Compositions and diagnostic techniques for tumour and methods of treating it
SUBSTANCE: invention refers to immunology and biotechnology. What is offered is a TAT 10772 antibody which is characterised by the presence of six CDR. What is described is a method for identifying the antibody which binds TAT 10772 polypeptide. What is disclosed is using the antibody according to claim 1 for TAT 10772 expressing cell growth inhibition, and for therapeutic treatment of a tumour in a mammal where the tumour expresses TAT 10772. There are described: a presence-absence test of TAT 10772 protein in a sample which is supposed to contain it, and a method of diagnostic detection of a TAT 10772 expressing tumour, based on using the antibody according to claim 1.
EFFECT: presented inventions can find further application in therapy and diagnostics of TAT 10772 expressing tumours.
31 cl, 37 dwg, 11 tbl, 18 ex
The text descriptions are given in facsimile form.
1. The selected antibody that contains three hypervariable region of the light chain (HVR-L1=SEQ ID NO:14, HVR-L2=SEQ ID NO:35 and HVR-L3 is SEQ ID NO:59) and three hypervariable region of the heavy chain (HVR-H1=SEQ ID NO:74, HVR-H2=SEQ ID NO:94 and HVR-H3=SEQ ID NO:113), where
(a) sequence HVR-L1 can be replaced by one of the sequences represented by SEQ ID NO:15-34;
(b) sequence HVR-L2 can be replaced by one of the sequences represented by SEQ ID NO:36-58;
(C) sequence HVR-L3 may be replaced by one of the sequences presented in SEQ ID NO:60-73;
(g) a sequence of HVR-H1 can be replaced by one of the sequences presented in SEQ ID NO:74-93;
(d) sequence HVR-H2 can be replaced by one of the sequences presented in SEQ ID NO:95-112; and
(e) sequence HVR-H3 may be replaced by one of the sequences presented in SEQ ID NO:114-118, where the specified antibody binds to the polypeptide having SEQ ID NO:2.
2. The selected antibody according to claim 1, further containing a sequence of the acceptor human consensus wireframe plot VH selected from one of the sequences presented in SEQ ID NO:184-193.
3. The selected antibody according to claim 1, further containing a sequence of the acceptor human consensus frame section VL selected from one of the sequence is, presented in SEQ ID NO:194-197.
4. The selected antibody according to claim 1, further containing a sequence of the acceptor human consensus wireframe plot VH selected from one of the sequences presented in SEQ ID NO:184-193, and the sequence of the acceptor human consensus frame section VL selected from one of the sequences presented in SEQ ID NO:194-197.
5. The antibody according to claim 1, represents a fragment of the antibody.
6. The antibody according to claim 1, which represents a chimeric or humanitariannet antibody.
7. The antibody of claim 1 conjugated with inhibiting the growth of the agent.
8. The antibody of claim 1 conjugated with a cytotoxic agent.
9. The antibody of claim 8, in which the cytotoxic agent is selected from the group including toxins, antibiotics, radioactive isotopes or nucleotidase enzymes.
10. The antibody of claim 8, in which the cytotoxic agent is a toxin.
11. The antibody of claim 10, in which the toxin is selected from the group comprising maytansinoid and calicheamicin.
12. The antibody of claim 10, in which the toxin is maytansinoid.
13. The antibody according to claim 1, which is produced in bacteria.
14. The antibody according to claim 1, which is produced in Cho-cells.
15. The antibody according to claim 1, which induces death of cells with which it is associated.
16. Antibody pop, where the cell is a cancer cell of the ovary.
17. The antibody according to claim 1, which is detectable label.
18. The manner of identification of an antibody that binds to the polypeptide having SEQ ID NO:2, and the second antibody, where the second antibody is an antibody according to claim 1, namely, that determine the capacity of the first antibody to block the binding of the second antibody, with the polypeptide having SEQ ID NO:2, where the first ability of antibodies to block the binding of the second antibody, with the polypeptide having SEQ ID NO:2 is at least 40%, and when using the same concentration of antibodies indicates that the first antibody has the ability to contact the epitope is associated with the second the antibody.
19. The use of antibodies according to claim 1 for inhibiting growth of cells that expresses a protein having the amino acid sequence represented in SEQ ID NO:2.
20. The application of claim 19, in which the cell is a cancer cell of the ovary.
21. The application of claim 19, in which the indicated antibody conjugated with a cytotoxic agent.
22. The use of antibodies according to claim 1 for therapeutic treatment of a mammal, which has a malignant tumor containing cells that Express a protein having the amino acid sequence of which is presented in SEQ IDNO:2.
