St. Elizabeth's Medical Center of Boston, Inc.

Genentech, Inc.

Warner-lambert Company

Case Western Reserve University

Boston Scientific Corporation

Summit Technology, Inc.

Caritas St. Elizabeth's Medical Center of Boston, Inc.

Steward St. Elizabeth's Medical Center of Boston, Inc.

Genesys Research Institution Inc.

Jeffrey M Isner

Takayuki Asahara

Douglas W Losordo

Napoleone Ferrara

Ralph H Schwall

David F Muller

Patrice Denefle

Kenneth Walsh

Didier Branellec

Richard H Clarke

Linda Isner, Legal Representative

In accordance with the present invention, EC progenitors can be used in a method for regulating angiogenesis, i.e., enhancing or inhibiting blood vessel formation, in a selected patient and in some preferred embodiments for targeting specific locations. For example, the EC progenitors can be used to enhance angiogenesis or to deliver an angiogenesis modulator, e.g. anti- or pro-angiogenic agents, respectively to sites of pathologic or utilitarian angiogenesis. Additionally, in another embodiment, EC progenitors can be used to induce reendothelialization of an injured blood vessel, and thus reduce restenosis by indirectly inhibiting smooth muscle cell proliferation.

Compositions and methods for regulating angiogenesis

A method for treating peripheral neuropathy, particularly ischemic peripheral neuropathy, is provided. The method involves administering to subjects in need of such treatment an effective amount of an angiogenic growth factor to alleviate a symptom of the neuropathy.

Angiogenic growth factors for treatment of peripheral neuropathy

The present invention generally provides methods for modulating formation of new blood vessels. In one embodiment, the methods include administering to a mammal an effective amount of granulocyte macrophage-colony stimulating factor (GM-CSF) sufficient to form the new blood vessels. Additionally provided are methods for preventing or reducing the severity of blood vessel damage in a mammal which methods preferably include administering to the mammal an effective amount of GM-CSF. Provided also as part of this invention are pharmaceutical products and kits for inducing formation of new blood vessels in the mammal.

Compositions and methods for modulating vascularization

Pharmaceutical products are provided comprising EC progenitors for use in methods for regulating angiogenesis, i.e., for enhancing or inhibiting blood vessel formation, in a selected patient and in some preferred embodiments for targeting an angiogenesis modulator to specific locations. For example, the EC progenitors can be used to enhance angiogenesis or to deliver an angiogenesis modulator, e.g., anti- or pro-angiogenic agents, respectively to sites of pathologic or utilitarian angiogenesis. Additionally, in another embodiment, EC progenitors can be used to induce reendothelialization of an injured blood vessel, and thus reduce restenosis by indirectly inhibiting smooth muscle cell proliferation.

Pharmaceutical products comprising endothelial cell precursors

The present invention provides a method for inducing reendothelialization of the lining of an injured blood vessel comprising contacting the injured portion of the vessel with nucleic acid encoding an endothelial cell mitogen operably linked to a promoter (nucleic acid cassette) to result in expression of the mitogen when delivered to the cells at the site of vascular injury. The resulting reendothelialization of the injured blood vessel inhibits smooth muscle cell proliferation and consequently reduces restenosis. The methods of the present invention may be used to treat any blood vessel injury that results in denuding of the endothelial lining of the vessel wall, including, for example, those injuries resulting from balloon angioplasty and deployment of endovascular stents.

Treatment of vascular injury

The present invention is directed to the use of a group of ACE inhibitors to stimulate angiogenesis in mammals or in mammalian tissue in vitro. Specifically, the present invention is directed to inducing or enhancing angiogenesis through the administration of a group of ACE inhibitors and to ACE inhibitor-containing compositions for effecting the inducement or enhancement of angiogenesis. The ACE inhibitors may also be useful in the promotion of angiogenesis, such as in the promotion of wound healing, bone healing, and in the treatment of bums, as well as in promoting the formation, maintenance, and repair of tissue. In a preferred embodiment, the ACE inhibitor, quinapril, or quinaprilat, is used to treat, prophalactically or otherwise, mammals in need of angiogenic-treatment.

Method of using angiotensin converting enzyme inhibitor to stimulate angiogenesis

Methods for enhancing angiogenesis in a mammal using hepatocyte growth factor ('HGF') are provided. In the methods, HGF can be administered to mammals suffering from, for instance, vascular insufficiency or arterial occlusive disease. Articles of manufacture and kits containing HGF are also provided.

