Cd20 binding polypeptide compositions

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and is meant for treating CD20 expressing tumours. A CD20 antibody molecule merged with a IL2 molecule is disclosed. The antibody contains modified variable parts of a heavy and a light chain. Disclosed also is a pharmaceutical composition for treating a CD20 expressing tumour, which contains a merged polypeptide of the CD20 antibody, as well as a DNA molecule which codes the said merged polypeptide.

EFFECT: invention enables to lower immunogenicity of the modified anti-CD20 antibody compared to unmodified molecules and increase anti-tumour activity with respect to CD20.

15 cl, 17 dwg, 3 tbl, 8 ex

 

The text descriptions are given in facsimile form.

1. Molecule antibodies to CD20, merged with the IL2 molecule and having antitumor activity, where the antibody to CD20 includes:
(i) a modified variable area heavy chain polypeptide having the sequence of amino acid residues of SEQ ID NO: 9, but which includes at least one substitution of amino acid residue sequence selected from the group consisting of V12K, M20V And68T, Q82E, T87R, S91T, D93V and a114T; and (ii) a modified variable area light chain poly is eptide, having the sequence of amino acid residues of SEQ ID NO: 11, but which includes at least one substitution of amino acid residue sequence selected from the group consisting of L11I, S12T, A59S, S69T, L72M, R76S, R76S and V77L.

2. Fused protein antibodies to CD20 according to claim 1, where the molecule antibodies to CD20 has the form of a chimeric antibody and includes a constant section of the heavy chain of a human and a constant area light chain of a human.

3. Fused protein antibodies to CD20 according to claim 2, in which a constant site of the heavy chain of a human is a constant plot IgG.

4. Fused protein antibodies to CD20 according to claim 3, in which the constant-area IgG is a constant plot IgGl.

5. Fused protein antibodies to CD20 according to claim 2, in which the constant-area light chain human is a constant area light chain Kappa.

6. Fused protein antibodies to CD20 according to claim 1, comprising a variable region heavy chain having the amino acid sequence of SEQ ID NO: 10.

7. Fused protein antibodies to CD20 according to claim 1, including a variable area light chain having the amino acid sequence of SEQ ID NO: 12.

8. Fused protein antibodies to CD20 according to claim 1, including a variable plot heavy chain having the amino acid sequence of SEQ ID NO: 10 is the variable area light chain, which has the amino acid sequence of SEQ ID NO: 12.

9. Fused protein antibodies to CD20 according to claim 1, in which the cytokine is an IL-2.

10. Fused protein antibodies to CD20 according to claim 1, in which the C-terminal end of the polypeptide is fused with N-terminal end of a cytokine.

11. Pharmaceutical composition for the treatment of expressing CD20 tumor, including fused protein antibodies to CD20 according to claim 1 together with a pharmaceutically acceptable carrier, excipient, diluent.

12. A DNA molecule encoding a fused polypeptide antibody to CD20 according to claim 1.

All DNA according to item 12, selected from the group consisting of the sequence SEQ ID NO. 39, SEQ ID NO. 40, SEQ ID NO. 41, SEQ ID NO. 42, SEQ ID NO. 43.

14. The use of fused protein antibodies to CD20 according to claim 1 for obtaining a medicinal product for the treatment of tumors expressing CD20.

15. The application 14, where the tumor is b-cell lymphoma.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to immunology and biotechnology. Described are versions of the humanised antibody CD45RO/RB which carry a light and a heavy strand. Versions of the following are disclosed: isolated polynucleotide, coding antibody, expression vector containing a polynucleotide and host cells containing the expression vector. Described also is use of the antibody to treat and/or prevent various diseases, including as a component of a pharmaceutical composition.

EFFECT: invention provides antibodies identified as CD45RO and CD45RB, which can find use in medicine.

9 cl, 14 dwg, 2 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns methods and compositions for inducing apoptosis of cancer cells. Substance of the invention includes the modified antibodies-DR-5 agonists which in combination with apoptosis-inducing agents, synergetically induce apoptosis of cancer cells.

EFFECT: intensified antineoplastic activity.

19 cl, 51 ex, 2 tbl, 35 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns a prophylactic drug for vasculitis. Substance of the invention includes a preventive and/or therapeutic drug for vasculitis containing an antibody to an interleukine-6 (IL-6) receptor as an active ingredient and also method for vasculitis prevention and/or treatment.

EFFECT: development of the new drug expressing therapeutic effectiveness in vasculitis treatment.

39 cl, 4 ex, 6 dwg

FIELD: pharmacology.

SUBSTANCE: present invention refers to immunology and biotechnology. There are antibody-antagonist to CD40 with their variable areas derived from an antibody produced of hybridoma 4D11 (FERM BP-7758). The constant areas of antibodies are derived from human IgG4 with mutations S228P and L235E. There are described related coding polynucleotides and the based expression vector. There is disclosed host-cell containing said vector. There is described method for preparing monoclonal antibody and application thereof in the pharmaceutical composition.

