Antibody against il-6 receptor. RU patent 2505603.
 Microbiological synthesis method of target released protein in yeast saccharomyces cerevisiae / 2502805Method involves cultivation in the appropriate conditions of yeast Saccharomyces cerevisiae and release of target protein; besides, release is directed with leader polypeptide, which has amino acid sequence SEQ ID NO1 and representing a variant of a pro-area of leader polypeptide of protein PpPIRl Pichia pastoris. |
 Two-stranded rna modified with lipids and having powerful effect of rna interference / 2501859Invention describes two-stranded RNA modified with lipids and including antisense thread, the nucleotide sequence of which is complementary to target sequence in the target gene, and a sense thread, the nucleotide sequence of which is complementary to antisense thread. A two-stranded lipid is connected to the first nucleotide on the 5'-end of sense thread, either directly or through a linker. RNA has high stability to action of nuclease and is effectively absorbed with a cell, as well as generates excellent effect of RNA interference. |
 Glycerol-3-phosphatocyltransferase / 2499835Invention also refers to an expression vector and a transformant containing polynucleotide, as well as a production method of lipid composition or composition based on fat acids using the transformant. |
 Recombinant hybrid inhibitor of angiogenesis, and its production method / 2499802Recombinant hybrid inhibitor of angiogenesis represents a protein shown in dwg. 1. This protein includes amino acid sequence of plasminogen of a human being from amino acid 82 to 341 and sequence Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys, which are covalently connected to each other. An inhibitor production method involves expression of its gene in cells of E. coli producer strain, which are transfected with recombinant plasmid DNA pBSRK13 with a physical map presented in dwg. 2, which has the size of 4155 pairs of bases. This plasmid includes a gene coding the recombinant hybrid inhibitor of angiogenesis, as well as a gene of signal peptide OmpA, lac-operator, a gene of stability to kanamycin, replicative origin pUC ori and a gene coding the lac-operator under control of promoter T7. A target protein is extracted from periplasmatic area of bacterial cells by affine and gel-filtration chromatography. The invention can also be used in medicine for creation of new medicinal agents with antiangiogenic therapeutical effect. |
 Recombinant plasmid pad-sm, coding human proteins sox2 and c-myc, being base for production of virulent adenoviruses designed for production of induced pluripotent human cells / 2495127Genetic structure pAd-SM is produced, being built by homological recombination of the vector pAdEasy-1, containing the main part of genome of adenovirus and plasmid pAdTrack-CMV, where cDNA fragments of human genes SOX2 and C-MYC are placed, being connected with a nucleotide sequence that codes P2A-peptide. The plasmid pAd-SM produced as a result of homological recombination contains a fragment SOX2-P2A-C-MYC under control of a constitutive promotor CMV. |
 Cell for production of heteroproteins and method of production on its basis / 2494148Method is proposed to produce a polypeptide, including cell cultivation, which intensely expresses a bicarbonate carrier and has a transferred DNA, which codes the desired polypeptide. |
 Chiral diacyl-hydrazine ligands for modulating expression of exogenic genes by means of ecdysone-receptor complex / 2490253Invention relates to compounds of general formula III and their pharmaceutically acceptable salts, A represents (C1-C6)alkyl-O-, phenyl-(C1-C6)alkyl-O-; aryl, selected from phenyl, naphthyl, and which is possibly substituted by 1-3 substituents, given in the invention formula; or heteroaryl, which has four or five carbon atoms and one heteroatom, selected from oxygen, nitrogen and sulphur, which is possibly substituted by 1-3 substituents, given in the invention formula; B represents phenyl, possibly substituted by 1-3 substituents, where substituents are selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halogeno; and R1 and R2 independently represent (C1-C6)alkyl, phenyl-(C1-C6)alkyl-, hydroxy-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C2-C6)alkenyl or (C2-C6)alkynyl; on condition that R1 is different from R2; where absolute configuration of asymmetric R1 and R2 -carrying carbon atom is mainly R-configuration. Invention also relates to pharmaceutical composition, possessing ability to modulate gene expression, methods of modulation of gene expression in host cell, method of regulating expression of endogenous or heterologous gene in transgenic subject, method of regulating transgenic expression in transgenic subject, method of polypeptide production and to method of obtaining formula IV compound. Method includes stages: a) interaction of formula V compound with formula IV compound with obtaining formula VII compound; b) reduction of formula VII compound with obtaining formula VIII compound, b) interaction of formula VIII compound with formula B-CO-LG compound, where B has values, given above, and LG is leaving group representing -F, -Cl or -Br, with formation of formula IX compound, d) removal of group R7CO2- from formula IX compound with obtaining formula X compound, e) interaction of formula X compound with formula A-CO-LG compound, where A has values, given above, and LG is leaving group, representing -F, -Cl or -Br, with obtaining formula IV compound ( compounds of formulas V, VI, VII, VIII, IX, X are given in the invention formula). |
