Antibody against il-6 receptor

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 descriptions are given in facsimile form.

1. Antibody against IL-6, containing the variable region of the heavy chain and the variable region of light chain, in which:
(1) variable regions CDR1 of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which Ser at position 1 is replaced by Asp,
(2) variable regions CDR2 of the heavy chain consists of amino acid sequence SEQ ID NO:2, in which Thr at position 9 and Ser at position 16 is replaced by Asn and Gly, respectively,
(3) the CDR3 of the variable region of the heavy chain consists of amino acid sequence SEQ ID NO:3,
(4) variable regions CDR1 light chain consists of amino acid sequence SEQ ID NO:4, in which Arg at position 1 is replaced by Gln,
(5) CDR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:5, in which Thr at position 2 and Arg at position 4 is replaced by Gly and Glu, respectively, and
(6) CDR3 of the variable region of the light chain consists of amino acid sequence SEQ ID NO:6, in which Thr at position 5 is replaced by Ser.

2. Antibody against the receptor of IL-6, containing the variable region of the heavy chain and the variable region of light chain, in which:
(1) variable regions CDR1 of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which Ser at position 1 is replaced by Asp,
(2) variable regions CDR2 of the heavy chain consists of amino acid sequence SEQ ID NO:2, in which the Thr at position 9 and Ser at position 16 is replaced by Asn and Gly, respectively,
(3) the CDR3 of the variable region of the heavy chain consists of amino acid sequence SEQ ID NO:3, in which Ser at position 1 and Thr at position 5 was replaced by Val and Il respectively,
(4) variable regions CDR1 light chain consists of amino acid sequence SEQ ID NO:4, in which Arg at position 1 is replaced by Gln,
(5) CDR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:5, in which Thr at position 2 and Arg at position 4 is replaced by Gly and Glu, respectively, and
(6) CDR3 of the variable region of the light chain consists of amino acid sequence SEQ ID NO:6, in which Gln at position 1 and Thr at position 5 is replaced by Gly and Arg, respectively.

3. Antibody against the receptor of IL-6, containing the variable region of the heavy chain and the variable region of light chain, in which:
(1) variable regions CDR1 of the heavy chain consists of amino acid sequence SEQ ID NO:1, in which Ser at position 1 is replaced by Asp,
(2) variable regions CDR2 of the heavy chain consists of amino acid sequence SEQ ID NO:122,
(3) the CDR3 of the variable region of the heavy chain consists of amino acid sequence SEQ ID NO:3, in which Ser at position 1 and Thr at position 5 was replaced with Leu and Ala, respectively,
(4) variable regions CDR1 light chain consists of amino acid sequence SEQ ID NO:4, in which Arg Polo is attachment 1 and Gln at position 4 is replaced by Gln and Glu, respectively,
(5) CDR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:126, and
(6) CDR3 of the variable region of the light chain consists of amino acid sequence SEQ ID NO:6, in which Gln at position 1 and Thr at position 5 is replaced by Gly and Arg, respectively.

4. Antibody against the receptor of IL-6 according to claim 1, where:
(7) FR1 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:7, in which Arg at position 13, Gln at position 16, Thr at position 23, and Thr at position 30 replaced with Lys, Glu, Ala and Ser, respectively,
(8) FR2 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:8, in which Arg at position 8 is replaced by Glu,
(9) FR3 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:9, in which Met at position 4, Leu at position 5, Arg at position 16, and Val at position 27 is replaced by Il, Ser, Lys and Ala, respectively,
(10) FR4 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which Gln at position 3 and Ser at position 5 is replaced by Glu and Thr, respectively,
(11) FR1 variable region of the light chain consists of amino acid sequence SEQ ID NO:11, in which Arg at position 18 is replaced by Ser,
(12) FR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:12, in which Lys at position 11 samananda Glu,
(13) FR3 variable region of the light chain consists of amino acid sequence SEQ ID NO:13, in which Gln at position 23, Pro at position 24 and Il in position 27 is replaced by Glu, Ala and Ala, respectively, and
(14) FR4 variable region of the light chain consists of amino acid sequence SEQ ID NO: 14, in which Lys at position 10 is replaced by Glu.

