125 results about "Vascular endothelial growth factor B" 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.

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.

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.

This invention relates to expression vectors comprising VEGF-D and its biologically active derivatives, cell lines stably expressing VEGF-D and its biologically active derivatives, and to a method of making a polypeptide using these expression vectors and host cells. The invention also relates to a method for treating and alleviating melanomas or tumors expressing VEGF-D and various diseases.

VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

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 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 present invention provides a method for purifying recombinant peptides, polypeptides or proteins away from truncated or other full-length forms of these molecules. In particular the invention contemplates a method of purifying a vascular endothelial growth factor (VEGF) molecule by subjecting a biological sample containing the molecule to be purified to affinity chromatography under conditions sufficient for the full length molecules to bind and not the truncated or clipped forms. In the preferred embodiment there are two columns, the first is based on affinity for a poly his tag, the second column based on heparin binding affinity. Particularly preferred VEGF molecules are untagged VEGF-B167, hexa-His-tagged VEGF-B167, hexa-His-tagged VEGF-B186 and hexa-His-tagged VEGF-B10-108.

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.

The present invention relates generally to the field of cancer therapy and prophylaxis. More particularly, the present invention provides growth factor antagonists which inhibit the growth of cancers including tumors and pre-cancerous tissue. Even more particularly, the present invention is directed to antagonists of vascular endothelial growth factor-B and their use to inhibit the growth of cancer including tumor tissue and pre-cancerous tissue.

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 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 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 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.

The invention relates to a humanized monoclonal antibody against a human vascular endothelial growth factor and preparation and application thereof. In the humanized monoclonal antibody against the human vascular endothelial growth factor, the light chain has an amino acid sequence expressed by SEQ ID No: 1, and the heavy chain has an amino acid sequence expressed by SEQ ID No: 2. The antibody of the invention can be used for treating multiple diseases such as tumor, rheumatoid arthritis, psoriasis, atherosclerosis, diabetes, other proliferative retina diseases and the like, in particular treating age-related macular degeneration (AMD).

The invention provides a double-targeted fusion protein of target programmed death-1 (PD-1) or target programmed death-1 ligand (PD-L1) and a target vascular endothelial cell growth factor (VEGF) family. The double-targeted fusion protein comprises (i) an anti-PD-1 antibody or an anti-PD-L1 antibody and (ii) a VEGF family inhibiting domain (VID) effectively connected to the C end of each of two heavy chains of the anti-PD-1 antibody or the anti-PD-L1 antibody. The invention further provides polynucleotide coding the double-targeted fusion protein, a carrier containing the polynucleotide, a host cell containing the polynucleotide or the carrier, and application of the double-targeted fusion protein to therapy, prevention and / or diagnosis of diseases related to PD-1 activity, PD-L1 activityand VEGF family activity in an individual.

The invention discloses a vascular endothelial growth factor specifically combined with collagen and an application thereof. The vascular endothelial growth factor specifically combined with collagenis a recombination protein obtained by fusing a collagen combination domain with the amino terminal or carboxyl terminal of the vascular endothelial growth factor by connecting peptide; and the aminoacid sequence of the collagen combination domain is the sequence 2 in a sequence list from the amino terminal position 178 to position 184. The invention also discloses an encoding gene of the vascular endothelial growth factor specifically combined with the collagen. The vascular endothelial growth factor specifically combined with the collagen is favorable for solving the problems of low activity and high risk caused by the indiffusion of the vascular endothelial growth factor, and provides a new method for repairing myocardial damage.

A mouse monoclonal antibody for antagonizing and inhibiting binding of a vascular endothelial 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 cDNA encoding a soluble neuropilin protein (sNP) which is isolated from neuropilin (NP) producing cells or is recombinantly engineered from NP-encoding DNA. NP-1 and NP-2 are preferred NPs but any neuropilin or VEGF receptor (VEGFR), where the constituents share at least about 85% homology with either of the above VEGF165R / NP-1 and NP-2. More preferably, such constituent shares at least 90% homology. Still more preferably, each constituent shares at least 95% homology.