Method for malignant cell elimination
SUBSTANCE: what is described is a method for malignant cell elimination with the use of an effective amount of an immunotoxin with a common structure, containing a core unit of gelonin toxin and a one-chained antibody specifically targeted on a malignant cell. According to the invention, the immunotoxin can be an ingredient of a pharmaceutically acceptable composition. The immunotoxin can be delivered to the malignant cell by introduction into a cell of an immunotoxin-expressing construct which is a viral vector.
EFFECT: immunotoxins according to the invention exhibit lower antigenic specificity with preserved biological activity, therefore the method and the composition used in the method have substantial positive properties for a subject requiring such method.
12 cl, 11 dwg, 9 tbl, 6 ex
The text descriptions are given in facsimile form.
1. Way to destroy cancer cells, providing the cell an effective amount of immunotoxin containing crustal region of the toxin gelonin and single-chain antibody, which is specifically aimed at this malignant cell.
2. The method according to claim 1, where the immunotoxin contains SEQ ID NO:1.
3. The method according to claim 1, where the antibody is targeted to a tumor antigen.
4. The method according to claim 1, where the antibody is a murine antibody.
5. The method according to claim 1, where the malignant cell is a melanoma cell.
6. The method according to claim 5, where the 9.2.27 antibody contains or ZME-018.
7. The method according to claim 5, where the immunotoxin is scfvMEL-2018 or scfvMEL-2025.
8. The method according to claim 1, where the cell is in a patient.
9. The method of claim 8, where the immunotoxin is a pharmaceutically acceptable composition.
10. The method according to claim 1, where the immunotoxin is delivered into the cell by introducing into a malignant cell expressing constructs that can Express this immunotoxin.
11. The method according to claim 10, where expressing the construct is a viral vector.
12. The method according to claim 1, where the viral vector is an adenoviral vector, adeno-associated viral vector, hepatitis virus, herpes virus, lentivirus, retrovirus or vaccinia virus.
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
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: described is expression in plants of the mutant polypeptide of the CDK (CKI) inhibitor, having dominant-negative antagonistic activity towards wild-type CKI proteins.
EFFECT: high plant vigour, root mass and size of seeds, enhancement of plant growth at an early stage.
68 cl, 4 dwg, 3 tbl, 13 ex
SUBSTANCE: constructed are recombinant plasmid DNA pAUTL-GFP bearing a hybrid gene coding green fluorescent protein (GFP) and a signal sequence of autolysin from Chlamydomonas reinhardtii. The produced plasmid is used to transform an Agrobacterium strain. A suspension of the transformed agrobacterial cells in a logarithmic growth stage is incubated with cells of Chlorella microalgae for 14-16 hours A protein secretion level is evaluated by measuring fluorescence of a culture environment.
EFFECT: new compounds show effective biological properties.
2 cl, 1 dwg, 1 tbl, 2 ex
SUBSTANCE: plant material is treated with mutagen or is transformed with a polynucleotide structure, containing a sequence of nucleic acid coding mutant polypeptide of large subunit of acetohydroxyacidsynthase (AHASL).
EFFECT: plants acquire tolerance to wide range of herbicides.
74 cl, 2 dwg, 6 tbl, 4 ex
SUBSTANCE: invention refers to producing versions of group I Poaceae (holy grass) allergen, also can be used either for specific immunotherapy (hyposensitisation) of patients with grass pollen allergy, or for preventive immunotherapy of grass pollen allergies. The produced versions are characterised by Cys41 Ser, Cys57Ser, Cys69Ser, Cys72Ser, Cys77Ser, Cys83Ser and Cysl39Ser substitutes in a Phi p1 mature protein sequence. Also, a structure of the allergen versions can be presented with no fragments relevant to amino acid residues 1-6, 1-30, 92-104, 115-119, 175-185 and 213-220 or 1-6, 115-119 and 213-220 as a part of a primary sequence of Phi p1 mature protein.
EFFECT: invention allows producing a version of group I Poaceae allergen characterised lower IgE responsiveness as compared with common wild allergen and substantially maintained responsiveness to T-lymphocytes.
