87results about How to "Prolonged Circulatory Half-Life" patented technology

Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and / or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.

The present invention is directed to uricase modified with polyethylene glycol and to methods of treating different illnesses characterized by increased circulating uric acid levels, including but not limited to, hyperuricemia and tumor lysis syndrome.

A method of conjugating peptides and proteins by means of glycosyltransferase is provided.

Method of conjugating glycoproteins by means of chemical modification is provided as well as new modified glycoproteins.

IL-28A, IL-28B, IL-29, and certain mutants thereof have been shown to have antiviral activity on a spectrum of viral species. Of particular interest is the antiviral activity demonstrated on viruses that infect liver, such as hepatitis B virus and hepatitis C virus. In addition, IL-28A, IL-28B, IL-29, and mutants thereof do not exhibit some of the antiproliferative activity on hematopoietic cells that is observed with interferon treatment. Without the immunosuppressive effects accompanying interferon treatment, IL-28A, IL-28B, and IL-29 will be useful in treating immunocompromised patients for viral infections.

Disclosed are Fc-interferon-beta (Fc-IFN-β) fusion proteins and nucleic acid molecules encoding them. The Fc-IFN-β fusion proteins include variants of the interferon-beta (IFN-β) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and / or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

Use of the protein HMGB1 or a variant or fragment thereof or a polynucleotide encoding therefor for inducing the activation of an antigen presenting cell (APC).

The present invention provides compositions and methods for reducing the immunogenicity and increasing the circulating half-life of therapeutic proteins such as Factor VIII. The compositions comprise lipidic structures such as liposomes, micelles and cochleates comprising a negatively charged lipid and polyethylene glycol derivatized phosphatidyl ethanolamine.

This invention provides for a fusion protein between an IL2αβγ Selective Agonist protein (IL2 Selective Agonist) and a IgG Fc protein. The IL2 Selective Agonist moiety provides a therapeutic activity by selectively activating the IL2αβγ form of the receptor, thus selectively stimulating Tregs. The Fc moiety provides a prolonged circulating half-life compared to the circulating half-life of IL-2 or an IL2SA protein.

This invention provides for a fusion protein between an IL2αβγ Selective Agonist protein (IL2 Selective Agonist) and a IgG Fc protein using a linker. The IL2 Selective Agonist moiety provides a therapeutic activity by selectively activating the IL2αβγ form of the receptor, thus selectively stimulating Tregs. The Fc moiety provides a prolonged circulating half-life compared to the circulating half-life of IL-2 or an IL2SA protein.

A circulatory long-lived cholinesterase (ChE) protein, such as acetylcholinesterase (AChE) or butyrylcholinesterase (BChE), which is a ChE protein modified with a non-antigenic polymer. The ChE may be AChE, such as native AChE of mammalian origin or of non-mammalian origin, or recombinant AChE. The recombinant AChE may be mutated at one or more amino-acid residues. The BChE may be native BChE of mammalian origin or of non-mammalian origin.

The present invention relates to compositions and methods for the prevention and / or treatment of bone loss associated with cancer. More particularly, the invention relates to OPG compositions and methods for the prevention and / or treatment of bone loss comprising said compositions. The invention also relates to the use of OPG compositions for the treatment of multiple myeloma.

The invention provides a target hydrophilic polymer-triptolide conjugate (I), wherein P represents a water-soluble polymer; D represents triptolide; T represents a target molecule; and L and Z represent linking groups. The conjugate improves water solubility of triptolide, reduces toxicity of triptolide and prolongs circulating half-life period of triptolide in a living body.

The invention concerns an improved therapeutic regimen for the treatment of thrombolytic disorders, such as acute myocardial infarction (AMI). In particular, the present invention concerns the treatment of thrombolytic disorders, e.g. AMI, with a combination of a tissue plasminogen activator (t-PA) variant having improved fibrin specificity and extended plasma half-life when compared with wild-type human t-PA and a low molecular weight heparin.

The present invention provides compositions and methods for reducing the immunogenicity and increasing the circulating half-life of therapeutic proteins such as Factor VIII. The compositions comprise lipidic structures such as liposomes, micelles and cochleates comprising a negatively charged lipid and polyethylene glycol derivatized phospatidyl ethanolamine.

The present invention relates to the discovery of soluble isoforms of an Epidermal Growth Factor Receptor, or sErbB 1 / HER1 variants, the provision of the sequences of nucleic acids encoding these isoforms, purified recombinant proteins, novel antibodies specific for these isoforms, and the use of immunoassay and gene expression assay techniques to measure the concentration of these gene products in a patient biological sample. The present invention also provides methods for determining the presence of an ovarian carcinoma in the patient by assaying the concentration of soluble EGFR / ErbB1 variants in a biological sample from a patient.

The present invention relates to novel human growth hormone (h GH) variant(s) with one or more N-glycans. The hGH variants of the invention comprises an amino acid sequence which includes at least one N-glycosylation motif (N-X-S / T) arising from one or more mutations not present in the wild type hGH. The h GH variants of the invention have a prolonged circulatory half-life and thus can be effectively used as a protein therapeutic for disease states that will benefit from increased levels of h GH. The process of obtaining the hGH variants is also encompassed by the invention.

