67 results about "Angiostatin" patented technology

The present invention relates to compositions and methods for the treatment of tumor and / or malignant and / or cancerous cells. The present invention provides VSV vectors comprising nucleic acid encoding a cytokine, such as interleukin or interferon, or a suicide gene, such as thymidine kinase, or other biological protein, such as heat shock protein gp96, or endostatin or angiostatin, wherein said VSV vectors exhibit greater oncolytic activity against the tumor and / or malignant and / or cancerous cell than a wild-type VSV vector. The present invention also provides methods of making such vectors, host cells, expression systems, and compositions comprising such VSV vectors, and viral particles comprising such VSV vectors. The present invention also provides methods for producing oncolytic activity in a tumor and / or malignant and / or cancerous cell comprising contacting said cell with a VSV vector of the present invention. The present invention also provides methods for suppressing tumor growth comprising contacting said tumor with a VSV vector of the present invention. The present invention also provides methods for eliciting an immune response to a tumor cell in an individual.

The present invention provides adeno-associated viral (AAV) vectors encoding an angiostatin protein ("AAV-angiostatin vector") and / or a costimulatory molecule B7.1 ("AAV-B7.1 vector"). The AAV-angiostatin vector can be administered to a subject, alone or in combination, sequentially or simultaneously, with a AAV-B7.1 vector for treatment, management or prevention of metastatic tumors. Pharmaceutical compositions and vaccines comprising the AAV-angiostatin vector and / or the AAV-B7.1 vector and methods of manufacturing are also described. Administration of AAV-angiostatin and AAV-B7.1 vectors by intraportal and muscular injections are also provided.

The present invention is directed to a method of inhibiting at least one of vascular leakage, inflammation and fibrosis in an animal by administering to the animal a vascular leakage inhibiting amount of a composition, wherein at a substantially higher amount the composition is effective in inhibiting angiogenesis, and wherein the anti-angiogenic activity of the composition is separate from the vascular leakage inhibiting activity of the composition. The animal experiencing at least one of vascular leakage, inflammation and fibrosis has a disease selected from the group consisting of diabetes, chronic inflammation, brain edema, arthritis, uvietis, macular edema, cancer, hyperglycemia, a kidney inflammatory disease, a disorder resulting in kidney fibrosis, a disorder of the kidney resulting in proteinuria, and combinations thereof. The composition capable of inhibiting at least one of vascular leakage, inflammation and fibrosis is selected from the group consisting of angiostatin, fragments of angiostatin, analogs or derivatives of angiostatin, kringle 5 of plasminogen, fragments of kringle 5 of plasminogen, analogs or derivatives of kringle 5 of plasminogen, pigment epithelium-derived factor, fragments of pigment epithelium-derived factor, analogs or derivatives of pigment epithelium-derived factor and combinations thereof.

The invention provides, in a general sense, a new labeling strategy employing compounds that are are N2S2 chelates conjugated to a targeting ligand, wherein the targeting ligand is a disease cell cycle targeting compound, a tumor angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, amifostine, angiostatin, monoclonal antibody C225, monoclonal antibody CD31, monoclonal antibody CD40, capecitabine, a COX-2 inhibitor, deoxycytidine, fullerene, herceptin, human serum albumin, lactose, leuteinizing hormone, pyridoxal, quinazoline, thalidomide, transferrin, or trimethyl lysine. The present invention also pertains to kits employing the compounds of interest, and methods of assessing the pharmacology of an agent of interest using the present compounds.

The present invention relates generally to the fields of angiogenesis and cancer therapy. More particularly, it concerns the use of anti-angiogenic factors in cancer therapy. The present invention demonstrates that angiostatin or endostatin can sensitize a cell to radiation therapy. Methods and compositions for inhibiting growth, sensitizing a cell to radiotherapy and treating cancer growth by first inhibiting angiogenesis and then employing radiotherapy are described.

A method for encapsulating cisplatin and other positively-charged drugs into liposomes having a different lipid composition between their inner and outer membrane bilayers is disclosed. The liposomes are able to reach primary tumors and their metastases after intravenous injection to animals and humans. The encapsulated cisplatin has a high therapeutic efficacy in eradicating a variety of solid human tumors including but not limited to breast carcinoma and prostate carcinoma. Combination of the encapsulated cisplatin with encapsulated doxorubicin or with other antineoplastic drugs are claimed to be of therapeutic value. Also of therapeutic value in cancer eradication are claimed to be combinations of encapsulated cisplatin with a number of anticancer genes including but not limited to p53, IL-2, IL-12, angiostatin, and oncostatin encapsulated into liposomes as well as combinations of encapsulated cisplatin with HSV-tk plus encapsulated ganciclovir.

