Nk cytolergy control compositions and methods

FIELD: medicine.

SUBSTANCE: there are offered specific antibodies linked at least with KIR2DL1, KIR2DL2, KIR2DL3 human receptor, neutralise KIR-mediated NK cytolergy inhibition in relation to Cw3+ or Cw4+ target-cells. There are described: B-lymphocyte hybrid cell for producing the antibodies, versions of the method for producing the antibody, as well as a method for detecting a NK-cell, a method for purifying the NK-cells with the use of the antibody and versions of the pharmaceutical antibody composition. Using the antibody for preparing a medicinal agent is offered.

EFFECT: use of the invention provides producing the antibody which controls NK cytolergy of various types, intensifies cytotoxicity, increases NK cytolergy or cytotoxicity in individuals.

63 cl, 13 dwg, 3 tbl, 8 ex

 

The text descriptions are given in facsimile form.

1. Antibody that binds at least with KIR2DL1 receptor human receptor KIR2DL2 person and KIR2DL3 receptors of the human receptor gene products of the human inhibitory killer Ig-like receptor (KIR receptor, named the antibody is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity of NK cells against Cw3+ or Cw4+ target cells expressing NK cells, at least one of KIR2DL1, KIR2DL2, and KIR2DL3 receptors man, this antibody is not NKVSF1, where called antibody obtained by selection from a library or set of monoclonal EN) - Rev. Itel or their functional fragments, or by immunization of a mammal an immunogen, containing KIR2DL, with subsequent selection of antibodies, where each of these selections antibodies carry out assessment of their ability to restore the lysis of NK cells Cw3+ or Cw4+ cells targets, and named the antibody is optionally conjugated or covalently linked to a toxin, a detectable label or a solid substrate.

2. The antibody according to claim 1, where the above mentioned antibody binds to KIR2DL1 receptor of human and KIR2DL2/3 receptors person.

3. The antibody according to claim 1, where the above mentioned antibody inhibits the binding molecule HLA-C allele having Lys residue at position 80, with human KIR2DL1 receptor and the binding molecules of the HLA-C allele, with the Asn residue at position 80 to human KIR2DL2/3 receptors.

4. The antibody according to claim 3, which competes with DF200 produced by cells of the CNCM 1-3224, for binding to the KIR2DL1 receptor human KIR2DL2/3 receptors person, or with both KIR2DL1 and KIR2DL2/3.

5. Antibody that binds at least with KIR2DL1 receptor human receptor KIR2DL2 person and KIR2DL3 receptors of the human receptor gene products of the human inhibitory killer Ig-like receptor (KIR receptor, named the antibody is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity of NK cells against Cw3+ or Cw4+ target cells expressing NK cells, at least one of KIR2DL1, KIR2DL2 THE KIR2DL3 receptors person, and named the antibody is not NKVSF1, where called antibody obtained by selection from a library or set of monoclonal antibodies or their functional fragments, or by immunization of a mammal an immunogen containing KIR2DL, with subsequent selection of antibodies, where each of these selections antibodies carry out assessment of their ability to restore the lysis of NK cells Cw3+ or Cw4+ cells targets, and named the antibody competes with DF200 produced by cells of the CNCM 1-3224, for binding to the KIR2DL1 receptor human KIR2DL2/3 receptors person, or with both KIR2DL1 and KIR2DL2/3 receptors person.

6. The antibody according to claim 4 or 5, which contains one or more CDRs of the heavy chain variable region DF200 produced by cells of the CNCM 1-3224 as shown in SEQ ID No. 10, 11 and 12.

7. The antibody according to claim 4 or 5, which contains a heavy chain variable region DF200 produced by cells of the CNCM 1-3224 as shown in SEQ ID No 9.

8. The antibody according to claims 1-7, which is a monoclonal antibody or a functional fragment of a monoclonal antibody.

9. The antibody of claim 8, which is a monoclonal antibody DF200 produced by cells of the CNCM 1-3224, or its fragment.

10. The antibody according to claim 1, which is an antibody fragment selected from Fab, Fab', Fab'-SH, F(ab')2, Fv, dia-antibody or single-chain fragment antibodies.

