Genetic nucleotide sequences of artificially modified gdnf with deleted pro-region, product of which has improved properties neural inductor and stimulator of formation of neural processes, suitable for therapy of neural injuries, ischemic strokes and neurodegenerative diseases, expression vector, modified with gdnf

FIELD: biochemistry.

SUBSTANCE: invention relates to biochemistry. Disclosed is cDNA of natural GDNF gene artificially modified by removal of pro-region, which in mammalian cells or tissues in standard vectors produces active specific GDNF. Invention also relates to an expression vector containing said cDNA, as well as to active specific GDNF encoded by said cDNA. During translation in cells and tissues said GDNF stimulates neural differentiation of stem and progenitor cells with formation of neural processes.

EFFECT: invention increases activity of GDNF as neural inductor and stimulator of formation of neural processes and can be used in therapy of neurodegenerative disorders, traumatic disorders of innervation as well as ischemic cerebral apoplexies of mammals, including humans.

3 cl, 13 dwg, 5 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to field of biotechnology, namely to internalisation of therapeutic molecules into cell, and can be applied in medicine. Obtained is composition for delivering molecules of nucleic acids into cells, containing at least one peptide with at least 92% identity to GAAEAAARVYDLGLRRLRQRRRLRRERVRA (SEQ ID NO: 2); IREIMEKFGKQPVSLPARRLKLRGRKRRQR (SEQ ID NO: 3); or YLKVVRKHHRVIAGQFFGHHHTDSFRMLYD (SEQ ID NO: 4), bound to one or several molecules of nucleic acids.

EFFECT: invention makes it possible to increase efficiency of delivery of molecules of nucleic acids into mammalian cell due to peptide, capable of internalisation into mammalian cell with efficiency, constituting at least 200% of efficiency of internalisation of peptide TAT, which has amino acid sequence GRKKRRQRRRPPQ (SEQ ID NO: 1).

8 cl, 16 dwg, 1 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to methods for the treatment or prevention of diseases, caused by the neovascularisation of the human choroid (neovascular maculopathy), as well to pharmaceutical compositions, containing as an active ingredient at least one peptide from peptides, containing an amino acid sequence, obtained from VEGF-receptor 1 protein, and possessing activity to induce cyctotoxic T-cells in the presence of antigen-presenting cells and at least one peptide from peptides, containing an amino acid sequence, obtained from VEGF-receptor 2 protein and possessing activity to induce cyctotoxic T-cells in the presence of antigen-presenting cells or polynucleotides that code them, where cells of the vascular epithelium, involved into the neovascularisation of the human choroid, express VEGFR-1 receptor protein on the surface of cells.

EFFECT: group of inventions is effective in the treatment or prevention of diseases, caused by the neovascularisation of the human choroid (neovascular maculopathy).

36 cl, 19 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology. A disclosed polypeptide having the amino acid sequence which has a sequence identity of not less than 80% to the amino acid sequence shown in SEQ ID NO: 1 or 2, revealed in description, which polypeptide has a capable of expressing the polynucleotide activity. Also a polynucleotide encoding D-lactate dehydrogenase originated from DNA construct in which the polynucleotide and a promoter capable of expressing the polynucleotide are linked is introduced. Also described a transformant for production of lactic acid, or transformed yeast, in which the polynucleotide or the DNA construct is introduced. A method of producing D-lactic acid, which comprises the step of culturing the said transformant.

EFFECT: transformant capable of highly producing D-lactic acid compared to the D-lactic acid produced with host cell.

15 cl, 2 dwg, 4 tbl, 13 ex

FIELD: biotechnology.

SUBSTANCE: method comprises immunoaffinity chromatography using mini-antibodies a-hLF-1 and a-hLF-4, which amino acid sequences are presented as SEQ ID NO:1 and SEQ ID NO:2. The invention may be used to obtain highly purified fraction of human lactoferrin.

EFFECT: invention enables to carry out with high efficiency the separation of proteins of lactoferrin of human and goat consisting in milk, using the single-domain mini-antibodies.

6 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to biotechnology and can be used for recombinant production of human tissue factor (hTF). Constructed is a plasmid pHYP-10ETFCS6 having a length of 5,912 b.p. with a physical map presented on Fig. 2, for expression in a bacterium of the genus Escherichia, which is a precursor of the mutant [C245S] hTF containing an inseparable N-terminal leader peptide containing a deca-histidine cluster and an enterokinase identification sequence fused in a frame with a sequence coding the above mutein fused in the frame with the sequence coding the additional inseparable C-terminal peptide containing the deca-histidine cluster. A method for producing the precursor of the mutein[C245S]hTF contains culturing the producing bacterium in a nutrient medium, recovering inclusion bodies, solubilising the precursor protein, performing a metal chelator chromatography in the denaturation environment, re-folding and diafiltration of the protein solution. A method for producing the mature mutein[C245S] hTF involves detecting the N-terminal leader peptide from the above mutein precursor with using enterokinase and recovering the target protein.

EFFECT: invention enables increasing the level of biosynthesis and yield of pro-coagulation active hTF.