The invention discloses a pharmaceutical composition for treating tumor diseases, a preparation method of the pharmaceutical composition and application of the pharmaceutical composition in preparing the medicines for treating tumor diseases, wherein the pharmaceutical composition consists, in a fixed dosage, of N-[4-(1-cyan cyclopentyl)phenyl]-2-(4-picolyl) amidogen-3-pyridinecarboxamide or pharmaceutically acceptable salts thereof and angiostatin or pharmaceutically acceptable salts thereof, or N-[4-(1-cyan cyclopentyl)phenyl]-2-(4-picolyl) amidogen-3-pyridinecarboxamide or pharmaceutically acceptable salts thereof and gefitinib or pharmaceutically acceptable salts thereof.

The present invention provides plasminogen fragments containing kringle region domains having anti-angiogenic activity and termed angiostatin protein. The plasminogen fragments of the present invention may be used for the treatment of angiogenesis-dependent diseases such as cancer.

Compounds, compositions and methods for promoting or inhibiting angiogenesis, and screening methods for identifying compounds are disclosed. The compounds bind to F1 ATP synthase particularly to the alpha and / or beta subunits of F1 ATP synthase. When bound to these subunits, they can function as angiostatin agonists, antagonists, partial agonists, inverse agonists, or allosteric modulators. When the compounds mimic or enhance the activity of angiostatin, they inhibit angiogenesis. When the compounds inhibit the ability of angiostatin to bind F1 ATP synthase and are either inactive at inhibiting angiogenesis or directly promote angiogenesis, or if they inhibit the activity of angiostatin, they promote angiogenesis. The compounds can be, for example, antibodies, antibody fragments, enzymes, peptides, nucleic acids such as oligonucleotides, or small molecules. The antibodies can be monoclonal, humanized, or polyclonal antibodies. The compounds can be conjugated to or combined with various cytotoxic agents and / or labeled compounds. Methods for promoting angiogenesis can be used to introduce vasculature to areas in a patient that can benefit from such increased vasculature. Methods for inhibiting angiogenesis can be used to treat disorders mediated by angiogenesis, for example, tumors, autoimmune disorders such as rheumatoid arthritis, and the like.

A homodimeric protein of the invention has angiogenesis inhibiting activity. The homodimeric protein consists of two identical fusion proteins bound together as a homodimer. Each fusion protein comprises an immunoglobulin Fc region and a first target protein linked to the immunoglobulin Fc region. The first target protein has an angiogenesis inhibiting activity of angiostatin or endostatin, and is selected from the group consisting of a plasminogen fragment and a collagen XVIII fragment. The immunoglobulin Fc region comprises a hinge region, a CH2 region, and a CH3 region.

A method for encapsulating cisplatin and other positively-charged drugs into liposomes having a different lipid composition between their inner and outer membrane bilayers is disclosed. The liposomes are able to reach primary tumors and their metastases after intravenous injection to animals and humans. The encapsulated cisplatin has a high therapeutic efficacy in eradicating a variety of solid human tumors including but not limited to breast carcinoma and prostate carcinoma. Combination of the encapsulated cisplatin with encapsulated doxorubicin or with other antineoplastic drugs are claimed to be of therapeutic value. Also of therapeutic value in cancer eradication are claimed to be combinations of encapsulated cisplatin with a number of anticancer genes including but not limited to p53, IL-2, IL-12, angiostatin, and oncostatin encapsulated into liposomes as well as combinations of encapsulated cisplatin with HSV-tk plus encapsulated ganciclovir.

A homodimeric protein of the invention has angiogenesis inhibiting activity. The homodimeric protein consists of two identical fusion proteins bound together as a homodimer. Each fusion protein comprises an immunoglobulin Fc region and a first target protein linked to the immunoglobulin Fc region. The first target protein has an angiogenesis inhibiting activity of angiostatin or endostatin, and is selected from the group consisting of a plasminogen fragment and a collagen XVIII fragment. The immunoglobulin Fc region comprises a hinge region, a CH2 region, and a CH3 region.

The invention provides human angiostatin interacting and tumor metastasis involving protein (HAI-TMIP) isoforms, namely HAI-TMIP variants 1 to 7, and human protein complexes comprising HAI-TMIP variant 1, 2, 3, 4, 5, 6 or 7. The invention also provides antibodies that immunospecifically bind to HAI-TMIP variant 1, 2, 3, 4, 5, 6 or 7 or a complex comprising such a variant, and uses of such antibodies. The present invention provides peptides which may be used as immunogens to distinguish between the HAI-TMIP variants. The invention further provides compounds that modulate the expression and / or activity of HAI-TMIP variant 1, 2, 3, 4, 5, 6 or 7, or a complex comprising such a variant, and uses of such compounds in the prevention, treatment and / or management of various disorders, in particular, cancer.

