Antibodies with reduced total positive charge
The invention relates to medicine and relates to antibodies with reduced total positive charge. The invention includes a composition comprising a monoclonal antibody conjugated with Biotin, at least one of the many free amino groups present in the antibody, obtaining a modified antibody having smaller compared with the intact antibody total positive charge, increased antigennegative specificity, the invention also concerns a method for obtaining this composition, and a method of localization of the antigen in the mammal. The advantage of the invention is to improve the specificity of antibodies and improved pharmacokinetic characteristics. 3 S. and 13 C.p. f-crystals, 3 tab., 19 Il. Description text in facsimile form (see graphic part).
Claims1. A composition comprising a monoclonal antibody conjugated with Biotin at least one of the many free amino groups present in the antibody, obtaining a modified antibody having smaller compared with the intact antibody total positive charge, increased antigennegative juicy between velocities clearance F(ab)2fragments and intact antibodies of the same type, and chemical residue that is attached to the modified antibody.2. The composition according to p. 1, characterized in that the chemical balance is the label.3. The composition according to p. 2, characterized in that the label is a radioactive isotope.4. The composition according to p. 3, wherein the modified antibody is attached to a radioactive isotope of a halogen or technetium.5. The composition according to p. 4, characterized in that the radioactive isotope selected from the group consisting of125I and131I.6. The composition according to p. 2, characterized in that the specified mark is recorded by a magnetic resonance tomography.7. The composition according to p. 1, characterized in that the chemical balance is a biologically active molecule.8. The composition according to p. 7, characterized in that the biologically active molecule is selected from the group consisting of a toxin, drug, and chelate.9. The composition according to p. 8, characterized in that the said drug is selected from the group consisting of methotrexate, 5-fluorouracil, CIS-platinum and adriamycin.10. A method of obtaining a composition according to any one of paragraphs.1-9, including the production of monoclonal antibodies, which inbrisbane modified antibodies with less as compared with intact antibody total positive charge, increased antigennegative specificity, low nonspecific binding, and characterized by the rate of clearance in vivo, intermediate between the velocities clearance F(ab)2fragments and intact antibodies of the same type; and the marking of the modified antibodies radioactive isotope, a toxin, a drug, or a chelate with the formation of the labeled modified antibody.11. The method of localization of the antigen in the mammal with the composition obtained by the method according to p. 10, which includes obtaining labeled modified monoclonal antibodies that have less as compared with intact antibody total positive charge, increased antigennegative specificity, low nonspecific binding, characterized by the rate of clearance in vivo, intermediate between the velocities clearance F(ab)2fragments and intact antibodies of the same type, and contains the registered label; the introduction of the labeled modified antibody to a mammal to bind in vivo antigen labeled with modified antibody and detect the B. p. 11, characterized in that the labeled modified monoclonal antibody tagged with a radioactive isotope.13. The method according to p. 12, wherein the radioactive isotope is selected from the group consisting of a radioactive isotope of a halogen and technetium.14. The method according to p. 11, wherein the detection step includes immunoscintigraphy.15. The method according to p. 14, characterized in that immunoscintigraphy includes the use of gamma cameras.16. The method according to p. 11, wherein the intact antibody chemically conjugated with heterobifunctional reagent.
FIELD: medicine, oncology, immunology, tumor biology.
SUBSTANCE: invention relates, in particular, to methods for enhancing cytotoxicity based on applying anti-CD38-immune toxins. Method involves carrying out the treatment of patient with pathophysiological state taken among the group including myelomas and leukosis and involves the following stages: a) administration to the indicated patient the pharmacologically effective dose of retinoid that enhances expression of antigen CD38; and b) administration to the indicated patient the pharmacologically effective dose of immune toxin acting against effectively expressing antigen CD38. Method provides enhancing the cytotoxicity with respect to above said diseases in their resistance to anti-tumor medicinal agents.
EFFECT: enhanced and valuable method for treatment.
6 cl, 1 tbl, 9 dwg, 10 ex
SUBSTANCE: method involves applying effective doses of epidermis growth factor receptors antagonists being active ingredient in drug for inhibiting various types of resistant human tumors. The epidermis growth factor receptor antagonists are combined with other chemotherapeutic agents like Cisplatin, Irinotecan or ionizing radiation.
EFFECT: enhanced effectiveness of treatment.
50 cl, 2 tbl
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, oncology.
