Human antibodies against human 4-1bb (cd137)

FIELD: medicine.

SUBSTANCE: human antibodies or their antigen-binding fragments are fully described, which specifically bind to human 4-1BB, and which provide for binding of human 4-1BB to human 4-1BB ligand. Antibody includes variable areas of light and heavy chains with amino-acid sequence, given in formula, and may in one of aspects represent IgG4 antibody. Invention presents polynucleotides, which code amino-acid sequences of heavy chain and light chain of monoclonal antibody. Pharmaceutical compositions are described for cancer treatment on the basis of monoclonal antibody or its fragment and method for treatment of disease in subject, which consists in introduction of therapeutically efficient amount of antibody to this subject.

EFFECT: antibodies of invention have agonistic activity and may be used for treatment or prevention of human diseases, such as cancer, infectious and autoimmune diseases.

10 cl, 24 dwg, 1 tbl, 3 ex

 

The text descriptions are given in facsimile form.

1. Monoclonal antibody, or antigennegative fragment that specifically bind to the 4-W containing the variable region of the light chain and the variable region of the heavy chain, characterized in that the variable region light chain contains CDR1, CDR2 and CDR3 shown in figure 4, and the specified variable region of the heavy chain contains CDR1, CDR2 and CDR3, is shown in figure 3.

2. Monoclonal antibody, or antigennegative fragment according to claim 1, characterized in that the light chain contains a variable region depicted in Figure 4, and the said heavy chain contains a variable region is shown in figure 3.

3. Monoclonal antibody specifically binding to the 4-W containing the light chain and heavy chain, characterized in that the light chain contains amino acid residues 21-236 SEQ ID N0:6, and the said heavy chain contains amino acid residues 20-467 SEQ ID:3.

4. Pharmaceutical composition for treating cancer containing the monoclonal antibody or its antigennegative fragment according to claim 1 and pharmaceutically priemel the range of the media.

5. Pharmaceutical composition for treating cancer containing the monoclonal antibody according to claim 3 and a pharmaceutically acceptable carrier.

6. A method of treating cancer in a subject, which consists in the introduction of a specified subject a therapeutically effective amount of monoclonal antibody or its antigennegative fragment according to claim 1.

7. Selected polynucleotide containing a nucleotide sequence that encodes the amino acid sequence of the heavy chain of the monoclonal antibody according to claim 3.

8. Polynucleotide according to claim 7, containing the nucleotide sequence of SEQ ID N0:1.

9. Selected polynucleotide containing a nucleotide sequence that encodes the amino acid sequence of the light chain of the monoclonal antibody according to claim 3.

10. Polynucleotide according to claim 9, containing the nucleotide sequence of SEQ ID N0:4.



 

Same patents:

FIELD: chemistry.

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

FIELD: chemistry, medicine.

SUBSTANCE: novel antibodies and fragments of human antibodies are bound with GDF-8 in a specific way and inhibit its activity in vitro and/or in vivo. On the basis of said invention pharmaceutical composition is created, which can be used for diagnostics, prevention or treatment of degenerative dysfunctions of muscle or bone or disorders of insulin metabolism.

EFFECT: extending range of arsenal of technical means used in treatment of diseases related to muscular, bone tissue or insulin metabolism.

FIELD: medicine.

SUBSTANCE: polypeptides include single-domain antibody against vWF, A1 domain of vWF, A1 domain of activated vWF, A3 domain of vWF, gp1b and/or collagen. Invention claims methods of obtaining indicated polypeptides, methods of coating devices applied in medical practice (e.g. in X-ray structural analysis, endoprosthetics) with indicated polypeptides.

EFFECT: obtainment of polypeptides for treatment of diseases requiring modulation of thrombocyte-mediated aggregation.

40 cl, 69 ex, 30 dwg, 32 tbl

FIELD: biotechnology.

SUBSTANCE: present invention relates to biotechnology and immunology. Proposed here is a polynucleotide, encoding a cyclic single-stranded tri-specific antibody. The antibody is directed against human ovarian carcinoma in vitro, has mass of approximately 84 kD and consists of three components: an antibody against human ovarian carcinoma cells, anti-CD3 antibody and anti-CD28 antibody, which are joined together by peptide interlinks such that, they form a cyclic antibody. Invented is an expression vector, containing a coding polynucleotide and versions of E.coli host cell based on the polynucleotide and expression vector.