 Antibody against nr10 and its application / 2487136Antibodies are used as pharmaceutical means for treatment or prevention of inflammatory diseases. |
 Stable recombinant adenosine deaminase / 2486246Isolated recombinant adenosine deaminase is described, which comprises polypeptide SEQ ID NO: 1 or a version polypeptide SEQ ID NO: 1 of isolated recombinant adenosine deaminase, where the version polypeptide SEQ ID NO: 1 comprises one or more amino acid substitutions selected from the group consisting of: Gin instead Lysl98; Ala instead Thr245; and Arg instead of Gly351, and DNA encoding it. The conjugate of polyalkylene oxide with the said adenosine deaminase for treatment of adenosine deaminase-mediated diseases is presented where adenosine deaminase comprises from 11 to 17 chains of polyalkylene oxide with a molecular weight of 5 kDa for ADA protein. The methods of purification of the recombinant adenosine deaminase are proposed, including protein purification using ion exchange chromatography, or protein purification using hydrophobic interaction chromatography. Also the preparations of recombinant adenosine deaminase produced by these methods are provided. |
 Method of producing cell capable to produce heteroproteins with high yield / 2486245Method comprises culturing CHO cell in which the gene of taurine transporter (TauT) was artificially transferred, the DNA encoding the desired polypeptide and the DNA encoding dihydrofolate reductase (DHFR) was introduced in the presence of methotrexate concentration at which 90% or more cells, in which TauT was not introduced die within three weeks after subculturing. From the number of surviving CHO cells the CHO cell is selected which is capable to produce a desired polypeptide with a high yield. The cell prepared in this manner produces a desired polypeptide in higher yield than the CHO cell transfected with DNA encoding the desired polypeptide and DNA encoding DHFR, but not the genome of taurine transporter. The method of producing a desired polypeptide comprises culturing the above mentioned cell and isolating the desired peptide. |
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 Antibodies to her / 2504553Invention describes versions of bispecific antibodies specifically bound to EGFR and HER3, which contain amino-acid sequences of variable regions of heavy and light chains respectively, SEQ ID NO: 30 and 29; or SEQ ID NO: 28 and 27; or SEQ ID NO: 28 and 29; or contain complementary regions CDR of heavy and light chains of the above sequences of variable regions. The invention describes nucleic acid coding a versions antibody, and a host cell containing the above nucleic acid and used for expression of the anitbody. Immunoconjugate containing antibody versions and cytotoxic agent used for treatment of cancer containing cells that express EGFR and HER3 are presented. A method for obtaining a bispecific antibody, which involves cultivation of a host cell so that an antibody is generated, is described. The invention describes a pharmaceutical composition for treatment of cancer containing EGFR- and HER3-expressing cells, which contains effective amount of bispecific antibody and pharmaceutically acceptable carrier. The invention proposes a treatment method of cancer containing EGFR- and HER3-expressing cells and an inhibition method of biological activity of EGFR and/or HER3 of a specimen, which involve introduction of effective amount of a bispecific antibody. Use of the above antibody in production of a remedy for treatment of cancer, the cells of which express EGFR and HER3, is described. |
 Improved humanised antibody to human α9-integrin / 2503720Invention describes polynucleotide, expression vector, host cell and production method of humanised antibody together with their use, as well as medical preparation against rheumatoid arthritis, prophylaxis or treatment method of rheumatoid arthritis and use of humanised antibody at production of pharmaceutical preparation for prophylaxis or treatment of rheumatoid arthritis. This invention can be used in therapy of human diseases associated with α9 integrin. |