11. The antibody of claim 8, which is the humanized antibody.

12. The antibody of claim 8, which is a human antibody.

13. The antibody of claim 8, which is a chimeric antibody.

14. Cell, including:
(a) In the cage of the host mammal, not a man who had been immunized with recombinant KIR2DL-protein, merged with
(b) immortalizing cell,
and named the cell produces a monoclonal antibody described in item 8, the specified antibody is not an antibody that cross-reacts only with KIRDL2, KIRDL3, but with any other inhibitory KIR2DL receptors.

15. Cell at 14, where named the antibody binds to KIR2DL1 and KIR2DL2/3.

16. Cell by 14, which produces an antibody that inhibits the binding molecule HLA-c allele having Lys residue at position 80, receptor KIR2DL1 human, and the binding molecules of the HLA-C allele, with the Asn residue at position 80, receptor KIR2DL2/3 human.

17. The cell of clause 15, which produces an antibody that competes with monoclonal antibody DF200 produced by hybridoma CNCM I-3224, for binding to the KIR2DL1 receptor human KIR2DL2/3 receptors person, or with both KIR2DL1 and KIR2DL2/3 receptors person.

18. Cell by 14, which is hybridoma DF200 CNCM I-3224.

19. A method of obtaining antibodies described in claim 1, comprising the stage of:
(a) immunizing a mammal (not human) immunogen is m, including inhibitory KIR2DL polypeptide;
(b) preparing antibodies from these immunized animal, where these antibodies bind to named the KIR2DL polypeptide,
(C) selection of antibodies (b), which cross-react at least with KIR2DL1 receptor human receptor KIR2DL2 person and KIR2DL3 receptors man and
(g) selection of antibodies (in), which is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity in NK population of NK cells expressing called KIR2DL1, KIR2DL2, and KIR2DL3 receptors man,
moreover, the order of stages (C) and (d) may, if desired, be converted, and called the antibody is not an antibody that cross-reacts only with KIR2DL2, KIR2DL3, but with any other inhibitory KIR receptors.

20. The method according to claim 19, in which the antibody obtained in stage (b), is a monoclonal antibody.

21. The method according to claim 19, in which inhibitory KIR polypeptide used for immunization, is the KIR2DL polypeptide, and antibodies selected in stage (C), cross-react at least with KIR2DL1 and KIR2DL2/3.

22. The method according to item 21, which is called the antibody selected in stage (b)inhibits the binding molecule HLA-c allele having Lys residue at position 80, with human KIR2DL1 receptor and the binding molecules of the HLA-C allele, with the Asn residue at position 80 to human KIR2DL2/3 receptors.

23. The method according to claim 19, in which the above mentioned antibody or antibody fragment that competes with DF200 produced by cells of the CNCM 1-3224, for binding to the KIR2DL1 receptor human KIR2DL2/3 receptors person, or with both KIR2DL1 and KIR2DL2/3.

24. The method according to claim 20, comprising the additional step of preparation of fragments of the selected monoclonal antibodies.

25. A method of obtaining antibodies described in item 8, which is associated at least with KIR2DL1 receptor human receptor KIR2DL2 person and KIR2DL3 receptor, is called the antibody is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity in NK population of NK cells expressing KIR2DL1, KIR2DL2, and KIR2DL3, which includes stages:
(a) selection from a library or set of monoclonal antibodies or fragments of antibodies, which cross-reacts at least with KIR2DL1, KIR2DL2, and KIR2DL3 and
(b) selection of antibodies (a), which is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity in NK population of NK cells expressing mentioned at least KIR2DL1, KIR2DL2, and KIR2DL3,
and named the antibody is not an antibody that cross-communicates only with KIR2DL2, KIR2DL3, but with any other inhibitory KIR receptors.

26. The method according A.25, which is called the antibody selected in stage (b), inhibits the binding of mol is kuly HLA-c allele, having a Lys residue at position 80, with human KIR2DL1 receptor and the binding molecules of the HLA-C allele, with the Asn residue at position 80 to human KIR2DL2/3 receptors.

27. The method according to p, which is called the antibody competes with DF200 produced by cells of the CNCM 1-3224, for binding to the KIR2DL1 receptor human KIR2DL2/3 receptors person, or with both KIR2DL1 and KIR2DL2/3.