23. The application of article 22, in which a malignant tumor is a tumor of the ovary.
24. The application of article 22, in which the indicated antibody conjugated with a cytotoxic agent.
25. The method of determining the presence of TAT protein 10772 in the sample, which assumes the presence of a specified protein, which consists in the fact that the treated sample with an antibody according to claim 1 and determine the binding of an antibody to the polypeptide having SEQ ID NO:2, where the binding of an antibody to the specified polypeptide indicates the presence of the indicated protein in the sample.
26. The method according A.25, in which the sample contains a cell, which is expected expresses this protein.
27. The method according to p, in which the cell is a cancer cell of the ovary.
28. The method according to item 27, in which the antibody carries a detectable label.
29. The diagnostic method of identifying a tumor that expresses TAT 10772 antigen, namely, that bring into contact a test sample of tissue cells obtained from the body of the mammal with an antibody according to claim 1, and reveal the formation of a complex between the antibody and the polypeptide having SEQ ID NO:2, in the test sample, where the formation of the complex indicates the presence of tumor in the body of a mammal.
30. The method according to item 27, in which the test sample of tissue cells obtained from the organism of the individual, is vtorogo assumes the presence of a malignant tumor.
31. The method according to p in which a malignant tumor is a tumor of the ovary, breast or pancreas.
SUBSTANCE: what is described are drug conjugates which contain an incretin therapeutic or diagnostic agent who is fused or conjugated with an antigen-binding antibody fragment which binds serum albumin.
EFFECT: conjugates have prolonged in vivo half-life in comparison with an unconjugated or unfused therapeutic or diagnostic agent.
27 cl, 19 dwg, 8 tbl, 18 ex
SUBSTANCE: there are offered versions of human IL22 specific antibodies. The antibodies are differed by the fact that they are produced of different hybridomas PTA-7312, PTA-7315, and PTA-7319. The PTA-7312 antibody is characterised by the fact that it inhibits STAT3 activation by reaching IC50 in the concentration 0.14 mcg/ml whereas the PTA-7315, PTA-7319 antibodies are characterised by Kd less than 1 nM.
EFFECT: use of the invention can find further application in therapy of the IL22 mediated immune disorders.
24 cl, 41 dwg, 1 tbl, 26 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology and represents OX40L antibodies which contain a Fc-fragment produced from a human body, and do not bind with a complement Clq factor. Besides vectors, cells, methods of producing the antibody, a composition and applications of the antibody for preparing a drug are presented.
EFFECT: antibodies exhibit new and patentable signs, particularly advantage to a patient which suffers inflammatory diseases.
19 cl, 7 tbl, 23 ex
SUBSTANCE: offered is a fused protein containing from an amino-terminus to carboxyl terminus: binding domain polypeptide which is bound with a biological target molecule; human one-cysteine "link" region IgGl peptide; immunoglobulin heavy chain CH2 constant region polypeptide and immunoglobulin heavy chain CH3 constant region polypeptide. The fused protein represents mixed monomers and dimers, has ADCC, CDC or both cytotoxicities. Also, described are a pharmaceutical composition and a method of treating a B-cell disorder with using the fused protein.
EFFECT: use of the invention can find the further application in medicine in treating B-cell disorders.
26 cl, 26 dwg, 9 ex
SUBSTANCE: claimed are versions of separated monoclonal antibody, specific to INNAR-1. Described are: bispecific molecule, immunoconjugate and compositions for treatment of IFNAR-1-mediated diseases and disorders based on monoclonal antibody. Also described are methods of inhibiting biological activity of type I interferons, method of treating diseases and disorders, mediated by type I interferon with application of antibody. Claimed are nucleic acid, which codes antibody, vector for antibody expression, cell, transformed by vector, as well as method of obtaining antibodies and antibody-producing hybridoma.
EFFECT: application of invention provides novel IFNAR-1 inhibiting antibodies, which block IFNAR-1 and bind its other epitope, in comparison with known antibody 64G12.
29 cl, 15 dwg, 6 tbl, 9 ex
SUBSTANCE: claimed are versions of polypeptides with Fc-segment from IgG, which possess increased binding FcRn due to introduction of mutation 308C, 308F, 308W, 308Y or modified binding with introduction of mutation 252Y/308F, 257L/308F, 257L/308Y, 257N/308Y, 279Q/308F, 279Y/308F, ^281S/308F, ^A281S/308Y, 284E/308F, 298A/308F/333A/334A, 308F/332E, 308F/311V, 308F/G385H, 308F/428L, and 308F/434Y. Described is antibody with said mutations in Fc region, as well as application of said Fc regions for obtaining fused protein. Application of the invention provides novel Fc-versions with modified FcRn binding.
EFFECT: possibility of application in medicine for obtaining various constructions, with prolonged time of preservation in blood serum in vivo or, vice versa, in case of therapy with application of radioactive medications, with reduced time of preservation in blood serum in vivo.