EFFECT: application of the invention provides reduced ADCC and CDC activity that can find application in therapy of autoimmune diseases and graft rejection.

10 cl, 26 dwg, 2 tbl, 22 ex

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

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: chemistry.

SUBSTANCE: invention relates to molecular pharmacology and specifically to a peptide which is part of an interleukine-15 (IL-15) sequence which can inhibit biological activity of the said molecule.

EFFECT: obtaining a peptide which inhibits T cell proliferation induced by IL-15, and apoptosis caused by tumour necrosis factor when bonding with the alpha subunit of the (IL-15R) receptor.

8 cl, 4 dwg, 5 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention pertains to biotechnology. The invention describes an antibody which specifically identifies a membrane or secretory protein selected from several proteins with sequences given in the application materials, or functional fragment thereof. The invention discloses a hybridoma which produces the said antibody and is deposited under inventory No. FERM BP-10376. A medicinal agent used in an autoimmune disease and which contains the described antibody or its functional fragment as an active ingredient is proposed. Described also, is a T cell adhesion inhibiting agent which contains the described antibody or its functional fragment as an active ingredient. The invention discloses a method of screening a substance which inhibits dendritic cell activation, or its salts or solvate involving the following steps: bringing the said antibody or its functional fragment into contact with a dendritic cell in the presence or absence of the substance under test and measuring the activation level of the said dendritic cell.

EFFECT: invention widens the range of agents for treating rheumatoid arthritis.

18 cl, 24 dwg, 12 ex

FIELD: medicine.

SUBSTANCE: invention refers to biology and veterinary medicine, namely to methods for making a complex preparation for prevention and treatment of diseases in animals. The method for making a complex preparation for prevention and treatment of diseases in animals includes mixing of 90 weight fractions of 0.2-0.3% agar suspensions, 2.5 weight fractions of concentrated purified polysaccharide complex, 3.5 weight fractions of (-)2,3,5,6-tetrahydro-6-phenylimidazo-[2,1-b]-thiazole hydrochloride, 0.2 weight fractions of formalin and 0.1 weight fraction of tetracycline hydrochloride; the preparation volume is brought to 100 weight fractions. The preparation is bottled and sterilised.

EFFECT: invention provides higher therapeutic effectiveness of the preparation.

2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to veterinary medicine and pharmacology. A method for making a preparation for prevention and treatment of inflammatory processes and improvement of non-specific resistance and immunogenesis in animals, involving mixing of 90 weight fractions of 0.2-0.3% agar suspensions, 2.5 weight fractions of concentrated purified polysaccharide complex, 3.5 weight fractions of (-)2,3,5,6-tetrahydro-6-phenylimidazo-[2,1-b]-thiazole hydrochloride and 0.2 weight fractions of formalin, differing that when mixing, 7.2 million UN of antibiotic extencylline is added, and the preparation volume is brought to 100 weight fractions. The preparation is bottled and sterilised.

EFFECT: invention provides higher therapeutic effectiveness of the preparation.

2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds having inhibitory effect on focal adhesion kinase (FAK) and/or anaplastic lymphoma kinase (ALK) of formula (I)

, where R0 denotes hydrogen; R1 is a saturated 6-member monocyclic or 10-member bicyclic heterocycle containing 1 or 2 heteroatoms independently selected from nitrogen and oxygen, which can be substituted with piperidinyl, (C1-C7)alkylpiperidinyl, hydroxy, (C1-C7)alkyl, piperazinyl, (C1-C7)alkylpiperazinyl; R2 and R3 together with the carbon or nitrogen atom to which they are bonded form a 5- or 6-member heterocycle containing one heteroatom selected from a nitrogen atom which is substituted with (C1-C7)alkyl and/or oxo- group, R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; R8 is hydrogen; halide, (C1-C7)alkoxy; carbamoyl which is unsubstituted or substituted with (C1-C7)alkyl; (C1-C7)alkoxy(C1-C7)alkoxy; 5- or 6-member heterocycle containing one or two heteroatoms independently selected from nitrogen or oxygen, and is unsubstituted or substituted with a substitute independently selected from hydroxy, (C1-C7)alkyl, mono- or di(C1-C7)alkylamino, 6-member heterocycle containing one or two nitrogen ring atoms which are unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle(C1-C7)alkoxy containing one nitrogen ring atom which is unsubstituted or substituted with (C1-C7)alkyl; R9 is hydrogen; R10 is hydrogen, halide or (C1-C7)alkoxy; or their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and use of formula (I) compounds.

EFFECT: obtaining novel compounds with inhibitory effect on focal adhesion kinase (FAK) and/or anaplastic lymphoma kinase (ALK), having formula (I) .

