295results about How to "Improve in vivo stability" patented technology

New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2′-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are “anti-reverse cap analogs” (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog m7GpppG.

Cluster clearing agents (CCAs) and the use thereof are discussed. CCAs are composed of a hepatic clearance directing moiety which directs the biodistribution of a CCA-containing construct to hepatic clearance; and a binding moiety which mediates binding of the CCA to a compound for which rapid hepatic clearance is desired.

The present invention is based, in part, on the discovery that endogenous mRNAs can be recruited for translational repression of target mRNAs. The RNA-silencing agents and the methods described herein, thereby provide a means by which to treat genetic (e.g., genetic neurodegenerative diseases such as Huntington's Disease) or non-genetic diseases by, for example, blocking the synthesis of proteins that contribute to the diseases. Accordingly the RNA-silencing agents of the present invention have an mRNA targeting moiety, a linking moiety, and an mRNA recruiting moiety.

The present invention relates to chemically modified, linked double-stranded (ds)RNA compositions comprising two or more double-stranded (ds) oligoribonucleotides linked by at least one linking moiety and methods of formulating and delivering such compositions to modulate gene expression through target-specific RNA co-interference (RNAco-i). The compositions of the invention may optionally comprise a conjugation or a complex with one or more small molecule drugs, protein therapeutics, or other dsRNA molecules. The present invention is directed at the methods of production for, methods of use of, and therapeutic utilities for RNAi co-interference therapy utilizing the compositions of the invention.

The present invention is generally directed to methods of producing an increase in the enrichment and / or recovery of preferred forms of monoclonal antibodies. More particularly, the invention relates to methods for eliminating disulfide heterogeneity in the hinge region of recombinant IgG2 antibody proteins.

The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and / or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and / or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.

The invention is directed to compounds of formula (I) wherein X is O or NH; R' is a hydrocarbon chain; R<3 >and R<4 >are hydrogen, OH or a monosaccharide; R<5 >is hydrogen or a monosaccharide; Q' is optionally present and may be a C1-10 hydrocarbon; X' is optionally present and may be O, S or NR<8>; and Q<3 >may be a hydrocarbon or hydrogen. The invention is also directed to the use of the compounds for treating cancer, infectious diseases and autoimmune diseases. The invention is also directed to syntheses of the compounds of formula (I).

In certain aspects, the present invention provides compositions and methods for increasing red blood cell and / or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.

Peptides exhibiting anti-viral and anti-fusogenic activity are modified to provide greater stability and improved half-life in vivo. The selected peptides include fusion inhibitors DP178 and DP107 and related peptides and analogs thereof. The modified peptides are capable of forming covalent bonds with one or more blood components, preferably a mobile blood component.

The invention is directed to compounds of formula (I) wherein X is O or NH; R′ is a hydrocarbon chain; R3 and R4 are hydrogen, OH or a monosaccharide; R5 is hydrogen or a monosaccharide; Q′ is optionally present and may be a C1-10 hydrocarbon; X′ is optionally present and may be O, S or NR8; and Q3 may be a hydrocarbon or hydrogen. The invention is also directed to the use of the compounds for treating cancer, infectious diseases and autoimmune diseases. The invention is also directed to syntheses of the compounds of formula (I).

A protein conjugate having a prolonged in vivo half-life of a physiological activity, comprising i) a physiologically active polypeptide, ii) a biocompatible non-peptidic polymer, and iii) an immunoglobulin, is useful for the development of a peptide drug due to the enhanced in vivo stability and prolonged half-life in blood, while reducing the possibility of inducing an immune response.

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

The present invention provides compositions and methods for treating and / or preventing age related macular degeneration and other conditions involving macular degeneration or choroidal neovascularization. Certain of the compositions comprise a poxvirus complement control protein or a complement binding fragment or variant thereof. Other compositions comprise a poxvirus complement control protein linked to a moiety that binds to a component present on or at the surface of cell or noncellular molecular entity, e.g., a component present in the eye of a subject at risk of or suffering from age related macular degeneration or a related condition or choroidal neovascularization. Certain of the methods comprise administering a poxvirus complement control protein or complement binding fragment or variant thereof to a subject.

New and improved compounds for use in diagnostic imaging or therapy having the formula M-N-O-P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N-O-P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and / or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.

Disclosed are a fusion protein comprising enzyme β-glucuronidase and short peptide consisting 4-15 acidic amino acids attached to the enzyme on its N-terminal side, pharmaceutical composition containing the fusion protein, and a method for treatment of type VII mucopolysaccharidosis using the fusion protein. Compared with the native enzyme, the fusion protein exhibits higher stability in the blood.

The invention relates to a folate-targeted reduction sensitive drug-carrying polymer nano-micelle as well as a preparation method and application thereof. The delivery carrier is prepared by taking anamphiphilic triblock copolymer PCL-ss-PEG-ss-PCL as a material, and a chemotherapeutic drug adriamycin amycin and a photosensitizer indocyanine green are entrapped in a hydrophobic core of the micelle. Besides, phospholipid DSPE-PEG-NH2 with an active group is introduced into the preparation process, the DSPE end of the phospholipid has strong hydrophobic property and is inserted into the hydrophobic PCL core of the polymer micelle, the flexible hydrophilic PEG long chain exists on the outer surface of the micelle, FA with a targeting effect is connected to a PEG active distal end of the surface of the polymer micelle, and functions of active tumor targeting and reduction response drug release are integrated. The folate-targeted reduction sensitive drug-carrying polymer nano-micelle disclosed by the invention has the advantages of being small in particle size, high in dispersion property, high in drug loading capacity and encapsulation efficiency and excellent in photothermal conversion effect, can realize reduced trigger drug release, fluorescence imaging of tumor sites, tumor targeting drug delivery and chemotherapy-photothermal combination therapy and improve the tumor inhibition effect, and has wide application prospects in the targeted combination therapy aspect of tumors.