28. The method according to p. 25, comprising the additional step of preparation of fragments of the selected monoclonal antibodies.

29. A method of obtaining antibodies described in item 8, which includes stages:
(a) culturing cells according to any one of p-18, leading to the expression called monoclonal antibodies, and
(b) the Department called monoclonal antibodies from these cells.

30. The method according to clause 29, comprising the additional step of making fragments called monoclonal antibodies.

31. A method of obtaining antibodies described in item 8, which includes stages:
(a) isolation of cells according to any one of p-18 DNA that encodes a named monoclonal antibody;
(b) if necessary, modification of the said DNA so that it encodes a modified or transformed antibody selected from gumanitarnogo antibodies, chimeric antibodies, single-chain antibodies or immunoreactive fragment of the antibody;
(C) scrivani is called DNA or modified DNA into the expression vector, leading to the expression of these antibodies or fragments of antibodies, when called expression vector represented in the host;
(d) transfection of the host cells mentioned expression vector, where the named host cell does not otherwise immunoglobulin protein;
(d) culturing named transtitional the host cells, leading to expression of the above antibody or antibody fragment; and
(e) isolation of the antibody or antibody fragment produced called transtitional the host cell.

32. The antibody obtained according to any one of p-31, which is not an antibody NKVSF1 and which is associated at least with KIR2DL1 receptor human receptor KIR2DL2 person and KIR2DL3 receptors of the human receptor gene products of the human inhibitory killer Ig-like receptor (KIR-receptor), which named the antibody is capable of neutralizing KIR mediated inhibition of cellular cytotoxicity of NK cells against Cw3+ or Cw4+ target cells expressing NK cells, at least one of KIR2DL1, KIR2DL2, and KIR2DL3 receptors person.

33. Pharmaceutical composition, enhance NK cytotoxicity, containing an effective amount of an antibody described in claim 1 or 5, for detection of amplification of cellular cytotoxicity of NK in a patient or in a biological way is e, including NK cells, antibodies, and a pharmaceutically acceptable carrier or excipient, and these antibodies are antibodies that cross-interact only with KIRDL2 and KIRDL3, but with any other inhibitors KIR receptors.

34. The composition according to p, which is called the antibody is an antibody according to any one of claims 1 to 13 or 32.

35. Pharmaceutical composition, enhance NK cytotoxicity, which contains antibodies described in claim 1 or 5, and named the antibodies present in an amount, effective for detectable amplification of the cellular cytotoxicity of NK in a patient or in a biological sample containing NK cells; a pharmacologically acceptable carrier or excipient; and an additional therapeutic agent selected from an immunomodulatory agent, a hormonal agent, a chemotherapeutic agent, an anti-angiogenic agent, an apoptotic agent, an anti-apoptotic agent, a secondary antibody that is attached and inhibits inhibitory KIR receptor, anti-infectious agent, the agent against the owner or adjuvant connection.

36. The composition according to p, additionally comprising a therapeutic agent selected from an immunomodulatory agent, a hormonal agent, a chemotherapeutic agent, an anti-angiogenic agent, an apoptotic agent,an anti-apoptotic agent, the secondary antibody, which binds to and inhibits inhibitory KIR receptor, anti-infectious agent and agent against the owner or adjuvant connection.

37. The composition according to p or 36, in which the named immunomodulatory agent selected from IL-1α, IL-1β, IL-2, IL-3, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-21, TGF-β, GM-CSF, M-CSF, G-CSF, TNF-α, TNF-β, LAF, TCGF, BCGF, TRF, BAF, BDG, MP, LIF, OSM, TMF, PDGF, IFN-α, IFN-β or IFN-γ.

38. The composition according to p or 36, in which the named chemotherapeutic agent is selected from alkylating agents, antimetabolites, cytotoxic antibiotics, adriamycin, dactinomycin, mitomycin, karminomitsin, daunomycin, doxorubicin, tamoxifen, Taxol, Taxotere, vincristine, vinblastine, vinorelbine, etoposide (VP-16), 5-fluorouracil (5FU), cytosine arabinoside, cyclophosphamide, thiotepa, methotrexate, camptothecin, actinomycin D, mitomycin C, cisplatin (CDDP), aminopterine, combretastatin(s), other Vinca alkaloids and their derivatives or prodrugs.