8 cl, 9 dwg, 2 tbl, 3 ex
SUBSTANCE: nucleus fractions are extracted from plant cells, from which histone cromatin proteins are extracted using ion-exchange chromatography with amberlite IRC-50 in discontinuous gradient of guanidine hydrochloride.
EFFECT: method enables profound study of molecular-genetic mechanisms of cell nucleus structures and the role of protein components in their organisation.
3 dwg, 1 tbl
SUBSTANCE: biologically active peptide WAMP-1 having the following amino acid sequence: Ala1-Gln2-Arg3-Cys4-Gly5-Asp6-Gln7-Ala8-Arg9-Gly10-Ala11-Lys12-Cys13-Pro14-Asn15-Cys16-Leu17-Cys18-Cys19-Gly20-Lys21-Tyr22-Gly23-Phe24-Cys25-Gly26-Ser27-Gly28-Asp29-Ala30-Tyr31-Cys32-Gly33-Ala34-Gly35-Ser36-Cys37-Gln38-Ser39-Gln40-Cys41-Arg42-Gly43-X, where X-Cys44 or Cys44-Arg45, expresses antimicrobial action.
EFFECT: peptide can be used for protection of plants and foodstuff against pathogenic fungi and bacteria.
3 dwg, 2 tbl, 4 ex
FIELD: genetic engineering.
SUBSTANCE: in a genetically transformed plant, activity of protein Rpi-blb2 is increased.
EFFECT: resistance of the plant to Oomycetes pathogens.
13 cl, 31 dwg, 8 tbl, 17 ex
SUBSTANCE: in plant expression is increased for at least one protein Bax inhibitor - 1 (BI1) in at least one vegetable tissue. At the same time expression in leaves epidermis is left mainly invariable. Plants are transformed by recombinant expression cassettes and vectors, which include sequence of nucleic acids that codes BI-protein under control of tissue-specific promoter, which mainly does not have activity in epidermis of leaves.
EFFECT: transformation provides for arrangement or improvement of resistance to at least one biotic or abiotic stress factor in plants, preferably to vegetable pathogens.
13 cl, 16 dwg, 7 tbl, 8 ex
SUBSTANCE: invention includes obtaining and applying the versions of allergens of 5 Pooideae group, which are characterised by decreased IgE reactivity in comparison to known wild-type allergens and at the same time by essentially retained reactivity in comparison to T-lymphocytes. Versions of allergens, as per the invention, do not have at least one section or a combination of sections corresponding to amino-acid sequence of sections Phl p5a 94-113 or 175-198, which is given in the description. Versions of allergens have been obtained by gene-engineering methods. In the invention is opened DNA molecule encoding the version of allergen, recombinant expression vector, host organism, expression version of allergen and method of obtaining the version of allergen by using the above described means. Such hypoallergic versions of allergens can be used as a remedy against allergies determined by allergens of 5 Pooideae group for specific immunotherapy (hyposensitisation) of the patients having grass pollen allergy or for preventive immunotherapy of grass pollen allergies by using pharmaceutical composition.
EFFECT: preparations based on versions of allergens, as per the invention, have decreased IgE reactivity and the retained reactivity in relation to T-lymphocytes.
12 cl, 17 dwg, 3 tbl
SUBSTANCE: into plant or its part it is introduced nucleic acid, which encodes product, capable to support plant of family Solanaceae and its posterity by stability against injury by oomycetes fungus Phytophthora infestans.
EFFECT: ability to potato and tomato kinds steady against buck eye rot.
28 cl, 26 dwg, 4 tbl, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics, and concerns applications of amphiphilic block copolymers for treating and preventing cancer, particularly by reduced cancer cell growth and proliferation rate. Besides, the amphiphilic block copolymers can be used for blocking of platelet and fibroblast growth factor linking with related receptors on a membrane. Preferential block copolymers contain a basic hydrophobic chain, preferentially a polypropylene oxide chain whereto there are attached at least two hydrophilic side chains, preferentially a polyethylene oxide chain with mean ethylene oxide making less than 80 % of said amphiphilic block copolymer and molecular weight of the basic hydrophobic polymeric chain making at least 2000 g/mol.
EFFECT: invention provides new chemotherapeutic polymer drug for various types of cancer, having an effect of reduced cancer cell proliferation rate.
18 cl, 13 dwg, 11 tbl