EFFECT: use of the invention provides for a stable antibody molecule, optimum for activation of T-cells, which can be used in curing human ovarian carcinoma.

8 cl, 12 dwg

FIELD: biology; biotechnology.

SUBSTANCE: invention concerns biotechnology. It claims linking molecule represented by monoclonal antibody or its fragment capable of binding human NogoA polypeptide, human NogoA 623-640. Polynucleotide encoding the claimed molecule is presented. Expression vector including indicated polynucleotide is described. Host cell including indicated polynucleotide or vector is described. Pharmaceutical composition for treatment of diseases related to nerve reconstruction and containing indicated molecule is described.

EFFECT: obtainment of antibodies capable of binding NogoA 623-640.

9 cl, 1 dwg, 3 tbl, 7 ex

FIELD: medicine; bioengineering.

SUBSTANCE: are offered variants of antibodies, specifically recognizing two regions of peptide β-A4, characterised by amino-acid residual list. The first region of recognised peptide contains amino-acid sequence AEFRHDSGY or fragment thereof, while the second region contains amino-acid sequence VHHQKLVFFAEDVG or fragment thereof. Described are nucleic acid molecules coding molecules of antibodies, offered in invention, vectors and hosts containing specified nucleic acid molecules. Discovered are methods of antibodies production and optimisation, pharmaceutical compositions based on specified antibodies and method of production thereof, as well as antibodies-based set and various applications of antibodies. Invention application provides high-avidity antibodies of peptide β-A4 that can be applied for diagnostics of various peptide β-A4 mediated diseases.

EFFECT: efficient application of compositions.

29 cl, 15 dwg, 10 tbl, 16 ex

FIELD: biochemistry.

SUBSTANCE: invention refers to antibodies that link with CTGF. Antibodies, in particular, are directed to the areas of CTFG participating in different types of biological activity related to fibrosis. The invention also refers to the method of antibodies application in pharmaceutical compositions for the treatment of CTGF-related diseases including localised and systemic fibrotic diseases such as diseases of lungs, liver, heart, skin and kidneys, for neutralisation of biological activity of CTGF and method of treatment and prophylaxis of CTGF-related diseases. The invention covers polynucleotide sequence and its variants coding the specified antibody as well as the host cell and cell line № PTA-6006 (ATCC) producing the specified antibody.

EFFECT: use of the invention provides new specific means - antibodies which effectively neutralise certain types of CTGF activity in pathology and provide specificity and pharmacokinetic profile suitable for a therapeutic agent.

82 cl, 33 dwg, 4 tbl, 12 ex

FIELD: bioengineering.

SUBSTANCE: versions of the molecule binding CD45RO and CD45RB, and the anti-CD45RO and anti-CD45RB antibody are invented. In one of versions, the said molecule contains at least one antigen-binding site and includes the subsequently located hypervariable sites CDR1, CDR2 and CDR3. The molecule represents the humanised or monoclonal antibody. CDR1 has the amino acid sequence NYIIH, CDR2 has the amino acid sequence YFNPYNHGTKYNEKFKG and CDR3 has the amino acid sequence SGPYAWFDT. The molecule can additionally contain the subsequently located hypervariable sites CDR1', CDR2' and CDR3'. CDR1' has the amino acid sequence RASQNIGTSIQ, CDR2' has the amino acid sequence SSSESIS and CDR3' has the amino acid sequence QQSNTWPFT. In another version, the molecule contains both heavy and light chains where the amino acid sequences contain the corresponding CDR. The versions of the corresponding coding polynucleotide are disclosed; expression vector and based on it expression system. The host cell is disclosed basing on the expression system. The application of the molecule in treatment of autoimmune diseases, graft rejection, psoriasis, intestine inflammatory disease and allergy is described. The pharmaceutical composition for the said application is disclosed.

EFFECT: enables immunosuppressant induction; inhibiting T-cell response and primary lymphocyte response in mixed lymphocyte culture (MLC); prolongs survival period in mice with severe combined immunodeficiency SCID.

