59 results about "Anti tnf alpha" patented technology

The invention provides a liquid pharmaceutical formulation which does not include NaCl and comprises more than 20 mg of a polyol and at least about 100 mg / mL of a human anti-TNF-alpha antibody, or antigen-binding portion thereof. The invention provides a high concentration antibody formulation having long-term stability and advantageous characteristics for subcutaneous administration.

The invention provides a liquid aqueous pharmaceutical formulation comprising a human anti-TNFa antibody, or antigen-binding portion thereof, which reduces pain associated with injection in a subject by at least about 50% when compared to injecting an otherwise identical formulation comprising at least one salt and / or at least one buffer. The invention also provides a liquid aqueous pharmaceutical formulation comprising a human anti-TNFa antibody, or antigen-binding portion thereof, having increased bioavailability upon subcutaneous administration into a subject. The formulation may comprise a therapeutic protein, such as a human anti-TNF-alpha antibody, or an antigen-binding portion thereof, or a biosimilar thereof.

Substances comprising disaccharides and substances comprising carboxylated and / or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF- alpha ) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and / or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF- alpha . The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.1 mg / kg human, or at intervals of up to about 5-8 days, preferably once a week.

The present disclosure relates to a novel class of anti-TNFα monoclonal antibodies or antigen binding fragments comprising a homogeneous population of anti-TNFα IgG molecules having the same N-glycan on each of Fc. The antibodies of the invention can be produced from anti-TNFα monoclonal antibodies by Fc glycoengineering. The glycoantibodies of the invention may have improved therapeutic values compared to the corresponding monoclonal antibodies that have not been glycoengineered.

The present invention provides assays for detecting and measuring the presence or level anti-TNFα drugs and / or the autoantibodies to anti-TNFα drugs in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFα drug therapeutics to detect the presence or level of autoantibodies against the drug. The present invention also provides methods for selecting therapy, optimizing therapy, and / or reducing toxicity in subjects receiving anti-TNFα drugs for the treatment of TNFα-mediated disease or disorders.

The invention discloses an immunosensor based on hybrid chain reaction and single molecule counting. The immunosensor consists of a capturing antibody, a detection antibody, streptavidin, a biotinylated primer and a hairpin probe, wherein the capturing antibody is anti-TNF-alpha; the detection antibody is Bio-anti-TNF-alpha; a base sequence of the biotinylated primer (Bio-I) is 5'-AGT CTA GGA TTC GGC GTG GGT TAA TTT TTT TTT-biotin-3'; the hairpin probe consists of a hairpin probe H1 and a hairpin probe H2; a base sequence of the hairpin probe H1 is 5'-TTA ACC CAC GCC GAA TCC TAG ACT CAA AGT AGT CTA GGA TTC GGC GTG-3'; a base sequence of the hairpin probe H2 is 5'-AGT CTA GGA TTC GGC GTG GGT TAA CAC GCC GAA TCC TAG ACT ACT TTG-3'. The invention also provides a preparation method of the immunosensor and application of the immunosensor in detection of the TNF-alpha. The immunosensor disclosed by the invention has the advantages of high detection sensitivity, small sample use amount, no need of enzyme amplification and the like, and quantitative detection on low-concentration TNF-alpha can be realized.

The present invention provides assays for detecting and measuring the presence or level of anti-TNFα drugs and / or the autoantibodies to anti-TNFα drugs in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFα drug therapeutics to detect the presence or level of autoantibodies against the drug. The present invention also provides methods for selecting therapy, optimizing therapy, and / or reducing toxicity in subjects receiving anti-TNFα drugs for the treatment of TNFα-mediated disease or disorders.

The invention discloses a cation exchange chromatographic purification method an anti-TNF alpha-type monoclonal antibody. The method includes: adding urea and a betaine surfactant in the process of CEX multistep elution to remove pollutants in a mixture containing the antibody and the pollutants to separate a polymer from the antibody. The method has good pollutant separation effect, the chromatographic process is simple in sample adjusting, drastic changes of pH value are avoided, and content of the polymer in a final purified product is lowered remarkably.

This invention relates to a full human anti-TNF-alpha monocloned antibody with strong specificity and low immunogenicity as well as its preparation and medicinal composition therewith.

The invention relates to clinical application of a substituted aryl hydrazone compound and a derivative thereof serving as an anti-tumor necrosis factor inhibitor. A test result shows that the compound has a lower cytotoxicity in animal bodies, so the medical compound is expected to be used as an anti-TNF-alpha and TNF-beta inhibitor in the clinical application and is mainly used for treating some TNF related immunological diseases such as rheumatic arthritis, inflammatory bowel diseases, diabetes, hematosepsis, psoriasis, ankylosing spondylitis and some communicable diseases including HIV. A current TNF related research also shows that the medical compound can be used for treating clinical blood and solid tumor such as myelodysplastic syndrome, myelofibrosis, acute bone marrow cell leucocythemia, acute / chronic graft-versus-host reaction, ovarian cancer, nephrocyte cancer and the like.

