Novel anti-igf-ir and their application

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to immunology and biotechnology. Claimed are versions of antibodies or their functional fragments, which are bound with receptor of human insulin-like growth factor I IGF-IR, and/or natural binding of its ligands IGF1 and/or IGF2 and/or are capable of specific inhibition of tyrosine kinase activity of said IGF-IR. Antibodies contain respective CDR sections of light and heavy chains. Described is mouse hybridoma I-3193 for production of antibodies. Composition for prevention or treatment of cancer, based on antibody application. Described is application of antibodies and/or composition for obtaining respective medication. Claimed is method of diagnostics in vitro of diseases, caused by over-expression or insufficient expression of receptor IGF-I based on antibodies..

EFFECT: invention application ensures antibodies able to bind with isophorms A and B insulin, insulin/ IGF-1 of hybrid receptors which can be applied in medicine for tumour treatment.

15 cl, 8 dwg, 2 tbl, 4 ex

 

The text descriptions are given in facsimile form.

1. An isolated antibody, or one of the e is about functional fragments, moreover, the specified antibody or one of its specified functional fragments, capable of binding with the receptor IGF-IR, insulin-like growth factor I of the person and, if necessary, the inhibition of natural join its ligands IGF1 and/or IGF2, and/or capable of specific inhibition tyrosinekinase activity specified IGF-IR, characterized in that include a light chain containing 3 CDR sequences of SEQ ID No.l, 2, and 3, and a heavy chain containing 3 CDR sequences of SEQ ID No.4, 5 and 6.

2. The antibody according to claim 1, referred to as 13F5 and characterized in that it comprises a heavy chain sequence containing the amino acid sequence of SEQ ID N.20, and the fact that it also includes a light chain sequence containing the amino acid sequence of SEQ ID N.19.

3. Mouse hybridoma capable of secretion of antibodies according to one of claims 1 or 2, deposited at the CNCM, Institut Pasteur, Paris, March 25, 2004 under the number I-3193.

4. Antibody Sekretareva hybridomas according to claim 3 or one of its functional fragments, capable of binding with the receptor IGF-IR, insulin-like growth factor I of the person and, if necessary, the inhibition of natural join its ligands IGF1 and/or IGF2, and/or capable of specific inhibition tyrosinekinase activity specified IGF-IR.

5. The antibody or the Dean of its functional fragments according to claim 1, characterized in that said antibody or one of its functional fragments, is a chimeric antibody and, in addition, includes a constant sections of the light chain and heavy chains, obtained from antibody species heterologous mouse.

6. The antibody or one of its functional fragments according to claim 5, characterized in that said heterologous species is man.

7. Composition for preventing or treating cancer comprising as active principle a compound consisting of an antibody or one of its functional fragments according to one of claims 1, 2 and 4-6, and the dose of the composition is adapted for a particular patient.

8. The composition according to claim 7, characterized in that it includes, in addition, as a combination product for simultaneous, separate or sequential use antibody, a cytotoxic/cytostatic agent and/or inhibitor tyrosinekinase activity of receptors for IGF-I and/or EGF, respectively.

9. Composition according to one of claims 7 or 8 as a medicine.

10. The use of antibodies or one of its functional fragments according to one of claims 1, 2, 4 and 6 and/or composition according to any one of claims 7 to 9, for obtaining a drug intended for the prevention or treatment of cancer, psoriasis or atherosclerosis, are associated with the overexpression and/or an abnormal activation of the receptor for IGF-I, is/or related overactivity path signal transduction mediated by the interaction of IGF1 or IGF2 with IGF-IR.

11. The use of claim 10 for obtaining a drug intended for inhibiting the transformation of healthy cells into cells with tumor nature, preferably IGF-dependent, especially IGF1 and/or IGF2-dependent cells.

12. The use of claim 10 for obtaining a drug intended for inhibiting the growth and/or proliferation of tumor cells, preferably IGF-dependent, especially IGF1 and/or WR-dependent cells.

13. Use PP-12, characterized in that the cancer is a prostate cancer, osteosarcoma, lung cancer, breast cancer, endometrial cancer, or cancer of the rectum.

14. The method of in vitro diagnosis of diseases caused by overexpression or lack of expression of the receptor for IGF-I from a biological sample, which assumes the presence of abnormal receptor IGF-I, characterized in that said biological sample is introduced into contact with an antibody according to one of claims 1, 2, 4 and 6, with the indicated antibody can be, if necessary, labeled.

15. The antibody according to any one of claims 1, 2, 4 and 6, characterized in that it is capable of binding to the hybrid-R isoform(s) a and/or b and/or inhibiting the binding of its native ligand, preferably designated here as IGF1 and/or IGF2 and/or insulin, and/or capable to specific the mu inhibition tyrosinekinase activity of these hybrid-R isoforms(isoforms) a and/or B.



 

Same patents:

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

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: binding molecule represents a CD45RO and CD45RB chimeric antibody. The molecule contains two domains with consistent hypervariable sites CDR1, CDR2 and CDR3, and CDR1', CDR2' and CDR3', CDR1 has amino acid sequence NYIIH, CDR2 has amino acid sequence YFNPYNHGTKYNEKFKG, and CDR3 has amino acid sequence SGPYAWFDT. CDR1' has amino acid sequence RASQNIGTSIQ, CDR2' has amino acid sequence SSSESIS, and CDR3' has amino acid sequence QQSNTWPFT. Related coding polynucleotide is described.