A slow-releasing composite anticancer injection containing angiostatin is composed of the slow-release microballs containing active anticancer component chosen from angiostatin, anticancer antibiotic and antimetabolitic medicine and slow-release auxiliary, and the special solvent containing suspending aid.

A recombinant herpesvirus carrying the endostatin and angiostatin fused gene for effectively treating colloima features that its original virus HSV-1 contains a long nonrepetitive region (UL) and a short one (US). After the ICP6 gene in the UL is partly removed, the human endostatin and angiostatin is inserted to obtain the fused gene.

The invention relates to a composition of angiostatin or its medicinal salt, and a preparation method and a use thereof. The composition comprises 25-45wt% of angiostatin (a compound of formula I) or its pharmaceutically acceptable salt, and a medicinal excipient which can be used for treating over-proliferation diseases, such as cancers.

Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.

An anticarcinogenic slow release injection carrying an angiogenesis inhibitor and a synergist thereof is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active components are angiogenesis inhibitors such as gefitinib, erlotinib, lapatinib, vatalanib, pelitinib, thalidomide, ranolamine, angiostatin, endostatin, imatinib, thalidomide, ranolamine, simatinib, dasatinib, avastin, kanatini, sorafenib, sunitinib, telstar or panitoma, and the like, and / or cytotoxic drugs selected from a phosphoinositide-3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecule; the viscosity of the suspending agent is 100cp-3,000cp (at the temperature of 20-30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can be also made into a slow release implant, and the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like, can be improved when the slow release injection is injected or placed in tumors or around the tumors.

The invention relates to a method for cloning, identifying and expressing fusion and non-fusion genes of angiostatin Kringle 5. The method comprises the following steps: 1, preparation of ThioA / L15 / 7and E. coli PET32 (vector) plasmid DNA; 2, PCR of the target gene Kringle5; 3, extraction and purification of a PCR product; 4, double digestion of the PCR product and the vector plasmid DNA; 5, reclamation of DNA gel; 6, preparation of the recombinant vector pET32 / kringle5; 7, preparation of a competent cell; 8, conversion of the competent cell; 9, miniature fermentation and induction expressionof the recombinant protein; and 10, culture and plasmid extraction, and identification of agarose gel electrophoresis after double digestion. The method successfully constructs the non-fusion expression vector of the pET28a (+)-K5 gene, and establishes foundation for non-fusion expression of the K5 gene in colibacillus.

The present invention relates to a recombinant herpes simplex virus and a method of gene treat of human tumour by using the recombinant virus, particularly relates to a recombinant herpes simplex virus with blood vessel chalone and endodermis chalone albumen, and its application in treating lung cancer. The invention also relates to medicine compound containing the recombinant virus. The recombinant herpes simplex virus of the invention can represent blood vessel chalone and endodermis chalone amalgamation albumen having effect of restraining the generation of blood vessel in the tumour cell, and the virus disintegratively increases in the tumour, such that the purpose of treating lung cancer by restraining the generation of blood vessel and disintegratively decomposing tumour cell is achieved.

The invention discloses a medicinal application of angiostatin; the angiostatin can be used as an active component for preparing anti-inflammatory medicaments; when determined by a reductive SDS-PAGE method, the angiostatin used as an active component of an anti-inflammatory medicament exhibits two bands which are an alpha chain and a beta chain respectively; the molecular weights are 12000-22000 Dalton and 9000-19000 Dalton respectively; the amino acid sequence of the alpha chain is shown in SEQ ID NO.1, and the amino acid sequence of the beta chain is shown in SEQ ID NO.2; after dimensional electrophoresis, three isomers corresponding to the alpha chain and three isomers corresponding to the beta chain are respectively generated. The angiostatin found in the research of the invention can be used as a novel natural protein anti-inflammatory medicament, which has no obvious toxic or side effect on human body, has wide application prospects, and provides another development of traditional anti-inflammatory medicament research.

We have discovered that endothelial progenitor cells (EPC) are particularly suitable for use in a sensitive assay for antiangiogenic factors. We have found that EPC mobilization and differentiation is greatly inhibited by antiangiogenic factors as evidenced in vivo by VEGF inducing a massive mobilization of EPC into the blood circulation which effect is significantly inhibited by endostatin treatment, and, in vitro, human blood-derived EPC forming adherent colonies, which colonies, in the presence of angiogenic factors, give rise to differentiated EC, and which differentiation is disrupted and cell growth is inhibited in the presence of angiostatin and endostatin.

