Children's Medical Center Corporation

Other

University of Pennsylvania

The Upjohn Co.

Takeda Chemical Industries, Inc.

Beth Israel Deaconess Medical Center, Inc.

Vermillion Corporation

Judah M Folkman

Robert J D'Amato

Ofra Benny-Ratsaby

Robert Samuel Langer

Donald Elliot Ingber

Paul B Weisz

Ronit Satchi-Fainaro

John M McCall

Tai-Tung Yip

Wendell Wierenga

Michael S O'Reilly

Kashi Javaherian

Yuen W Shing

Takeshi Fujita

Tsuneo Kanamaru

Raghu Kalluri

Vladimir Podust

William E Rich

Yihai Cao

Robert Tjin Tham Sjin

Jan Andersson

Edward Dallas Hall

Giannoula Lakka Klement

Maria Ann Rupnick

Karen S Moulton

Lars Holmgren

John M Braughler

Dean S Hsieh

Harold Brem

Anna-Lena Spetz-Holmgren

H Paul Ehrlich

Christian Becker

Ronit Satchifainaro

Described herein are MetAP-2 inhibitors and compositions and formulations thereof, and more particularly compositions and formulations of MetAP-2 inhibitors wherein the MetAP-2 inhibitor is associated with a block copolymer comprising a hydrophilic polymer moiety and a hydrophobic polymer moiety. The present invention also relates to compositions and formulations comprising MetAP-2 inhibitors for oral administration or administration via routes such as topical or ocular administration. The present invention also provides methods to treat conditions associated with or related to the over-expression or over-activity of MetAP-2 by administering the compositions and formulations comprising MetAP-2 inhibitors as disclosed herein.

MetAP-2 inhibitor polymersomes for therapeutic administration

Methods and compositions for treating and/or preventing a pregnancy related disease or disorder are provided. The methods involve administration of 2-methoxyestradiol, or an analog thereof, to a subject. Also provided are methods for diagnosing or predicting a pregnancy related disease or disorder. The methods involve detection of 2-methoxyestradiol, or a precursor or metabolite thereof.

Methods and compositions for treatment of preeclampsia

The present invention relates to the fields of immunology and biochemistry. Particularly, the present invention describes methods, devices and kits for early detection of clinical conditions having associated changes in systemic angiogenic activity, particularly cancers, inflammatory conditions, infections, and events associated with pregnancy and abortion.

Platelet biomarkers for cancer

Provided herein are peptides from the N-terminal of endostatin proteins, including the first histidine of the protein, nucleic acids encoding the peptides, pharmaceutical compositions comprising the nucleic acids and proteins and methods for using the pharmaceutical compositions to treat or prevent endometriosis in a subject.

Anti-angiogenic peptides for treating or preventing endometriosis

Provided herein are anti-angiogenic comprising the N-terminal end of endostatin, nucleic acids encoding the same, pharmaceutical preparations comprising an effective amount of the peptide and nucleic acids and use of the pharmaceuticals in treating or preventing diseases or conditions associated with undesirable angiogenesis.

Anti-angiogenic peptides from the N-terminus of endostatin

The present invention relates to conjugates of water-soluble polymers and o(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

TNP-470 polymer conjugates and use thereof

The present invention relates to conjugates of water-soluble polymers and o-(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

TNP-470 species, polymer conjugates and use thereof

The present invention provides a method for treating cardiovascular ailments. The method involves first screening an individual to determine their risk of having the potential for unstable plaques. Such individuals can be selected by looking at one of the following criteria: (i) increased plaque neovascularization, (ii) area ratio of intima to wall area of a plaque, (iii) evidence of plaque hemorrhage, or (iv) inflammatory cells associated with plaque vessels. Looking at these criteria permits one to select individuals having the potential for unstable plaques. The method then involves treating the selected individual with an effective amount of an angiogenesis inhibitor.