5. Antibody against the receptor of IL-6 according to claim 2, where:
(7) FR1 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:7, in which Arg at position 13, Gln at position 16, Thr at position 23, and Thr at position 30 replaced with Lys, Glu, Ala and Ser, respectively,
(8) FR2 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:8, in which Arg at position 8 is replaced by Glu,
(9) FR3 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:9, in which Met at position 4, Leu at position 5, Arg at position 16, and Val at position 27 is replaced by Il, Ser, Lys and Ala, respectively,
(10) FR4 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which Gln at position 3 and Ser at position 5 is replaced by Glu and Thr, respectively,
(11) FR1 variable region of the light chain consists of amino acid sequence SEQ ID NO:11, in which Arg at position 18 is replaced by Ser,
(12) FR2 variable region of the light chain consists of amino acid is posledovatelnosti SEQ ID NO:12, in which Lys at position 11 is replaced by Glu,
(13) FR3 variable region of the light chain consists of amino acid sequence SEQ ID NO:13, in which Gln at position 23, Pro at position 24 and Il in position 27 is replaced by Glu, Ala and Ala, respectively, and
(14) FR4 variable region of the light chain consists of amino acid sequence SEQ ID NO:14, in which Lys at position 10 is replaced by Glu.

6. Antibody against the receptor of IL-6 according to claim 2, where:
(7) FR1 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:7, in which Arg at position 13, Gln at position 16, Thr at position 23, and Thr at position 30 replaced with Lys, Glu, Ala and Ser, respectively,
(8) FR2 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:8, in which Arg at position 8 is replaced by Glu,
(9) FR3 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:184,
(10) FR4 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which Gln at position 3 and Ser at position 5 is replaced by Glu and Thr, respectively,
(11) FR1 variable region of the light chain consists of amino acid sequence SEQ ID NO:l1, in which Arg at position 18 is replaced by Ser,
(12) FR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:12, in which Lys at position 11 is replaced by Glu,
(13) FR variable region of the light chain consists of amino acid sequence SEQ ID NO:13, in which Gln at position 23, Pro at position 24 and Il in position 27 is replaced by Glu, Ala and Ala, respectively, and
(14) FR4 variable region of the light chain consists of amino acid sequence SEQ ID NO:14, in which Lys at position 10 is replaced by Glu.

7. Antibody against the receptor of IL-6 according to claim 3, where:
(7) FR1 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:7, in which Arg at position 13, Gln at position 16, Thr at position 23, and Thr at position 30 replaced with Lys, Glu, Ala and Ser, respectively,
(8) FR2 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:8, in which Arg at position 8 is replaced by Glu,
(9) FR3 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:184,
(10) FR4 variable regions of the heavy chain consists of amino acid sequence SEQ ID NO:10, in which Ser at position 5 is replaced by Il,
(11) FR1 variable region of the light chain consists of amino acid sequence SEQ ID NO:11, in which Arg at position 18 is replaced by Ser,
(12) FR2 variable region of the light chain consists of amino acid sequence SEQ ID NO:12, in which Lys at position 11 is replaced by Glu,
(13) FR3 variable region of the light chain consists of amino acid sequence SEQ ID NO:13, in which Gln at position 23, Pro at position 24 and Ile at position 27 is replaced by Glu, Ala and Ala with therefore, its, and
(14) FR4 variable region of the light chain consists of amino acid sequence SEQ ID NO:14, in which Lys at position 10 is replaced by Glu.

8. Pharmaceutical composition for treating diseases associated with IL-6 containing the antibody according to any one of claims 1 to 7.



 

Same patents:

FIELD: biotechnologies.

SUBSTANCE: method 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.

EFFECT: invention enlarges the range of methods for obtaining target protein in yeast Saccharomyces cerevisiae and increases possibilities for effective synthesis of such proteins.

2 dwg, 4 ex

FIELD: biotechnologies.

SUBSTANCE: invention 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.

EFFECT: improvement of efficiency.

15 cl, 14 dwg, 3 ex

FIELD: biotechnologies.

SUBSTANCE: invention 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.

EFFECT: invention allows producing a new ferment with improved properties, which has glycerol-3-phosphatocyltransferase activity.

11 cl, 4 dwg, 14 tbl, 4 ex

FIELD: biotechnologies.

SUBSTANCE: recombinant 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.

EFFECT: invention allows producing a new protein having antiangiogenic activity and increased selectivity of action in relation of tumoral endothelium.

