Fusion serpine polypeptides and methods for their application

FIELD: biotechnology.

SUBSTANCE: invention relates to the field of fusion proteins for serine proteases inhibition, and can be used in medicine. Fusion proteins having at least one human alpha-1 antitrypsin (AAT) polypeptide operably linked to an immunoglobulin Fc polypeptide having an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:6 are obtained.

EFFECT: invention allows to obtain a fusion polypeptide capable of effectively inhibiting the activity of serine proteases and thereby alleviating the symptoms of diseases or disorders associated with overexpression or serine protease activity in a subject in need thereof.

18 cl, 4 dwg, 4 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology, specifically to novel hetero-multimeric proteins obtained from modified ubiquitin, and can be used in medicine to treat or diagnose diseases associated with hyperprodution of the extradomain B of fibronectin (ED-B). The protein includes two monomeric ubiquitin links which are differently modified through substitutions of at least 6 amino acids in positions 4, 6, 8, 62, 63, 64, 65 and 66 of SEQ ID NO: 1. In the first monomer link the substitutions include: F4W, K6(H, W or F), Q62N, E64(K, R or H), S65(L, F or W), T66(S or P), and in the second monomer link: K6(T, N, S or Q), L8(Q, T, N or S), Q62(W or F), K63(S, T, N or Q), E64(N, S, T or Q), S65(F or W), T66(E or D).

EFFECT: invention enables to obtain a modified heterodimeric ubiquitin protein, capable of binding with ED-B with high affinity.

28 cl, 18 dwg, 3 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to field of biotechnology and transplantation medicine and represents peptide with amino acid succession SEQ ID NO: 40. Peptide has ability to regenerate bone tissue and specifically bind with surface of apatite mineral.

EFFECT: peptide is able to be stably immobilised on apatite surface for preservation of useful activity and rendering influence on bone regeneration for long time.

9 cl, 3 dwg, 3 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to biotechnology. There are presented versions of a humanised anti-CD79b antibody, each of which is characterised by the presence of a light and heavy chain and a set of 6 CDR with a specified amino acid sequence and at least one free cysteine amino acid residue specified in A118C (according to the European Numeration) in the heavy chain and V205C (according to the Kabat numeration) in the light chain. There are disclosed: versions of a conjugate compound of the antibody and a drug preparation, wherein the antibody is bond to the drug preparation through free cysteine; an antibody-based pharmaceutical compound for treating cancer; method for detecting CD79b or cancer cells, as well as a method for inhibiting cell proliferation using the conjugate compound. What is described is a method for producing the conjugate compound.

EFFECT: invention can find further application in the therapy of CD79b-associated cancer diseases, including treating haemopoietic tumours in mammals.

70 cl, 20 tbl, 9 ex, 51 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to biotechnology, namely to novel IL-17-inhibiting polypeptides, corresponding to fused proteins, to compositions and their application for medicinal purposes. Polypeptide contains amino acid sequence, which is selected from group, consisting of GVTLFVALYD YKAFWPGDLS FHKGEKFQIL RTSDGDWWEA RSLTTGETGY IPSNYVAPVD SIQ (SEQ ID NO: 39), GVTLFVALYD YKAFWPGDIS FHKGEKFQIL RTSDGEWWVA RSLTTGEEGY IPSNYVAPVD SIQ (SEQ ID NO: 57) or GVTLFVALYD YKAFWPGDIS FHKGEKFQIL RTSDGEWWIA RSLTTGEEGY IPSNYVAPVD SIQ (SEQ ID NO: 107); amino acid sequence, which has, at least, 80%, preferably, at least, 90%, more preferably, at least, 95% identity of amino acid sequence with SEQ ID NO: 39, SEQ ID NO:57 or SEQ ID NO: 107; fragment or functional derivative of SEQ ID NO: 39, SEQ ID NO: 57 or SEQ ID NO: 107, obtained due to substitution, addition and/or removal of not more than 5 amino acids.

EFFECT: invention makes it possible to bind IL-17 with high specificity and affinity.

33 cl, 17 dwg, 3 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: presented group of inventions concerns fused proteins, nucleic acids coding these proteins, an expressing cartridge providing nucleic acid expression, a vector comprising this cartridge, a diagnostic technique for in vitro borreliosis, a kit for this diagnostic technique, which use these proteins, as well as a vaccine composition for preventing borreliosis containing these proteins. The characterised fused proteins contain (i) at least one sequence of DbpA protein of the species Borrelia specified in B. afzelii, B. burgdorferi sensu stricto and B. garinii, and (ii) least one sequence of OspC protein of the species Borrelia specified in B. afzelii, B. burgdorferi sensu stricto and B. garinii.

