ANTITUMOR AGE NT
International application PCT/RU2016/000467, priority 20.07.15
International application PCT/RU2014/000947, priority 16.12.2013
Patents for invention
Patent applications for inventions
- Europe No.3325511 stated 16.02.2018,
- China No. 108137692 stated 07.03.2018,
- USA No. 2019002580 stated 16.01.2018,
- JapanNo.2018530993 stated 11.01.2018,
- India No. 201817002242 stated 19.01.2018.
Universal monoclonal antibodies have been developed for the treatmentof tumor diseases.This is MABto legumain (AEP), which targets the surface antigen of tumor cells overexpressed in most (over 80%)tumors, including breast, colon, pancreatic,central nervous system tumors.This is also a MAb tosyndecan-1 (CD138). The important role of these molecules is proved for tumor cells and a littleimportance is known for the functioning of normal cells of various tissues of the body.
The developed antibodies have a high affinity to the antigen, low immunogenicity and high cytotoxicity,they can be obtained in large quantities in a short period of time.
The high frequency of target molecule expression in a variety of human tumors ensures the versatility ofthe developed MAB.
The developed antibodies are humanized. The proposed humanized antibodies bind highly affine tolegumain/syndecan-1 overexpressed on tumor cells due to humanization of variable fragments. Humanization can also reduce the immunogenicity of the drug and improve its tolerability.
The design of the proposed antibodies is able to provide their independent cytotoxic effect on theantibody-dependent and complement-dependent mechanisms. This eliminates the use of a cytotoxicagent.In addition, there is an antimetastatic effect due to blocking of intercellular endopeptidase C13(legumain).
The introduction of a signal secretory sequence at the N-end of the heavy and light chains, as well as thecodon optimization of nucleotide sequences encoding them for expression in mammalian cells allows toobtain antibodies in large quantities for a short time in such cells.
Result from the use of the antibody is also expressed in the reduction of stress on the body of ananticancer drug, due to the fact that the active agent is a monoclonal antibodymolecule–the one ofprotein nature which is subsequently degraded to amino acids, i.e., its use excludes any impact ofpotential absence of excretion from the body during any time of the active agent (chemical substance ofnon-protein nature), or the products of its decay.
The safety, specificity and efficacy of the MABs developed have been experimentally proven in animalsand in vivo models, respectively. The proposed humanized antibodies have antitumor effect: not onlyinhibit tumor growth and cell migration, but also contribute to their elimination in a natural way.
Assessment of the significance of this development