SUBSTANCE: method includes the consecutive stages: (a) administration of at least one dose of anti-angiogenic cyclo-(arginine-glycine-asparagine acid)-containing pentapeptide (pentapeptide cRGD), such as cyclo-(Arg-Gly-Asp-D-Phe-[N-Me]-Val); (b) administration of anti-tumor effective amount of radio immunotherapeutic agent(RIT) not later than in 1 hour following administration of pentapeptide cRGD at stage (a); and (c) administration of at least two additional doses of pentapeptide cRGD, where the first additional dose is administered within 2 days after RIT and each additional dose of pentapeptide cRGD is administered with intervals between doses not more than 2 days.
EFFECT: invention provides the synergic effect in regard to apoptosis of tumor cells and endothelial cells of tumor vessels.
30 cl, 6 dwg, 2 tbl
FIELD: medicine; immunology.
SUBSTANCE: sorbent is offered to remove immunoglobulin from human blood plasma. This sorbent contains agarous matrix covalently combined with ligand. As a ligand at that it contains F(ab)2 fragments of specific affinely-purified polyclonal antibodies blocking human immunoglobulin G. Sorbent is actually biologically inert, biocompatible agarous matrix. Sorbent is characterized with higher sorptive capacity and safety of immunosorbents used practical purposes, specifically for therapeutic aphaeresis in comparison to well-known polyclonal bodies based sorbents.
EFFECT: considerable reduction of prospective immunological response of human body for foreign protein.
1 ex, 1 tbl
FIELD: medicine; oncology.
SUBSTANCE: invention can be used for treatment of an acute myelogenetic leukemia or myelodysplastic syndrome. For this purpose use a combination of preparations hemetuzumab ozohamicin, daunorubicin and cytarabinum in certain doses and regimens.
EFFECT: invention promotes effective treatment of the specified diseases due to synergistic effect at influence of these preparations on an organism.
2 cl, 2 ex
SUBSTANCE: invention refers to medicine, namely to ophthalmology, and can be used in treating the patients with macular oedemas of various geneses. That is ensured by the therapy that starts with 6 sessions of plasma exchange every 2 days. It is followed by a single intravitreal introduction of antivasoproliferative preparation Avastin in dosage 1.25 mg or Lucentis in dosage 0.5 mg.
EFFECT: method allows improving clinical effectiveness combined with reduced intravitreal introduction of the antivasoproliferative preparations, due to involving pathogenetic mechanisms, namely elimination of pathological immune complexes, stabilisation of pro- and anti-inflammatory cytokines.
2 cl, 2 ex
SUBSTANCE: copolymers of hetero-chain aliphatic poly-N-oxides of general formula (I) , where R=N, CH; x=2-4; y=0, 2; n=10-1000; q=(0.1-0.9)n; z=(0.1-0.9)n. Copolymers possess anti-oxidant action, therapeutic action as detoxicant and immunomodelling agent. Copolymers of formula (I) can be used as immunomodulating carrier for obtaining vaccinating medication and as carrier of medications for obtaining medications.
EFFECT: copolymers of hetero-chain aliphatic poly-N-oxides represent novel class of compounds possessing wide spectrum of pharmacological and vaccinating action, aimed at increase of safety in application, increase of technological and economical effectiveness and ecological safety of production of medications.
20 cl, 2 dwg, 13 tbl, 22 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology and represents methods of treating an autoimmune disease involving administering into an individual a pharmaceutical composition containing a pharmaceutically acceptable carrier and a humanised anti-CD4-antibody, able to activate the regulatory C-cells CD4+CD25+, wherein the above antibody contains V-domain of H-chain containing the sequences DCRMY, VISVKSENYGANYAESVRG and SYYRYDVGAWFAY, and V-domain of L-chain containing the sequences RASKSVSTSGYSYIY, LASILES and QHSRELPWT; the above composition is administered subcutaneously into the individual in a dose of the humanized anti-CD4-antibody 20 to 200 mg or 8 to 60 mg/m2 of the individual's body surface, or 0.2 to 2 mg/kg. The present invention also discloses the pharmaceutical compositions applicable in the above methods of treating the autoimmune disease.
EFFECT: invention enables administering the pharmaceutical composition containing the humanised anti-CD4-antibody in higher doses losing no therapeutic effect and causing no intensification of any side effects.
46 cl, 20 dwg, 21 tbl, 8 ex