Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Kenneth A Thomas, Jr

Richard L Kendall

Marvin L Bayne

Gregory L Conn

Andrew J Tebben

Xianzhi Mao

David L Linemeyer

Andrew J Bett

William R Huckle

Corey K Goldman

The vascular endothelial cell growth factor (VEGF) inhibitors of the present invention are naturally occurring or recombinantly engineered soluble forms with or without a C-terminal transmembrane region of the receptor for VEGF, a very selective growth factor for endothelial cells. The soluble forms of the receptors will bind the growth factor with high affinity but do not result in signal transduction. These soluble forms of the receptor bind VEGF and inhibit its function.

Inhibitor of vascular endothelial cell growth factor

Vascular endothelial cell growth factor II is purified from the culture media used to maintain mammalian glioma cells. The protein is a heterodimer, stimulates mitogenesis of mammalian vascular endothelial cells and is useful for the promotion of vascular development and repair. This unique growth factor is also useful in the promotion of tissue repair.

DNA molecules encoding vascular endothelial cell growth factor II subunits

An isolated nucleic acid molecule encoding a novel human receptor type tyrosine kinase gene, KDR, is disclosed. The isolation of this KDR cDNA sequence results in disclosure of purified forms of human KDR protein, recombinant vectors and recombinant hosts which express human KDR.

Human receptor tyrosine kinase, KDR

Vascular endothelial cell growth factor C subunit DNA is prepared by polymerase chain reaction techniques. The DNA encodes a protein that may exist as either a heterodimer or homodimer. The protein is a mammalian vascular endothelial cell mitogen and as such is useful for the promotion of vascular development and repair. This unique growth factor is also useful in the promotion of tissue repair.

Vascular endothelial cell growth factor C subunit

The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with solid tumor growth, tumor metastasis, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration Gene therapy methodology is disclosed for inhibition of primary tumor growth and metastasis by gene transfer of a nucleotide sequence encoding a soluble form of a VEGF tyrosine kinase receptor to a mammalian host. The transferred nucleotide sequence transcribes mRNA and a soluble receptor protein which binds to VEGF in extracellular regions adjacent to the primary tumor and vascular endothelial cells. Formation of a sVEGF-R/VEGF complex will prevent binding of VEGF to the KDR and FLT-1 tyrosine kinase receptors, antagonizing transduction of the normal intracellular signals associated with vascular endothelial cell-induced tumor angiogenesis. In addition, expression of a soluble receptor tyrosine kinase may also impart a therapeutic effect by binding either with or without VEGFs to form non-functional heterodimers with full-length VEGF-specific tyrosine kinase receptors and thereby inhibiting the mitogenic and angiogenic activities of VEGFs.

Gene therapy for inhibition of angiogenesis

Vascular endothelial cell growth factor II

The vascula endothelial cell growth factor (VEGF) inhibitors of the present invention are naturally occurring or recombinantly engineered soluble forms with or without a C-terminal transmembrane region of the receptor for VEGF, a very selective growth factor for endothelial cells. The soluble forms of the receptors will bind the growth factor with high affinity but do not result in signal transduction. These soluble forms of the receptor bind VEGF and inhibit its function.

Growing community of inventors

Chatham Borough, NJ, United States of America

Kenneth A Thomas, Jr