EFFECT: presented group of inventions enables performing more sensitive and specific analyses related to the presence of certain pathogenic species Borrelia.

11 cl, 8 tbl, 7 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: chemistry.

SUBSTANCE: inventions relate to chimeric proteins, nucleic acid, coding such a protein, an expression cassette, providing the expression of nucleic acid, a vector, including the expression cassette, a method of diagnostics and a set for diagnostics. The characterised chimeric Borrelia protein includes at least one sequence of an extracellular domain of the VlsE Borrelia protein of the first type, corresponding to a certain strain, and at least one sequence of IR6 area of the VlsE Borrelia protein of the second type or Borrelia of the first type, but corresponding to a strain, different from the strain of the first type, with Borrelia being selected from Borrelia stricto-sensu, Borrelia afzelii and Borrelia garinii.

EFFECT: claimed inventions make it possible to carry out diagnostics of Lyme-borreliosis with an increased specificity and sensitivity.

15 cl, 8 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biochemistry, in particular, to novel mutants of streptokinase. Claimed are both mutant streptokinase polypeptides and fusion proteins, possessing streptokinase activity. Claimed streptokinases are included into formulations of pharmaceutical compositions, suitable for treatment of blood circulation diseases, in particular thromboses.

EFFECT: invention makes it possible to obtain more effective mutant polypeptides with streptokinase activity in treatment of blood circulation diseases.

20 cl, 37 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of biochemistry, in particular to single variable domain, aimed against IL-6R, to polypeptide and construction, directed against IL-6R, containing said single variable domain, as well as to methods of obtaining them. Disclosed are nucleic acids, coding said single variable domain, polypeptide and construction, as well as genetic constructions, containing said nucleic acids. Described are host cells and host organisms, containing said nucleic acids. Invention also deals with composition for blocking interaction of IL-6/IL-6R, containing effective quantity of described single variable domain, polypeptide, construction, nucleic acid or genetic construction. Also disclosed is method of prevention and/or treatment of at least one of diseases or disorders, associated with IL-6, IL-6R, complex IL-6/IL-6R and/or signal pathways, in which IL-6, IL-6R or complex IL-6/IL-6R is involved and/or biological functions and reactions, win which IL-6, IL-6R or complex IL-6/IL-6R takes part with application of described single variable domain, polypeptide, construction or composition.

EFFECT: invention makes it possible to block interaction of IL-6/IL-6R effectively with increased affinity and biological activity.

25 cl, 70 dwg, 56 tbl, 61 ex

FIELD: biotechnologies.

SUBSTANCE: invention represents a combined recombinant protein of the formula: S-L-R, including SR10, SR13, SR15, SdR10, SdR13 or SdR15, which specifically recognises melanoma cells, where S - streptavidin monomer, L - linker having amino-acid sequence Ser-Arg-Asp-Asp-Asp-Asp-Lys containing a restriction site with enteropeptidase and marked as "d", or amino-acid sequence Ser-Arg-Ala-Gly-Ala,R - melanoma-addressing oligopeptide representing R10 having amino-acid sequence Asp-Gly-Ala-Arg-Tyr-Cys-Arg-Gly-Asp-Cys-Phe-Asp-Gly, or R13 having amino-acid sequence Leu-Ser-Gly-Cys-Arg-Gly-Asp-Cys-Phe-Glu-Glu, or R15 having amino-acid sequence Asp-Gly-Phe-Pro-Gly-Cys-Arg-Gly-Asp-Cys-Ser-Gln-Glu. This invention also describes recombinant plasmid DNAs pSR and pSdR for expression of the specified combined proteins, bacterial strains Escherichia coli MG1655/pSR and MG1655/pSdR, producers of the specified combined proteins and a producing method of melanoma-addressing oligopeptide R from combined recombinant proteins SdR10, SdR13 or SdR15.

EFFECT: invention allows producing combined proteins that provide selective and effective binding to receptors on the surface of melanoma cells and can be used in diagnostics and therapy of cancer of a human being.

9 cl, 7 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to the field of biotechnology. Claimed are versions of a humanised anti-CD79b antibody, each of which is characterised by the presence of a light and heavy chain and a set of 6 CDR with a determined amino acid sequence. An epitope of the antibody from 11 amino acids is determined by the Biacore method. Disclosed are: an immunoconjugate of the antibody with a medication or means for inhibiting cell growth, where the antibody is bound with means covalently, and versions of the composition, based on an effective quantity of the immunoconjugate or the antibody, used for inhibiting B-cell proliferation; as well as a method of determining CD79b in a sample with the application of the antibody. Described are: an antibody-coding polynucleotide, as well as an expression vector and an isolated cell, containing the vector for obtaining the antibody. Disclosed are versions of applying the antibody or immunoconjugate for obtaining the medication for inhibiting the growth of CD79b-expressing cells for the treatment of an individual, affected with cancer, for the treatment of proliferative disease or for inhibiting B-cell proliferation.

