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The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising cancer antigenic peptides and uses there of.

Methods and compositions disclosed herein generally relates to methods of determining minimum hematopoietic stem cell (HSC) chimerism and gene dosage for correction of a hematopoietic disease; in particular, in in vivo models. The invention also relates to modified lentiviral expression vectors for increase a viral titer and various methods for increasing such titers as well as expression vectors capable of enhancing such titers. The invention also relates to CHS4 chromatin insulator-derived functional insulator sequences. The invention further relates to methods for genetic correction of diseases or reducing symptoms thereof, such as sickle cell anemia, a lysosomal storage disease. The invention further relates to a method of improving and / or correcting one or more central nervous system (CNS) abnormalities caused by one or more lysosomal storage disease. The invention further relates to methods of improving titer in transfection-based bioreactor culture production or transfection-based production systems using eukaryotic cells.

The present invention concerns methods and nucleic acid based reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, veterinary, agricultural, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to double strand forming oligonucleotides (DFO) that can self assemble to form double stranded oligonucleotides, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA) molecules, and modulate gene expression, for example by RNA interference (RNAi). The self complementary DFO nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The invention describes improved methods and compositions for producing a recombinant protein, e.g., an antibody, in mammalian cell culture. In addition, the invention provides improved cell culture media, including improved production media, feed solutions, and combination feeds, which may be used to improve protein productivity in mammalian cell culture.

Disclosed are water-soluble gel-based compositions for the delivery of recombinant adeno-associated virus (rAAV) vectors that express nucleic acid segments encoding therapeutic constructs including peptides, polypeptides, ribozymes, and catalytic RNA molecules, to selected cells and tissues of vertebrate animals. Also disclosed are gel-based rAAV compositions are useful in the treatment of mammalian, and in particular, human diseases, including for example, cardiac disease or dysfunction, and musculoskeletal disorders and congenital myopathies, including, for example, muscular dystrophy, acid maltase deficiency (Pompe's disease), and the like. In illustrative embodiments, the invention provides rAAV vectors comprised within a biocompatible gel composition for enhanced viral delivery / transfection to mammalian tissues, and in particular to vertebrate muscle tissues such as a human heart or diaphragm tissue.

The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes and associated metabolic disorders. In particular, the invention provides novel acylated glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y12 inhibitors and as anti-thrombotic agents, etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) antibodies having improved potency and breadth.

The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, preferably, but not limited to, fed-batch cell cultures. In one aspect, the methods comprise the addition of glucocorticoid compound during the culturing period. The addition of glucocorticoid compound sustain a high viability of the cultured cells, and can yield an increased end titer of protein product, and a high quality of protein product, as determined, e.g., by sialic acid content of the produced protein.

The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising Mycobacterium tuberculosis antigenic peptides and uses there of.

The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, preferably, but not limited to, fed-batch cell cultures. In one aspect, the methods comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. Throughout their duration, the culturing processes of the invention involving two or more downward shifts in temperature sustain a high viability of the cultured cells, and can yield an increased end titer of protein product, and a high quality of protein product, as determined, e.g., by sialic acid content of the produced protein. In another aspect, the methods comprise the delayed addition of polyanionic compound during the culturing period. The delayed addition of polyanionic compound sustains a high viability of the cultured cells, and can extend the growth phase, delay the onset of the death phase, and arrest the death phase.

The present invention provides an improved method for the biological production of 1,3-propanediol from a fermentable carbon source in a single microorganism. In one aspect of the present invention, an improved process for the conversion of glucose to 1,3-propanediol is achieved by the use of an E. coli transformed with the Klebsiella pneumoniae dha regulon genes dhaR, orfY, dhaT, orfX, orfW, dhaB1, dhaB2, dhaB3, and orfZ, all these genes arranged in the same genetic organization as found in wild type Klebsiella pneumoniae. In another aspect of the present invention, an improved process for the production of 1,3-propanediol from glucose using a recombinant E. coli containing genes encoding a G3PDH, a G3P phosphatase, a dehydratase, and a dehydratase reactivation factor compared to an identical process using a recombinant E. coli containing genes encoding a G3PDH, a G3P phosphatase, a dehydratase, a dehydratase reactivation factor and a 1,3-propanediol oxidoreductase (dhaT). The dramatically improved process relies on the presence in E. coli of a gene encoding a non-specific catalytic activity sufficient to convert 3-hydroxypropionaldehyde to 1,3-propanediol.

The invention relates to an anti-mouse TIGIT (T cell Ig and ITIM domain), and a hybridoma cell strain mTIGIT-mAb-13G6 (the preservation NO: CCTCC NO: C201299) for producing the monoclonal antibody, and further relates to a preparation method and the application of the monoclonal antibody. The monoclonal antibody can efficiently prevent combination of mTIGIT and mPVR (poliovirus receptor), and can be used for Western blot, ELISA and Flow Cytometry for mTIGIT molecule detection.