39. The composition according to p or 36, in which the named hormonal agent selected from leuprorelin, goserelin, triptorelin, buserelin, tamoxifen, toremifene, flutamide, nilutamide, cyproterone bikalutamid of anastrozole, eksemestana, letrozole, fadrozole, medroxy, chlormadinone, megestrol, other LHRH agonists, other anti-estrogens, other anti-androgens, the other in which autorow aromatase and other Progestogens.

40. The composition according to p or 36, in which the named additional agent selected from phenothiazines, substituted benzamido, antihistamines, butyrophenones, corticosteroids, benzodiazepines, cannabinoids, zolendronic acid, pamidronic acid, erythropoietin, G-CSF, filgrastim, lenograstim, darbepoetin, other anti-Ametistov, other antagonists of serotonin, other biphosphonates, other hematopoietic growth factors.

41. The composition according to p or 36, which is called the anti-apoptotic agents are antisense nucleotide sequence and RNA, siPHK, or a small molecule chemical compound, which inhibits expression of a gene selected from bcr-abl, bcl-2, Bck-xl, Mcl-1, Bak, A1 or A20.

42. The composition according to p or 36, which is called the anti-angiogenic agent selected from neutralizing antibodies, antisense RNA, siPHK, and-RNA, RNA aptamers or ribozymes directed against the gene encoding VEGF, a gene encoding VEGF receptor, VEGF or VEGF receptor; or variants of VEGF, which has antagonistic properties against VEGF.

43. The composition according to p or 36, which called secondary antibody, which binds to and inhibits inhibitory KIR receptor is an antibody or its derivative, or fragment which binds to the epitope inhibitory KIR receptor that is distinct from the epitope, include the named nogo antibody which is associated with a common determinant, presents at least two different gene products inhibitory KIR receptors person.

44. The use of a composition according to any one of p-43 for the preparation of medicines for the potentiation of the activity of NK cells in a patient in need of this potentiation.

45. The application of item 44, wherein the specified patient suffering from cancer and other proliferative diseases, immune diseases or infectious diseases.

46. The application of item 45, wherein the specified patient suffers from squamulose cell carcinoma, leukemia, acute linfocitos leukemia, acute lymphoblastic leukemia, lymphomas of b-cell lymphoma T-cell, Hodgkin's lymphoma, non-Hackintosh lymphoma, hairy cell lymphoma, lymphoma of Burkets, acute or chronic myelogenous leukemia, promyelocytic leukemia, fibrosarcoma, rhabdomyosarcoma; melanoma, seminoma, teratocarcinoma, neuroblastomas, gliomas, astrocytomas, schwannomas; fibrosarcoma, rhabdomyosarcoma, osteosarcoma, melanoma, xeroderma pigmentosum, keratoacanthoma, seminoma, thyroid follicular cancer, teratocarcinoma, other carcinomas of the urinary bladder, breast, colon, kidney, liver, lung, ovary, prostate, pancreas, stomach, cervix, thyroid or skin, the other is their hematopoietic tumors of lymphoid clones other hematopoietic tumors of myeloid origin, other tumors of mesenchymal nature, other tumors of the Central or peripheral nervous system or other tumors of mesenchymal nature.

47. The application of item 45, wherein the specified patient suffering from acute myeloid leukemia (AML).

48. The application of item 45, wherein the specified patient suffering from lymphoma non-Hodgkin's lymphoma.

49. The application of item 45, wherein the specified patient suffering from breast carcinoma.

50. The application of item 45, wherein the patient is suffering from carcinoma of the ovary.

51. The application of item 45, wherein the specified patient suffering from hematopoietic tumors of lymphoid clones.

52. The application of § 51, wherein said tumor is selected from T-prolymphocytic leukemia (T-PLL), including small cell and brain cell type; large granular limfocitna leukemia (LGL) T-cell type, syndrome Caesar (SS); acute T-cell lakeline lymphoma (ATLL), a/d T-NHL hepatoblastoma lymphoma; peripheral post-timesnow T-cell lymphoma pleomorphism or immunoblastic subtype; angio-immunoblastic T-cell lymphoma; angiocentricity (nasal) T-cell lymphoma; anaplastic (Ki 1+) both lymphoma; putting in T-cell lymphoma; T-lymphoblastic leukemia; or lim the WMD/leukemia (T-LbLy/T-ALL).

