Human il-13 antibodies and their therapeutic application

FIELD: medicine.

SUBSTANCE: offered are versions of IL-13 antibodies each of which contains respectively three CDR heavy and three CDR light chains. A pharmaceutical composition of antibodies for asthma treatment is described.

EFFECT: use of the invention can find further application in therapy of the IL-13 mediated B-cell disorders.

11 cl, 6 tbl, 2 ex

 

The text descriptions are given in facsimile form.

1. Selected antigennegative plot antibodies to IL-13 or its functionally active fragment containing the H-CDR1-, H-CDR2 and H-CDR3 - and L-CDR1 and L-CDR2 and L-CDR3, areas which have amino acid sequences selected from (I) - (II):
(I) SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 16, SEQ ID NO: 19, SEQ ID NO: 20;
(II) SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10 and SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21; and
(III) SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10 and SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22.

2. Dedicated human or humanitariannet antibody to IL13 containing the selected antigennegative plot according to claim 1.

3. The antibody according to claim 2, which contains at least one antigennegative center, including domain heavy chain that has the amino acid sequence selected from any of SEQ ID NO: 23, 27, 31 and 35.

4. The antibody according to claim 3, which contains at least one antigennegative center, including domain light chain that has the amino acid sequence selected from any of SEQ ID NO: 25, 29, 33 and 37.

5. Antibody to IL13 according to claim 3, which contains at least one antigennegative center, including domain light chain having the amino acid sequence selected from any of SEQ ID NO: 25, 29, 33 and 37.

6. Antibody to IL13 according to claim 4, containing the variable region of the heavy chain, which has the sequence of SEQ ID NO: 23, and the variable region of light chain, which has the sequence of SEQ ID NO: 25.

7. Antibody to IL13 according to claim 4, containing the variable region of the heavy chain, which has the sequence of SEQ ID NO: 27 and a variable region light chain, which has the sequence of SEQ ID NO: 29.

8. Antibody to IL13 according to claim 4, with the containing a series of variable region of the heavy chain, which has the sequence of SEQ ID NO: 31, and the variable region of light chain, which has the sequence of SEQ ID NO: 33.

9. Antibody to IL13 according to claim 4, containing the variable region of the heavy chain, which has the sequence of SEQ ID NO: 35, and a variable region light chain, which has the sequence of SEQ ID NO: 37.

10. The IL13 antibody to one of claim 2 to 9, representing the IgG1 or IgG4.

11. The pharmaceutical composition intended for the treatment of disorders or conditions that are associated with the presence of cellular IL-13 receptor target, such as asthma, containing antibody or functionally active fragment according to one of claim 2 to 10 and a pharmaceutically acceptable carrier or excipient.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to biotechnology and represents stable and soluble scFv-antibody and Fab-fragment, specific with respect to TNFα, which contain specific sequences of light chain and heavy chain, optimised as to stability, solubility, in vitro and in vivo TNFα binding and low immunogenity. Also claimed are antibody-coding DNA-sequence, vectors, host-cell, as well as method of obtaining antibody with application of said cells. In addition claimed are therapeutic and diagnostic compositions and stable water pharmaceutically ready form based on antibodies, as well as method of treating TNFα-associated disease.

EFFECT: invention can be efficiently used for diagnostics and treatment of TNFα-associated disorders.

61 cl, 18 dwg, 5 tbl, 5 ex

Immunoglobulins // 2404192

FIELD: medicine.

SUBSTANCE: invention represents immunoglobulins, in particular antibodies, which specifically bind to human interleukin 13 (hIL-13). Claimed are recombinant or transfected mammalian host cell, for cloning, as well as for expression of vectors, coding antibodies. Claimed are antibody-containing pharmaceutical composition, set, containing said pharmaceutical composition and pharmaceutical composition, containing monoclonal antibody against IL-4, such as pascolizumab. Claimed is method ob obtaining antibody, and applications of said antibodies.

EFFECT: antibodies can be used for treatment of various diseases to disorders, responsible for modulation of hIL-13 interaction with human IL-13 receptor.