The invention relates to a pH / reduction dual-sensitive multifunctional nano-micelle for tumor chemotherapy and photothermal combined therapy and application of the pH / reduction dual-sensitive multifunctional nano-micelle. The pH / reduction dual-sensitive multifunctional nano-micelle is characterized in that a PCL-acetal-PEG polymer with pH sensitive characteristic, a PCL-ss-PEG-ss-PCL polymer withreduction sensitive characteristic and a phospholipid DSPE-PEG-NH2 with an active group are used as raw materials and are blended to prepare a pH / reduction intelligent responsive polymer nano-micelleas a carrier; a chemotherapeutic drug and a photosensitizer coat a hydrophobic core of the micelle; a casing is made of hydrophilic PEG and has the characteristic of long circulation and space stability; a folic acid targeting group is modified on the surface of the micelle by a covalent bond; the drug loading capacity is 4 to 10 percent, and the mass ratio of the chemotherapeutic drug to the photosensitizer is 0.5 to 2; the particle size is smaller than 200 nm. The pH / reduction dual-sensitive multifunctional nano-micelle disclosed by the invention has the advantages of good dispersity, smallparticle size, better photothermal conversion effect and high drug loading capacity and encapsulation efficiency; the effect of improving tumor suppression by tumor targeted administration, fluorescence imaging of a tumor site, pH / reduction triggered drug release and chemotherapy and photothermal combined therapy can be realized; the pH / reduction dual-sensitive multifunctional nano-micelle has a broad clinical application prospect in combined targeting therapy of tumors.

The present invention relates to the identification of nucleic acid and amino acid sequences that are characteristic of tumor tissues such as ovarian tumor and lung tumor tissues and which represent targets for therapy or diagnosis of tumor diseases in a subject.

A method of treating or preventing disease, said method comprising administering to a subject, simultaneously, sequentially or separately, an antigen and a chemotherapeutic agent or agents comprising the steps of: administering the chemotherapeutic agent or agents, and administering an antigen up to 6 weeks after the chemotherapeutic agent.

The present invention relates to a proteinaceous extract derived from tortoise spleen and to a tetrapeptide FTGN, which have stimulatory activity on hematopoietic cells. In particular, this tetrapeptide enhances hemopoietic reconstruction, and bone marrow re-population, reduced as a consequence of a high dose of radiation or chemotherapy exposure. The invention further provides pharmaceutical compositions comprising as an effective ingredient the proteinaceous extract or the FTGN tetrapeptide and ex vivo and in vivo methods of treatment employing them.

The invention provides a fusion protein used for detecting and treating human I-type diabetes mellitus and human II-type diabetes mellitus and obesity as well as a preparation and an application of the fusion protein. The fusion protein contains a human FGF21 or a mutant thereof and a human IgG2-Fc (hinge region -CH2-CH3) or a human IgG2-Fc mutant ( T250Q / M428L and T307Q / N434A), can improve the living condition of the obesity patients, reduce the blood sugar level of diabetics, effectively reduce aggregation and degradation of the FGF21 protein, and meanwhile prolong in vivo half-life period of the FGF21, and especially through the fusion of the FGF21 and the mutant and the IgG-Fc (T250Q / M428L and T307Q / N434A) mutant, the affinity with FcRn is enhanced, and in vivo half-life period of the FGF21 is further prolonged.

The present invention provides compositions and methods for treating and / or preventing age related macular degeneration and other conditions involving macular degeneration or choroidal neovascularization, ocular inflammation, or any combination of these. Certain of the compositions comprise a poxvirus complement control protein or a complement binding fragment or variant thereof. Other compositions comprise a poxvirus complement control protein linked to a moiety that binds to a component present on or at the surface of cell or noncellular molecular entity, e.g., a component present in the eye of a subject at risk of or suffering from age related macular degeneration or a related condition or choroidal neovascularization, ocular inflammation, or any combination of these. Certain of the methods comprise administering a poxvirus complement control protein or complement binding fragment or variant thereof to a subject.

Provided is a fusion protein comprising, at its carboxy terminal of human erythropoietin (EPO), a mutant having one to four amino acid substitutions in the carboxy terminal peptide (CTP) fragment of a human chorionic gonadotropin (HCG) β subunit, for increasing an in vivo half-life activity of EPO. The in vivo half-life can be greatly elongated while retaining the intrinsic activity of the EPO, without increasing the sugar chain content.

In certain aspects, the present disclosure provides compositions and methods for increasing red blood cell and / or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans. In some embodiments, the compositions of the disclosure may be used to treat or prevent sickle-cell disease or one or more complications associated with sickle-cell disease.

Provided are an siRNA-polymer conjugate, and a method for preparing the same, and more specifically, to a hybrid conjugate formed by covalently bonding siRNA and a polymeric compound for improving the in vivo stability of siRNA, and to a preparation method of the hybrid conjugate. The conjugate of the present invention can improve the in vivo stability of siRNA, thereby achieving an efficient delivery of therapeutic siRNA into cells and exhibiting the activity of siRNA even with a small dose of a relative low concentration. Therefore, the conjugate can advantageously be used as not only an siRNA treatment tool for cancers and other infectious disease, but also a novel type siRNA delivery system.