9 cl, 5 dwg, 1 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of biotechnology, namely to obtaining oligopeptide compounds, containing a motive, interacting with a proliferating cell nuclear antigen (PCNA) and can be used in medicine. The oligopeptide compound consists of 14-70 amino acids and contains. a PCNA-interacting motive, representing [K/R]-[F/Y/W]-[L/I/V/A]-[L/I/V/A]-[K/R], at least one signal sequence of nuclear localisation and at least one signal sequence of penetration into a cell, with the PCNA-interacting motive being located towards an N-end relative to the signal sequence.

EFFECT: invention makes it possible to carry out the efficient treatment of hyperproliferative disorders by the application of the oligopeptide compound in cyctostatic therapy or in radiotherapy as a sensitising substance.

34 cl, 6 dwg, 4 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to antibodies including human antibodies and their antigen-binding portions, which specifically bind to CCR2, in particular to human CCR2, and can act as CCR2 inhibitors. Anti-CCR2 antibodies are those binding to first and/or second extra-cellular CCR2 loops. The present invention also refers to human anti-CCR2 antibodies and to their antigen-binding portions. The present invention refers to the recovered heavy and light chains of immunoglobulin initiated from human anti-CCR2 antibodies, and to nucleic acid molecules coding such immunoglobulins. The present invention also refers to methods for preparing human anti-CCR2 antibodies and their antigen-binding portions, to compositions containing such antibodies or their antigen-binding portions, and to methods for using antibodies and their antigen-binding portions, and compositions for diagnosing and treating.

EFFECT: invention refers to methods for gene therapy with the use of nucleic acid molecules coding molecules of heavy and light chains of immunoglobulin, wherein the above molecules contain anti-CCR2 antibodies and their antigen-binding portions.

25 cl, 24 dwg, 8 tbl, 17 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, specifically to a fused protein containing a variant of rodostomin, and can be used in medicine. An ανβ3 integrin selective polypeptide consisting of an amino acid sequence SEQ ID NO:1 conjugated on the N terminal by a linker amino acid sequence containing a combination of the amino acids glycine and serine with a variant of a human serum albumin (HSA) with SEQ ID NO:4.

EFFECT: invention enables the higher therapeutic effectiveness in the diseases related to ανβ3 integrin.

12 cl, 14 dwg, 2 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and immunology. Presented are antibodies targeting integrin α2β1 containing humanised anti-integrin alpha-2 (α2) antibodies, as well as a method of treating by the integrin α2 antibodies. The humanised integrin α2 antibodies comprise a variable region of a light chain domain, a constant human light chain domain and a variable constant heavy chain domain of human IgG1, which exhibit the altered effector function. The variable constant heavy chain domain of human IgG1 comprises an S324N substitution. The invention can be used in medicine.

EFFECT: antibodies exhibit complement-dependent cytotoxicity, improved antibody-dependent cell-mediated cytotoxicity and improved CDC and ADCC.

33 cl, 3 dwg, 1 tbl, 2 ex

Siglec-15 antibody // 2539790

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and immunology. What is described is a pharmaceutical composition used for treating and/or preventing pathological bone metabolism and containing this antibody. The invention can be used in medicine.

EFFECT: antibody and its functional fragment specifically recognising human Siglec-15 and possessing the osteoclast inhibitory activity are described.

73 cl, 57 dwg, 4 tbl, 33 ex

FIELD: biotechnologies.

SUBSTANCE: physiologically active protein or polypeptide are fused with version of alpha-1-antitrypsin, which has at least one mutated aminoacid residue. Mutations are performed in the following positions: asparagine residue instead of proline residue in position 357; or asparagine residue instead of proline residue in position 357 and threonine residue instead of serine in position 359; or asparagine residue instead of proline residue in position 357 and serine residue instead of cysteine in position 232; or asparagine residue instead of proline residue in position 357, threonine residue instead of serine in position 359 and serine residue instead of cysteine in position 232.

EFFECT: invention allows increasing half lifetime of physiologically active protein or polypeptide in vivo by maintaining its stable circulation in blood.

7 cl, 13 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of biotechnology, namely to method of obtaining purified recombinant GDF-5-like protein. Method includes destruction of E.coli cells by homogeniser of high pressure at pressure of destruction from 800 to 900 bar. Inclusion bodies are separated from destructed cells E.coli by centrifugation. Separated inclusion bodies are processed with denaturate buffer, which contains carbamide and L- arginine, for solubilisation. Solubilised monomer of recombinant GDF-5-like protein is purified by centrifugation and chromatography.

EFFECT: invention makes it possible to obtain purified recombinant GDF-5-like protein with high output.

7 cl, 10 dwg, 2 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to molecular biology, specifically proteins regulating cell differentiation by Wnt family protein inhibition and may be used in medicine for prevention and treatment of the diseases caused by disturbed Wnt signal path activity. e.g. colon cancer, melanoma, carcinoma.

EFFECT: invention enables blocking a signal path activated by the Wnt8 family factor in the animal cells by the introduction of nogginI or noggin2 protein into tissue containing Wnt8 protein in the amount effective for Wnt8 activity inhibition.