53. The application of item 45, wherein the named patient suffering from a proliferative disorder selected from hyperplasia, fibrosis, angiogenesis, psoriasis, atherosclerosis, stenosis or restenosis after angioplasty and other diseases characterized by proliferation of smooth muscle of blood vessels.

54. The application of item 45, wherein the named patient suffering from an infectious disease caused by a virus selected from hepatitis virus type a, hepatitis type b, hepatitis type C, influenza, varicella, adenovirus, simplex herpes virus type I (HSV-1), simplex herpes virus type 2 (HSV-2), rinderpest virus of cattle, rhinovirus, Echovirus, rotavirus, respiratory Intellinova virus, human papilloma virus, cytomegalovirus, echinodorus, arbovirus, Hantavirus, virus cocksackie, the mumps virus, measles virus, rubella virus, the polio virus or human immunodeficiency virus type 1 or type 2 (HIV-1, HIV-2).

55. The application of item 45, wherein the named patient suffering from an infectious disease caused by the bacterium, a simple or a parasite selected from Staphylococcus, S. pyogenes, Enterococcus, Bacillus anthracis, Lactobacillus, Listeria, Corynebacterium diphteria, G. vaginalis; Nocardia; Streptomyces; Thermoactinomyces vulgaris; Treponema; Camplyobacter; Raeruginosa; Legionella; N. meningitides; F. Meningosepticum; F. Adoratum; Brucella; B. pectussis; B. bronchiseptica; E. coli; Klebsiella; Enterobacter; S. Marcescens; S. liquefacies; Edwardsiella; P. Mirabilis; P. Vulgaris; Streptobacillus; R. Fickettsfi; C. psittaci; C. trachomatis; M. tuberculosis, M. intracellulare, M. folluitum; M. laprae, M. avium; M. bovis; M. afncanum; M. kansasii; M. intracellulare; M. lepraemurium; Nocardia; other Streptococcus, other Bacillus, other Gardnerella, other Pseudomonas, other Neisseria, other Flavobacteria, other Bordetella, other Escherichia, other Serratia, other Proteus, other Rickettsiaceae, other Chlamydia, other Micobacterium, leyshmany, coccidia, Trypanosoma, chlamydia or Rickettsia.

56. The application of item 45, wherein the drug is used in combination with acceptable additional therapeutic agent selected from an immunomodulatory agent, a hormonal agent, a chemotherapeutic agent, an anti-angiogenic agent, an apoptotic agent, a secondary antibody, which binds to and inhibits inhibitory KIR receptor, anti-infectious agent, the agent against the owner or adjuvant compounds, where the named additional therapeutic agent is introduced called the patient as a single dosage form with the aforementioned antibody, or as a separate dosage form.

57. Use p at which the specified patient suffering from hematopoietic tumors of lymphoid clones, acute myeloblastic leukemia (AML) or lymphoma non-Hodgkin's lymphoma.

58. Use p at which the specified patient suffering from carcinoma of the breast or ovary.

59. The antibody according to claim 1, which con is Pirovano or covalently linked to a toxin, detectable label or a solid substrate.

60. The method of detecting the presence of NK cells, bearing on their cell surface inhibitory KER2DL, in a biological sample or a living organism, called the method involves the following stages:
a) contacting called a biological sample or a living organism with the antibody according to claim 1, where the above mentioned antibody is conjugated or covalently associated with detectable structure, and
b) detecting the presence of these antibodies in the said biological sample or a living organism whose presence indicates the presence of NK cells.

61. The method of purification from a sample of NK cells bearing inhibitory KIR2DL on their cell surface, which includes stages
a) contacting the named sample with the antibody of claim 1 under conditions that allow named NK cells bearing an inhibitory KIR on their cell surface, to communicate with the named antibody, where the above mentioned antibody is conjugated or covalently linked to a solid substrate, and
b) elution named associated NK cells from these antibodies, conjugated or covalently linked to a solid substrate.