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 Purification of antibodies with cation-exchange chromatography / 2498991Disclosed is a method of purifying antibodies, including human CD20 and VEGF binding antibodies, from a composition which contains an antibody and at least one impurity compound, said method comprising the following steps: (a) loading the composition on a cation-exchange material, where said composition has first pH value from 4.0 to 6.0; (b) washing the cation-exchange material with a first washing buffer at pH higher than that of composition (a), where pH of the first washing buffer ranges from 6.8 to 9.0; (c) washing the cation-exchange material with a second washing buffer at pH lower than that of the first washing buffer; where the second washing buffer has conductivity from 0.5 to 3.0 mS/cm and pH from 5.0 to 6.0; and (d) elution of the antibodies from the cation-exchange material with an elution buffer at conductivity which is at least 2 mS/cm higher than that of the second washing buffer, where pH of the second washing buffer and pH of the elution buffer are approximately equal, and where pH of the elution buffer ranges from 5.0 to 6.0. Described is a conjugation method, which involves conjugating the purified product obtained using said method with a heterologous molecule. Also disclosed is a method of producing a pharmaceutical composition, which involves combining said purified product with a pharmaceutically acceptable carrier. |
 Humanised cd19 antibodies and using them for treating transplantation-related oncological and autoimmune disease / 2495882Present invention refers to immunology. What is presented is a humanized human monoclonal CD19 antibody prepared of an HB12B antibody, or a fragment thereof characterised by amino acid sequences of variable domains. Also, there are presented nucleic acids coding polypeptides having the sequences of the variable domains, and a cell expressing the antibody under the invention, and a pharmaceutical composition, and a method for treating a B-cell diseases or disorders in a human. |
 Gm-csf receptor binder / 2495050Present invention refers to biochemistry and immunology. What is considered is an isolated antibody molecule which binds an alpha chain of human granulocyte/macrophage colony stimulating factor receptor (GM-CSFRα) and inhibits GM-CSF binding to human GM-CSFRα. There are presented: a composition for GM-CSFRα inhibition or neutralisation and a composition for treating rheumatoid arthritis, asthma, chronic obstructive pulmonary disease or myeloid leukaemia, containing the antibody under the invention; the isolated nucleic acid molecule coding the antibody under the invention, a host cell and a method for preparing the antibody under the invention, as well a method for inhibiting or neutralising GM-CSFRα activity and a method of treating rheumatoid arthritis, asthma, chronic obstructive pulmonary disease or myeloid leukaemia in a patient. |
 Human monoclonal antibodies specific for programmed cell death 1 (pd1) protein and methods of treating cancer with using anti-pd1 antibodies either individually, or in combination with other immunotherapeutic agents / 2494107Invention refers to biotechnology and immunology. There are presented: a method for tumour cell growth inhibition in an individual and a method for immune response enhancement in an individual involving the introduction of a PD-1 monoclonal antibody and a CTLA-4 10D1 monoclonal antibody to the individual. The PD-1 monoclonal antibody has the following properties: it binds to human PD-1 having the value KD equal to 1×10-8 M or less; however it binds neither to human CD28, nor to CTLA-4, nor to ICOS; it is able to enhance the T-cell proliferation in the mixed lymphocyte reaction (MLR) analysis; it is able to enhance the gamma interferon production in the MLR analysis; it is able to enhance the interleukine-2 (IL-2) secretion in the MLR analysis. |
 Antibodies-antagonists against notch3 and their application for prevention and treatment of notch3-related diseases / 2493167Antagonistic antibody is proposed, which specifically binds with a conformational epitope from a fragment 1378-1640 of an amino acid sequence Notch3, given in the description, and inhibits activation of Notch3. The specified antibody is characterised by the fact that it contains variable areas of light and heavy chain, with a set of appropriate CDR1-CDR3, amino acid sequences of which are given in the description. An antibody may additionally contain a mark. The following is proposed: versions of a coding nucleic acid, an expressing vector, a cell for antibody production, containing the specified vector. The method is described to produce antibodies by means of cell cultivation. Versions of antibodies application are disclosed: to detect a disease related to Notch3, for production of a medicinal agent for treatment of an individual with a disorder or a disease related to Notch3, for treatment of Notch3-related disease or disorder. |
