DR. VICTOR GUREWICH, M.D.
Osteopathic Medicine at Mount Auburn St, Cambridge, MA

5626841, May 6, 1997

Jun 7, 1994

8/254922

Victor Gurewich - Cambridge MA

A61K 3849, C12N 964, C12N 972

424 9463

A method of adjunctive therapy to inhibit reocclusions in a patient, e. g. , after thrombolytic therapy or angioplasty, by administering to the patient a bolus of an amount of purified pro-urokinase ("pro-UK") that inhibits the formation of occlusive thrombi without inducing a systemic effect in the patient, the pro-UK is administered after the completion of the thrombolytic treatment and periodically thereafter for the duration of therapy, and becomes incorporated into the outer membrane of the platelets of the patient, thereby increasing the T. sub. 1/2 of the pro-UK in plasma, which is about 7 to 8 minutes, to about 4 to 5 days, and inhibiting reocclusion without inducing a systemic effect.

2009022, Sep 10, 2009

Jul 1, 2008

12/165904

Victor GUREWICH - Cambridge MA, US
Jian-Ning LIU - Brighton MA, US
Paolo SARMIENTOS - Milano, IT

A61K 38/49, C12N 9/72, C12Q 1/48

424 9464, 435215, 435 15

It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.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.

2009022, Sep 10, 2009

Jun 30, 2008

12/165082

Victor Gurewich - Cambridge MA, US
Jian-Ning Liu - Brighton MA, US
Paolo Sarmientos - Milano, IT

A61K 38/45, A61P 9/00

424 945

It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.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.

2009013, May 28, 2009

Aug 7, 2008

12/187807

Victor Gurewich - Cambridge MA, US
Jian-Ning Liu - Brighton MA, US
Paolo Sarmientos - Milano, IT

A61F 2/02, A61K 38/48

424423, 424 9463

It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.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.

2007014, Jun 28, 2007

Jun 6, 2006

11/447455

Victor Gurewich - Cambridge MA, US
Jian-Ning Liu - Newton MA, US
Paolo Sarmientos - Lecco, IT

Thrombolytic Science, Inc. - Cambridge MA

A61K 38/48

424094640

It has now been discovered that certain mutant forms of pro-urokinase (“pro-UK”), such as so-called pro-UK mutant “M5” (Lys.sup.300.fwdarw.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.

2009001, Jan 8, 2009

Jul 1, 2008

12/215966

Victor Gurewich - Cambridge MA, US
Ralph Pannell - Brighton MA, US

A61K 38/49, A61P 7/00

424 9463

A mutant prourokinase plasminogen activator (M5) was developed to make prouPA less subject to spontaneous conversion to tcuPA in blood at therapeutic concentrations. Two-chain M5 was shown to form complexes with C1-inhibitor, which was the principal inhibitor of tcM5 in plasma. The effect of supplemental additions of C1-inhibitor on fibrinolysis and fibrinogenolysis by M5 was determined. Supplemental C1-inhibitor restored the stability of high-dose M5 and prevented fibrinogenolysis but not fibrinolysis, the rate of which was not compromised by the inhibitor. Due to higher dose tolerance of M5 in the presence of supplemental C1-inhibitor, the rate of fibrin-specific lysis reached that achievable by nonspecific fibrinolysis, which is the maximum possible for a plasminogen activator. Plasma C1-inhibitor stabilized M5 in plasma by inhibiting tcM5 which would otherwise greatly amplify non-specific plasminogen activation causing more tcM5 generation from M5. This unusual dissociation of inhibitory effects, whereby fibrinogenolysis and not fibrinolysis is inhibited, has significant implications for improving the safety and efficacy of fibrinolysis. Methods of reducing bleeding and non-specific plasminogen activation during fibrinolysis by administering M5 along with exogenous C1-inhibitor are disclosed.

2010014, Jun 10, 2010

Dec 9, 2008

12/330557

Victor Gurewich - Cambridge MA, US

A61K 38/48, A61P 9/00

424 9464

Treatment or prevention methods are described wherein t-PA and C1-inhibtor are used together in order to minimize the hemorrhagic complications of tPA Preferably, C1-inhibitor is infused prior to treatment with t-PA, thereby allowing for a safer thrombolysis without the excessive and dangerous bleeding associated with the use of t-PA alone particularly in the treatment of ischemic stroke.

5472692, Dec 5, 1995

Jul 2, 1993

8/087163

Jian-Ning Liu - Brighton MA
Victor Gurewich - Cambridge MA

New England Deaconess Hospital Corporation - Boston MA

C12N 972, C12N 948, A61K 3849

424 9463

The invention relates to thrombolytically active pro-urokinase (pro-UK) mutants comprising the amino acid sequence of native pro-UK, but including a mutation which causes the pro-UK mutants to induce less fibrinogenolysis and non-specific plasminogen activation than native pro-UK, to have at least a 10-fold lower intrinsic activity than native pro-UK, and to have substantially the same fibrin promotion and thrombolytic activity after plasmin activation compared to native pro-UK when administered to a patient.