Compositions and methods for treating and diagnosing asthma

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology, immunology and medicine. Application of antibody binding to IL-13 is disclosed as medicinal agent for treating asthma in humans. Wherein patient has high expression levels of POSTN in relation to average or median level of POSTN expression. Method of treating asthma subtype using such antibodies is also described.

EFFECT: disclosed group of inventions can be used in medicine.

23 cl, 49 dwg, 13 tbl, 9 ex

 



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to field of biochemistry, in particular to antibody or its antigen-binding fragment, which is specifically bind with human TNFα. Also disclosed are: separated molecule of nucleic acid, which codes said antibody, vector of expression, which contains said molecule of nucleic acid, and host cell, which contains said vector, for expression of said antibody. Disclosed are pharmaceutical composition for treatment of TNFα-mediated disease, which contains therapeutically effective quantity of said antibody, and method of treating TNFα-mediated disease with application of claimed composition.

EFFECT: invention makes it possible to effectively treat TNFα-mediated diseases.

16 cl, 9 dwg, 2 tbl, 2 ex

FIELD: biotechnologies.

SUBSTANCE: strain of cells of the Chinese hamster ovaries CHO-Inflix 20/5 is produced, transfected by vectors, expressing light and heavy chains of chimeric antibody against tumour necrosis factor alpha (TNF-α) of human being is produced. The strain is deposited into the Russian collection of cellular cultures under No. RKKK(P)760D.

EFFECT: invention allows to produce chimeric antibody with the specific efficiency no less than 33,5 picograms per cell a day.

4 dwg, 2 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of biochemistry, in particular to a humanised antibody to a tumour necrosis factor-α or its antigen-binding fragment Fab. Also disclosed are: gene, coding the protein of the antibody or Fab, genetic material, expressing the said antibody or Fab-fragment. Disclosed are: application of the antibody of Fab for obtaining a medication for the prevention or treatment of diseases, associated with the human tumour necrosis factor-α and a pharmaceutical composition for the treatment of diseases, associated with the human tumour necrosis factor-α, containing an effective quantity of the said antibody or Fab.

EFFECT: invention possesses a reduced immune response, in comparison with the pharmaceutical antibody Remicade, which makes it possible to treat diseases, associated with the human tumour necrosis factor-α, in an effective way.

23 cl, 5 dwg, 9 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of biotechnology and immunology. Described is antibody, which specifically binds denatured CD70. Claimed group of inventions can be used in medicine.

EFFECT: disclosed is method of diagnostics, prediction, prevention and treatment of malignant tumours of ovaries, pancreas and other malignant tumours with application of antibodies.

5 cl, 10 dwg, 2 tbl, 9 ex

FIELD: biotechnologies.

SUBSTANCE: invention offers recombinant plasmid DNA coding a chimeric antibody against human tumour necrosis factor-alpha (TNF-alpha) based on pOptiVECTM-TOPO® plasmid. Invention refers to eukaryotic cell line as a producer of antibody to TNF-alpha, method of cell line obtainment by transfection of plasmid DNA according to the invention, and method of chimeric antibody obtainment for TNF-alpha by cultivation of cell line according to the invention.

EFFECT: increased synthesis level for antibodies against TNF-alpha by producer cells.

12 cl, 8 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and immunology. Described are various variants of anti-IL-1R1 antibodies. The disclosed antibodies can be applicable for treating IL-1R1-mediated disorders, including rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease (COPD).

EFFECT: presented group of inventions can be used in medicine.

21 cl, 14 dwg, 12 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of obtaining and separation of single-domain molecules (SDAB). Described is a method of the separation or purification of the SDAB molecule, which represents a trivalent molecule of a ATN-103 nanobody, targeting TNFα and HAS, from a mixture, containing the said SDAB molecule and one or more polluting substances. The mixture is brought in contact with a cation-exchange carrier under conditions, which make it possible for the SDAB molecule to bind with the carrier or be absorbed on the carrier. One or more polluting substances are removed and SDAB is selectively eluted from the carrier. The conductivity of a conditioning medium (CM), used for the carrier loading, constitutes from approximately 12 to 9 mS/cm and pH under conditions of loading is corrected to a value from 4.0 to 4.3. The buffer for elution corresponds to approximately 50 mM of sodium chloride or less and has pH from approximately 5.5 to 7.2. Disclosed is a method or a process of obtaining recombinant SDAB of ATN-103. A host-cell is supported in the conditions at which recombinant ATN-103 SDAB is expressed. The mixture of molecule SDAB and one or more polluting substances is obtained. ATN-103 SDAB is purified or separated with the application of cation-exchange chromatography, as said above.

