kondo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 12:31
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6456; C12N9/6459; A; A61; A61K; A61K47/00; A61K47/06; A61K47/16; A61K47/18; A61K47/183; A61K9/00; A61K9/0012; A61K9/0019; C07; C07K; C07K16/00; C07K16/40; C12N9/96; C12Y; C12Y304/00; C12Y304/21; C12Y304/21069; A61K38/00
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
134 words
An aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration comprising: (1) an aqueous medium; (2) a tissue plasminogen activator as protein dissolved in said aqueous medium in an amount of 3,000 to 50,000 U/ml based on the aqueous solution; and (3) at least one member selected from the group consisting of lysine, ornithine and salts thereof dissolved in said aqueous medium at a concentration of 1 mM to a value corresponding to the saturation solubility of said at least one member in said aqueous medium, said tissue plasminogen activator having a purity of 3,000 to 50,000 U/mg-protein, the tissue plasminogen activator concentration of said aqueous solution being higher than that of an aqueous solution of the tissue plasminogen activator in which said at least one member is not contained.
Claim 2
Dependent Claim
134 words
An aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration comprising: (1) an aqueous medium; (2) a tissue plasminogen activator as protein dissolved in said aqueous medium in an amount of 3,000 to 50,000 U/ml based on the aqueous solution; and (3) at least one member selected from the group consisting of lysine, ornithine and salts thereof dissolved in said aqueous medium at a concentration of 1 mM to a value corresponding to the saturation solubility of said at least one member in said aqueous medium, said tissue plasminogen activator having a purity of 3,000 to 50,000 U/mg-protein, the tissue plasminogen activator concentration of said aqueous solution being higher than that of an aqueous solution of the tissue plasminogen activator in which said at least one member is not contained.
Claim 3
Dependent Claim
23 words
An aqueous solution according to claim 1, wherein the tissue plasminogen activator concentration is 10,000 to 50,000 U/ml based on the aqueous solution.
Claim 4
Dependent Claim
23 words
An aqueous solution according to claim 2, wherein the tissue plasminogen activator concentration is 30,000 to 50,000 U/ml based on the aqueous solution.
Claim 5
Dependent Claim
27 words
An aqueous solution according to claim 1, wherein said at least one member is dissolved in the aqueous medium at a concentration of 5 to 100 mM.
Claim 6
Dependent Claim
27 words
An aqueous solution according to claim 4, wherein said at least one member is dissolved in the aqueous medium at a concentration of 10 to 50 mM.
Claim 7
Dependent Claim
27 words
An aqueous solution according to claim 1, wherein said tissue plasminogen activator is one obtained from the culture fluid of cells derived from a normal human tissue.
Claim 8
Dependent Claim
16 words
An aqueous solution according to claim 6, wherein said cells are derived from human embryonic lung.
Claim 9
Dependent Claim
16 words
An aqueous solution according to claim 6, wherein said cells are derived from human embryonic foreskin.
Claim 10
Dependent Claim
16 words
An aqueous solution according to claim 6, wherein said cells are derived from human embryonic kidney.
Claim 11
Dependent Claim
23 words
An aqueous solution according to claim 1, wherein said tissue plasminogen activator is one obtained from the culture fluid of human melanoma cells.
Claim 12
Dependent Claim
40 words
An aqueous solution according to claim 1, wherein said tissue plasminogen activator is one obtained from the culture fluid of microorganisms or cells which have been prepared by recombinant DNA technique and are capable of producing a tissue plasminogen activator.
Claim 13
Independent Claim
161 words
A method for increasing a solubility of a tissue plasminogen activator in an aqueous medium, which comprises: adding to a solution of a tissue plasminogen activator as protein in an aqueous medium at least one member selected from the group consisting of lysine, ornithine and salts thereof in an amount such that the concentration of said at least one member in the resulting aqueous solution becomes 1 mM to a value corresponding to the saturation solubility of said at least one member in said resulting aqueous solution, said tissue plasminogen activator having a purity of 3,000 to 50,000 U/mg-protein, thereby enabling the tissue plasminogen activator to dissolve in the aqueous medium at an increased concentration such that the tissue plasminogen activator concentration of said resulting aqueous solution is higher than that of the aqueous solution of the tissue plasminogen activator in which said at least one member is not contained and 3,000 to 50,000 U/ml based on said resulting aqueous solution.
Claim 14
Independent Claim
161 words
A method for increasing a solubility of a tissue plasminogen activator in an aqueous medium, which comprises: adding to a solution of a tissue plasminogen activator as protein in an aqueous medium at least one member selected from the group consisting of lysine, ornithine and salts thereof in an amount such that the concentration of said at least one member in the resulting aqueous solution becomes 1 mM to a value corresponding to the saturation solubility of said at least one member in said resulting aqueous solution, said tissue plasminogen activator having a purity of 3,000 to 50,000 U/mg-protein, thereby enabling the tissue plasminogen activator to dissolve in the aqueous medium at an increased concentration such that the tissue plasminogen activator concentration of said resulting aqueous solution is higher than that of the aqueous solution of the tissue plasminogen activator in which said at least one member is not contained and 3,000 to 50,000 U/ml based on said resulting aqueous solution.
Claim 15
Dependent Claim
20 words
A method according to claim 12, wherein the concentration of said at least one member is 5 to 100 mM.
Claim 16
Dependent Claim
20 words
A method according to claim 13, wherein the concentration of said at least one member is 10 to 50 mM.
Claim 17
Dependent Claim
26 words
A method according to claim 12, wherein said tissue plasminogen activator is one obtained from the culture fluid of cells derived from a normal human tissue.
Claim 18
Dependent Claim
15 words
A method according to claim 15, wherein said cells are derived from human embryonic lung.
Claim 19
Dependent Claim
15 words
A method according to claim 15, wherein said cells are derived from human embryonic foreskin.
Claim 20
Dependent Claim
15 words
A method according to claim 15, wherein said cells are derived from human embryonic kidney.
Claim 21
Dependent Claim
22 words
A method according to claim 12, wherein said tissue plasminogen activator is one obtained from the culture fluid of human melanoma cells.
Claim 22
Dependent Claim
40 words
An aqueous solution according to claim 12, wherein said tissue plasminogen activator is one obtained from the culture fluid of microorganisms or cells which have been prepared by recombinant DNA technique and are capable of producing a tissue plasminogen activator.
References Cited (Backward Citations)
US3950513A
Cited
US3555000A
Cited
US3904480A
Cited
US3998947A
Cited
US3930945A
Cited
US4083961A
Cited
US4082612A
Cited
US4328314A
Cited
US4317882A
Cited
US4442213A
Cited
GB2119804A
Cited
US4505893A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-02-03 | 1989-08-05 | 1990-02-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-02-03 | 1993-08-05 | 1994-02-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-02-03 | 1997-08-05 | 1998-02-04 | $7700.00 | Window Closed / Lapsed |