EFFECT: invention provides novel antibodies, which can find further application in the therapy of proliferative CD79b-associated diseases.

91 cl, 8 tbl, 9 ex, 20 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: presented invention refers to immunology. What is presented is a monoclonal anti-IFNAR1 antibodies with L234F, L235E and P331S Fc mutations of human IgG1 possessing a lower affinity to Fcgamma RI, Fcgamma RIIIA and c1q receptors as compared to a non-modified antibody. There are described the recovered nucleic acid providing expression of the above antibody containing a nucleotide sequence coding the antibody, and a pharmaceutical composition based on the above antibody.

EFFECT: using the invention provides the antibody possessing the lower affinity to Fcgamma RI, Fcgamma RIIIA and c1q receptors that provides reducing the undesired effector functions in treating chronic inflammation and autoimmune conditions.

9 cl, 34 dwg, 7 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of biochemistry, in particular to method of obtaining bivalent bispecific antibody, which includes transformation of host cell by vectors, containing molecules of nucleic acids, coding first light chain and first heavy chain of bivalent bispecific antibody, and vectors, containing molecules of nucleic acids, coding second light chain and second heavy chain of bivalent bispecific antibody, cultivation of host cell under conditions, providing synthesis of molecule of bivalent bispecific antibody from said culture. Said antibody contains first light chain and first heavy chain of antibody, specifically binding with first antigen, and second light chain and second heavy chain of antibody, specifically binding with second antigen, in which variable domains VL and VH of second light chain and second heavy chain are replaced by each other and constant domains CL and CH1 of second light chain and second heavy chain are replaced by each other.

EFFECT: invention makes it possible to increase output of correct bispecific antibody by increasing the level of correct heterodimerisation of heavy chains of wild type and modification of heavy chains resulting from crossing over.

2 cl, 31 dwg, 3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: present invention refers to immunology. Presented is a molecule of bispecific single-chain antibody containing a first binding domain able to bind to epitope of CD3-epsilon-chain of human and Callithrix jacchus (tamarin), Saguinus oedipus (cotton-top tamarin) and Saimiri sciureus (squirrel monkey), and a second binding domain able to bind to an antigen specified in a group consisting of: PSCA, CD19, C-MET, endosialin, EGF-like domain 1 EpCAM coded by exon 2, FAP-alpha or IGF-IR (or IGF-1R) or a human and/or a primate. The epitope CD3e contains an amino acid sequence disclosed in the description. Disclosed are a nucleic acid coding the above molecule of the bispecific single-chain antibody, an expression vector, a host cell and a method for producing the antibody, as well as the antibody produced by the method. Described is a based pharmaceutical composition containing the molecule of the bispecific single-chain antibody and a method for preventing, treating or relieving cancer or an autoimmune antibody. Presented is using the above molecule of the bispecific single-chain antibody for making the pharmaceutical composition for preventing, treating or relieving cancer or the autoimmune disease.

EFFECT: using the invention provides the clinical improvement in relation to T-cell redistribution, reducing it, and the improved safety profile.

23 cl, 74 dwg, 17 tbl, 33 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to immunology. What is presented is a polypeptide containing two binding fragments presented by antibodies; the first of them binds to CD3e(epsilon) chain epitope of a human or a primate, other than a chimpanzee, particularly Callithrix jacchus, Saguinus oedipus and Saimiri sciureus; the second one - to EGFR, Her2/neu or IgE of a human or a primate, other than a chimpanzee, with the above CD3e epitope containing the amino acid sequence Gln-Asp-Gly-Asn-Glu. There are also disclosed a coding sequence of the nucleic acid, a vector, a host cell and a method for preparing the above peptide, as well as a pharmaceutical composition and using the polypeptide in preventing, treating or relieving a proliferative disease, a malignant disease or an immunological disorder.

EFFECT: invention provides the clinical improvement of T-cell redistribution and the enhanced safety profile.

17 cl, 8 tbl, 26 dwg, 26 ex

FIELD: biotechnology.

SUBSTANCE: bispecific antibody is proposed, that binds to both the blood coagulation factor IX/activated blood coagulation factor IX and with the blood coagulation factor X, and functionally replaces the function of blood coagulation factor VIII. The nucleic acid is considered, encoding the antibody of the invention, a vector, a cell and a method of producing the antibody, and also a pharmaceutical composition and a kit for use in the method of preventing and/or treating bleeding or diseases associated with or caused by bleeding.

