50 results about "Neuropilin" patented technology

The invention provides a peptide radioactive medicine comprising an iRGD sequence. The sequence of the peptide comprises CRGDKGPDC or CRGDRGPDC or CRGDKGPEC and is formed by marking through coupling radioactive metal nuclides or positron nuclides, the peptide radioactive medicine comprising the iRGD sequence has three functions of molecular target integrin alpha v beta 3 receptor, Neuropilin-l receptor and cellular transduction, and the peptide radioactive medicine comprising the iRGD sequence can be used as a diagnostic medicine capable of greatly increasing the target / non-target ratio, so that the sensitivity can be effectively improved, and the development quality can be improved, and the peptide radioactive medicine can be used as a therapeutic medicine capable of obviously improving the treatment effect.

The invention belongs to the field of pharmacy and relates to a D-configuration polypeptide and a gene delivery system of the D-configuration polypeptide and particularly relates to the D-configuration polypeptide which has high combining activity with neuropilin NRP-1 and has the brain tumor targeting and tumor tissue penetrating capabilities. The D-configuration polypeptide provided by the invention can mediate a nano delivery system to deliver drugs to tumors in a targeted manner for realizing targeted treatment of brain in-situ glioma. In vivo and in vitro experiments show that the genetic vector modified by the D-configuration polypeptide can remarkably improve the gene transfection efficiency. The genetic vector entrapping the therapeutic gene pORF-hTRAIL can remarkably prolong the lifetime of a nude mouse of brain glioma in-situ mode.

The invention provides crystal structures of neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) fragments alone and in complex with anti-neuropilin antibodies, and method for their use. The invention further provides anti-Nrp antibodies and methods for their therapeutic applications.

The invention discloses a tumor homing cell-penetrating peptide tLyP-1 modified apoferritin nano-cage and a preparation method thereof. The protein nano-cage is hollow cage-shaped protein formed by self-assembling 24 protein subunits; and one tumor homing cell-penetrating peptide tLyP-1 is modified on an N end of each protein subunit by utilizing a gene recombination technology to obtain a recombinant human body heavy-chain ferritin nano-cage with a tLyP-1 modified surface. According to the protein nano-cage provided by the invention, a medicine is loaded into the nano-cage through adjusting depolymerization and recombination of the protein subunits; the nano-cage has good water solubility and biocompatibility, has excellent stability in a human body and has a uniform size; the nano-cage can be specifically combined with a lot of neuropilin receptors 1 (NRP-1) which are expressed in tumor neovascularization and tumor cells of malignant tumors including gliomas, breast cancer, pancreatic cancer, gastric cancer, colorectal cancer, non-small cell lung cancer and the like; and types of the tumors treated by the nano-cage are greatly increased and the targeting ability of tumor treatment is improved. The protein nano-cage provided by the invention has an extremely great application prospect in the aspects of tumor diagnosis and treatment and the like.

The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In (particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGFm / m) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)-a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons. The present invention relates in particular to the isoform VEGF165 which stimulates survival of motor neurons via binding to neuropilin-1, a receptor known to bind semaphorin-3A which is implicated in axon retraction and neuronal death, and the VEGF Receptor-2. The present invention thus relates to the usage of VEGF, in particular VEGF165, for the treatment of neuron disorders and relates, in addition, to the usage of polymorphisms in the VEGF promotor for diagnosing the latter disorders.

The present invention relates to a neuropilin-1 ligand polypeptide-polyethylene glycol-phospholipid composite, its active targeting liposome vector system and a preparation method thereof. The liposome vector system comprises the following components: a: phospholipid, b: cholesterol, c: methoxy polyethylene glycol-phospholipid composite (with the molecular weight of methoxy polyethylene glycol ranging from 400 to 6000), and d: a RPAKPAR sequence-containing polypeptide-polyethylene glycol-phospholipid composite (with the molecular weight of polyethylene glycol ranging from 400 to 8000). And for the components, a and b are in a molar ratio of 5:1-1:5, a and c are in a molar ratio of 1000:1-1000:100, and a and d are in a ratio of 1000:0.1-1000:100. The system can make a liposome passively drained into a lymphatic system through subcutaneous interstitial injection or intramuscular injection, and can make the liposome targeted to a lymphatic metastasis lesion through the mediation effect of RPAKPAR. The system can also make the liposome targeted to a primary tumor and a hematogenous metastasis lesion directly through intravenous injection administration, through a tumor EPR (electron paramagnetic resonance) effect and the mediation effect of RPAKPAR. The liposome vector system of the invention can be used for targeted drug delivery in diagnosis or treatment of prostate cancer primary tumors and metastatic tumors.