62. The composition enhances NK cytotoxicity, containing an effective amount of an antibody described in claim 1, in which the indicated antibodies included in liposomes.

63. The composition according to item 62, to omnitele containing agent, selected from a molecule of nucleic acids for gene delivery for gene therapy; the nucleic acid molecule for the delivery of antisense RNA, and RNA or siPHK to suppress gene expression in NK cell; or toxin or drugs for the targeted destruction of NK cells, in addition vklyuchennyi specified in the liposome.
Priorities for items:

01.07.2004 on pp.5-9, 11-18, 23-58;

02.07.2003 according to claims 1, 8, 10-16, 19-22, 24-26, 28-63;

19.02.2004 according to claims 1, 8, 10-16, 19-22, 24-26, 28-63.



 

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EFFECT: invention enables to obtain MCA with specificity to VP35 protein of the Marburg virus (Popp strain), suitable for immunodiagnosis of Marburg haemorrhagic fever.

2 cl, 3 dwg, 1 tbl, 5 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and can be used in immunodiagnosis of human cytomegalovirus. The strain of hybrid animal cells Mus musculus L.5F10 is obtained by merging mouse myeloma cells p3-X63/Ag8.653 (NS/1) with mouse spleen cells BALBc, immunised by an affinity purified recombinant protein pp65. The hybridoma strain is deposited in the collection of cell cultures of The State Research Center of Virology and Biotechnology VECTOR and is used as a producer of monoclonal antibodies for detecting the pp65 protein of human cytomegalovirus.

EFFECT: invention enables to widening of range of strains of hybrid cells Mus musculus L - producers of MCA for detecting the pp65 protein of human cytomegalovirus and production of domestic diagnostic test-systems for detecting cytomegaly.

2 dwg, 1 tbl, 5 ex

FIELD: medicine; pharmacology.

SUBSTANCE: allocated human monoclonal antibodies which specifically bind a receptor of the epidermal growth factor (EGFR), and also corresponding compositions on the basis of antibodies and a biospecific molecule are described. Human antibodies can be received with use of the transgenic mouse capable to formation of set of isotypes of human monoclonal antibodies by recombination V-D-J and switching of isotypes. The pharmaceutical compositions containing human antibodies for treatment or prevention of diseases, mediated by expression EGFR, the transgenic animals distinct from a human, the specified expressing antibodies, hybridomes and transfectomes which produce human antibodies are also presented. Ways of therapy and diagnostics of the diseases mediated by expression EGFR, with use of human antibodies or their antigen-binding of fragments, and also methods of growth suppression of the cells expressing EGFR, and an induction of cytolysis of the specified cells are described.

EFFECT: invention allows obtaining therapeutic and diagnostic preparations of antibodies with improved properties.

53 cl, 22 dwg, 4 tbl, 11 ex

FIELD: biotechnology, immunology, medicine, oncology.

SUBSTANCE: strain of hybrid cultured mammalian cells Mus musculus VKPM H-98 is prepared by the hybridoma technology method. This strain is a producer of monoclonal antibodies possessing individual specificity to hypoglycosidated and deglycosidated isoforms of tumor-associated human antigen Muc I. Productivity of the strain and specificity of produced antibodies is estimated based on the immunoenzyme assay using some markers of specificity: natural purified antigen Muc I isolated from human milk; VNTR22-polypeptide; synthetic monomeric polypeptide (TR1); deglycosidated antigen Muc I (de-Muc I) prepared by chemical oxidation of natural Muc I; hypoglycosidated antigen Muc I (o-Muc I) prepared by periodate oxidation of natural Muc I. Monoclonal antibodies produced by the claimed strain recognize clinically significant isoforms of antigen Muc I and allows assaying its concentrations in human serum blood in carrying out the early diagnosis of tumors. Invention can be used in preparing monoclonal antibodies to tumor-associated human antigen Muc I.

EFFECT: valuable properties of strain.

2 dwg, 3 ex

FIELD: biotechnology, immunology, medicine, oncology.

