162 results about "Vascular endothelial growth factor C" patented technology

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.

An encased stent that discourages restenosis by having a homogenous endothelial cell lining along the inner wall of the stent. The endothelial cell lining may be coated on the stent before the stent is placed in the artery, or the endothelial cell lining may be grown after placement by several factors that encourage such growth and discourage restenosis. The endothelial cells to coat the stent may be genetically modified to enhance the growth of the endothelial cells into a homogeneous lining. The stent has a continuous lining in the form of a multi-layer polymer coating, including a conducting biocorrosion inhibiting layer and a continuous film of polyurethane coupled by a coupling agent to polyethylene glycol. Various drugs and cell factors may be incorporated into the lining, such as anti-thrombin, anti-inflammatory and anti-coagulant drugs, cell cycle inhibitors, and vascular endothelial growth factors.

The present invention provides a method of treating a breast cancer disease in a patient who has failed prior treatment with an anti-VEGF antibody, comprising administering to the patient a therapeutically effective amount of an anti-HER2 antibody while continuing said anti-VEGF antibody therapy. The invention also provides corresponding pharmaceutical kits and pharmaceutical compositions.

Methods are provided for designing and selecting antibodies against human antigens with high affinity and specificity in silico and in vitro. In some particular embodiments, methods are provided for designing and selecting humanized or fully human antibodies against vascular endothelial growth factor (VEGF) with high affinity and specificity. In another aspect of the invention, monoclonal antibodies against VEGF are provided. In particular, humanized or human anti-VEGF monoclonal antibodies are provided with ability to bind to human VEGF with high affinity, inhibit VEGF-induced proliferation of endothelial cells in vitro and inhibit VEGF-induced angiogenesis in vivo. These antibodies and their derivative can be used in a wide variety of applications such as diagnosis, prevention, and treatment of diseases such as cancer, AMD, diabetic retinopathy, and other diseases derived from pathological angiogenesis.

A biosensor for detection of vascular endothelial growth factor (VEGF) hybridization uses an array of parallel capacitors to detect electrochemical binding of circulating VEGF to immobilized anti-VEGF monoclonal half-antibodies (a-VEGF mhAb). Binding of a-VEGF mhAb modulates the threshold voltage of a circuit, changing the impedance of the circuit. An electrode coated with a p-Si substrate enhances the affinity between the VEGF molecules. A fluid cell delivers VEGF samples onto the active surface of the chip. An array of parallel capacitors arranged in an interdigitated pattern detects the VEGF in the fluid. The detector provides an accurately measured and quantifiable rate of change of the VEGF molecules in vivo, providing real time feedback which is used to measure response of the tumor to delivered chemotherapeutic agents and biological response modifiers (BRMs) for the purpose of determining tumor burden and efficacy of the chemotherapy as part of a homeostatic loop for chemotherapy.

The present invention provides a method of treating a breast cancer disease in a patient who has failed prior treatment with an anti-VEGF antibody, comprising administering to the patient a therapeutically effective amount of an anti-HER2 antibody while continuing said anti-VEGF antibody therapy. The invention also provides corresponding pharmaceutical kits and pharmaceutical compositions.

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.

The present invention provides polypeptides that bind cellular receptors for vascular endothelial growth factor polypeptides; polynucleotides encoding such polypeptides; compositions comprising the polypeptides and polynucleotides; and methods and uses involving the foregoing. Some polypeptides of the invention exhibit unique receptor binding profiles compared to known, naturally occurring vascular endothelial growth factors.

This invention discloses a method for preparing a complex comprised of a VEGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a VEGF Nucleic Acid Ligand by SELEX methodology and associating the VEGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more VEGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a VEGF Nucleic Acid Ligand or Complex and methods for making the same.

The present invention provides vascular endothelial cell growth factor (VEGF) antagonists and methods of using VEGF antagonists. VEGF antagonists contemplated by the invention include VEGF antibodies and VEGF receptor fusion proteins. Methods of treating edema and stroke using VEGF antagonists are also provided.

A mouse monoclonal antibody for antagonizing and inhibiting binding of a vascular endothelial cell growth factor (VEGF) and its receptor (VEGF-R), and a heavy chain variable region and light chain variable region amino acid sequence thereof. Also disclosed are a humanized preparation process of the antibody and a heavy chain variable region and light chain variable region amino acid sequence of the humanized antibody. The humanized antibody or its derivative can act as an ingredient of a pharmaceutical composition or be prepared into a suitable pharmaceutical preparation, is administered alone or in combination with a chemotherapy drug or other treatment means, and is used in broad-spectrum treatment of various solid tumors such as colon cancer, breast cancer and rhabdomyosarcoma.

