49 results about "VEGF binding" patented technology

Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

Anti-angiogenic peptides that inhibit activation or proliferation of endothelial cells are disclosed. Such peptides may be used to inhibit VEGF binding to the VEGFR2 receptor (also known as the kinase domain receptor or KDR) and bFGF binding to its receptor. Such peptides may also be used to inhibit, VEGF, bFGF, or integrin activation of endothelial cells in angiogenesis-associated diseases such as cancer, leukemia, multiple myeloma, inflammatory diseases, eye diseases and skin disorders.

Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naïve libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.

Anti-angiogenic peptides that inhibit activation or proliferation of endothelial cells are disclosed. Such peptides maybe used to inhibit VEGF binding to the VEGFR2 receptor (also known as the kinase domain receptor or KDR) and bFGF binding to its receptor. Such peptides may also be used to inhibit, VEGF, bFGF, or integrin activation of endothelial cells in angiogenesis-associated diseases such as cancer, leukemia, multiple myeloma, inflammatory diseases, eye diseases and skin disorders.

Bispecific binding molecules, in particular immunoglobulin single variable domains such as VHHs and domain antibodies, comprising a VEGF-binding component and a Dll4-binding component in one molecule. Pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- and Dll4-mediated effects on angiogenesis. Nucleic acids encoding the bispecific binding molecules, host cells and methods for preparing same.

The invention discloses a VEGF-resistant and PD-1-resistant difunctional antibody and application thereof, belonging to the technical field of molecular immunology. The VEGF-resistant and PD-1-resistant difunctional antibody contains a light chain an a heavy chain, wherein the light chain has an amino acid sequence as shown in SEQ ID NO.2, and the heavy chain has an amino acid sequence as shown in SEQ ID NO.4 or SEQ ID NO.6. Meanwhile, the invention provides a gene for encoding the difunctional antibody and the application of the difunctional antibody. The difunctional antibody provided by the invention can be combined with PD-1 and VEGF, has very high affinity, can be used for effectively simulating T cells to secrete IL2 and induce T cells to secrete IFN-gamma and can also be used for remarkably inhibiting the growth of tumor of a mouse so as to have a huge potential in application to preparation of anti-cancer drugs.

The present invention provides peptides and mimetics thereof that bind to VEGF. In preferred embodiments, the peptides of the invention are D type optical isomers which can bind VEGF and which can inhibit or reduce VEGF biological activity.

The invention discloses a murine monoclonal antibody resistant to human vascular endothelial growth factors (VEGFs), a combination reagent containing the murine monoclonal antibody and used for detecting the human VEGF level in a biological sample, a reagent box containing the combination reagent and a use method of the reagent box. The combination KD value of the murine monoclonal antibody and the human VEGFs reaches 0.01 nM, and the combination reagent containing the murine monoclonal antibody and the reagent box containing the combination reagent have the advantages of being high in detection sensitivity and specificity.

Described herein are peptide compositions of a prominin-1, which have regenerative activity. As such the peptides are useful when regeneration is needed, for example, to enhance angiogenesis, increase VEGF binding to endothelial cells, promote vasodilation, enhance cell migration, enhance cell proliferation, stimulate neuronal growth, prevent neurodegeneration, and / or promote neuroregeneration.

Described have herein are peptide analogs of a prominin-1 peptide, DRVQRQTTTVVA (SEQ. ID. NO:1) which have enhanced regenerative and / or angiogenesis activity, increase VEGF binding to endothelial cells, and / or increase wound healing activity relative to the peptide of SEQ ID NO: 1. Provided herein are fusion proteins and compositions comprising these pep tide analogs and uses thereof.

Disclosed herein are fully human antibodies and antigen-binding fragments thereof that specifically bind human VEGF and inhibit VEGF binding to VEGF-R1 and VEGF-R2, and therefore inhibit VEGF signaling. The antibodies and antigen-binding fragments disclosed herein may be used, for example, to treat angiogenesis and conditions associated with angiogenesis both in vivo and in vitro.

Provided are monoclonal antibodies and antigen binding fragments thereof that specifically bind vascular endothelial growth factor (VEGF). The anti-VEGF monoclonal antibodies block VEGF binding to its receptors (e.g., VEGFR1 and / or VEGFR2) and prevent phosphorylation of VEGFR2 by VEGF. Also provided are methods of using the monoclonal anti-VEGF antibodies for treatment of disease, including cancer.

Disclosed are novel peptides inhibitory of the activity of vascular endothelial growth factor (VEGF) and their use in the treatment of angiogenesis-related diseases, including cancer. A combinatorial library of peptides consisting of six amino acid residues were chemically synthesize and, from the library, specific amino acid residues for each amino acid position were screened by comparing their inhibitory activity against VEGF binding to the cell surface receptor. The novel peptide sequences thus obtained bind to VEGF and block the binding of VEGF to its receptors present on the surface of vascular endothelial cells, thereby inhibiting the hormonal activity of VEGF. The peptides inhibit the angiogenesis induced by VEGF and human cancer cells. Also, the peptides inhibit growth and metastasis of human cancer cells transplanted to mice. Thus, the peptides can be used to treat angiogenesis-related diseases, including cancer, diabetic retinopathy, rheumatoid arthritis, etc.

The present invention relates a peptide having cancer selective translocation function, and the use thereof, and more particularly to a VEGF-binding protein transduction domain (VPTD) represented as SEQ ID NO: 1 or a heparin-binding protein transduction domain (HPTD) represented as SEQ ID NO: 2, which bind specifically to VEGF and heparin, which are overexpressed specifically in tumor cells or tumor tissues, and to a conjugate comprising a drug linked to the peptide.The peptide and the peptide-drug conjugate bind specifically to VEGF and heparin in tumor cells or tumor tissue and accumulate in the tumor cells or tumor tissue, and thus can be used for the accurate diagnosis and treatment of cancer. Also, the non-specific distribution of the peptide or the conjugate in the body after administration is inhibited, and thus the side effects thereof can be minimized. Accordingly, the peptide or the conjugate is useful for the diagnosis and treatment of cancer.