A method of treating patients with coronary heart failure (CHF) by the intermittent administration of Angiotensin Converting Enzyme (ACE) inhibitors and / or angiostatin II receptor agonists (ARBs) is disclosed. The ACE inhibitor is administered to the patient during a treatment period and the levels of hematopoietic stem cells (HSC) in the patient's blood is determined. Treatment with the ACE inhibitor is discontinued (during a recovery period) when the measured level of hematopoietic cells drops below a given point and is re-administered when levels rise above a given point. Alternating, treatment and recovery periods can be repeated a plurality of times. Levels of HSC may be determined based on ACE+ cell levels or by monitoring CD34 levels and the results used to determine optimum points for the administration of drugs which reduce HSC levels.

Provided are methods and compositions for the photodynamic therapy (PDT) of ocular conditions characterized by the presence of unwanted choroidal neovasculature, for example, neovascular age-related macular degeneration. The selectivity and sensitivity of the PDT method can be enhanced by combining the PDT with an anti-angiogenesis factor, for example, angiostatin or endostatin, or with an apoptosis-modulating factor. Furthermore, the selectivity and sensitivity of the PDT may be further enhanced by coupling a targeting moiety to the photosensitizer so as to target the photosensitizer to choroidal neovasculature.

The invention was involved in that target protein expression strain and molecular partner were expressed in E.coli.at the same time at low temperature to prevent the formation of target protein inclusion body effectively and increase yields of soluble production largely. Soluble recombinant human endostatin and human angiostatin were increased largely by the technique. It provided a new simple and cheap technique to produce soluble recombinant protein with biological activity. It was applied in bioengineering pharmaceutical factory, gene engineering, biochemistry and molecular biology with high efficiency, cheap price, wide application and strong promotion.

The slow released injection containing blood vessel inhibitor and its synergist consists of slow released microsphere and solvent. The slow released microsphere includes effective anticancer component and slow releasing supplementary material, and the solvent is special solvent containing suspending agent. The effective anticancer component is blood vessel inhibitor carboxyl amino triazole, Irotinat, Lapatinat, etc and / or blood vessel inhibitor synergist selected from toporase inhibitor and tetrazin compound. The slow releasing supplementary material is one of difatty acid-sebacic acid copolymer, poly(erucic acid dipolymer-sebacic acid), poly(fumaric acid-sebacic acid), polylactic acid, etc or their composition. The suspending agent is carboxymethyl cellulose, etc. and has viscosity of 100-3000 cp at 20-30 deg.c. The slow released microsphere may be also prepared into slow released implanting agent for improving the treating effect of chemotherapeutic and / or radiotherapeutic medicine.

The present invention is directed to a method of inhibiting at least one of vascular leakage, inflammation and fibrosis in an animal by administering to the animal a vascular leakage inhibiting amount of a composition, wherein at a substantially higher amount the composition is effective in inhibiting angiogenesis, and wherein the anti-angiogenic activity of the composition is separate from the vascular leakage inhibiting activity of the composition. The animal experiencing at least one of vascular leakage, inflammation and fibrosis has a disease selected from the group consisting of diabetes, chronic inflammation, brain edema, arthritis, uvietis, macular edema, cancer, hyperglycemia, a kidney inflammatory disease, a disorder resulting in kidney fibrosis, a disorder of the kidney resulting in proteinuria, and combinations thereof. The composition capable of inhibiting at least one of vascular leakage, inflammation and fibrosis is selected from the group consisting of angiostatin, fragments of angiostatin, analogs or derivatives of angiostatin, pigment epithelium-derived factor, fragments of pigment epithelium-derived factor, analogs or derivatives of pigment epithelium-derived factor and combinations thereof.

Disclosed is an anticancer slow release injection carrying both blood vessel inhibiting agent and its synergistic agent, which comprises slow release microspheres and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anti-cancer active constituents include blood vessel inhibiting agent selected from gefinitib, erlotinib, lapatinib, angiostatin, endostatin, imatinib, sorafenib, sunitinib, Toaosta, Panitoma and / or cytotoxic drugs selected from phosphoinositide 3-enzyme inhibitor, pyrimidine analog and / or DNA restoring enzyme inhibitor, the slow release auxiliary materials include biocompatible high polymers, the viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose.

An anticarcinogenic slow release injection carrying an angiogenesis inhibitor and a synergist thereof is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active components are angiogenesis inhibitors such as gefitinib, erlotinib, lapatinib, vatalanib, pelitinib, thalidomide, ranolamine, angiostatin, endostatin, imatinib, thalidomide, ranolamine, simatinib, dasatinib, avastin, kanatini, sorafenib, sunitinib, telstar or panitoma, and the like, and / or cytotoxic drugs selected from a phosphoinositide-3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecule; the viscosity of the suspending agent is 100cp-3,000cp (at the temperature of 20-30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can be also made into a slow release implant, and the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like, can be improved when the slow release injection is injected or placed in tumors or around the tumors.

Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.