The present invention relates to binding proteins specific for Vascular Endothelial Growth Factor A (VEGF-A), in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx (wherein xxx denotes the amino acid length of the VEGF-A mature protein) binding to Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

The invention discloses a VEGF (Vascular Endothelial Growth Factor) single-domain antibody as well as a fusion antibody and a polymer antibody of the VEGF antibody. The invention also discloses a nucleotide sequence for encoding the antibodies, an expression vector containing the nucleotide sequence, a recombinant bacterium containing the nucleotide sequence as well as a preparation method and applications of the antibodies. The VEGF antibody is low in molecular weight, high in plasticity and wide in application prospect.

The invention provides a human anti-vascular endothelial cell growth factor (VEGF) antibody as well as a coding gene and an application thereof. According to the invention, by virtue of genetic engineering means and a phage surface display technology, an anti-VEGF genetic engineering single-chain antibody is screened from a complete synthesis single-chain human antibody library, a variable region gene sequence of the anti-VEGF genetic engineering single-chain antibody is obtained, amino acids in a CDR (complementary determining region) of the anti-VEGF genetic engineering single-chain antibody are transformed by virtue of bioinformatics means, and finally a series of high-affinity anti-VEGF antibodies are obtained by constructing and screening mutation libraries and utilizing a chain exchange method, wherein affinity of the anti-VEGF antibodies with human VEGF is 10<-9>-10<-11>M. According to the invention, identification on immunocompetence and biological activity of the antibody is completed, the anti-VEGF antibody is verified to have the characteristic of being antagonistic to combination of VEGF and VEGFR2 and can effectively inhibit proliferation of vascular endothelial cells induced by VEGF. The invention provides a new specific candidate antibody molecule for resisting tumour and senile macular degeneration targeted by VEGF in future.

The present invention provides vascular endothelial cell growth factor (VEGF) antagonists and methods of using VEGF antagonists. VEGF antagonists contemplated by the invention include VEGF antibodies and VEGF receptor fusion proteins. Methods of treating edema and stroke using VEGF antagonists are also provided.

Disclosed herein is a rational, multi-tier approach to the administration of growth factor proteins in the treatment of heart disease. Also disclosed is a method to evaluate the effectiveness of the administration of growth factor proteins comprising the clinical assay of CPK-MB levels in a patient undergoing treatment with growth factor proteins. In addition, there is disclosed a method for treatment of heart disease comprising administration of a therapeutically effective amount of a growth factor protein by oral inhalation therapy.

There is provided a panel of biomarkers of tumour metastasis comprising any two of carbonic anhydrase-9 (CAIX), vascular endothelial growth factor C (VEGF-C), ephrin A5 (EFNA5), eph receptor B2 (EPHB2), transforming growth factor beta 3 (TGF-β3), pyruvate dehydrogenase kinase isoenzyme-3 (PDK3), carbonic anhydrase-12 (CAXII), keratin 14 (KRT14), hypoxia inducible factor 1 alpha subunit (HIF-1α), or tenascin C (TNC). CAIX, VEGF-C, EFNA5, EPHB2, TGF-β3 or PDK3 may be indicators of moderate metastatic potential, while CAXII, KRT14, HIF-1α, or TNC may be indicators of high metastatic potential. There is also provided a method of determining risk of tumour metastasis using the aforementioned biomarkers is also provided. The biomarkers may be used in diagnosis, prognosis, treatment selection, or to test putative therapeutics. The biomarkers may be used to assess malignancies or cancers having hypoxic regions, such as breast cancer.

The present invention is directed to VEGF-2 polynucleotides and polypeptides and methods of using such polynucleotides and polypeptides. In particular, provided are methods of treating retinal disorders with VEGF-2 polynucleotides and polypeptides.

The present invention involves the preparation of vascular endothelial growth actor (VEGF) variants which provide materials that are selective in respect to binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.

The invention discloses a soluble VEGFR (Vascular Endothelial Growth Factor Receptor) difunctional chimera receptor VEGFR31-Ig as well as a preparation method and application thereof in preparing antineoplastic drugs. The soluble VEGFR difunctional chimera receptor VEGFR31-Ig disclosed by the invention can not only be combined with VEGF-A and VEGF-B, but also be combined with VEGF-C or VEGF-D, and can be used for preparing the antineoplastic drugs.

The present invention provides moieties that bind to the most membrane-proximal Ig-like domain of the ectodomain (D7) of vascular endothelial growth factor (VEGF) receptors, wherein the moieties antagonize the activity of the VEGF receptor.