EFFECT: invention may find further application in the treatment of diseases associated with impaired blood clotting.

16 cl, 2 ex, 6 dwg

FIELD: chemistry.

SUBSTANCE: claimed is bispecific antibody, which is bound with both blood coagulation factor IX/activated blood coagulation factor IX and with blood coagulation factor X and functionally replaced function of blood coagulation factor VIII. Described are nucleic acid, coding antibody by invention, vector, cell and method of obtaining antibody, as well as pharmaceutical composition and set for application in method of prevention and/or treatment of bleeding or diseases, associated with or induced by bleeding.

EFFECT: invention can be applied in therapy of diseases, associated with blood coagulation disorders.

16 cl, 2 ex, 6 dwg

FIELD: medicine.

SUBSTANCE: what is presented is a fused protein that is a Notch1 antagonist, which consists of a human Fc region fused with the EGF-like repeat 1-13 of Notch1 or the EGF-like repeat 1-24 of Notch1. Fc-portion is localised on a carboxy-terminal portion of the EGF-repeat. There are described a pharmaceutical composition for the protein-based Notch signal transmission inhibition and using it for preparing the pharmaceutical composition for treating an individual suffering from: tumour; ovarian cancer; metabolic disorder; vascular proliferative retinopathy. What is presented is using the fused protein for producing the pharmaceutical composition for inhibition: angiogenesis in the individual; physiological lymphangiogenesis or pathological lymphangiogenesis in the individual; tumour deposits in the individual.

EFFECT: using the invention provides the proteins expressed in a supernatant at a level by several times more than the fused protein containing the EGF-like repeats 1-36 of Notch1; they penetrate into the tumour better, maintain a ligand-binding ability with the fused protein containing the repeats 1-24, binds to DLL4 and JAG1, whereas the fused protein containing the repeats 1-13 only binds to DLL4, but not to JAG1 that can find application in therapy of various diseases related to the Notch1 activity.

18 cl, 124 dwg, 10 ex

FIELD: medicine.

SUBSTANCE: inventions relate to the field of immunology. Claimed are a single-chain antibody, specific to a carcinoembryonic antigen, a chimeric mononuclear T-cell receptor, a vector, a host cell and a method of diagnostics or treatment of diseases, characterised by the presence of antigens, capable of binding with the chimeric receptor. Described is a genetic construction, coding chimeric monomolecular T-cell receptors, in which an effector fragment of the T-cell receptor is combined with an antigen-recognising part, which represents variable fragments of two different antibodies to the carcinoembryonic antigen (CEA).

EFFECT: claimed inventions can be used in T-cell cancer therapy.

7 cl, 4 dwg, 3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and immunology. What is presented is an antibody representing a neutralising VEGFR-2/KDR antibody with its hypervariable regions being identical to the hypervariable regions of TTAC 0001 of VEGFR-2/KDR antibody fused with a binding domain of angiopoietin 2 which is Tie-2 ligand for treating cancer by angiogenesis inhibition. A DNA coding the above antibody, an expression vector containing the above DNA, and a CHO host cell transformed by the above vector for preparing the antibody are also described. What is also presented is a method for preparing the antibody involving: host cell incubation, and the antibody recovery from a culture fluid of CHO cell. What is described is a pharmaceutical composition for treating an angiogenesis-related disease, containing an effective amount of the above antibody and at least one pharmaceutically acceptable carrier.

EFFECT: invention enables preparing the VEGFR-2/KDR antibody fused with the binding domain of angiopoietin 2 which may be used for effective treatment of a disease related to excessive angiogenesis.

13 cl, 10 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology, specifically to novel hetero-multimeric proteins obtained from modified ubiquitin, and can be used in medicine to treat or diagnose diseases associated with hyperprodution of the extradomain B of fibronectin (ED-B). The protein includes two monomeric ubiquitin links which are differently modified through substitutions of at least 6 amino acids in positions 4, 6, 8, 62, 63, 64, 65 and 66 of SEQ ID NO: 1. In the first monomer link the substitutions include: F4W, K6(H, W or F), Q62N, E64(K, R or H), S65(L, F or W), T66(S or P), and in the second monomer link: K6(T, N, S or Q), L8(Q, T, N or S), Q62(W or F), K63(S, T, N or Q), E64(N, S, T or Q), S65(F or W), T66(E or D).

EFFECT: invention enables to obtain a modified heterodimeric ubiquitin protein, capable of binding with ED-B with high affinity.

28 cl, 18 dwg, 3 tbl, 7 ex

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