The present invention relates to a stable anti-TNF-alpha antibody preparation and uses thereof. Particularly the preparation comprises: (i) a therapeutically effective amount of an anti-TNF-alpha antibody, (ii) a buffer system containing 0.8-6.2 mg / ml histidine, (iii) an osmotic pressure adjusting agent, and (iv) a surfactant, wherein the pH value of the preparation is 5.5-6.5. According to the present invention, with the preparation, the chemical degradation reaction rate of the anti-TNF-alpha monoclonal antibody can be effectively reduced, the chemical stability of the antibody can be improved, the shelf life of the product can be prolonged, the side effect at the injection site of the patient can be eliminated or reduced, and the medication comfort of the patient can be improved. In addition, the present invention further discloses a method for stabilizing the antibody and the uses of the preparation.

The present invention relates to a method for predicting the response of a patient to treatment with an anti-TNFα therapy, in particular an anti-TNFα antibody, the method comprising: (a) providing an in vitro sample of T cells from the patient; (b) exposing said T cells to an anti-TNFα therapy; and (c) determining whether regulatory T cells are induced in said sample of T cells wherein the induction of regulatory T cells indicates that the patient is likely to respond to treatment with said anti-TNFα therapy.

The invention relates to the modification of antibodies reactive to human tumor necrosis factor alpha (TNF alpha) to result in anti-TNF alpha antibodies that are substantially non-immunogenic or less immunogenic than any non-modified parental antibody when used in vivo. The invention relates also to peptide molecules comprising T-cell epitopes of the V-regions of the parental antibody which are modified by amino acid alteration in order to reduce or eliminate said T-cell epitopes.

The invention provides an antibody composition for TNF-alpha, and an application thereof. The solvent of the composition comprises water, and the solute of the composition comprises an anti-TNF-alpha antibody; and the pH value of the composition is 4.0-8.0, and the pH value is adjusted through introducing carbon dioxide to the solvent and solute mixture of the composition. Compared with antibody compositions in the prior art, the antibody composition contains no common buffer systems, adopts carbon dioxide introduction to substitute a buffer system and keep the pH value of a preparation stable, reduces the pains and discomfort during patient injection, and is of great significance to treating TNF-alpha-related diseases.

The present invention provides assays for detecting and measuring the presence or level of autoantibodies to anti-TNFa drug therapeutics in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFa drug therapeutics to detect the presence or level of autoantibodies against the drug. The present invention also provides methods for selecting therapy, optimizing therapy, and / or reducing toxicity in subjects receiving anti-TNFa drugs for the treatment of TNFa-mediated disease or disorders.

The invention relates to a cellular expression system for stably expressing an anti-TNF-alpha monoclonal antibody, and a construction method and application of the cellular expression system. According to the cellular expression system, light and heavy chain encoding genes of the anti-TNF-alpha monoclonal antibody are optimized according to cell codon preference so as to construct anti-TNF-alpha human-mouse chimeric monoclonal antibody homologous recombination vector with a Bak1 gene and the like as a drone, meanwhile, a CRISPR / Case9 vector with a specific cutting effect is constructed for exon regions of drone genes such as Bak1, two vectors are commonly guided into Chinese hamster ovary cells (CHO) by lipofection transfection, and a positive cell strain capable of stably expressing the anti-TNF-alpha monoclonal antibody is obtained through screening. The cellular expression system can be applied to efficient production of the anti-TNF-alpha monoclonal antibody, and the anti-TNF-alpha monoclonal antibody can be used for treating diseases such as rheumatoid arthritis and ankylosing spondylitis.

The invention provides stable liquid formulations for a recombinant biopharmaceutical protein comprising a fully human anti-TNF monoclonal antibody.

The invention relates to an anti-TNF-alpha monoclonal antibody chromatographic method, and belongs to the field of biotechnology. In particular, the method for removing host proteins and multimers during a process of purification of a TNF-alpha monoclonal antibody is disclosed. An ion exchange and hydrophobic composite chromatographic filler is used, a low-pH buffer solution is used for removing contaminants, and then a lower-pH elution buffer solution is used for eluting the target antibody. The method can remove a part of the multimers s and most of the host proteins, significantly improves the purity of the antibody, is cheaper in price, has no protein A falling off, is simple and convenient, has no need for adjusting the sample pH value and electric conductance, and is suitable for process amplification and industrial production.

