Methods, devices, and compositions for lysis of occlusive...

Details Methods, devices, and compositions for lysis of occlusive... Methods, devices, and compositions for lysis of occlusive...

2006-07-11

2006-07-11

Wax, Robert A. (Department: 1653)

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

C435S215000, C435S226000, C514S012200, C536S023200

Reexamination Certificate

active

07074401

ABSTRACT:
It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys300→His), perform in the manner of pro-UK in lysing “bad” blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called “good” blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated.

REFERENCES:
patent: 5472692 (1995-12-01), Liu et al.
patent: 5626841 (1997-05-01), Gurewich
patent: 5759542 (1998-06-01), Gurewich
patent: 5866358 (1999-02-01), Brandazza et al.
patent: 6364893 (2002-04-01), Sahatjian et al.
patent: 6409716 (2002-06-01), Sahatjian et al.
patent: 2002/0098179 (2002-07-01), Brearley et al.
patent: 2002/0138858 (2002-09-01), Pinsky
Parsons et al., “Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke,” Ann Neurol 51(1):28-37, 2001.
Barnwell et al., “Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke,” Am J Neuroradiology, 15(10):1817-1822, 1994.
Gurewich et al., “Effective and Fibrin-specific Clot Lysis by a Zymogen Precursor Form of Urokinase (Pro-urokinase)”, J. Clin. Invest., vol. 73, pp. 1731-1739 (1984).
Heckel et al., “Prediction of the three-dimensional structure of the enzymatic domain of t-PA”, J. Comp. Aided Mol. Des., vol. 2, pp. 7-14 (1988).
Liu et al., “A Comparative Study of the Promotion of Tissue Plasminogen Activator and Pro-Urokinase-induced Plasminogen Activation by Fragments D and E-2 of Fibrin”, J. Clin. Invest., vol. 88, pp. 2012-2017 (1991).
Liu et al., “Inactivation of the Intrinsic Activity of Pro-urokinase by Diisoprophyl Fluorophosphate Is Reversible”, The Journal of Biological Chemistry, vol. 270(15), pp. 8408-8410 (1995).
Liu et al., “Fragment E-2 from Fibrin Substantially Enhances Pro-urokinase-Induced Glu-Plasminogen Activation. A Kinetic Study Using the Plasmin-Resistant Mutant Pro-urokinase Ala-158-rpro-UK”, Biochemistry, vol. 31, pp. 6311-6317 (1992).
Liu et al., Prourokinase Mutant That Induces Highly Effective Cost Lysis Without Interfering With Hemostatsis, Circulation Research, vol. 90, pp. 757-763 (2002).
Liu et al., “A Site-Directed Mutagenesis of Pro-Urokinase at the Flexiblr Loop Region of Active Domain”, Advances in Gene Technology: Protein Engineering and Beyond, Abstract Only.
Nienaber et al., “Conformational Similarities between One-Chain and Two-Chain Tissue Plasminogen Activator (t-PA): Implications to the Activation Mechanism on One-Chain t-PA”, Biochemistry, vol. 31, pp. 3852-3861 (1992).
Orsini et al., “Efficient renaturation and fibrinolytic properties of prourokinase and a deletion mutant expressed inEscherichia colias inclusion bodies”, Eur. J. Biochem., vol. 195, pp. 691-697 (1991).
Pannell et al., “Activation of Plasminogen by Single-Chain Urokinase or by Two-chain Urokinase—A Demonstration That Single-Chain Has a Low Catalytic Activity (Pro-Urokinase)”, Blood, vol. 69(1), pp. 22-26 (1987).
Peterson et al., “Quenching of the Amidolytic Activity of One-Chain Tissue-Type Plasminogen Activator by Mutation of Lysine-416”, Biochem., vol. 29, pp. 3451-3457 (1990).
Verde et al., “Identification and primary sequence of an unspliced human urokinase poly(A)+RNA”, Proc. Natl. Acad. Sci., vol. 81, pp. 4727-4731 (1984).
Notification of Transmittal of the International Search Report and Written Opinion of the International Searching Authority (and including the International Search Report and Written Opinion of the International Searching Authority ) mailed Apr. 5, 2005.
Yuming et al., “High-level Expression and Purification of Human Pro-UK cDNA inEscherichia coli”, Chinese Journal of Biotechnology, vol. 13(4), pp. 233-238 (1998).

Affiliated with

Also associated with

Rating

Methods, devices, and compositions for lysis of occlusive... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods, devices, and compositions for lysis of occlusive..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods, devices, and compositions for lysis of occlusive... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3610121