20 cl, 5 dwg, 2 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: described humanised and chimeric CD20 antibodies are designed for treatment of CD20-positive malignant and autoimmune diseases. Antibody is effective with respect to depletion of B-cells of mammals in vivo, contains in variable region of H-chain of CDR3- sequence from antibody to human CD20 and practically all remains of consensus frame region (FR) of human H-chain of subgroup 111. According to invention antibody is used in composition or product, binding CD20. Besides, antibody is used for apoptosis induction, treatment of CB20-positive cancer, autoimmune disease, and rheumatic arthritis. Invention contains nucleic acid (NA) coding antibody, expression vector containing specified NA, and host cell producing recombinant antibody, as well as method of specified antibody production. According to invention antibodies are characterised by minimum antigenicity or no antigenicity at all, that enables to use them for continuous treatment overcoming limits of existing therapeutic compositions application.

EFFECT: enables to use for continuous treatment.

83 cl, 32 dwg, 12 tbl, 16 ex

FIELD: medicine, molecular biology, antibodies.

SUBSTANCE: invention relates to an antibody raised against CCR5 and comprising: (i) two light chains wherein each light chain comprises product of plasmid expression and designated as pVK:HuPRO140-VK (ATCC - PTA-4097), and (ii) two heavy chains wherein each heavy chain comprises product of plasmid expression and designated as pVg4:HuPRO140 HG2-VH (ATCC - PTA-4098), or plasmid designated as pVg4:HuPRO140 (mut B+D+I)-VH (ATCC - PTA-4099), or fragment of such antibody binding with CCR5 on a human cell surface. Invention relates to nucleic acid encoding light and heavy chains of antibody, expression vector, cell-host transformed with at least one vector, and a method for preparing antibody. Antibody is used as an active component in composition used for inhibition of infection of cells CD4 + HIV-1, and to a pharmaceutical composition used in treatment of a patient with HIV-1 infection. Also, invention relates to antibody conjugate against CCR5 and its using. Use of antibodies provides enhancing effectiveness of prophylaxis and treatment of HIV-1 infection.

EFFECT: valuable medicinal properties of antibody.

31 cl, 23 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: method is suggested for production of antibody for binding to NK-cells, which crossly interacts with products of gene KIR2DL1 and KIR2DL2/3 and neutralises inhibitor activity of such KIR. Mentioned method includes selection of such antibodies that crossly interact at least with products of gene KIR2DL1 and KIR2DL2/3, are able to restore lysis with NK cells Cw3+ or Cw4+ target cells and are bound with NK cells or polypeptide of KIR primate. Antibodies produced by this method are described, as well as their derivatives, where antibody is linked with toxin, radionuclide, recognisable aggregation, solid carrier or polyethylene glycol.

EFFECT: invention provides for preparation of single type of antibodies, which controls activity of NK cells of various type, provides for amplification of their cytotoxicity, which may find application in therapy, for increase of activity or cytotoxicity of NK cells in individuals without preliminary detection of HLA type in individual.

7 cl, 13 dwg, 4 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: there is described a humanised CD4 antibody or its fragment able to activate regulatory CD25+CD4+ T-cells, which includes complementarity-determining regions (CDRs) of mice monoclonal CD4 B-F5antibody. There is offered medicinal composition for prevention and/or treatments of dysimmunity containing described antibody or its fragment in effective amount. There is disclosed method of treating a person that implies introduction of the offered composition to said person. The described antibody is able to activate regulatory CD25+CD4+ T-cells.

EFFECT: described antibody can be used for preparing immunosuppressive compositions.

16 cl, 14 dwg, 4 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention concerns obtainment of cells of monocyte origin, inducing transplant acceptance, expressing antigens CD3 and CD14, and can be applied in transplantology. Monocytes are extracted from blood, reproduced in cultural medium with 1-20 mcg/l of cell growth factor M-CSF and cultivated for 24-72 hours in cultural medium with 0.1-20 ng/ml of interferon γ-IFN. Further the cells are extracted from cultural medium. For cell CD3 and CD14 expression antibodies produced by hybridoma DSM ACC2542 are used. If necessary, obtained cells are suspended and freezed.

EFFECT: obtainment of cells of monocyte origin, inducing transplant acceptance and suppressing transplant rejection reaction.