The invention relates to a reagent kit and the preparation method thereof which are used to detect cardiac muscle troponin I; the reagent kit provided by the invention comprises a reagent strip; the reagent strip contains cardiac muscle troponin I monoclonal antibody labeled by colloid gold, unlabeled cardiac muscle troponin I monoclonal antibody and the second antibody of anti-myocardial troponin I monoclonal antibody; the invention also provides the preparation method of the reagent kit of detection. The reagent kit of detection can detect cardiac muscle troponin I in blood sample drawn from human body swiftly, conveniently and delicately; the cardiac muscle troponin I can be used to diagnose myocardial infarction.

A method and system used for treating proliferative disorders using carotenoids, carotenoid analogs, and / or carotenoid derivatives. The method and system may be used for chemoprevention and / or chemotherapy. The method and system may induce apoptosis in target cells, tissues, and / or organs. The analog, derivative, or intermediate may be administered to a cell, a group of cells, a tissue, an organ or a subject, such that at least a portion of the undesirable consequences of the proliferative disorder are thereby reduced.

Pharmaceutical combinations comprising a beta-3 adrenergic receptor agonist and a muscarinic receptor antagonist, and methods for their use are disclosed. Methods of using the pharmaceutical combinations for the treatment of one or more symptoms associated with overactive bladder, for example, frequency of urgency, nocturia, and urinary incontinence, are also disclosed.

Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) potent VRC01-like (PVL) antibodies targeted to gp120 having an amino acid substitution in the heavy chain at a residue in the anti-CD4 binding site PVL antibody that is equivalent to Phe43 in CD4 and an amino acid substitution in the light chain, these antibodies having improved potency and breadth.

Described are methods for production of RNA transcripts using a non-amplified, linearized DNA template in an in vitro transcription reaction. Enzymatic 5′ capping and oligo dT purification can also be included in the methods.

This invention relates to the use of a composition comprising a polysaccharide and a botulinum toxin for reducing a skin wrinkle. In some embodiments, the polysaccharide comprises disaccharides. In some embodiments, the average molecular weight of a disaccharide unit of the polysaccharide is between about 345 D and about 1,000 D.

The invention provides health-care food for beautifying and brightening hair of a dog, belonging to the field of animal health-care products. The health-care food formula comprises the following components by weight based on 1kg: 10-30g of deep sea fish oil, 10-30g of linseed oil, 5-20g of poppyseed oil, 10-30g of perilla oil, 10-30g of grape seed oil, 10-30g of lecithin, 5-20g of chelate iron, 1-10g of chelate manganese, 5-20g of chelate zinc, 1-5g of chelate copper, 0.05-0.2g of yeast selenium, 150-250g of methionine, 50-150g of lysine, 1-4g of vitamin E, 0.05-0.2g of vitamin D, 0.5-2g of vitamin A, 0.05-0.2g of vitamin B1, 0.1-0.4g of vitamin B2, 0.05-0.2g of vitamin B6, 0.05-0.4g of vitamin B12, 0.05-0.2g of biotin, 0.1-0.4g of nicotinic acid, 1-5g of bacillus, 1-5g of yeast, 120-180gof chicken liver powder, 50-80g of Rosmarinus officinalis and the balance of yeast powder. The components are made into a tablet with the specification of 0.7-0.9g according to a regular tabletting process, and the water content is less than 10%. The health-care food provided by the invention has the advantages of high titer and strong stability and is capable of improving the fur health of the dog, protecting hair follicles and hair shafts against damage, enabling the hair to be smooth and soft, reducing hair slip, promoting regeneration of furs, improving immunity comprehensively and ensuring the dog in a healthy and vital state.

A method for preparing a concentrated, immunoglobulin composition for treating subjects vaccinated against or infected with a pathogenic microorganism, comprising: (a) selecting a population of individuals previously vaccinated against one or more antigens associated with the pathogenic microorganism; (b) determining the level of specific antibodies immunoreactive with the pathogenic microorganism in a blood or blood component of the individuals to identify very high titre individuals having a very high titre of the specific antibodies; (c) combining blood or blood components comprising immunoglobulins from the very high titre individuals; and (d) purifying and / or concentrating the product of step (c), thereby obtaining a concentrated immunoglobulin composition. Also disclosed is a concentrated immunoglobulin composition comprising specific antibodies immunoreactive with a pathogenic microorganism, characterized in that the titre of specific antibodies of the composition is at least 5 times higher than the average titre of specific antibodies of a population of individuals previously vaccinated against one or more antigens associated with the pathogenic microorganism. The composition has a relatively high protein concentration and a low percentage of protein aggregates, and is therefore suitable for both iv and im administration. In a preferred embodiment, the pathogenic microorganism is smallpox virus or vaccinia virus.

