Claims
- 1. Method for treating a thromboembolic condition comprising administering to a subject in need thereof an amount of a thrombolytically active protein selected from the group consisting of (a) the protein consisting of the amino acid sequence set forth in SEQ ID NO: 1, and (b) the protein consisting of amino acids 1-5 and 86-527 of wild type t-PA, wherein said thrombolytically active protein
- i) has a pharmakokinetic profile 4.5-9.5 times greater than that of wild type t-PA,
- ii) has a pharmacodynamic profile 4.0-11.5 times greater than that of wild type t-PA, and
- iii) prolongs bleeding time no more than about two times base line bleeding time,
- sufficient to lyse thrombi in said subject.
- 2. Method according to claim 1 wherein the pharmacokinetic profile is characterized by a half life about 3-8 times greater than that of wild type t-PA.
- 3. Method according to claim 2 wherein the pharmacokinetic profile is characterized by an average half-life 4.5-5 times that of wild type-tPA.
- 4. Method according to claim 3 wherein the pharmacokinetic profile is characterized by an average clearance rate of about 3-16 times less than that of wild type t-PA.
- 5. Method according to claim 1 wherein the pharmacokinetic profile is characterized by an average clearance rate 6.9-9.0 times less than that of wild type t-PA.
- 6. Method of claim 5 wherein the area under the curve is 3-18 times greater than that of wild type t-PA.
- 7. Method according to claim 1 wherein the pharmacokinetic profile is characterized by an average area under the curve 8.0-9.5 times greater than that of wild type t-PA.
- 8. Method according to claim 1 wherein the pharmacodynamic profile is characterized by an effective dose about 4.0-11.5 times less than that of wild type t-PA.
- 9. Method according to claim 1 wherein the pharmacodynamic profile of said thrombolytically active protein is characterized by an average reperfusion time of 9-44 minutes.
- 10. Method according to claim 9 wherein the reperfusion time is 15-31 minutes.
- 11. Method of claim 1, wherein said thrombolytically active protein consists of the amino acid sequence set forth in SEQ ID NO: 1.
- 12. Method of claim 1, wherein said thrombolytically active protein consists of amino acids 1-5 and 86-527 of wild type t-PA.
- 13. Method of claim 1, wherein said thromboembolic condition is acute myocardial infarction.
- 14. Method of claim 1, wherein said thromboembolic condition is a pulmonary embolism.
- 15. Method of claim 1, wherein said throboembolic condition is a stroke.
RELATED APPLICATIONS
This application is a continuation-in-part of application Ser. No. 08/130,005 filed on Sep. 30, 1993, now abandoned, which is a divisional application of Ser. No. 07/968,171, filed on Oct. 29, 1992 and now abandoned, which is a continuation of Ser. No. 07/585,129 filed on Sep. 28, 1990, now U.S. Pat. No. 5,223,256, and U.S. patent application Ser. No. 165,577, filed Dec. 13, 1993, now abandoned, which is a continuation of Ser. No. 892,629 filed Jun. 2, 1992, abandoned, which is a continuation of Ser. No. 527,498 filed May 23, 1990 now abandoned. The patent and application are incorporated by reference in its entirety.
Foreign Referenced Citations (2)
Number |
Date |
Country |
8804319 |
Feb 1988 |
DKX |
302456 |
Feb 1988 |
EPX |
Non-Patent Literature Citations (4)
Entry |
Collen, D. et al., Blood 71:216-219 (1988). |
Saito, et al. Ann. N.Y. Acad. Sci 613:452-454. |
Suzuki, et al. Thromb. & Haemost. 62(1):393 (1989). |
Fu, K.P. et al. Thrombosis Research 50:33-41 (1988). |
Divisions (1)
|
Number |
Date |
Country |
Parent |
968171 |
Oct 1992 |
|
Continuations (3)
|
Number |
Date |
Country |
Parent |
585129 |
Sep 1990 |
|
Parent |
892629 |
Jun 1992 |
|
Parent |
527498 |
May 1990 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
130005 |
Sep 1993 |
|