 Human anti-cd40 antagonist monoclonal antibody / 2491295Present invention refers to immunology. What is presented is a low-immunogenicity anti-CD40 monoclonal antibody prepared of a chimeric 5D12 (ch5D12) antibody. There are also described: a nucleic acid, a cell and a cell culture for preparing the antibody according to the invention, a method for preparing it, a pharmaceutical composition, using the antibody for preparing a drug and a method for administering the antibody according to the invention to an individual for the purpose of relieving the symptoms of an autoimmune disease, an inflammatory disease, for the purpose of suppressing a graft rejection reaction and/or treating CD40-positive cancer. |
| Antibodies against tenb2 constructed with cysteine, and conjugates, antibody-drug / 2505544 There proposed is an antibody specific to TENB2 containing light and heavy chains. Heavy chain contains substitution for free (reaction capable) cysteine A121C that corresponds to A114C (Kabat numbering) or A118C (Eu numbering). Conjugate versions are proposed for prostate cancer treatment containing antibody covalently bound to auristatin, also by means of linker. The following is described: pharmaceutical composition for prostate cancer treatment that uses as active beginning the antibody or its conjugate; product for prostate cancer treatment on the basis of such composition. The invention proposes: method for defining protein TENB2 in the sample - on the basis of antibody as well as analysis for revealing prostate cancer cells at mammal and method for cell proliferation inhibiting on the base of antibody conjugate and auristatin. There described is the method for obtaining antibody conjugate (Ab) and auristatin (D) with expression Ab-(L-D)p, where p is equal from 1 to 4, and L is linker. |
FIELD: biotechnologies.
SUBSTANCE: invention pertains to the versions of antibodies against IL-6 receptor, variable regions of light and heavy chains of which are modified by introduction of amino-acid replacement. There revealed is a pharmaceutical composition for treating the diseases associated with IL-6 and containing the said version of antibody.
EFFECT: invention allows efficient treatment of the diseases associated with IL-6.
8 cl, 48 dwg, 16 tbl, 20 ex
The text of the description is given in facsimile form.
1. Antibody against the receptor IL-6, containing region of the heavy chain and area light chain, in which: (1) CDR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which the Ser in position 1 replaced with Asp, (2) CDR2 variable field of the heavy chain consists of amino acid sequence SEQ ID nos:2, which Thr 9 and Ser in the position 16 replaced by Asn and Gly respectively, (3) CDR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:3, (4) CDR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:4, where Arg is in position 1 replaced by Gln, (5) CDR2 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:5, which Thr in position 2 and Arg in position 4 of the replaced and Gly Glu respectively, and (6) CDR3 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:6 which Thr in position 5 replaced on Ser.
2. Antibody against the receptor IL-6, containing region of the heavy chain and area light chain, in which: (1) CDR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which the Ser in position 1 replaced with Asp, (2) CDR2 variable field of the heavy chain consists of amino acid sequence SEQ ID nos:2, which Thr 9 and Ser in the position 16 replaced by Asn and Gly respectively, (3) CDR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:3, in which the Ser in position 1 and in Thr position 5 were replaced with Val and Il respectively, (4) CDR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:4, where Arg is in position 1 replaced by Gln, (5) CDR2 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:5, which Thr in position 2 and Arg in position 4 of the replaced and Gly Glu respectively, and (6) CDR3 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:6 which Gln in position 1 and Thr in position 5 replaced by Gly Arg respectively.
3. Antibody against the receptor IL-6, containing region of the heavy chain and area light chain, in which: (1) CDR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which the Ser in position 1 replaced with Asp, (2) CDR2 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:122, (3) CDR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:3, in which the Ser in position 1 and Thr in position 5 were replaced with Ala Leu and respectively, (4) CDR1 the variable region of the light chain consists of amino acid sequence SEQ ID NO:4, where Arg is in position 1 and Gln in position 4 of the replaced with Gln and Glu respectively, (5) CDR2 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:126, and (6) CDR3 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:6 which Gln in position 1 and Thr in position 5 replaced by Gly Arg respectively.