Described herein are peptide compositions of a prominin-1, which have regenerative activity. As such the peptides are useful when regeneration is needed, for example, to enhance angiogenesis, increase VEGF binding to endothelial cells, promote vasodilation, enhance cell migration, enhance cell proliferation, stimulate neuronal growth, prevent neurodegeneration, and / or promote neuroregeneration.

The invention discloses a preparation method of artificial alveoli. The method comprises the following steps: firstly, preparing gelatin micro-spheres with uniform diameters from a gelatin aqueous solution through a microfluidic device, obtaining gelatin brackets which are regularly arranged through a self-assembly method, heating the gelatin brackets to be closely arranged, then filling a PU solution, performing freeze drying to remove the solvent, and removing a gelatin template by a water bath method to obtain a three-dimensional porous PU bracket with an inverse opal structure; then, performing ammonia plasma treatment on the PU bracket to graft the amino group, connecting heparin to the amino group through EDC / NHS, then adding VEGF, and combining the VEGF to the heparin; and finally,rotationally inoculating MRC-5 cells to the VEGF-modified PU bracket, proportionally inoculating mixed cell suspensions of HUVECs and NL20 cells, and performing co-culture to obtain tissue engineeringartificial alveoli. The diameters of the prepared artificial alveoli can be effectively regulated and controlled to be about 300 microns by regulating and controlling the concentration of the gelatinsolution and polyurethane, the flow rate and the passage diameter of a water phase and an organic phase as well as the self-assembly temperature and time.

Fusion proteins containing a PDGF binding portion, a VEGF binding portion, and an Fc antibody region are described. Also described are nucleic acids encoding the fusion proteins, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing clinical conditions characterized by abnormal angiogenesis, such as vascular permeability, edema or inflammation.

Provided are methods and compositions for treatment of angiogenic disorders using anti-VEGF agents. The anti-VEGF agents comprise VEGF binding domains and have the ability to bind vitreous. Provided are exemplary embodiments of Fc-IgG fusion proteins with VEGF binding domains with strong heparin-binding characteristics, strong inhibition of VEGF mitogenic activity, and improved pharmacokinetics, namely longer half-lives of the anti-VEGF agents and consequently less frequent dosing.

The invention provides compositions and methods for treating a disease or disorder associated with vascular endothelial growth factor (VEGF). Specifically, the invention relates to an oligomerized VEGF binding domain to provide VEGF antagonism, and thereby treat diseases associated thereof.

The invention, belonging to the technical field of biology, particularly discloses an anti-VEGF / anti-OPN double variable region IgG molecule like bispecific antibody VEGF / OPN-BsAb, its preparation method and application in preparing antitumor drugs. The antibody disclosed herein has amino acid sequences represented by SEQ ID No:10 and SED ID No:12, can be combined with VEGF and OPN, and has anti-neoplastic treatment effect similar with combing with Bevacizumab and hu1A12.

The invention provides a human derived heavy chain variable region possessing human vascular endothelial growth factor(VEGF) binding activity. Concretely, the invention provides an antibody single heavy chain variable region which is from fully human derived monoclonal antibody and possesses the human vascular endothelial growth factor binding activity. The single heavy chain variable region can be taken as an antibody fragment, the human VEGF binding activity of complete immunoglobulin can be reserved, the proliferation of human vascular endothelial cells (HUVEC) can be inhibited in dose dependent mode. The invention also provides a method for preparing the antibody fragment and its application.

Bispecific binding molecules, in particular immunoglobulin single variable domains such as VHHs and domain antibodies, comprising a VEGF-binding component and a DII4-binding component in one molecule. Pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF- and DII4-mediated effects on angiogenesis. Nucleic acids encoding the bispecific binding molecules, host cells and methods for preparing same.

Described have herein are peptide analogs of a prominin-1 peptide, DRVQRQTTTVVA (SEQ. ID. NO:1) which have enhanced regenerative and / or angiogenesis activity, increase VEGF binding to endothelial cells, and / or increase wound healing activity relative to the peptide of SEQ ID NO: 1. Provided herein are fusion proteins and compositions comprising these pep tide analogs and uses thereof.

Disclosed is providing, a novel VEGF-binding aptamer whose affinity to VEGF is higher than those of known VEGF-binding aptamers. By a in silico maturation method starting from a known VEGF-binding aptamer, 4 kinds of aptamers whose affinities to VEGF are higher than that of the known VEGF-binding aptamer were prepared. By linking two molecules of an obtained aptamer to each other via a linker, an aptamer having an even higher affinity to VEGF was obtained. The polynucleotide of the present invention contains the base sequence of any one of SEQ ID NOs:1 to 4, and binds to vascular endothelial growth factor.

The invention describes a new method for in vivo measurement and control of intraocular VEGF concentration using bioluminescence resonance energy transfer (BRET) of a VEGF-binding biosensor. Furthermore, the method is suitable for highly sensitive in vitro determination of VEGF concentration from a small sample volume.

Provided are monoclonal antibodies and antigen binding fragments thereof that specifically bind vascular endothelial growth factor (VEGF). The anti-VEGF monoclonal antibodies block VEGF binding to its receptors (e.g., VEGFR1 and / or VEGFR2) and prevent phosphorylation of VEGFR2 by VEGF. Also provided are methods of using the monoclonal anti-VEGF antibodies for treatment of disease, including cancer.