51 cl, 29 dwg, 22 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to molecular pharmacology and specifically to a peptide which is part of an interleukine-15 (IL-15) sequence which can inhibit biological activity of the said molecule.

EFFECT: obtaining a peptide which inhibits T cell proliferation induced by IL-15, and apoptosis caused by tumour necrosis factor when bonding with the alpha subunit of the (IL-15R) receptor.

8 cl, 4 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: there are offered versions of human IL-13 antibodies, including based on CDR antibody BAK278D6. There is described a based composition, and also isolated nucleic acid, a host cell for preparing antibodies and versions of the method for preparing antibodies. There is disclosed application of antibodies for preparing a drug and a composition for treating various diseases mediated by IL-13 activity. Application of the invention provides antibodies neutralising IL-13.

EFFECT: applicable in medicine for preparing a vaccine.

52 cl, 32 dwg, 7 tbl, 29 ex

FIELD: medicine.

SUBSTANCE: there is offered a monoclonal antibody specific to human interleukine-4 (hIL-4) containing two domains with the related CDR1-3 region. There are described versions thereof that contain specified CDR, polynucleotide coding said antibody. There are described an expression vector and a host-cell for preparing the antibody to human interleukine-4 (hIL-4). There are opened: application of the antibody for preparing a pharmaceutical agent for treating the diseases mediated by interleukine-4 and/or IgE. There is discovered the pharmaceutical composition for treating the diseases mediated by interleukine-4 and/or IgE is opened.

EFFECT: application of the invention ensured the high-affinity neutralised monoclonal antibodies to human interleukine-4.

14 cl, 1 tbl, 6 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns immunology and biotechnology. There is offered human monoclonal antibody specific to TNF-alpha containing light and heavy chain with appropriate CDR3 sites. There are described versions thereof including those based on heavy and light chains and coded by human genes VH3-33 and A30VK1 or VH3-53 and L2VK3 respectively. There are disclosed: the method for estimating the TNF-alpha content in the patient's sample with using specified antibodies, and application of antibodies for preparing a medical product. There are described: compositions for diagnostics and treatment of the conditions associated with TNF-alpha activity on the basis of antibodies. There is disclosed coding nucleic acid, a cell for making said antibodies and the method for making said antibodies.

EFFECT: application of the invention ensured high-affinity neutralizing monoclonal antibodies with improved Kd and IC50 in comparison with Infliximab, Adalimumab or Etanercept that can find application in medicine for treatment and diagnostics of the diseases associated with TNF-alpha hyperactivity.

35 cl, 13 dwg, 36 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: there are disclosed polypeptide variants containing Fc-areas IgG, having amino acid modifications providing changed effector functions Fc in specified polypeptides. There is disclosed composition for antibody targeting on antigen, containing the specified polypeptide. There is described method for preparing the specified polypeptide. Also, there are disclosed the methods for treating V-cell tumour or a malignant disease characterised by V-cell expression of CD20, treating chronic lymphocytic leukosis, relieving the symptoms of the V-cell controlled autoimmune disease, treating a angiogenesis-associated disorder, treating HER2-expressing cancer, treating LFA-1-mediated involvement, treating IgE-mediated involvement wherein specified methods imply introduction to the patient of the therapeutically effective amount of said polypeptide.

EFFECT: higher clinical effectiveness.

63 cl, 6 ex, 13 dwg, 10 tbl

FIELD: biotechnology.

SUBSTANCE: present invention relates to biotechnology. Proposed is an antibody against interferon-α/β-binding protein I or against its mutein, obtained through conservative substitution. Proteins, against which the antibody is directed, are extracted from urine and link interferon-α/β-binding protein I with Kd constant from 3.6x10-9 to 1.6x10-10 M.

EFFECT: use of the invention allows for detecting presence of interferon-α/β-binding protein I in different samples.

5 cl, 10 dwg, 6 tbl, 17 ex

FIELD: chemistry, biochemistry.