EFFECT: application of the invention provides new methods of the separation or purification of the nanobody, which can be applied in obtaining the ATN-103 nanobody.

19 cl, 4 dwg, 6 ex

FIELD: biotechnology.

SUBSTANCE: monoclonal antibody against human interleukin-6 is represented, which comprises hypervariable regions of the heavy chain CDRH-1: GFSLSTSGMGVG; CDRH-2: HIWWDDDKYYNPSLKS; and CDRH-3: RANYGTSYDYGMDY; and the hypervariable regions of the light chain CDRs CDRL-1: KASQSVSDVLT; CDRL-2: YASNRYT; and CDRL-3: QQGYRSPYT. In addition, the invention also relates to a hybridoma strain deposited in the Russian Collection of Cell Cultures under number RKKK(P) 751D, and producing the said antibody.

EFFECT: invention enables to expand the range of antibodies against human IL-6, having high ability to inhibit IL-6.

4 cl, 3 dwg, 2 tbl, 4 ex

FIELD: biotechnology.

SUBSTANCE: humanised monoclonal antibody against TNF and its application are described.

EFFECT: invention enables to reduce significantly the immunogenicity of murine antibody while maintaining the ability of the antibody to recognise the antigen as compared with the conservative chimeric murine antibody, increased antibody safety in clinical applications.

11 cl, 3 dwg, 5 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of immunology and biotechnology. Described are: humanised antibody and its antigen-binding fragment (Fab), which selectively bind human IFN-γ and contain variable site of heavy chain (VH) and variable site of light chain (VL), where VH and VL have sequences of amino acids respectively SEQ ID NO:1 and 2, presented in description. Also disclosed are fragments of DNA, which code said antibody and its Fab-fragment; plasmid DNA for expression of said specific proteins; and modified cells of bacteria and eukaryotes, which contain said plasmid DAN and intended for expression of said antibody and its Fab-fragment. Claimed are methods of obtaining said antibody and its Fab-fragment, which include cultivation of said modified cells in nutritional medium and isolation of antibody and its Fab-fragment by claimed invention from cultural liquid.

EFFECT: invention makes it possible to obtain humanised antibody or its Fab-fragment, binding with IFN-γ with kD 4,6 and IC50 not less than 1,5 nM in test on cells U937, with preservation of affinity of initial mouse monoclonal antibody.

13 cl, 3 dwg, 1 tbl, 8 ex

Crystals // 2556206

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes crystals of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulphonyl)acetamide ("compound A"), as a form I of the compound A crystal, which shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in its power X-ray diffraction spectrum, as a form II of the compound A crystal, which shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in its power X-ray diffraction spectrum, as a form III of the compound A crystal, which shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in its power X-ray diffraction spectrum. There are also described methods for producing the forms I, II and III of the compound A crystal, based pharmaceutical composition and PGI2 receptor agonist agent, an accelerating agent for angiogenic therapy, gene engineering or autoimmune bone marrow transplantation, and an accelerating agent for angiogenesis for peripheral artery recovery or angiogenic therapy on the basis thereof; there are also described a preventive or therapeutic agent for a wide range of diseases and conditions.

EFFECT: preparing the new therapeutic agent for the wide range of diseases and conditions.

11 cl, 6 dwg, 6 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel compound of formula

(I)

or its pharmaceutically acceptable salt, possessing properties of the IKKβ and TNFα inhibitor. The compound can be used with an additional therapeutic agent, selected from vincristine, camptothecin hydrochloride (CPT-11), lefunomid, dexamethasone and TNFα. Preferable are compounds of formula (I), corresponding to 2-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide and 2-{5-chloro-2-[(1R,2S)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide.

