The United States of America, as Represented by the Secretary, Department of Health and Human Services

The United States of America as Represented by the Department of Health

Other

Genetics Institute, Inc.

Giovanna Tosato

Sandra E Pike

Lei Yao

Yoshiyasu Aoki

Robert Yarchoan

Matthew L Sherman

Gene M Shearer

Richard S Little

Kathleen Wyvill

Jill Lietzau

James M Pluda

Ellen Feigal

Cecilia Sgadari

Anne L Angiolillo

Masashi Narazaki

Michael J DiPrima

Harald Schwalbe

Alix Tröster

Denis Kudlinzki

Nathalie Jores

Hidetaka Ohnuki

M Wayne Saville

Kazuyuki Taga

Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating certain cancers.

Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder

Methods and kits for preparing re-usable single cells are described. Cell components are anchored using a nano-scale scaffold to create a re-usable single cell. The nano-scale scaffold may be a polyacrylamide nano-scale scaffold. Methods to determine modifications of the genome, transcriptome, or epigenome are described.

Methods of preparing a re-usable single cell and methods for analyzing the epigenome, transcriptome, and genome of a single cell

Disclosed is a hetero-bifunctional ligand for use in inducing internalization of a target receptor. The hetero-bifunctional ligand includes a target receptor-binding agent that specifically binds the target receptor linked to an internalizing receptor-binding agent that specifically binds to an internalizing receptor, where the two binding agents are non-identical. Also disclosed is a method of inducing the internalization of a target receptor on a cell. The method includes contacting a cell with a hetero-bifunctional ligand, where binding of the hetero-bifunctional ligand induces internalization of a target receptor of the cell. Also disclosed a method of treating a disease or condition associated with a target receptor using the disclosed hetero-bifunctional ligand and pharmaceutical compositions including a hetero-bifunctional ligand.

Induced internalization of surface receptors

Specific fragments of vasostatin are disclosed. These fragments are of use in methods of stimulating the proliferation or survival of a hematopoietic cell exposed to a chemotherapeutic agent or irradiation. Methods of stimulating the proliferation or survival of a hematopoietic cell using these fragments are also disclosed. In one embodiment, methods are disclosed for stimulating the growth or survival of a hematopoietic stem cell with a fragment of vasostatin, in the presence of a growth factor.

Vasostatin as marrow protectant

Methods for inhibiting endothelial cell growth and angiogenesis, and suppressing tumor growth using calreticulin, fragments of calreticulin and variants of calreticulin are provided. Such methods are useful for the treatment of cancer and diseases associated with unwanted angiogenesis, for example chronic retinal detachment.

Use of calreticulin and calreticulin fragments to inhibit endothelial cell growth and angiogenesis, and suppress tumor growth

Specific fragments of vasostatin are disclosed. Also disclosed is a method of stimulating the proliferation or survival of a hematopoietic cell exposed to a chemotherapeutic agent or irradiation using these fragments. A method of stimulating the proliferation or survival of a hematopoietic cell is also disclosed. In one embodiment, the method is disclosed for stimulating the growth or survival of a hematopoietic stem cell with a fragment of vasostatin, in the presence of a growth factor.

A specific binding agent is provided, wherein the specific binding agent specifically binds Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), and the specific binding agent neutralizes an activity of vIL-6. In one embodiment, the specific binding agent is an antibody. Methods are provided for using a specific binding agent that binds vIL-6, and neutralizes a biological activity of vIL-6. Methods of treatment for a KSHV-associated disorder are also provided. Methods for diagnosing a KSHV-associated disorder are provided, as are kits that include a specific binding agent of the invention. A method is also provided for testing an agent for effectiveness in treating a KSHV-associated disorder. The method includes incubating the agent with a cell free system comprising a vIL-6 receptor component and vIL-6, and comparing the binding of vIL-6 and the receptor component in the presence of the agent to binding of vIL-6 to the receptor component in the absence of the agent. A decrease in the binding of vIL-6 to the receptor component in the presence of the agent indicates that the agent is effective for treating the KSHV-associated disorder.

Specific binding agents for KSHV vIL-6 that neutralize a biological activity

Methods are provided for using IL-12 to treat Kaposi's sarcoma (KS), particularly AIDS-associated KS.

Treatment of Kaposi's sarcoma with IL-12

The present invention is interferon-inducible protein 10 and fragments and analogs of interferon-inducible protein 10 as inhibitors of angiogenesis. The present invention is also the use of interferon-inducible protein 10 (IP-10) as well as fragments and analogs of IP-10 as potent inhibitors of angiogenesis. IP-10 profoundly inhibited basic fibroblast growth factor (bFGF)-induced neovascularization in immunocompromised mammals. In addition, IP-10, is useful in a dose-dependent fashion in suppressing endothelial cell differentiation into tubular capillary structures.

Growing community of inventors

Bethesda, MD, United States of America

Giovanna Tosato