14 cl, 44 dwg, 4 ex
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: 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 an antibody which bonds with OX40L and variants of this antibody which contain certain Fc-fragments obtained from the human body and do not bond with the complement factor Clq. The monoclonal antibody is produced by a cell line selected from a group which includes cell lines deposited in the German collection of microorganisms and cell cultures (DSMZ) under inventory numbers No. DSM ACC 2685, DSM ACC 2686, DSM ACC 2688, DSM ACC 2689. The invention also relates to a method of obtaining such antibody, to nucleic acid molecules which code the disclosed antibody. The disclosed antibody has an advantage for patients suffering from inflammatory diseases.
EFFECT: antibody is used in diagnostic composition for detecting OX40L in vitro, in a pharmaceutical composition for preventing and treating inflammatory diseases, as well as in preparing a medicinal agent for preventing and treating inflammatory diseases.
9 cl, 20 dwg, 7 tbl, 23 ex
SUBSTANCE: proposed is a chimeric or humanised monoclonal antibody against hepatocyte growth factor, produced from L2G7 antibody. Invented is a mouse antibody L2G7, produced by hybridoma ATCC PTA-5162, and the said hydbridoma. Described is a cell line, producing a chimeric or humanised monoclonal antibody against hepatocyte growth factor. Proposed is a pharmaceutical composition and a method of treating tumours based on the said antibody.
EFFECT: use of the invention provides for a neutralising antibody against hepatocyte growth factor, which can be used in treating human cancer.
7 cl, 12 dwg, 1 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology, and represents an antibody able to bind a tumour-associated antigen TAT 10772 polypeptide. Besides, there are presented antibody conjugate with a drug, pharmaceutical composition, method of cell proliferation inhibition, method of treating the TAT 10772 expressing tumours , analysis for tumour cell detection, as well as kit for treating the tumours.
EFFECT: invention can be used in treating the tumours expressing the tumour associated antigen TAT 10772 polypeptide.
41 cl, 45 dwg, 11 tbl, 18 ex
SUBSTANCE: invention concerns anti-PSMA antibodies which contain variable sites of heavy and light chains; the antibody does not contain fucosyl residues. Amino acid sequences of said chains are presented in the formula. Antibodies under the invention are a monoclonal antibody, a humanised or chimeric antibody, a human antibody. Also, there is described a method of inhibition of PSMA+ cell growth, such as tumour cells by contact of said cells with the anti-PSMA antibodies.
EFFECT: antibodies show higher, antibody-dependent prostate cancer cell cytotoxicity as compared with a fucosyl antibody form.
32 cl, 3 tbl, 6 ex
SUBSTANCE: invention relates to biotechnology and represents antibody or its fragment, which is able to bind with homologue 10 of protein Frizzled (FZD10), such as monoclonal mouse antibody, hybrid antibody, chimeric and humanised antibody. Also claimed are hybridoma clones, producing antibody, as well as method of treatment of prevention of FZD10-associated disease; method of diagnostics or prediction of FZD10-associated disease; method of visualisation in vivo FZD10 in a subject; pharmaceutical composition and set, containing antibody.
EFFECT: treatment with claimed antibodies makes it possible to improve clinical outcome in case of diseases associated with homologue to of protein Frizzled.
44 cl, 45 dwg, 8 ex
SUBSTANCE: present invention refers to immunology and biotechnology. There is offered recovered human antibody to RG1 polypeptide. There are described versions of antibodies, including one-chain antibody, and immunoconjugate based on said antibodies. There are disclosed methods of selective cell destruction, cell inhibition, treatment of disease state, detection of disease state, detection of RG1, monitoring of clinical course of prostate cancer, prediction in a person with using antibodies and immunoconjugate.
EFFECT: application of the invention provides new antibodies to RG1 polypeptide that can find application in treating tumours with RG1 overexpression.
16 cl, 4 dwg, 1 tbl, 13 ex
SUBSTANCE: there is offered application of humanised fused protein for making a medicine used for stimulation of immune response and stabilisation of disease progressing in patients with GD2-positive tumours. The antibody contains antibody H14.18 caught with surface glycosphingolipid GD2 of human cells, and cytokine IL2. There is disclosed method of increase in ADCC and lysis activity of natural killers in cancer patients by introduction of the fused protein. The invention can be applied in GD2-overexpression cancer therapy.
EFFECT: application of the invention provides low-immunogenicity antibody.