EFFECT: compound can be applied in the treatment of inflammatory diseases such as rheumatoid arthritis, chronic obstructive lung disease, bronchial asthma, multiple sclerosis and intestinal inflammatory diseases, or cancer diseases, such as multiple myeloma, colon cancer, pancreas cancer and ovary cancer, by IKKβ inhibition.

30 cl, 4 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the novel and unexpected application of sulphated hyaluronic acid as a cytokine activity regulator for the prevention and/or treatment of asthma and degenerative joint osteoarthritis, associated with the activation of IL-1, IL-2, IL-6, IL-7, IL-8 and IL-12, the said sulphated hyaluronic acid has a molecular weight from 10000 to 50000 Da, from 150000 to 250000 Da and from 500000 to 750000 Da and where sulphated hyaluronic acid has a sulphation degree equal to 3.

EFFECT: invention provides the extension of an arsenal of means for the prevention and/or treatment of asthma and degenerative joint osteoarthritis.

3 cl, 25 ex, 4 tbl, 12 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline form of N-[-2[[(2,3-difluorophenyl)methyl]thio]-6-{[(1R,2S)-2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]-1-azatidine-sulphonamide, which has an X-ray powder diffractogram, measured with the application of a wavelength of X-rays of 1.5418 E and containing, at least, one crystalline peak with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1; or containing, at least, 2 crystalline peaks with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1; or containing, at least, 3 crystalline peaks with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1. The said crystalline form can contain additional crystalline peaks with a value 2-theta (in degrees), selected from 12.9 and 18.0, obtained under the said conditions.

EFFECT: crystalline form has the X-ray powder diffractogram, measured with the application of a wavelength of X-rays of 1,5418 E, with the crystalline peaks with a value 2-theta (in degrees) 12,9, 13,1, 18,0, 21,0, 22,5, 25,1, 25,3, 28,8, 29,1 and 30,4, and has melting point (beginning) 152,7°C.

6 cl, 3 dwg, 2 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a citrate of a compound described by formula (II) below, and a pharmaceutical composition containing said citrate.

EFFECT: experimental results of the present inventions prove that said citrate can inhibit activity of phosphodiesterase type 5 and can be used for treating erectile dysfunction, for inhibiting thrombocyte aggregation and treating thrombosis, for reducing pulmonary hypertension and treating cardiovascular diseases, asthma and diabetic gastroparesis.

2 cl

FIELD: medicine.

SUBSTANCE: baseline therapy is accompanied by administering "Enterosgel" 1.5-2 hours prior to or 2 hours after a meal or medication intake in the children aged from 5 to 10 years old in an amount of 15 g 2 times a day, aged from 11 to 15 years old in an amount of 15 g 3 times a day for 7 days; "Qudesan" is administered orally with a meal before noon in age-specific doses: from 5 to 7 years old - 10-16 drops (15-24 mg), from 8 to 15 years old - 16-20 drops (24-30 mg), diluted in a small amount of boiled water or any other beverage of room temperature, once a day for 30 days; "Pantogam" is administered orally 15-20 minutes after a meal in age-specific doses: from 5 to 7 years old - 500 mg 2 times a day, from 8 to 15 years old - 500 mg 3 times a day for 30 days; the combined administration of the above preparations is repeated every 6 months.

EFFECT: method enables reducing the risk of partially controlled forms of bronchial asthma considerably by the pronounced positive synergic effect of the above drug preparations.

4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents using sulphated hyaluronic acid for preparing a therapeutic agent for local administration for treating inflammatory/irritating skin diseases specified in dermatitis, atopic dermatitis, photocontact dermatitis, rash, vitiligo, eczema, psoriasis, all skin irritations related to activation of anti-inflammatory cytokines, such as IL-1, IL-2, IL-7, IL-8, IL-9 and TNF, wherein hyaluronic acid has a molecular weight falling within the ranges of 10000 D to 50000 D, 150000 D to 250000 D and 500000 D to 750000 D, and a sulphatation degree equal to 1.

EFFECT: invention provides stimulating the immune system protein synthesis for eliciting the immune response.