The invention provides tools for management of patients diagnosed with psoriatic arthritis, specifically, prior to the initiation of therapy with an anti-TNFα agent. The tools are specific markers and algorithms of predicting response to therapy based on standard clinical primary and secondary endpoints using serum marker concentrations. In one embodiment the baseline levels of VEGF, prostatic acid phosphatase, and adiponectin are used to predict the response at Week 14 after the initiation of therapy. In another embodiment, the change in a serum protein biomarker after 4 weeks of therapy is used such as MDC, lipoprotein a, and beta2-microglobulin.

In one aspect, the disclosure relates to highly galactosylated anti-TNF-alpha antibodies and compositions thereof. In one aspect, the disclosure relates to populations of anti-TNF-alpha antibodies with a high level of galactosylation, and compositions thereof. In one aspect, the disclosure relates to methods of production and use of highly galactosylated anti-TNF-alpha antibodies and populations of anti-TNF-alpha antibodies with a high level of galactosylation. In some embodiments, the anti-TNF-alpha antibody is adalimumab.

The invention discloses a preparation method of a recombinant anti-TNF-alpha completely humanized monoclonal antibody. The method comprises: synthesizing a nucleic acid sequence of a recombinant anti-TNF-alpha completely humanized monoclonal antibody, using the obtained nucleic acid sequence of the recombinant anti-TNF-alpha completely humanized monoclonal antibody to construct a carrier, transfecting a host cell, and screening high-expression cell clone to establish a cell bank; and using the obtained cell strain for culture, and performing separation and purification to obtain the recombinant anti-TNF-alpha completely humanized monoclonal antibody. Light chains and heavy chains of the recombinant anti-TNF-alpha completely humanized monoclonal antibody is designed and synthesized according to preferred codons of Chinese hamsters, an eukaryotic expression carrier is established, a host cell CHO-GS- is transfected, serum-free culture is adopted, and separation and purification are adopted to obtain the high-purity recombinant anti-TNF-alpha completely humanized monoclonal antibody. The preparation method is simple to operate, short in production period, and suitable for industrial production.

The invention discloses an anti-TNF-alpha monoclonal antibody drug antibody detection reagent kit. The reagent kit comprises biotinylation monoclonal antibody drugs, a calibrator, a quality control product, an enzyme conjugate, magnetic particle reagent, a chemiluminiscence substrate and cleaning fluid. In this way, the full-automatic magnetic particle chemiluminiscence detection method is adopted, an alkaline phosphatase (AP)-adamantane AMPPD system is selected, the method has the advantages that stability and repeatability are good, and sensitivity is high, meanwhile, detection time is greatly shortened, one test is completed within 50 minutes, operation is easy and convenient, and detection full automation is really achieved.

The present invention relates to a polypeptide binding with tumor necrosis factor (TNF-alpha), and applications thereof. According to the present invention, the polypeptide and TNF-alpha have high affinity, and the polypeptide can be bound with the excess TNF-alpha to make the apoptosis promoting protein Bid in the apoptosis-related mitochondrion apoptosis pathway be down-regulated while make the anti-apoptosis protein Bcl-2 be up-regulated in the apoptosis-related mitochondrion apoptosis pathway so as to inhibit the apoptosis caused by TNF-alpha, such that the polypeptide can be used for preparation of TNF-alpha-related disease treating drugs. The present invention further provides a method for screening at the molecular and cellular level and researching the influence of the polypeptide antagonist on the TNF-alpha physiological effect, and applications thereof so as to provide the effective method for development of the low-cost anti-TNF-alpha drug.

The invention relates to the use of SNP rs3794271, and / or an SNP that is in total linkage disequilibrium with same, as a marker in predicting the response to treatment with anti-TNF in a patient with RA. The invention also relates to methods for predicting the response to treatment with anti-TNF, as well as for deciding on or recommending a treatment for a patient with RA, based on determining the genotype for rs3794271 and / or an SNP that is in total linkage disequilibrium with same.

The invention relates to the technical field of biology, and discloses a whole human TNF alpha (tumor necrosis factor alpha) monoclonal antibody and preparation and application thereof. The invention adopts a whole human antibody technology and acquires an anti-human TNF alpha whole human antibody. Preliminary analyses on the physical, chemical and biological activities of the antibody indicate that the antibody has better affinity with TNF, and can effectively neutralize the killing effect of the TNF on L929 cells in vitro. The whole human TNF alpha monoclonal antibody disclosed by the invention minimizes the immunogenicity of a human body. A PEG (polyethylene glycol) surface modification technology is adopted, thus avoiding the defect of short half life of small molecule antibody, and the whole human TNF alpha monoclonal antibody is more suitable for application in vivo while keeping the anti-TNF alpha activity.

This invention provides methods for predicting response to anti-TNFα biological agent treatment in a rheumatoid arthritis patient and methods for selecting a treatment for a rheumatoid arthritis patient, the methods comprising determining the level of expression of PIK3CD as a biomarker, and optionally also determining the level of expression of CX3CL1 as a second biomarker. The invention additionally provides kits for carrying out the methods described.