SUBSTANCE: claimed invention relates to field of biotechnology. Claimed is antibody against interferon-α/β-connecting protein II or against its mutein, obtained by conservative substitutions. Here protein, against which antibody is directed, is separated from urine and connects interferon-α/β-connecting protein II with constant Kd equal 2.12x10-9 M.

EFFECT: obtaining possibility to detect interferon-α/β-connecting protein II presence in different samples.

5 cl, 10 dwg, 6 tbl, 17 ex

FIELD: chemistry; medicine.

SUBSTANCE: claimed are polypeptide and respective polynucleotide zcytor17lig and molecules of antibody against human zcytor17. Human zcytor17lig is novel cytokine. Claimed invention also relates to methods of protein obtaining, its application for stimulation of immune reaction in mammal. Described is method of obtaining antibodies to said protein and respective antibodies.

EFFECT: polypeptides can be used in realisation of methods stimulation of immune system, proliferation and development of hemopoietic cells in vitro and in vivo.

17 cl, 3 dwg, 21 tbl, 47 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, pulmonology, and can be used for combination therapy of bronchial asthma. That is ensured by drug-induced therapy, supravenous blood laser irradiation and infrared magnetic-laser therapy (IR-MLT) of a projection area of adrenal glands The supravenous blood laser irradiation is carried out for 15 minutes at wave length 0.63 mcm, power 5 mWt by a light guide tip. The first and fifth IR-MLT procedures are preceded by examining cortisol and estradiol levels in females and testosterone level in males. If the cortisol level is lower than 230 nmol/l, and the testosterone level is lower than 500 ng/dl in males, and the estradiol level is lower than 30 pg/ml in non-menopause females and lower than 15 pg/ml in menopause females, pulse repetition rate is specified 150 Hz and "НМП" - 50 mT. If the cortisol level is 230 to 750 nmol/l, the estradiol level is 30 pg/ml to 160 pg/ml in females, and the testosterone level 260 to 1593 ng/dl in males, pulse repetition rate is specified 80 Hz and "НМЛ" 25 mT. Total exposure time for one session is no more than 18 minutes. The therapeutic course is 10-12 procedures.

EFFECT: method allows higher clinical effectiveness, reduced time of treatment, eliminates side effects, corrects the hormone level and allows reducing a dosage of the prescribed preparations.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a derivative of 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine of formula

and its optical isomers and pharmaceutically acceptable salts where R1 represents CH3 or CH3CH2; R2 represents H, 2-F, 2-Cl, 3-F, 3-OCN3, 3-CN, 3-CF3, 3-CONH2 or 3-SO2CH3; R3 represents H or CH3; R4 represents H or CH3; and R5 represents H; or when R4 represents CH3, R5 represents H or F. Also, the invention refers to methods for producing the compounds of formula (I) and to pharmaceutical compositions exhibiting CX3CR1 receptor antagonist properties containing the compounds of formula (I).

EFFECT: production of 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine as selective CX3CR1 receptor antagonists.

15 cl, 2 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a new acid dihydrogenphosphate of 2-(3-{6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidine-4-yl}phenyl)-2-methylpropionic acid of formula optionally in a crystalline form exhibiting cAMP inhibitor properties. Also, the invention refers to a pharmaceutical composition.

EFFECT: compound can find application for treating the diseases associated with cell expression of prostaglandin D2 in such diseases, as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc.

3 cl, 12 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to crystalline tiotropium bromide anhydrate differing in X-ray diffraction values by the presence of an orthorhombic elementary cell with the parameters a=11.7420 (4) Å, b=17.7960 (7) Å, c=19.6280 (11) Å and the cell volume V=4101.5 (3) Å.

EFFECT: invention refers to method for preparing said form of tiotropium bromide and to a based pharmaceutical composition for treating respiratory diseases, first of all for treating chronic obstructive pulmonary disease and asthma.