8 cl, 33 ex, 15 dwg, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and aims at preventing and treating respiratory diseases, disorders or conditions. Implementing a method for preventing or treating the respiratory diseases, disorders or conditions involves administering a therapeutically effective amount of tetomilast and at least one beta2-adrenoreceptor agonist into the patient. According to the other embodiment, tetomilast and at least one beta2-adrenoreceptor agonist are administered together with at least one anti-inflammatory steroid. What is also presented is a pharmaceutical composition containing tetomilast and at least one beta2-adrenoreceptor agonist.

EFFECT: using the declared group of inventions provides the more effective prevention and treatments of respiratory diseases, disorders or conditions.

46 cl, 3 dwg, 6 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: treating bronchial asthma is ensured by superior laryngeal nerve anaesthesia with 0.5% Novocaine mixed with 96° rectified ethyl alcohol for the purpose of bronchial spasmolysis in bronchial asthma.

EFFECT: method enables reducing an episode of bronchial asthma quickly and for long duration by interrupting a flow of pathologic nerve impulses along the superior laryngeal nerve.

2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where: R1, R2, R3, R4, R5 and R6, each independently, denote hydrogen, halogen, cyano, nitro or C1-6alkyl; X denotes O or S; RYa denotes -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(S)NR1bR1c, -C(NNO2)NR1bR1c, -S(O)2R1a or -S(O)2NR1bR1c; under the condition that RYa is not -C(O)O-tert-butyl; and each R1a, R1b and R1c independently denotes hydrogen, C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, C6-14aryl, 5-10-member heteroaryl containing one, two or three heteroatoms selected from O, N or S, or morpholinyl; or each pair of R1b and R1c, together with the N atom to which they are bonded, independently forms morpholinyl; under the condition that the compound is not 4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulphonyl)piperazine-1-carbaldehyde; wherein each alkyl, alkenyl, aryl and 5-10-member heteroaryl, containing one, two or three heteroatoms selected from O, N or S, is optionally substituted with one or more groups, each independently selected from (a) cyano, halogen and nitro; (b) C1-6alkyl, C6-14aryl, furanyl and morpholinyl, each optionally substituted with one or more substitutes Q; (c) -C(O)Ra, -C(O)ORa, -ORa and -SRa, wherein each Q is independently selected from a group consisting of (a) cyano, halogen and nitro; (b) C1-6alkyl and C2-6alkenyl; and (c) -C(O)Re, -C(O)ORe, and -SRe; where each Re, Rf and Rg independently denotes (i) hydrogen; (ii) C1-6alkyl or C2-6alkenyl, which are suitable for modulating CCR3 activity.

EFFECT: obtaining compounds which are suitable for modulating CCR3 activity.

41 cl, 1 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of indolylpiperidine of the formula (I): wherein A1 means (C1-C7)-alkylene, (C1-C7)-alkyleneoxy-, (C1-C7)-alkylenethio-, (C1-C7)-alkanoyl, hydroxy-(C1-C7)-alkylene; A2 means a single bond, (C1-C7)-alkylene, (C2-C5)-alkenylene; W means a single bond, phenylene, furanylene that is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkoxy- and/or alkyl groups; R1 means hydrogen atom (H), (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C2-C5)-alkoxyalkyl, (C3-C7)-alkenyloxyalkyl, (C3-C7)-alkynyloxyalkyl, (C3-C7)-alkoxyalkoxyalkyl, phenyl-(C1-C7)-alkyl wherein phenyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy- or arylalkoxy- (preferably with phenylalkoxy-) groups, or means (C3-C10)-cycloalkyl-(C1-C7)-alkyl wherein cycloalkyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy-groups; R2 means hydrogen atom (H), halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-; R3 means carboxyl, tetrazolyl, and to their pharmaceutically acceptable salts. Compounds of the formula (I) elicit antihistaminic and anti-allergic activity that allows their using in composition used for treatment of allergic diseases including bronchial asthma, rhinitis, conjunctivitis, dermatitis and nettle rash. Also, invention describes methods for preparing compounds of the formula (I).

EFFECT: valuable medicinal properties of compounds.

15 cl, 2 sch, 3 tbl, 162 ex

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