2 cl, 8 dwg, 1 tbl, 2 ex
SUBSTANCE: invention concerns immunology area. Versions of the artificial fused protein consisting of an antibody (or its fragment) and cytokine, fused through a link peptide are offered. The antibody or its fragment is chosen from an antibody 225, 425, KS 1/4, 14.18, anti-CDx-antibody where x has the whole value 1-25. Each of versions of the fused protein has lowered quantity T-epitopes, at least, in the component of the fused protein presented by an antibody, and as consequence, possesses the lowered adjuvanticity, in comparison with an initial molecule. Identification of T-lymphocyte epitopes is performed by the automated calculation of sizes for the binding centres of class II MHC molecules with the subsequent experimental test of the obtained versions of protein for presence of the lowered adjuvanticity. The automated way of T-epitopes calculation is based on use of the Bjom's function modified in such manner that contribution of Van-der-vaals repulsion and lipophilic interaction in pairs between all lipophilic atoms of the chosen segments of the fused protein and a binding groove of a MHC P molecule is taken into account. Also a way of protein construction on the basis of the modified function Bjom's function with the subsequent experimental test of the received versions for presence of the lowered adjuvanticity is revealed, and also application of the fused protein for preparation of a pharmaceutical composition for tumour treatment is in addition considered.
EFFECT: invention use allows obtaining the fused proteins with the lowered adjuvanticity and, basically, keeping identical biological activity in comparison with a parent molecule; it can be used in treatment of tumours.
4 cl, 6 dwg, 22 tbl, 19 ex
SUBSTANCE: proposed is a recombinant single-strand trispecific antibody for treating tumours which express CEA. The said antibody consists of a series of three antibody fragments: anti-CEA-scFv, anti-CD3-scFv and VH CD28-antibody, linked by two intermediate linkers (intermediate linker Fc and intermediate linker HSA). If necessary, a c-myc-mark or (His)6-mark can be added at the C-end. Described is DNA, which codes the antibody, expression vector based on it and E.coli cell, containing the vector.
EFFECT: use of the invention is more beneficial in clinical use compared to bispecific antibodies and known trispecific antibodies, makes easier clearing and expression of an antibody, which can further be used in treating CEA-mediated tumours.
10 cl, 21 dwg, 11 ex
SUBSTANCE: versions of the bond intended for linkage with the external domain B (ED-B) of a fibronectin are offered. The bond includes an antigen-binding fragment of one-chained antibody L19 and a cysteinum-containing linker for hanging of a radioactive label. Versions of a pharmaceutical composition for diagnostics and treatment of angiogenic diseases on the basis of the specified bond are opened. Application of bond for linkage with radioactive bond is described. The method of reception of bond in eucariotic cells is opened, including in Pichia pastoris and a set for reception is radioactive labelled agents on the basis of bond.
EFFECT: high-avid bond accumulation in solid tumours.
23 cl, 4 dwg, 5 tbl, 15 ex
FIELD: immunology, antibodies.
SUBSTANCE: invention elates to human monoclonal antibodies to MN and antibody fragments to MN that are targeted to repeat sequence GEEDLP within proteoglycan domain. Binding with a desired epitope is confirmed by competitive immunoenzyme analysis method ELISA wherein ELISA signal is attenuated in combined incubation with peptide comprising this repeat sequence (PGEEDLPGEEDLP). Binding inhibition can be confirmed by the Biacore study also wherein binding required antibodies with immobilized MN or proteoglycan peptides can be inhibited by peptide repeat sequence. In addition to binding with human peptide repeat sequence anti-MN can inhibit adhesion of CGL-1 cells to plastic plates covered by MN. Human antibodies anti-MN can be used in treatment of cancer diseases or for diagnosis of cancer diseases wherein the level of MN is increased.
EFFECT: valuable medicinal properties of antibodies.
11 cl, 8 dwg, 2 tbl, 13 ex
FIELD: oncology and biotechnology.
SUBSTANCE: invention concerns conjugates used for treatment of malignant tumor. Conjugate includes staphylococcal or streptococcal wild-type superantigen or modified superantigen and antibody constituent. Bacterial superantigen is modified to reduce serum reactivity with preserved its antigenic activity. Amino acid sequence of superantigen incorporates A-E regions determining binding to TCR and MHC molecules class II. Invention is directed to preparing antitumor drug and also to preparing pharmaceutical composition.
EFFECT: use of the conjugate according to invention activate immune system and, therefore, resistance of mammalian against malignant tumor.
67 cl, 11 dwg, 1 tbl, 11 ex
SUBSTANCE: invention describes application of IL-17-binding molecules for producing a drug for growth inhibition of solid malignant proliferative diseases or hematological proliferative diseases. The IL-17-binding molecules include variable domains of heavy and light chains. The molecules include at least one antigen binding site containing variable domains of heavy and light chains of immunoglobulin. The domains consistently include hypervariable CDR regions with certain amino acid sequences. What is described is a method of growth inhibition of solid or haematological malignant proliferative diseases with using the pharmaceutical composition containing the IL-17-binding molecule.
EFFECT: antibodies under the invention are capable to block IL-17 action and are applicable for prevention and treatment of IL-17-mediated diseases, including for inhibition of solid or haematological malignant proliferative diseases.
5 cl, 4 tbl, 7 ex