7 cl, 155 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I') which have inhibitory effect on ALK kinase: , where n' is selected from 1 and 2; R'2 is selected from halogen; R'3 is selected from -S(O)2NR'5R'6, -S(O)2R'6 and -C(O)NR'5R'6, where R'5 is selected from hydrogen and C1-6alkyl, and R'1 is selected from C1-6alkyl; and R'1 is selected from phenyl which is substituted with 3 radicals independently selected from C2-6alkoxy group, C1-6alkyl, -X'R'4 and -OXR'4, where X' denotes a bond, and R'4 is selected from piperazinyl, piperidinyl, pyrrolidinyl, morpholino, where R'4 can be optionally substituted with 1-3 radicals independently selected from C1-6 alkyl, provided that the following compound is excluded .

EFFECT: design of a method of inhibiting and using compounds for making a medicinal agent for treating diseases which respond to ALK kinase inhibition.

7 cl, 61 ex

FIELD: medicine.

SUBSTANCE: invention relates to veterinary. Method of manufacturing biogenic stimulator, which includes 50% of biologically active mass from drone larvae, 49.7% of sodium chloride solution and 0.3% of preservative, consists in the following: in order to obtain preparation comb with alive healthy 18-22 days old drone brood is kept in refrigerator at temperature 3-4°C during 5-6 days, after that comb with brood is opened and drone larvae of the same size, light-gray colour are selected, after which drone larvae are crushed in sterile laboratory mill, diluted with sterile sodium chloride solution with concentration 0.9% in ratio 1:1 and autoclaved at temperature inside boiler 120°C and steam pressure in jacket 1.5 atmosphere for one hour, after that the mass is filtered through two layers of gause into sterile measure vessel, brought to initial volume with sterile solution of sodium chloride with concentration 0.9%, preservative (phenol) is added, preparation is poured into prepared sterile vessels observing rules of asepsis, vessels are hermetically closed, autoclaved at 120°C and steam pressure in jacket 1.5 atmosphere for 20 minutes.

EFFECT: method allows to reduce considerably terms of preparation manufacturing, increase its safety, increase storage terms Biogenic stimulator obtained in said way contributes to improvement of animal growth and development, increase of offspring preservation, reduction of feed cost per unit of body weight increase, increase of general and specific resistance of organism.

3 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to veterinary, in particular to development of complex medications for prevention and treatment of malfunctions of metabolic and immune processes in animals. Method of obtaining complex medication for prevention and treatment of malfunctions metabolic and immune system includes mixing of succinic acid, novocaine, immunostimulant, dissolving of obtained medication in distillated water and sterilising by autoclaving. As immunostimmulant applied is sodium nucleinate or derinate with the following component ratio, wt %: succinic acid 1.5; sodium nucleinate or derinate 2.0; novocaine 0.25; distillated water - the remaining part.

EFFECT: invention insures increasing of medication efficiency.

4 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to high-molecular compounds for medical purposes. Water-soluble polymeric complexes of antiviral agent arbidol of general formula: are described, where: Arb - arbidol: ethyl ester 6-bromo-4-dimethyl-aminometil-1-methyl-5-oxy-2-feniltiometilindolinil-3-carboxylic acid hydrochloride monohydrate; m1=100-(m2+m3) mol %; m2=(7.6-9.8) mol %; m3=(11.5-13.6) mol %; content of Arb=26.4-32.1 wt %.

EFFECT: obtained water-soluble polymeric complexes of arbidol may find application in pharmacology, as they can serve as basis for new effective and safe antiviral drugs and their dosage forms.

1 cl, 6 ex, 4 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to surgery, and can be applied for prevention of purulent complications of post-operational wounds and for treatment of infected post-operational wounds without festering. Method includes carrying out antibiotic therapy and immunotherapy. For immunotherapy blood sampling in patient is carried out, its cell part is separated. Erythrocytic mass is returned to patient. Remaining cell mass is cultured with 500000 IU of interleukin-2 for 60 minutes at temperature 37°C, with following centrifugation and separation of 60-80 ml of supernatant fluid. This fluid, which contains cytokines, is introduced subcutaneously symmetrically at the distance 1.5 cm from borders of post-operational wound until creation of infiltration bank in terms of 10 ml of solution per each 5 cm of wound length from each side. Such introduction is performed on 1, 3 and 5 day of post-operation period.

EFFECT: method increases efficiency of prevention of suppuration in treatment of infected post-operational wound due to creation of high concentration of preparation around wound with enhance of non-specific immune response and healing of wound by primary intention.

2 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention pertains to biotechnology. The invention describes an antibody which specifically identifies a membrane or secretory protein selected from several proteins with sequences given in the application materials, or functional fragment thereof. The invention discloses a hybridoma which produces the said antibody and is deposited under inventory No. FERM BP-10376. A medicinal agent used in an autoimmune disease and which contains the described antibody or its functional fragment as an active ingredient is proposed. Described also, is a T cell adhesion inhibiting agent which contains the described antibody or its functional fragment as an active ingredient. The invention discloses a method of screening a substance which inhibits dendritic cell activation, or its salts or solvate involving the following steps: bringing the said antibody or its functional fragment into contact with a dendritic cell in the presence or absence of the substance under test and measuring the activation level of the said dendritic cell.

EFFECT: invention widens the range of agents for treating rheumatoid arthritis.

18 cl, 24 dwg, 12 ex

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