The invention belongs to the technical field of genetic engineering antibodies and particularly relates to a whole human source single chain antibody which is designed and expressed by genetic engineering and has specific affinity towards human vascular endothelial growth factor receptor 2 (VEGFR-2). The invention also provides a nucleotide sequence of heavy chain variable region and light chain variable region immunoglobulin molecules, a nucleotide sequence which comprises the heavy chain variable region and light chain variable region immunoglobulin molecules, an amino acid sequence which comprises variable heavy chain and variable light chain immunoglobulin molecules, and a sequence which corresponds to CDR1, CDR2 and CDR3 of a complementary determining region. The invention also provides a method for generating and expressing the anti-VEGFR-2 single chain antibody, by cycling operations of gathering-elution-gathering, an antibody which has specific affinity towards the human vascular endothelial growth factor is screened, and then the single chain antibody is obtained through a prokaryotic cell secretion and expression system and an affinity purification system. The antibody can be coupled with a detectable substance and therapeutic agent.

This invention relates to therapeutic organic compounds and inhibition of secretion of vascular endothelial growth factor (VEGF) and its effects, including angiogenesis.

The present invention is directed to an isolated nucleic acid encoding a fusion protein comprising (1) the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof; and (2) human vascular endothelial growth factor, or a truncated or mutated version thereof; wherein the fusion protein possesses ribosome inactivating activity and ability to bind to cellular VEGF receptors. The present invention is also directed to polypeptides the above combination of toxin and growth factor, as well as expression vectors and transformed cells incorporating the above nucleic acid. The invention is also directed to pharmaceutical compositions and methods for treating patients suffering from diseases relating to angiogenesis.

The invention provides a human vascular endothelial cell culture solution. The human vascular endothelial cell culture solution is prepared from a basic culture medium, fetal calf serum, human recombined epidermal growth factors, human recombined fibroblast growth factors, vascular endothelial growth factors, insulin-like growth factors, vitamin C, cortisol, cholera toxin, aminoethanol and ethanolamine phosphate. Compared with a traditional vascular endothelial cell culture medium, the human vascular endothelial cell culture solution has the advantages that the culture solution can be suitable for multiple kinds of vascular endothelial cells, cell proliferation is effectively promoted, the division time is effectively shortened, the characteristics of the vascular endothelial cells are maintained, the passage number of the in-vitro human vascular endothelial cells is greatly increased, and the survival time of the in-vitro human vascular endothelial cells is greatly prolonged; meanwhile, all the ingredients of the cell culture solution can be obtained in a general laboratory, preparation is convenient, a special finished product culture medium is not needed, therefore, the cost for culturing the endothelial cells is greatly reduced, and the human vascular endothelial cell culture solution is suitable for application and popularization.

The invention relates to a genetic engineering antibody, in particular to a vascular Endothelial Growth Factor (VEGF) acceptor 2 / CD3 bispecific single-chain antibody. The bispecific single-chain antibody comprises two binding sites respectively having antigenic specificity on the VEGF acceptor 2 and CD3. The invention further relates to nucleotide sequence coding the bispecific antibody, a carrier containing nucleotide sequence, and a host cell transfected by the carrier. The VEGF2 / CD3 bispecific single-chain antibody has small molecular weight and immunogenicity, is easy to penetrate throughcompact tumor barrier and enters the microcirculation around solid tumor, thus having application prospects in preparing tumor treatment drugs.

A stable liquid formulation includes a fusion protein having an Fc domain of a human immunoglobulin G (IgG), in particular, a protein in which an Fc domain of a human immunoglobulin G (IgG) and a soluble extracellular domain of a vascular endothelial growth factor (VEGF) receptor are fused (e.g., aflibercept)). A composition for stabilizing a protein and a method for stabilizing a protein in which an Fc domain of an IgG and a soluble extracellular domain of a VEGF receptor are fused are disclosed. The present invention improves therapeutic effects on various ophthalmic diseases (e.g., retinal vein occlusion, diabetic macular edema, choroidal neovascularization and wet age-related macular degeneration, etc.) caused by abnormal angiogenesis, while pursuing stabilization of bioactivity through a stable liquid formulation suitable for intravitreal injection of an anti-VEGF-Fc fusion protein including aflibercept.

The present invention provides materials and methods for repairing tissue and using vascular endothelial growth factor C (VEGF-C) genes and / or proteins. Methods and materials related to the use of VEGF-C for the reduction of edema and improvement of skin perfusion is provided. Also provided is are materials and methods for using VEGF-C before, during, and after reconstructive surgery.

The invention relates to the fields of pharmaceutical chemistry and organic chemistry, in particular to isoquinolinone derivatives. The compounds can be used for treating various medical indications associated with postmenopausal symptoms, uterine fiber lesions and arterial smooth muscle cell proliferation, particularly ER-(+) breast cancer by inhibiting alpha-estrogen receptor subtype (ER alpha) and through vascular endothelial growth factor receptor (VEGFR-2) bi-target. Meanwhile, the compounds have an obvious inhibiting effect on tumor metastasis, and have a general formula I.