SUBSTANCE: strain of hybrid cultured mammalian cells Mus musculus VKPM H-97 is prepared by the hybridoma technology method. This strain represents a producer of monoclonal antibodies possessing specificity to conformation-dependent of tumor-associated human antigen Muc I. Productivity of the strain and specificity of produced antibodies is estimated based on immunoenzyme assay using some markers of specificity: natural purified antigen Muc I isolated from human milk; VNTR22-polypeptide; synthetic monomeric polypeptide (TR1); deglycosidated antigen Muc I (de-Muc I) prepared by chemical oxidation of natural Muc I; hypoglycosidated antigen Muc I (o-Muc I) prepared by periodate oxidation of natural Muc I. Monoclonal antibodies produced by the claimed strain recognize clinically significant isoforms of Muc I antigen and allows assaying its concentration in human serum blood in carrying out early diagnosis. Invention can be used for preparing monoclonal antibodies to tumor-associated human antigen Muc I.

EFFECT: valuable properties of strain.

2 dwg, 3 ex

FIELD: medicine, biotechnology.

SUBSTANCE: invention proposes variants of antibodies showing specificity to peptide domain located by both side of hinged site R76S77 in pro-BNP(1-108). Indicated antibodies recognize specifically also circulating pro-BNP(1-108) in human serum or plasma samples but they don't recognize practically peptides BNP(1-76) or BNP(77-108). Also, invention describes variants of peptides used in preparing antibodies. Amino acid sequence is given in the invention description. Also, invention discloses methods for preparing indicated antibodies and among of them by using indicated peptides. Also, invention describes methods for preparing antibody-secreting hybridoma, and hybridoma is disclosed prepared by indicated method. Also, invention describes a monoclonal antibody secreted by hybridoma 3D4 and deposited at number CNCM I-3073. Also, invention discloses variants for diagnosis of cardiac insufficiency in vitro and by using antibodies proposed by the invention. Also, invention describes a set used for detecting pro-BNP(1-108) in a biological sample. Using this invention simplifies detection of pro-BNP(1-108) circulating in human serum or plasma samples and provides specific detection of pro-BNP(1-108) that can be used in early diagnosis of human cardiac insufficiency.

EFFECT: valuable medicinal properties of antibodies.

24 cl, 16 dwg, 5 tbl, 20 ex

FIELD: immunology.

SUBSTANCE: invention relates to immunoenzyme analysis and can be used for assay of von Willebrand factor. Method involves immunoenzyme analysis wherein monoclonal antibody 5C3 is used as an immobilizing antibody, and a mixture of biotin-labeled monoclonal antibodies 2H2 and 7D12 is used as a detecting antibody. Also, invention relates to monoclonal antibodies produced by the strain of hybridoma cultured cells Mus musculus L. and directed against von Willebrand factor, and to strains of hybrid cultured cells Mus musculus L. producing indicated monoclonal antibodies. Invention provides the development of highly sensitive method for assay of von Willebrand factor.

EFFECT: improved method for analysis.

9 cl, 1 tbl, 2 dwg, 3 ex

The invention relates to biotechnology, in particular to recombinant IL4-antibodies used for treating disorders associated with the activity IL4

The invention relates to a monoclonal antibody having the ability to inhibit homing hematopoietic stem cells and to identify surface antigen stromal cells, having the ability to maintain homing hematopoietic stem cells, as well as to hybridoma producing monoclonal antibody

FIELD: medicine.

SUBSTANCE: there is described a recovered anti-FcγRIIB/anti-FcεRIα bispecific antibody unable of cross-linking with human FcγRIIA. There are offered methods of immune response inhibition in a mammal, immune response related histamine release inhibition in a mammal, and treatment involving the introduction of described bispecific antibody. There are presented a composition for FcεRI activity inhibition in the recovered cells of mammals, a composition for FcγRIIB activation in the recovered cells of mammals expressing FcγRIIB by combined aggregation of FcγRIIB and FcεRIα and a composition for FcεRI receptor expression inhibition in the recovered cells containing the described antibody as an active material.

EFFECT: invention allows making bispecific anti-FcγRIIB, anti-FcεRIα antibodies.

49 cl, 65 dwg, 2 tbl, 5 ex

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