26 cl, 29 dwg, 1 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: there is provided an antibody that binds with human IL-1R and inhibits binding human IL-1 with IL-1R. The antibody is produced from hybridoma cells of line DSM ACC 2601 or it represents chimeric, humanised or with eliminated T-cell epitope version of the specified antibody or its fragment. Antibodies inhibit secretion IL-8 and IL-6 in cells of human fibroblast of line type MRC5 (ATCC CCL 171), mediated by IL-1, with 1C50 4-35 pM.

EFFECT: application of the invention provides antibody, that does not possess significant function ADCC and CDC, it can be applied for inflammatory disease treatment.

8 cl, 17 dwg, 3 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: there described are antibodies to P-selectin and namely antibodies to P-selectin and their versions which include Fc-portion of human origin and do not bind Clq complement factor. There specified is pharmaceutical composition containing the above antibody.

EFFECT: possibility of being used for treatment of the patient suffering critical ischemia of limbs or occlusive disease of peripheral arteries(CIL/ODPA).

4 cl, 10 dwg, 6 tbl

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: medicine.

SUBSTANCE: invention refers to medicine and biotechnology area and concerns antibody polypeptides ensuring monovalent binding of CD40L. Substance of the invention involves antibody polypeptides ensuring monovalent binding of CD40L and can inhibit activity of CD40L while allowing avoiding potential undesirable results of application of antibodies able for bivalent and multivalent binding of CD40L. In one perspective, polypeptide of monovalent anti-Cd40L antibody consists of, or contains single variable immunoglobulin domain which specifically binds and inhibits activity of CD40L, preferentially to a wide extent not stimulating activity of CD40 and/or CD40L. In the other perspective, polypeptide of monovalent anti-Cd40L antibody represents human antibody polypeptide. The present invention also involves methods of CD40/CD40L interaction inhibition in a human organism and therapies of diseases or disorders involving CD40/CD40L interactions, including introduction to a patient of polypeptide of monovalent anti-CD40L antibody.

EFFECT: advantage of the invention consists in higher specificity.

73 cl, 9 ex, 13 dwg

FIELD: medicine.

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

FIELD: biotechnology.

SUBSTANCE: described is an antibody, which bonds IGF-IR and inhibits bonding of IGF-I and IGF-II with IGR-IR. The given antibody has the following characteristics: a) IgGI isotype; b) ratio of IC50 for inhibiting bonding of IGF-I with IGF-IR to inhibition of bonding of IGF-II with IGF-IR is 1:3-3:1; c) in concentration of 5 nM, it inhibits phosphorylation of IGF-IR by at least 80%, and d) does not have IGF-IR stimulating activity. A method is proposed for producing the said antibody. Invented is a pharmaceutical composition, which has anticancer activity and contains the said antibody. A method is described for producing the said pharmaceutical composition. Cell lines are presented with hybrid <IGF-IR> HUMAB Clone 18 (DSM ACC 2587) and <IGF-IR> HUMAB Clone 22 (DSM ACC 2594), which produce the said antibody. An expression vector is described, which contains nucleic acid, which codes the described antibody.

EFFECT: invention allows for producing a human antibody, which can be used in anticancer therapy.

11 cl, 15 dwg, 2 tbl, 16 ex

FIELD: chemistry.

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

FIELD: medicine.

SUBSTANCE: invention is related to compounds of formula I , or its pharmaceutically acceptable salt of this, in which: R1 means C1-6-aliphatic group, besides, R1 may be substituted with substituents in number of up to 2 groups, independently selected from -OR or -C1-3 halogenalkyl; each R independently means hydrogen or C1-4-aliphatic group; R2 means R, fluorine or chlorine; m means 0, 1 or 2; and R3 means hydrogen, C1-3-aliphatic group, fluorine or chlorine, to composition for inhibition of activity of protein kinase ERK1 or ERK2, on the basis of these compounds, to method for inhibition of activity of protein kinase ERK1 or ERK2, and also to use of compounds of formula I or composition on their basis, for treatment or reduction of disease severity.

EFFECT: new compounds are produced and described, which may be used as inhibitors of protein kinases.

11 cl, 7 ex, 3 tbl

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