EFFECT: use of the invention allows to induce immunosuppression, to inhibit T-cell response and primary lymphocyte reaction in the mixed culture, to prolong survival time in mice with severe combined immunodeficiency SCID.

6 cl, 5 dwg, 2 tbl, 8 ex

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

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

FIELD: medicine.

SUBSTANCE: invention refers to biotechnology. The pharmaceutical composition for destruction of tumor cells expressing the receptor CCR7 is described, which contains an antibody binding to the receptor CCR7, and a pharmaceutically acceptable carrier. Versions of methods of eradication of tumor cells expressing the receptor CCR7 are proposed, which include either contacting of the specified cells with an antibody that binds with the specified receptor CCR7, or administering to the patient a therapeutically effective amount of an antibody that binds with the specified receptor CCR7.

EFFECT: invention expands the amount of means for cancer treatment.

6 cl, 8 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to method of treating tumour by introduction to subject of c-met antagonist, where lung tumour contains hyperstabilised polypeptide of human c-met with deletion of amino acid part L964 - D1010 of amino acid sequence (given in formula), due to which c-met degradation is reduced in comparison with c-met if wild type. Hyperstabilised polypeptide of c-met binds c-met ligand and possesses c-met activity with respect to signal transmission. In invention it is shown that antagonist is introduced together with substance, inducing degradation of receptor protein. C-met antagonist can represent peptide-antagonist, antibody-c-met antagonist, in particular monovalent antibody, humanised, human or chimeric.

EFFECT: invention makes it possible to inhibit c-met activity with antagonist due to enhancement of cell degradation of hyperstabilised c-met protein either due to inhibition of phosphorolation of hyperstabilised c-met protein or member of cascade of HGF-c-met signal transmission.

10 cl, 1 ex, 18 dwg

FIELD: medicine.

SUBSTANCE: there is claimed isolated human antibody or its fragment, which binds to human EGFR. Antibody contains corresponding CDR areas of light and heavy chain. Its conjugate with anti-neoplastic means or marker is described. Also described are: coding nucleic acid, expression vector, recombinant cell-host for obtaining antibodies and method of inhibiting growth of tumor, expressing EGFR on the basis of antibody.

EFFECT: application of invention provides antibodies with affinity comparable or higher, than in IMC-C225, which neutralises EGFR activation, what can be applied in medicine for treatment of tumours.

36 cl, 14 dwg, 6 tbl, 13 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: present invention relates to immunology and biotechnology. The invention discloses versions of a cytotoxically active CD3-specific binding structure. The structure comprises a first domain specifically binding to human CD3 and an Ig-derived second binding domain which is specific to molecules on the cell surface. The invention describes a coding nucleic acid, a vector for expressing the structure and an eukaryotic cell transformed by the vector. The invention discloses versions of compositions based on the structure for treating, preventing or alleviating various diseases and corresponding methods of treating the diseases. A method of obtaining the structure is disclosed.

EFFECT: use of the invention provides a structure with low immunological potency, which has cytotoxicity comparable to the initial structure, which may find further use in medicine.

60 cl, 18 dwg, 15 tbl, 8 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and is a tumour necrosis factor receptor 1 antagonist which is a TNFR1 domain antibody (dAb). The invention also pertains to a TNFR1 domain antibody (dAb) monomer which binds the tumour necrosis factor receptor 1, as well as to a ligand which contains such a monomer. The invention also relates to a method of inhibiting signal transmission through the TNFR1 receptor using said antagonists. The invention also discloses nucleic acid which codes said antagonist, a vector containing said nucleic acid, a host cell containing said vector, a pharmaceutical composition containing said antagonist or said dAb monomer.

EFFECT: invention can be effective in treating inflammatory diseases (for example chronic inflammatory diseases).

57 cl, 99 dwg, 14 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention is a humanised form of mouse anti c-met antibody. The disclosed antibody enables different degrees of impairment of the HGF/c-met signalling pathway.

EFFECT: improved method.

29 cl, 17 dwg, 2 tbl, 1 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and is meant for treating CD20 expressing tumours. A CD20 antibody molecule merged with a IL2 molecule is disclosed. The antibody contains modified variable parts of a heavy and a light chain. Disclosed also is a pharmaceutical composition for treating a CD20 expressing tumour, which contains a merged polypeptide of the CD20 antibody, as well as a DNA molecule which codes the said merged polypeptide.

EFFECT: invention enables to lower immunogenicity of the modified anti-CD20 antibody compared to unmodified molecules and increase anti-tumour activity with respect to CD20.

15 cl, 17 dwg, 3 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to disalts of bis-(thio-hydrazide amides) represented by structural formula, selected from:

where M+ is selected from Na+, Li+, K+, NH3(C2H5OH)+, N(CH3)3(C2H5OH)+, and M2+ is selected from Mg + and Ca2+, enhancing anti-cancer activity of paclitaxel, to based on them pharmaceutical composition and to method of cancer treatment in which claimed disalts are uses in combination with paclitaxel, as well as to method of obtaining claimed compounds.

EFFECT: obtaining pharmaceutical composition based on salts which enhance anti-cancer activity.

31 cl, 2 tbl, 24 dwg, 19 ex

Up!