4. Antibody against the receptor IL-6 according to claim 1, where: (7) FR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:7, where Arg in position 13, Gln in position 16, Thr is in a position 23 and Thr in position 30 replaced by Lys, Glu, Ala and Ser respectively, (8) FR2 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:8 which Arg in position 8 replaced by Glu, (9) FR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:9 which Met in position 4, Leu in position 5, Arg in position 16 and Val in the position of 27 replaced with Il, Ser, Lys and Ala respectively, (10) FR4 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:10, which Gln in position 3 and Ser in position 5 replaced with Glu and Thr respectively, (11) FR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:11, where Arg in position 18 replaced the Ser, (12) FR2 variable region of the light chain composed of the amino acid sequence SEQ ID NO:12 which Lys regulation 11 replaced by Glu, (13) FR3 variable region of the light chain composed of the amino acid sequence SEQ ID NO:13, which Gln at position 23, Pro position 24 and Il in the position of 27 replaced with Glu, Ala and Ala respectively, and (14) FR4 the variable region of the light chain composed of the amino acid sequence SEQ ID NO: 14, which Lys in position 10 replaced with Glu.
5. Antibody against the receptor IL-6 in paragraph 2, where: (7) FR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:7, where Arg in position 13, Gln in position 16, Thr is in a position 23 and Thr in position 30 replaced by Lys, Glu, Ala and Ser respectively, (8) FR2 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:8 which Arg in position 8 replaced by Glu, (9) FR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:9 which Met in position 4, Leu in position 5, Arg in position 16 and Val in the position of 27 replaced with Il, Ser, and Ala Lys respectively, (10) FR4 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which the Gln in position 3 and Ser in position 5 replaced with Glu and Thr respectively, (11) FR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:11, where Arg in position 18 replaced the Ser, (12) FR2 variable region of the light chain composed of the amino acid sequence SEQ ID NO:12, which Lys regulation 11 replaced by Glu, (13) FR3 variable region light chain consists of amino acid sequence SEQ ID NO:13, which Gln at position 23, Pro in position 24 and Il in the position of 27 replaced with Glu, Ala and Ala respectively, and (14) FR4 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:14, which Lys in position 10 replaced with Glu.
6. Antibody against the receptor IL-6 in paragraph 2, where: (7) FR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:7, where Arg in position 13, Gln in position 16, Thr is in a position 23 and Thr in position 30 replaced by Lys, Glu, Ala and Ser accordingly, (8) FR2 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:8 which Arg in position 8 replaced by Glu, (9) FR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:184, (10) FR4 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which the Gln in position 3 and Ser in position 5 replaced with Glu and Thr respectively, (11) FR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:l1, where Arg in position 18 replaced the Ser, (12) FR2 variable region of the light chain composed of the amino acid sequence SEQ ID NO:12 which Lys regulation 11 replaced by Glu, (13) FR3 variable region of the light chain composed of the amino acid sequence SEQ ID NO:13, which Gln at position 23, Pro in position 24 and Il in the position of 27 replaced with Glu, Ala and Ala respectively, and (14) FR4 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:14, which Lys in position 10 replaced with Glu.
7. Antibody against the receptor IL-6 to 3, where: (7) FR1 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:7, where Arg in position 13, Gln in position 16, Thr is in a position 23 and Thr in position 30 replaced by Lys, Glu, Ala and Ser respectively, (8) FR2 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:8 which Arg in position 8 replaced by Glu, (9) FR3 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:184, (10) FR4 variable field of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which the Ser in position 5 replaced by Il, (11) FR1 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:11, where Arg in position 18 replaced the Ser, (12) FR2 variable region of the light chain composed of the amino acid sequence SEQ ID NO:12 which Lys regulation 11 replaced by Glu, (13) FR3 variable region of the light chain composed of the amino acid sequence SEQ ID NO:13, which Gln at position 23, Pro in position 24 and Ile in the position of 27 replaced with Glu, Ala and Ala respectively, and (14) FR4 the variable region of the light chain composed of the amino acid sequence SEQ ID NO:14, where Lys in position 10 replaced with Glu.
8. The pharmaceutical composition for the treatment of diseases associated with IL-6, containing the antibody on any one of claims 1 to 7.