The Johns Hopkins University

Leland Stanford Junior University

The United States Government As Represented by the Department of Veterans Affairs

Gregg L Semenza

Geoffrey C Gurtner

Jayakumar Rajadas

Mark R Nicolls

Xinguo Jiang

Gundeep Dhillon

Jordan J Green

Qiongyu Guo

Randall A Meyer

Corey J Bishop

Anand Kumar

The presently disclosed subject matter provides compositions, methods, and kits comprising shape memory particles that can be used for delivering a drug and/or treating a disease or disorder in a patient. Specifically, shape changes in the presently disclosed shape memory particles can be used to control drug delivery spatially and/or temporally in a patient. Also provided are compositions, methods, and kits comprising nanoparticles and hypoxia-inducible factor (HIF) inhibitors with or without chemotherapeutic agents for inhibiting HIF activity in a patient and/or treating a hypoxia-associated disease or disorder.

Shape memory particles for biomedical uses

Formulations and methods are provided for improving the function, i.e. clinical outcome, of solid organ transplants. Lung transplantation is of particular interest. In the methods of the invention, a nanoparticle formulation comprising an effective dose of an iron chelator active agent in nanoparticle form, including without limitation, deferoxamine (DFO), deferasirox (DFX), and deferiprone (DFP), etc. suspended in a carrier compatible with the tissue of interest, is topically applied to the surface of tissues at the site of anastomosis. The nanoparticles are comprised of the active agent and a pharmaceutically acceptable stabilizer.

HIF-1 modulator paint formulation and uses thereof

Formulations and methods are provided for improving the function, i.e. clinical outcome, of solid organ transplants. Lung transplantation is of particular interest. In the methods of the invention, a nanoparticle formulation comprising an effective dose of an iron chelator active agent in nanoparticle form, including without limitation, deferoxamine (DFO), deferasirox (DFX), and deferiprone (DFP), etc. is topically applied to the surface of tissues during episodes of graft rejection.

Iron chelators and use thereof for reducing transplant failure during rejection episodes

Substantially purified stable human hypoxia-inducible factor-1&agr; (sHIF-1alpha) proteins and polynucleotides encoding stable human hypoxia-inducible factor-1&agr; proteins are provided. A method is provided for treating a hypoxia-related tissue damage in a subject by administering to the subject a therapeutically effective amount of a sHIF-1alpha protein or a nucleic acid encoding a stable HIF-1alpha protein. Formulations are provided for the administration of stable human hypoxia inducible factor-1&agr; (HIF-1alpha) polypeptide or a polynucleotide encoding stable human hypoxia inducible factor-1alpha (HIF-1alpha) to a patient having or at risk of having hypoxia- or ischemia-related tissue damage.

Stable hypoxia inducible factor-1&agr; and method of use

The purified and characterization of hypoxia-inducible factor 1 (HIF-1) is described. HIF-1 is composed of subunits HIF-1&agr; and HIF-1&bgr;. Purified HIF-1&agr; polypeptide, its amino acid sequence and polynucleotide sequence are provided. A HIF-1&agr; variant that dimerizes to HIF-1&bgr; producing a nonfunctional HIF-1 complex is described. Methods for the prevention and treatment of hypoxia-related disorders are provided.

Hypoxia inducible factor-1 and method of use

Substantially purified stable human hypoxia-inducible factor-1.alpha. (sHIF-1.alpha.) mutein is provided. Polynucleotides encoding stable human hypoxia-inducible factor-1.alpha. mutein are also provided. A method is provided for treating a hypoxia-related tissue damage in a subject by administering to the subject a therapeutically effective amount of a sHIF-1.alpha. mutein or a nucleotide sequence including an expression control sequence operatively linked to a polynucleotide encoding a stable hypoxia-inducible factor-1.alpha. mutein. Formulations are provided for the administration of stable human hypoxia inducible factor-1.alpha. (HIF-1.alpha.) polypeptide or a polynucleotide encoding stable human hypoxia inducible factor-1.alpha. (HIF-1.alpha.) to a patient having hypoxia-related tissue damage.

Mutant hypoxia inducible factor-1 HIF-1

The purified and characterization of hypoxia-inducible factor 1 (HIF-1) is described. HIF-1 is composed of subunits HIF-1a and HIF-1.beta.. Purified HIF-1a polypeptide, its amino acid sequence and polynucleotide sequence are provided. A HIF-1.alpha. variant that dimerizes to HIF-1.beta. producing a nonfunctional HIF-1 complex is described. Methods for the prevention and treatment of hypoxia-related disorders are provided.

Nucleic acids encoding the hypoxia inducible factor-1

The purified and characterization of hypoxiainducible factor 1 (HIF-1) is described. HIF-1 is composed of subunits HIF-1.alpha. and HIF-1.beta.. Purified HIF-1.alpha. polypeptide, its amino acid sequence and polynucleotide sequence are provided. A HIF-1.alpha. variant that dimerizes to HIF-1.beta. producing a nonfunctional HIF-1 complex is described. Methods for the prevention and treatment of hypoxia-related disorders are provided.

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Towson, MD, United States of America

Gregg L Semenza