2 cl, 3 dwg, 1 tbl, 5 ex

FIELD: biotechnologies.

SUBSTANCE: genetic 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.

EFFECT: possibility to produce adenovirus particles for simultaneois delivery of genes and expression of proteins SOX2 and C-MYC in human cells, pAd-SM contains a gene that codes a fluorescent protein EGFP, under control of a CMV promotor, which makes it possible to track transduction of cells and elimination of virus DNA from a cell.

3 cl, 1 dwg

FIELD: biotechnologies.

SUBSTANCE: method 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.

EFFECT: invention makes it possible for the cell to produce the specified polypeptide and the appropriate cell.

12 cl, 15 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: invention 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).

EFFECT: obtaining formula III compounds, possessing ability to modulate gene expression.

19 cl, 4 ex, 2 tbl, 78 ex

FIELD: biotechnology.

SUBSTANCE: antibodies are used as pharmaceutical means for treatment or prevention of inflammatory diseases.

EFFECT: invention enables to obtain antibodies with effective neutralising activity against NR10.

7 cl, 33 dwg, 19 tbl, 10 ex

FIELD: biotechnology.

SUBSTANCE: isolated 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.

EFFECT: invention enables to obtain recombinant adenosine deaminase, having increased stability.

14 cl, 1 tbl, 10 ex

FIELD: biotechnology.

SUBSTANCE: method 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.

EFFECT: invention enables to produce the desired polypeptide with a high yield.

9 cl, 10 dwg, 6 ex

FIELD: biotechnologies.

SUBSTANCE: 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.

EFFECT: invention application provides conjugates with increased stability in serum in comparison with the same conjugates without A121C substitution in antibody that can be used in medicine.

33 cl, 18 dwg, 2 tbl, 4 ex

Antibodies to her // 2504553

FIELD: biotechnologies.

SUBSTANCE: invention 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.

EFFECT: invention allows obtaining bispecific antibodies binding EGFR and HER3, which are not conjugates of two antibodies.

22 cl, 33 dwg, 4 tbl, 19 ex

FIELD: biotechnologies.

SUBSTANCE: invention 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.

EFFECT: improved activity and thermal stability.

14 cl, 6 dwg, 6 tbl, 11 ex

FIELD: biotechnologies.

SUBSTANCE: invention proposes humanised anti-NKG2A antibody obtained from murine antibody Z270, which is characterised through amino-acid sequences of variable domains, and method of its obtainment. Besides, a pharmaceutical composition is described, which contains an antibody according to the invention, a treatment method and application of the antibody in production of a medicine to be injected into a patient who is a human being suffering the disorder chosen from cancer, virus disease, inflammatory disorder and autoimmune disorder.

EFFECT: invention can be further used in therapy.

14 cl, 20 dwg, 2 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: disclosed 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.

EFFECT: invention improves purification of antibodies used for treatment.

16 cl, 3 dwg, 4 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present 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.

EFFECT: invention can find further application in treating various CD19-associated diseases, including autoimmune diseases, and preventing or treating the graft-versus-host disease (GVHD), and the humoral rejection and post-transplantation lymphoproliferative disorder in a human graft recipient.

21 cl, 45 dwg, 40 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present 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.

EFFECT: invention can find further application in therapy of the GM-CSFRα-mediated diseases.

41 cl, 5 tbl, 9 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention 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.

EFFECT: invention provides a synergic effect when using the above antibodies in a combination.

4 cl, 54 dwg, 7 tbl, 25 ex

FIELD: biotechnologies.

SUBSTANCE: antagonistic 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.

EFFECT: using the invention may find application in medicine in treatment or prevention of Notch3-related diseases or disorders.

25 cl, 18 dwg, 4 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present 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.

EFFECT: what is described is a method for selecting the high-expression human anti-CD40 antibodies containing insertion, deletion, inversion and/or replacement of 1 to 5 amino acids as compared to the antibody according to the invention, and the antibody prepared by the above method for selecting.

31 cl, 21 dwg, 14 tbl, 10 ex

FIELD: biotechnologies.

SUBSTANCE: 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.

EFFECT: invention application provides conjugates with increased stability in serum in comparison with the same conjugates without A121C substitution in antibody that can be used in medicine.

33 cl, 18 dwg, 2 tbl, 4 ex

Up!