Angiogenesis using hepatocyte growth factor

The present invention provides a method for treating ischemic tissue in a mammal which comprises injecting said tissue with an effective amount of a nucleic acid capable of expressing an angiogenic protein. The method of the present invention may be used to treat any ischemic tissue, i.e., a tissue having a deficiency in blood as the result of an ischemic disease. Such tissues can include, for example, muscle, brain, kidney and lung. Ischemic diseases include, for example, cerebrovascular ischemia, renal ischemia, pulmonary ischemia, limb ischemia, ischemic cardiomyopathy and myocardial ischemia.

Method for treating ischemic tissue

In accordance with the present invention, EC progenitors can be used in a method for regulating angiogenesis, i.e., enhancing or inhibiting blood vessel formation, in a selected patient and in some preferred embodiments for targetting specific locations. For example, the EC progenitors can be used to enhance angiogenesis or to deliver an angiogenesis modulator, e.g. anti- or pro-angiogenic agents, respectively to sites of pathologic or utilitarian angiogenesis. Additionally, in another embodiment, EC progenitors can be used to induce reendothelialization of an injured blood vessel, and thus reduce restenosis by indirectly inhibiting smooth muscle cell proliferation.

Methods for enhancing angiogenesis with endothelial progenitor cells

The present invention relates to replication defective recombinant viruses which contain at least one inserted gene encoding all or part of the protein GAX or of a variant of this protein, and to their therapeutic use, in particular for treating post-angioplastic restenosis.

Viral vectors and their use for treating hyperproliferative disorders,

The present invention provides a method for inducing reendothelialization of the lining of an injured blood vessel comprising contacting the injured portion of the vessel with nucleic acid encoding an endothelial cell mitogen such as vascular endothelial growth factor (VEGF) operably linked to a promoter to result in expression of the mitogen when delivered to the cells at the site of vascular injury. The resulting reendothelialization of the injured blood vessel inhibits smooth muscle cell proliferation and consequently reduces restenosis. The methods of the present invention may be used to treat any blood vessel injury that results in denuding of the endothelial lining of the vessel wall, including, for example, those injuries resulting from balloon angioplasty and deployment of endovascular stents.

Treatment of vascular injury using vascular endothelial growth factor

The present invention provides a method for the delivery of a nucleic acid to an arterial cell comprising contacting the cell with a hydrophilic polymer incorporating the nucleic acid. The nucleic acid may be any nucleic acid, including antisense DNA or RNA. The nucleic acid may encode hormones, enzymes, receptors or drugs of interest. The nucleic acid is selected based upon the desired therapeutic outcome. For example, in the treatment of ischemic diseases, one would select a DNA encoding an angiogenic protein. The nucleic acid may be carried by a microdelivery vehicle such as cationic liposomes and adenoviral vectors. DNA encoding different proteins may be used separately or simultaneously.

Methods and products for nucleic acid delivery

A method and system for facilitating thrombolytic therapy includes a perfusion tube, in the form of an infusion guidewire or catheter, for delivering a lytic agent at a thrombosis. The perfusion tube includes, as an integral part thereof, at its distal end a sensor that connects to monitoring and announcing circuit. The monitoring and announcing circuit may include local and remote audio and visual announcing mechanisms for indicating the existence of blood flow above a predetermined minimum flow rate thereby to indicate lysis.

Method and apparatus for thrombolytic therapy

A laser therapy system having improved effectiveness in surgical use, particularly in laser angioplasty, can be formed by employing a pulsed source of radiation. The pulsed energy source is preferably an excimer laser having a coherent beam of ultraviolet radiation and preferably is employed in conjunction with a dye laser to produce an output beam which is tunable over a wide portion of the ultraviolet and visible spectrum. The output beam is coupled via a novel coupling device to an optical fiber disposed within a surgical instrument, for example, a percutaneous catheter. The operative components are sealed in a gas-tight, liquid-tight housing. An electronic controller monitors and adjusts the output energy density, duration, and pulse repetition rate. In operation, a pulsed, high energy beam of extremely short duration is available to remove atherosclerotic plague with less damage to the underlying tissue and less chance of perforating the blood vessel wall.

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Weston, MA, United States of America

Jeffrey M Isner