Antibodies neutralising granulocytic macrophageal colony-stimulating human factor

FIELD: medicine.

SUBSTANCE: invention represents a human monoclonal antibody or its fragment which specifically binds with primate GM-CSF and neutralise it. There are also presented a polynucleotide molecule, a pharmaceutical composition, application of the monoclonal antibody.

EFFECT: invention may be used for neutralising higher or undesired activity of primate GM-CSF.

22 cl, 34 dwg, 5 tbl, 11 ex

 

The text descriptions are given in facsimile form.

1. Human monoclonal antibody or fragment that specifically associated with GM-CSF (granulocyte-macrophage colony-stimulating factor) primates and neutralize it, where the specified human monoclonal antibody or its fragment contains variable regions of its light chain region CDR1 containing the amino acid sequence as shown in SEQ ID NO:16, the region CDR2 having the amino acid sequence as shown in SEQ ID NO:17, and a CDR3 region having the amino acid sequence as shown in SEQ ID NO:18; and containing the variable region and heavy chain region CDR1, containing the amino acid sequence as shown in SEQ ID NO:14, a region CDR2 having the amino acid sequence as shown in SEQ ID NO:15, and a CDR3 region having the amino acid sequence as shown in any of SEQ ID nos:1-13 or 56.

2. Human monoclonal antibody or its fragment according to claim 1, where the specified human monoclonal antibody or its fragment contains variable regions of its light chain region CDR1 containing the amino acid sequence as shown in SEQ ID NO:16, the region CDR2 having the amino acid sequence as shown in SEQ ID NO:17, and a CDR3 region having the amino acid sequence as shown in SEQ ID NO:18; and containing a variable region heavy chain region CDR1 containing the amino acid sequence as shown in SEQ ID NO:14, a region CDR2, having the amino acid sequence as shown in SEQ ID NO:15, and a CDR3 region having the amino acid sequence as shown in any of SEQ ID NO:2.

3. Human monoclonal antibody or its fragment according to claim 1, which specifically binds to an epitope of GM-CSF of the primacy containing amino acids 23-27 (RRLLN) and amino acids 65-77 (GLR/QGSLTKLKGPL).

4. Human monoclonal antibody or its fragment according to claim 3, where the specified epitope additionally contain what it amino acids 28-31 (LSRD).

5. Human monoclonal antibody or its fragment according to claim 3 or 4, where the specified epitope further comprises amino acids 32-33 (TA) and/or amino acids 21-22 (EA).

6. Human monoclonal antibody or its fragment according to claim 3, where the specified epitope is a continuous epitope.

7. Human monoclonal antibody or its fragment according to claim 1, where the specified Primate is a human or a Primate, non-human.

8. Human monoclonal antibody or its fragment according to claim 7, where the specified Primate, non-human, is a macaque of having, macaque-rhesus or Gibbon.

9. The human monoclonal antibody according to any one of claims 1 to 8, where the aforementioned antibody is an IgG.

10. The human monoclonal antibody according to claim 9, where the specified IgG is an IgGl or IgG4.

11. Fragment of a human monoclonal antibody according to claim 1, where the specified fragment is an scFv, a single domain antibody, Fv, ditelo, tandem diatel, Fab, Fab' or F(ab)2.

12. Human monoclonal antibody or its fragment according to claim 1, where the specified human monoclonal antibody or its fragment optionally contain variable regions of its light chain amino acid sequence as shown in SEQ ID NO:19, 54 or 55.

13. Human monocle the social antibody or fragment according to claim 1, where the specified human monoclonal antibody or its fragment containing the variable region heavy chain amino acid sequence as shown in any of SEQ ID NO:20-33, 52 or 53.

14. The human monoclonal antibody according to claim 1, containing the amino acid sequence of the light chain as shown in SEQ ID NO:34, amino acid sequence of the heavy chain as shown in any of SEQ ID nos:35-48.

15. The human monoclonal antibody according to claim 1, containing the amino acid sequence of the light chain as shown in SEQ ID NO:34, amino acid sequence of the heavy chain as shown in SEQ ID NO:35.

16. Polynucleotide molecule encoding a human monoclonal antibody according to any one of claims 1 to 15.

17. Pharmaceutical composition having neutralizing activity against GM-CSF primates containing human monoclonal antibody or fragment according to any one of claims 1 to 15 or polynucleotide molecule according to item 16 in the amount effective to neutralize, and a pharmaceutically acceptable carrier.

18. The use of human monoclonal antibody or its fragment according to any one of claims 1 to 15 or polynucleotide molecule according to item 16 in the manufacture of a medicinal product may contain one or more than one additional protivovospalitel the first agent, for the treatment of inflammatory diseases.