The invention relates to a glycocholic acid detecting reagent and a preparing method and a detecting method thereof, in particular to a glycocholic acid immunodetection reagent and a preparing method and a detecting method thereof. The glycocholic acid immunodetection reagent comprises a glycocholic acid specificity resisting antibody and an indicating reagent, wherein the indicating reagent is used for detecting the glycocholic acid specificity resisting antibody and a glycocholic acid composite; the glycocholic acid specificity resisting antibody is obtained from glycocholic acid immunogen immune animals. The glycocholic acid immunodetection reagent has the benefits that the glycocholic acid immunogen specificity is strong, the immunogenicity is high, and the prepared glycocholic acid specificity resisting antibody has strong specificity and high valence and does not have any cross reaction with 45 common drugs; a homogeneous enzyme immunodetection reagent containing the glycocholic acid specificity resisting antibody can conveniently, rapidly and accurately determine the content of glycocholic acid in a sample and can simultaneously test multiple samples on a fully-automatic biochemical analysis instrument; the high-throughout rapid measurement of the glycocholic acid is realized, the accuracy is high, the specificity is strong, and both the precision and the detection efficiency are greatly improved.

The invention discloses a carbamazepine immunogen, a carbamazepine specific antibody directly obtained through the immunogen, a detection reagent containing the specific antibody and a method for detecting the content of the carbamazepine in samples to be tested. The immunodetection reagent and the detection method have the advantages that the carbamazepine immunogen is strong in specificity and high in immunogenicity; the prepared carbamazepine immunogen is strong in specificity and high in titer and has no cross reaction with 45 common drugs; the homogeneous enzyme immunodetection reagent containing the carbamazepine specific antibody can conveniently, fast and accurately determine the content of the carbamazepine in the samples and can measure a plurality of samples simultaneously on a full-automatic biochemical analyzer, so that high-throughput and fast measuring of the carbamazepine are achieved, the accuracy is high, the specificity is strong, the accuracy and the detection efficiency are greatly improved compared with the prior art, full automation in the detection process is achieved simultaneously, the requirements on detection staff is not high, and the immunodetection reagent and the detection method are easy to achieve, popularize and use.

Provided is a process for the production of poliovirus, comprising the steps of:a) providing a serum-free suspension culture of cells, which are primary human retina (HER) cells that have been immortalized by expression of adenovirus E1 sequences,b) infecting the cells with poliovirus, at a cell density of between 2×106 cells / ml and 150×106 cells / ml, and c) harvesting poliovirus at a time of between 12 and 48 hours after infection.

The invention relates to an anti-Golgi protein antibody and an application thereof. The invention recombines human GP73 protein immunity animal to obtain an anti-GP73 polyclonal antibody and a monoclonal antibody which specifically aims at GP73 and builds a plurality of methods for detecting GP73 in clinical tissue sections and serum samples, such as immunohistochemical stain and double antibody sandwiched ELISA method and the like. Tests prove that the polyclonal and monoclonal antibodies can be used for preparing a plurality of GP73 detecting agents of different detecting methods.

The invention relates to retroviral vectors, especially to self-inactivating (SIN) gammaretroviral or lentiviral vectors, suitable for producing viral particles at high titers, which can be used for efficient gene transfer into mammalian cells, organs or organisms, e.g. for gene therapy. More specifically, the present invention provides modified 5′-promoter elements in the U3-region of the 5′-LTR of the vector plasmid and 3′-SIN elements modified in the U3-region of the 3′-LTR of the vector plasmid suitable for being comprised in retroviral vectors. It is a specific advantage of both the modified 5′-promoter element and of the modified 3′-SIN element, which are preferably contained in retroviral vectors in combination with one another, to increase both the titer of viral particles as well as to increase the expression of a transgene in recipient cells, which transgene is arranged between the modified LTRs according to the invention.

Expression of at least one plant oleosin gene in a microbial cell engineered to produce hydrophobic / lipophilic compounds significantly increases the overall titer of the compound. The hydrophobic nature of the oleosin core is believed to increase the microbial host cell's internal storage capacity for any hydrophobic / lipophilic compound. The method is exemplified using a bacterial host cell engineered to produce significant amount of various carotenoids.

A method for treating or preventing infections from yeast of the Candida species is provided wherein an immunoglobulin composition containing high titers of antibodies to staphylococcal adhesins ClfA and SdrG is administered in an amount effective to inhibit the growth and progression of Candidial infections. The compositions and methods of the present invention are advantageous in that they can be used to treat both staphylococcal and Candidial infections at the same time, and they are particularly effective in treating or preventing late-onset sepsis in neonates.