The invention discloses a preparation method of nanoparticles of an eight-arm PEG (polyethylene glycol)-oleanolic acid drug carrier. The preparation method comprises steps as follows: eight-arm PEG and oleanolic acid are subjected to an esterification reaction, and a conjugate of eight-arm PEG-oleanolic acid is obtained; 10-hydroxycamptothecine is wrapped with eight-arm PEG-oleanolic acid through self-assembly, and the nanoparticles are obtained. The nanoparticles have a double-layer structure, the outer layer is hydrophilic PEG, and the inner layer is hydrophobic oleanolic acid drug and 10-hydroxycamptothecine. The preparation method has the advantages that the drug loading capacity is greatly increased with the adoption of PEG; the water solubility and stability of oleanolic acid are increased, and the half-life period of oleanolic acid is prolonged; pH sensitive release of the drug in tumor cells can be realized; the toxic and side effects on normal tissue are reduced; the preparation process is simple and easy to operate.

The invention discloses a method for preparing target antineoplastic drug chlorinated nitidine compound, products thereof and an injection containing the products. The method for preparing the target antineoplastic drug chlorinated nitidine compound comprises the steps of pre-treating the chlorinated nitidine to acquire carboxylic acid-modified chlorinated nitidine, then using amphiphilic polymers to implement non-covalent functionalized modification on the outer wall of a single-wall carbon nano tube that is cut to be 20-500 nm long, and coupling the carboxylic acid-modified chlorinated nitidine with the single-wall carbon nano tube after the non-covalent functionalized modification by means of esterification and amidation reactions to acquire the compound. The preparation method of the compound is simple, the solubility of the resulting products can reach 5.0mg / mL, and the antineoplastic target is strong, thus favorably settling the problems of low solubility and strong toxicity of the chlorinated nitidine; in addition the invention can be applied clinically as a substitute for the chlorinated nitidine and provides a new water-soluble compound for the clinical trial of the chlorinated nitidine.

The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein a transglutaminase reaction is employed to covalently and site specifically conjugate the EPO molecule to a non-antigenic hydrophilic polymer that can also be covalently linked to an organic molecule either of which modification increases the circulating serum half-life of the composition.

Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.

The invention discloses a method for preparing self-assembled targeting nano drug carrier particles, comprising: esterifying eight-armed carboxypolyethylene glycol with dihydroartemisinin to obtain eight-armed polyethylene glycol-dihydroartemisinin The eight-arm polyethylene glycol-dihydroartemisinin conjugate is activated by NHS; the activated conjugate is further chemically linked to the targeting molecule transferrin by using an amide bond; the eight-arm modified transferrin The polyethylene glycol-dihydroartemisinin conjugate removes impurities by dialysis, is filtered and freeze-dried; self-assembles to obtain transferrin-modified nano drug carrier particles. The nanoparticle has a double-layer structure, the outer layer is hydrophilic polyethylene glycol, and the inner layer is hydrophobic small molecule drug dihydroartemisinin. The advantages of the present invention: the use of eight-arm carboxypolyethylene glycol greatly increases the drug loading; the targeting effect of drugs on tumor cells and the pH-sensitive release in tumor cells can be realized; the targeted therapy reduces the toxic and side effects on normal tissues ; The preparation process is simple and easy to operate.

Provided are human antibodies that can neutralize a H5N1 strain of influenza A virus. Also provided are antibodies that can neutralize a strain of influenza A virus in clade 2 of the H5 subtype, that can neutralize a H5N1 strain of influenza A virus and have a lambda light chain, and that are IgG antibodies (but not with a IgG1 heavy chain) that can neutralize a H5N1 strain of influenza A virus.

The invention described herein is a novel IL-2 protein with selective agonist activity for Regulatory T cells and with an additional amino acid substitution that enable chemical conjugation with Polyethyene Glycol (PEG) that increase circulating half-life compared to the IL-2 selective agonist alone. A preferred IL-2 selective agonist variant is IL2 / N88R / C125S / D109C.

A method of treating an avian influenza viral infection using a poly ICLC formulation with improved therapeutic efficacy is disclosed. The poly ICLC is encapsulated within liposomes which provides a drug delivery system with slow sustained release characteristic and which has the ability to target the drug to sites of viral infection without causing systemic burden to normal tissues, thereby enhancing the immunological and biological activities of poly ICLC. This poly ICLC formulation has been found to be particularly effective in treating an avian influenza viral infection and in particular, an avian H5N1 influenza viral infection.

The invention discloses an RGD-SSL lipidosome for packaging turtle shell peptide and a preparation method of the lipidosome. The turtle shell peptide long-cycle lipidosome modified by RGD comprises a lipidosome body and the turtle shell peptide (HGRFG) in the lipidosome body. The lipidosome body is prepared from egg yolk lecithin (EPC), cholesterol (Chol), mPEG2000-DSPE and RGD-PEG2000-DSPE according to the molar ratio of 50:25:1:0.6, and the weight ratio of the turtle shell peptide (HGRFG) to the EPC is 1:5 to 1:30. The defects that turtle shell peptide and other oligopeptides can easily degrade when orally taken and are low in bioavailability and short in half-life period are overcome; the RGD modified turtle shell peptide long-cycle lipidosome (RGD-SSL-turtle shell peptide) is obtained by packaging the turtle shell peptide with the granularity and RGD modified dual-control hepatic targeting lipidosome, the local biological effect and cycle half-life period are improved, the dosage frequency is reduced, and the lipidosome is suitable for treatment of hepatic fibrosis and other hepatic diseases.

Bispecific aptamers having a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein are provide. The bispecific aptamers can be used to treat cancer or virally infected cells. Generally, the bispecific aptamers bind to two surface proteins, preferably different proteins, on the same cell. In a preferred embodiment the bispecific aptamers bind to two different tumor markers, tumor antigens, tumor specific proteins and combinations thereof.