19. Use p where specified inflammatory diseases selected from the group consisting of rheumatoid arthritis (RA) (including RA, which is resistant to treatment converters TNF (tumor necrosis factor)-alpha), asthma, multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), inflammatory bowel disease (IBD), uveitis, macular degeneration, colitis, psoriasis, Malerovskoj degeneration, antiphospholipid syndrome (APS), acute coronary syndrome, restenosis, atherosclerosis, recurrent polychondritis (RP), acute or chronic hepatitis, unsuccessful implantation of orthopedic implants, glomerulonephritis, lupus or autoimmune disorders.

20. The use of human monoclonal antibody or its fragment according to any one of claims 1 to 15 or polynucleotide molecule according to item 16 in the manufacture of a medicinal product may contain one or more than one additional anticancer agent, for treatment of neoplastic disease or other condition with delayed apoptosis and increased survival of cells or proliferation.

21. The application of claim 20, where the specified neoplastic disease is own the th cancer.

22. Use item 21, where the specified cancer is a leukemia, multiple myeloma, gastric carcinoma or carcinoma of the skin.



 

Same patents:

FIELD: medicine.

SUBSTANCE: there are offered: recovered polynucleotides and polypeptides for binding human EGFR as a part of an antibody, a vector and a host cell for antibody expression, a method for producing an anti-EGFR antibody and an antibody fragment, the anti-EGFR antibody and the antibody fragment. There are discussed a composition containing the anti-EGFR antibody or its fragment, as well as applying the antibody and its fragment for treating EGFR-associated disorders. Besides, there are described versions of glycosylation of the anti-EGFR antibody or its fragment.

EFFECT: invention can find further application in therapy of various EGFR-mediated diseases.

30 cl, 6 ex, 32 dwg, 39 tbl

FIELD: medicine, pharmaceutics.

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52 cl, 18 dwg, 11 tbl, 9 ex

FIELD: medicine, pharmaceutics.

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34 cl, 31 dwg, 5 tbl, 19 ex

FIELD: medicine.

SUBSTANCE: polypeptide (versions) immunogenic with respect to meningococcal infections contains: an amino acid sequence at least 90 % identical to a sequence presented in the description (SEQ ID NO: 32), or said amino acid sequence, or a fragment of 80 sequenced amino acids of said sequence. What is described is an antibody which contacts with the polypeptide under the invention and which may be used as a drug. What is described is nucleic acid of the preset structure which codes the polypeptide or its versions and which may be used for treating or preventing a disease and/or an infection caused by Neisseria meningitides. The invention provides additional polypeptides applicable in advanced vaccines for preventing and/or treating meningococcal meningitis. The peptides can also find application in diagnosing of the disease and as targets of antibiotics.

EFFECT: higher clinical effectiveness for meningococcal meningitis.

19 cl, 2 tbl

FIELD: chemistry, pharmaceutics.

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22 cl, 33 dwg, 8 tbl, 7 ex

FIELD: medicine.

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15 cl, 3 dwg, 5 tbl, 6 ex

FIELD: immunology and bioengineering.

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10 cl, 28 dwg, 9 tbl, 12 ex

FIELD: medicine.

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227 cl, 25 dwg, 16 tbl, 14 ex

FIELD: medicine.

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43 cl, 20 dwg, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of immunology and biotechnology. Claimed are: versions of antibody and antigen-binding fragments of antibody to receptor Il-6 of humans. Considered are: isolated molecule of nucleic acid and vector which contains it. Described are: system "host-vector" and method of obtaining antibody or its antigen-binding fragment, as well as application of antibody or its antigen-binding fragment for obtaining medication.

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11 cl, 5 tbl, 7 ex

FIELD: medicine, pharmaceutics.

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102 cl, 21 dwg, 8 tbl, 7 ex

FIELD: medicine.

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EFFECT: invention extends the range of anti-inflammatory agents.

39 cl, 4 tbl, 16 ex

FIELD: medicine, pharmaceutics.

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EFFECT: inventions ensure higher efficiency of treatment of immune-mediated diseases, due to novel polypeptide of interleukin17 (IL-17) family.

25 cl, 20 dwg, 9 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for local introduction on the surface of epithelial tissue barrier, which contains scFv-antibodies, which specifically bind selected antigens and can be obtained by the method, including (i) selection from pool of soluble and stable frames of antibodies of soluble and stable frame, corresponding in the best way to the frame of non-human antibody against antigen with definite binding specificity, (ii) either providing said soluble and stable frame of CDR which bind specifically with said antigen, either mutation of this frame of said non-human antibody in direction of sequence of said soluble and stable frame for generation of scFv-antibodies, (iii) testing generated antibody for solubility and stability, and testing generated antibody for antigen binding and (iv) selection of scFv-antibody, which is stable, soluble and specifically binds with this antigen.

EFFECT: invention ensures improved ability of composition penetration into tissue.