3 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biochemistry. A method of cleaning thrombin solution from infectious particles is provided. Macromolecules are added to the starting thrombin solution. The obtained solution is then passed through a nanofilter to obtain a thrombin solution free from infectious particles. Said macromolecule is not a nonionic surfactant, is different from thrombin and can be selected from a polymer containing at least 3 monomers of sugar, amino acids, glycols, alcohols, lipids or phospholipids. A thrombin-containing solution obtained using said method is also provided.

EFFECT: invention increases efficiency of removing infectious particles from thrombin solution; thrombin output reaches 93% using said method.

20 cl, 2 dwg, 13 tbl

FIELD: medicine.

SUBSTANCE: peptide is described by general formula I: X1-X2-X3-X4-X5 (I) where XI represents Q or V; X2 represents P; X3 represents G or (β-A); X4 represents R, or X4 represents K with X1-Q or with X1-V and X3-(p-A); X5 represents G, where G is glycine, (β-A) is β-alanine, P is proline, V is valine, Q is glutamine, K is lysine, R is arginine.

EFFECT: invention presents extended range of effective therapeutic agents involved in liver regeneration.

4 dwg, 1 tbl, 3 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: present invention relates to molecular biology and can be used in designing agent and methods of modulating body functions associated with HGF/c-met signalling pathway. The invention discloses HGF/c-met polypeptide-antagonists which are mutant forms of HGF which contain a mutation in the N-terminal part of the β-chain and/or in its dimerisation part. The disclosed polypeptides have lower biological activity compared to wild type HGG and can be used in modulating activity of c-met, cell proliferation, cell migration and angiogenic cell activity.

EFFECT: invention describes a method of obtaining HGF muteins using DNA recombinant technology and agents which are necessary for its existence.

22 cl, 8 dwg, 1 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention pertains to biotechnology. In particular, the invention relates to an Escherichia coli BL21 (pVEGF-A165) strain and can be used to produce a vascular endothelial growth factor - GST-VEGF-A165 protein. A novel Escherichia coli BL21 (pVEGF-A165) cell strain is obtained, which is transformed by the pGEX-VEGF-A165 plasmid. This strain produces a recombinant GST-VEGF-A165 protein.

EFFECT: invention enables to obtain a Escherichia coli BL21 (pVEGF-A165) strain which is stably transformed by plasmid which codes VEGF, and which secrete this factor in extracellular space when cultured in vitro.

3 dwg, 4 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to molecular biology, specifically to proteins which regulate cell differentiation through inhibition of the TGF-beta cell superfamily. The invention is aimed at treating and preventing diseases related to human VgI orthologs. Noggin2 protein which contains VgI protein is injected into tissue in amount which is efficient for inhibiting VgI activity.

EFFECT: invention enables to solve the task of blocking the signal path activated by the TGF-beta factor of VgI in aniamal cells.

2 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: invention refers to biotechnology, specifically to Noggin2 proteins and can be used in medicine. The signalling cascade activin is blocked by introducing Noggin2 in an organism, tissue or cell in amount effective to inhibit or decrease activin activity.

EFFECT: invention allows blocking effectively activity of protein activin.

2 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns angiogenesis-preventing immunotherapy. Invention substance includes immunogenic compositions for treatment of disorders associated with angiogenesis intensification, containing oligonucleotides, coding polypeptides VEGFR2, introduced as a part of plasmid or viral vectors, as well as polypeptides VEGFR2, oligonucleotides, coding autologous VEGF with damaged function of receptor activation, polypeptides VEGF and their combinations. Immunogenic compositions can be used for treatment of malignant neoplasms and metastasises, at benign neoplasm and chronic inflammatory and autoimmune diseases. Advantage of invention lies in humoral and cellular immunity induction by means of specified compositions.

EFFECT: development of effective method angiogenesis preventive immunotherapy.

19 cl, 11 ex, 7 tbl

FIELD: biotechnology, molecular biology, medicine, genetic engineering, pharmacy.

SUBSTANCE: the hemopoietic protein comprises the amino acid sequence of the formula: R1-L1-R1, R2-L1-R1, R1-R2 or R2-R1 wherein R1 represents the modified ligand flt-3; R2 represents the modified human IL-3, the modified or unmodified colony-stimulating factor. Modification of R1 is carried out by addition of N-end with C-end directly or through linker (L2) that is able to join N-end with C-end to form new C- and N-ends. The modified human IL-3 is prepared by replacing amino acids at positions 17-123. The human G-CSF is modified by exchange of amino acids. The hemopoietic protein is prepared by culturing cells transformed with vector comprising DNA that encodes the hemopoietic protein. The hemopoietic protein stimulates producing hemopoietic cells and this protein is used as a component of pharmaceutical composition used in treatment of humans suffering with tumor, infectious or autoimmune disease. Invention provides preparing multifunctional hemopoietic proteins eliciting the enhanced activity with respect to stimulation of hemopoietic cells and eliciting the improved physical indices. Invention can be used for preparing chimeric multifunctional hemopoietic proteins.

EFFECT: improved preparing and producing method, valuable medicinal properties of protein.

22 cl, 19 dwg, 18 tbl, 117 ex

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