5 cl, 15 dwg, 18 tbl, 15 ex

Novel salt i // 2417220

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which is N-{2-[((2S)-3-{[1-(4-chlorobenzyl)piperidin-4-yl]amino}-2-hydroxy-2-methylpropyl)oxy]-4-hydroxyphenyl}acetamide benzoate or solvate thereof. The invention also relates to a pharmaceutical composition, dry inhalant powder, use of compounds in any of claims 1-6, as well as a method of modulating chemokine receptor 1 (CCR1).

EFFECT: obtaining a novel biologically active compound, having chemokine receptor 1 (CCR1) modulating activity.

13 cl, 6 ex, 2 tbl, 4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel optically active phenylthanolamine compounds of formula (I) having a (-)-configuration, or pharmaceutically acceptable salts thereof, which have β2-receptor agonist effect and can be used to treat asthma or bronchitis. In formula (I) R1 is H or halogen; R2 is CF3, CN or halogen; R3 is a straight or branched alkyl, having 1-6 carbon atoms or a cycloalkyl having 3-6 carbon atoms.

EFFECT: high efficiency of using the agents.

9 cl, 1 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula in which R1 and R2 independently denote C1-6alkyl; R4 denotes phenyl, substituted with trifluoromethyl if necessary; X denotes hydrogen or methyl; and Y denotes -C(O)R, where R denotes C1-6alkyl; or Y denotes -P(O)(OR5)2, where R5 denotes hydrogen or C1-6alkyl; or pharmaceutically acceptable salts thereof. Said compounds are prodrugs of adenosine A2B receptor. The invention also relates to a pharmaceutical composition which is an adenosine A2B receptor antagonist based on the compound of formula I.

EFFECT: formula I compounds and the pharmaceutical composition can be used in treating different diseases in mammals, such as gastrointestinal disorders, immunological disorders, allergic disorders, neurological disorders, cardiovascular disorders and diseases associated with cell hyperproliferation.

13 cl, 1 tbl, 15 ex

FIELD: medicine.

SUBSTANCE: compounds of the invention exhibit properties of β2- adrenoreceptor agonists. In formula (I) , R1 represents hydrogen; each R2, R3, R4, R5, R4' and R5' independently represents hydrogen or C1-C6alkyd; e is equal to 0 or 1; A represents C(O); D represents oxygen or sulphur; m is equal to an integer 0 to 3; n is equal to an integer 0 to 3; R6 represents the group -(X)p-Y-(Z)q-R10; each X and Z independently represents C1-C6akylene group; each p and q is independently equal to 0 or 1; Y represents a bond, oxygen, CH2 or NR9; R7a and R7b independently represent hydrogen or C1-C6alkyl; R9 represents C1-C6alkyl; R10 represents hydrogen or saturated or unsaturated 6-members ring system optionally containing at least one ring heteroatom, chosen of nitrogen. And this ring system is optionally substituted by C1-C6alkoxycarbonyl; R7 represents 6-12-members aromatic ring system which is optionally substituted by halogen, trifluoromethyl, hydroxyl, C1-C6alkyl, C1-C6alkoxy or NH2; provided R6 does not represent hydrogen or unsubsituted C1-C6alkyl group. Also, the invention refers to methods for producing compounds of formula (I), to a pharmaceutical composition exhibiting properties of β2- adrenoreceptor agonists containing the compound of formula (I) as an active ingredient, to application of the compound of formula (I) in preparing a drug, to a combination containing the compound of formula (I) and one or more agents.

EFFECT: improved properties of the composition.

27 cl, 2 tbl, 32 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.

EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.

26 cl, 40 dwg, 3 tbl, 38 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to arthrology, rheumatology, and can be used for treating rheumatoid arthritis. That is ensured by introducing human CD20 specific small modular immune-pharmaceutical (SMIP) protein in a therapeutically effective amount to the patient. The introduction is single, and the supporting treatment is not performed for approximately three months to two years after the introduction of a first single dose.

EFFECT: single introduction provides almost complete B-cell elimination and considerable prolonged rheumatoid factor level reduction in said category of patients.

24 cl, 4 tbl, 8 ex, 5 dwg

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