37 cl, 10 ex, 3 tbl, 19 dwg

FIELD: medicine.

SUBSTANCE: invention claims antibodies, which specifically bind with IL-13. Also claimed are nucleic acids, encoding antibodies, expression vectors, containing sequences of said nucleic acids, as well as cells, containing such cells. In addition claimed is method of diagnosing associated with IL-13 disorders, method of obtaining molecule of recombinant antibody, method of treating disorder, associated with IL-13 activity, method of determining IL-13 in sample and method of treating subject, demonstrating asthma attack.

EFFECT: invention can be efficiently applied in diagnostics and treatment of IL-13 mediated disorders.

116 cl, 16 dwg, 4 tbl, 21 ex

FIELD: chemistry.

SUBSTANCE: disclosed are antibodies which selectively neutralise bioactivity of at least two subtypes of interferon-alpha (IFNα) protein towards A, 2, B2, C, F, G, H2, I, JI, K, 4a, 4b and WA protein subtypes, and neutralise at least one bioactivity of IFNα protein subtype D. The invention also discloses application of the antibodies to prepare a medicinal agent. The invention also discloses a host cell producing the antibody and a hybridome. The disclosed antibodies are effective in detecting IFNα subtypes in a sample or tissue and/or for therapeutic application which involves treatment and/or amelioration in case of a disease associated with IFNα, such as SLE, lupus, type I diabetes, psoriasis, AIDS and graft-versus-host disease.

EFFECT: highly effective treatment.

37 cl, 17 dwg, 10 tbl, 11 ex

FIELD: medicine.

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

Immunoglobulins // 2429245

FIELD: chemistry.

SUBSTANCE: disclosed are antibodies which specifically bind the human Oncostatin M (hOSM) site II and inhibit reaction between hOSM and gp130. The invention also discloses a polynucleotide, a host cell, a vector, treatment methods and other uses of antibodies.

EFFECT: invention can be effectively used to treat diseases mediated by the reaction between hOSM and gp130.

31 cl, 52 dwg, 5 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: substance of the invention involves a humanised human osteopontin antibody containing a variable region of a heavy chain consisting of the amino acid sequence SEQ ID NO:1 and a variable region of a light chain consisting of the amino acid sequence SEQ ID NO:3. Furthermore, the invention involves a polynucleotide containing a sequence coding the variable region of the respective light and heavy chains of the humanised antibody, an expression vector containing polynucleotide, a host cell, a medicine, a method of producing the humanised antibody, a medicine for treating an autoimmune disease, a method of treating, and application of the humanised antibody for producing a pharmaceutical agent.

EFFECT: advantage of the invention consists in creation of the humanised antibody exhibiting improved activity or stability, than activity and stability of standard human osteopontin antibodies.

13 cl, 14 ex, 1 tbl, 16 dwg

FIELD: medicine.

SUBSTANCE: there are offered versions of antibodies and their antigen-binding IL-13, particularly human IL-13 specific fragments. There are described: a pharmaceutical composition, a pharmaceutical compound of the antibody, versions of coding and hybridising nucleic acids and expression vectors. There are offered versions of: cells and methods of producing the antibody, methods of treating IL-13 associated disorders. A method of IL-13 detection in a sample is described.

EFFECT: use of the invention provides new IL-13 antibodies with KD about 10-10 M which can be used for diagnosing, preventing or treating one or more IL-13 associated diseases.

87 cl, 37 dwg, 5 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to to new compounds of formula (1) or their pharmaceutically acceptable salts, optionally in the form of (1S)-isomers showing the properties of polo-like kinase (serine-threonine kinase) PLK1 inhibitor. In the compounds of formula (1) , R1 represents a halogen atom; a lower alkyl group having 1-2 carbon atoms, which can be substituted by 3 fluorine atoms; or a cyclopropyl group; R2 represents a hydrogen atom; one of R3 and R4 represents a hydrogen atom while the other one of R3 and R4 represents: a) a lower alkyl group substituted by NRaRb wherein each Ra and Rb, which can be identical or different, represent a lower alkyl group, or each Ra and Rb, which can be different, represent a hydrogen atom, a lower alkyl group or a cycloalkyl group having 3-6 carbon atoms wherein a cycloalkyl group can be substituted by one ore more substitutes which can be identical or different and specified in a group 1): a lower alkyl; b) a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; c) a lower alkyl group substituted by a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; d) a 6-member aromatic heterocyclic group specified in a pyridyl group wherein each of an aliphatic heterocyclic group and an aromatic heterocyclic group can be substituted by substitutes specified in a group 1) described above; R5 represents a hydrogen atom, a cyano group, a halogen atom or a lower alkyl group.

EFFECT: compounds can find application in treating oncological diseases.

10 cl, 4 dwg, 8 tbl, 42 ex

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