A tumor tissue-penetrating peptide specifically binding to neuropilin, or a fusion protein, a small molecule drug, a nanoparticle, or a liposome having the peptide fused therein is provided, as well as a method for preparing the same and a pharmaceutical composition comprising the same for treating, diagnosing, or preventing cancer or angiogenesis-related diseases. The tumor tissue-penetrating peptide is fused to the C-terminus of an anticancer antibody heavy-chain constant region (Fc) and the fused antibody specifically binds to neuropilin, and specifically accumulates in tumor tissue, widens intercellular gaps between tumor vascular endothelial cells, promotes extravasation, increases infiltration within tumor tissue, and shows a remarkably increased in vivo tumor-suppressing activity. Furthermore, the tumor tissue-penetrating peptide is fused into a fusion protein and inhibits the angiogenic function of neuropilin coreceptors resulting from targeting of neuropilin, and is expected to have an alleviating effect on angiogenesis-related diseases.

Disclosed is a therapeutic agent for treating a cellular immune disease, comprising as an active ingredient a substance that inhibits binding between Sema3A and a Neuropilin-1 / Plexin-A1 heteroreceptor. The substance includes, for example, a Sema3A neutralizing antibody, a Neuropilin-1 neutralizing antibody, or a soluble Neuropilin-1 or derivative thereof. Also disclosed is a method for screening a therapeutic agent for treating a cellular immune disease utilizing a signal generated by the interactions of Neuropilin-1, Plexin-A1 and Sema3A as a marker.

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.

The invention provides crystal structures of neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) fragments alone and in complex with anti-neuropilin antibodies, and method for their use. The invention further provides anti-Nrp antibodies and methods for their therapeutic applications.

The present invention relates to antagonists of neuropilin receptor function and use thereof in the treatment of cancer, particularly metastatic cancer, and angiogenic diseases.

Disclosed is a therapeutic agent for treating a cellular immune disease, comprising as an active ingredient a substance that inhibits binding between Sema3A and a Neuropilin-1 / Plexin-A1 heteroreceptor. The substance includes, for example, a Sema3A neutralizing antibody, a Neuropilin-1 neutralizing antibody, or a soluble Neuropilin-1 or derivative thereof. Also disclosed is a method for screening a therapeutic agent for treating a cellular immune disease utilizing a signal generated by the interactions of Neuropilin-1, Plexin-A1 and Sema3A as a marker.

The present invention relates to a compound of general formula (I),and to a pharmaceutical composition comprising a compound of general formula (I) or esters or salts thereof, in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.

This invention relates to oligonucleotides complementary to the neuropilin genes which modulate tumor cell growth and angiogenesis in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells and angiogenesis in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.

The present invention refers to an oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of neuropilin 1 (NRP1, CD304) of SEQ ID NO.1 (NM_003873.5), wherein the oligonucleotide inhibits at least 50% of the NRP1 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

The present invention relates to the combined use of a neuropilin-1 (Nrp-1) neutralizing agent and of a programmed cell death-1 (PD-1) neutralizing agent for killing cancer cells, typically for treating cancer, as well as to corresponding pharmaceutical compositions and kits, and to corresponding diagnostic and therapeutic methods. The invention further relates to in vitro, ex vivo and in vivo methods for detecting CD8+ TILs capable of recognizing cancer cells, for predicting the response of a subject to anti-PD-1 treatment of cancer, and for identifying a subject who responds therapeutically to a treatment of cancer with an antibody combination therapy comprising anti-Nrp-1 and anti-PD-1 antibodies.

The present invention provides NRP1 as a cell surface marker for isolating human cardiomyogenic ventricular progenitor cells (HVPs), in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Additional HVP cell surface markers identified by single cell sequencing are also provided. The invention provides in vitro methods of the separation of NRP1+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated NRP1+ ventricular progenitor cells are also provided. Methods of in vivo use of NRP1+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the NRP1+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.

The present invention provides NRP1 as a cell surface marker for isolating human cardiomyogenic ventricular progenitor cells (HVPs), in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Additional HVP cell surface markers identified by single cell sequencing are also provided. The invention provides in vitro methods of the separation of NRP1+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated NRP1+ ventricular progenitor cells are also provided. Methods of in vivo use of NRP1+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the NRP1+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.

The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and / or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.

Provided are therapies, including standalone and combination therapies, for treating neuropilin-2 (NRP2)-associated diseases and conditions, which include the use of at least one histidyl-tRNA synthetase (HRS) polypeptide.

The present invention concern a peptidic antagonist of class III semaphorins / neuropilins complexes comprising an amino acid sequence, which is derived from the transmembrane domain of a protein selected in the group consisting of neuropilin-1, neuropilin-2, plexin-A1, plexin-A2, plexin-A3, plexin-A4, Nr-CAM, L1-CAM, integrin Beta 1 and integrin beta 2, and including at least a GxxxG motif, eventually fused to an heterologous sequence; a nucleic acid encoding for said peptidic antagonist, a pharmaceutical composition comprising such a peptidic antagonist or a nucleic acid encoding thereof and uses thereof.

The present invention relates to identifying modulators of VEGF-C or VEGF-D ligand binding to the nervous system transmembrane protein neuropilin-2 and materials and methods for detecting said modulators.

An object of the present invention is to provide an antibody against VEGF that inhibits binding of a vascular endothelial growth factor (VEGF) to neuropilin-1 (NRP1). The present invention provides an antibody against VEGF that inhibits binding of VEGF to NRP1.