Method of treatment of cardiovascular injuries

A method and compositions for inhibiting excessive scar formation and adhesions by administering to a patient in need thereof an effective amount of an angiogenesis inhibitor. In the preferred embodiment, the angiogenesis inhibitor is selective, such as a fumagillol derivative like 0-chloroacetylcarbamoyl-Fumagillol (TNP-470, TAP Pharmaceuticals), thalidomide, or a selective drug having more than one activity, such as minocycline or penicilliamine which also have antibiotic activity. Less selective compounds can also be used, such as the cytokine IL12. Patients to be treated include those having experienced trauma, surgical intervention, burns, and other types of injuries. The inhibitor is administered in an amount effective to decrease excessive scarring, defined as formation of high density tissue including cells and connective tissue, without preventing normal wound closure. The inhibitors can be administered systemically and/or locally or topically, as needed. For prevention of adhesions, the angiogenesis inhibitor would typically be applied at the time of surgery, preferably in a controlled release formulation and/or using barrier technology.

Prevention of adhesions and excessive scar formation using angiogenesis inhibitors

The present invention relates to a method of of transferring genomic DNA from apoptotic bodies to engulfing cells, wherein DNA is transferred from a donor cell to a recipient cell. More specifically the method includes providing somatic donor cells comprising desired DNA; generating apoptotic bodies of said donor cells; incubation of the apoptotic bodies with engulfing recipient cells under biological conditions allowing uptake of DNA from the apoptotic bodies by said recipient cells; and optionally selecting recipient cells which have integrated DNA from the apoptotic bodies. The present method is useful in various pharmaceutical applications, such as in vaccine preparations and gene identification procedures. Further, the present invention also relates to a method of preventing and/or treating a clinical condition in a patient, which comprises isolating cells comprising genomic DNA; generating apoptotic bodies of said isolated cells; incubation of said apoptotic bodies with engulfing recipient cells under biological conditions allowing uptake of DNA from the apoptotic bodies, optionally, selecting cells containing DNA originating from the isolated cells; and administering cells in a pharmaceutically acceptable carrier to the patient, thus enabling a protective and/or therapeutic reaction against the clinical condition.

Method of DNA transfer

Angiogenesis inhibitors are administered to patients in an amount effective to regulate normal, non-transformed vascularized tissue size and/or growth by regulating its vascular compartment. Examples of tissues that can be controlled include adipose tissue, intestinal polyps, muscle (including cardiac) tissue, and endometrial tissue. The response of these tissues to the angiogenesis inhibitors is dose-dependent, reversible, and common to a variety of different angiogenesis inhibitors (examples use TNP-470, angiostatin, and endostatin), based on studies in animal models of obesity, intestinal polyps, cardiac hypertrophy, and endometriosis. Initial studies conducted in an adipose tissue model (genetically obese mice and normal control mice) showed that the growth and mass of adipose tissue is under the control of microvascular endothelium. Expansion of adipose tissue was associated with endothelial cell proliferation. Inhibition of angiogenesis led to reduction in adipose tissue mass. Weight gain in animals receiving angiogenesis inhibitors was significantly restricted, in spite of increases in appetite sufficient to cause weight gain in paired-fed mice. Discontinuation of the inhibitor resulted in rapid expasion of the adipose tissue. The effect was dose-dependent, repeatedly reversible, and occurred in response to all of the inhibitors tested. Significant inhibition was also observed in both the intestinal polyp and cardiac hypertrophy animal models, using dosages of two-thirds or less than the dosages used to treat tumors. Preliminary results in an endometriosis model also show a clear trend towards decreased development of endometriosis in animals treated with angiogenesis inhibitors at a dosage of one-third the dosage used to treat tumors. No effect on normal tissue that was not proliferating, other than adipose tissue, was observed.

Method for regulating size of vascularized normal tissue

Polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are disclosed. Compositions and methods for separating a molecular species, including but not limited to a biologically active protein, from a mixture, for the storage of protein factors and for the therapeutic biodelivery of protein factors which employ the polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are also disclosed.

Cyclodextrin polymers and cyclodextrins immobilized on a solid surface

A method for retaining ophthalmological agents in ocular tissues is provided comprising complexing an ophthalmological drug or reagent with a sulfated glucan sulfate such as cyclodextrin sulfate and contacting the complex so formed with the ocular tissue.

Method for retaining ophthalmological agents in ocular tissues

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Brookline, MA, United States of America

Judah M Folkman