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AGENT FOR PREVENTING OR IMPROVING CHRONIC LUNG ALLOGRAFT DYSFUNCTION

Foreign code F200010071
File No. 5989
Posted date May 15, 2020
Country WIPO
International application number 2019JP003794
International publication number WO 2019159731
Date of international filing Feb 4, 2019
Date of international publication Aug 22, 2019
Priority data
  • P2018-027063 (Feb 19, 2018) JP
Title AGENT FOR PREVENTING OR IMPROVING CHRONIC LUNG ALLOGRAFT DYSFUNCTION
Abstract A purpose of the present invention is to provide an immunosuppressant that can prolong suppression of rejection after lung transplant. An agent for preventing or improving chronic lung allograft dysfunction having an MEK inhibitor as an active ingredient can prolong suppression of rejection after lung transplant and makes it possible to prevent or improve chronic lung allograft dysfunction (CLAD). The agent for preventing or improving chronic lung allograft dysfunction having an MEK inhibitor as an active ingredient is administered to a lung transplant patient who has undergone treatment for acute immune rejection.
Outline of related art and contending technology BACKGROUND ART
Human lung transplantation is successful since the year 1983, the increase in the number of cases is increasing steadily. However, post-transplantation of the five-year survival rate remains 54% and 5, other solid organ transplantation is not satisfactory as compared with the performance. Death within one year of the 1 post-operative infection is, then a number of immunological rejection reaction is the cause of death due to the (non-patent document 1-3).
Lung transplantation rejection is acute rejection is classified as chronic rejection. Acute rejection occurs at an early stage after the surgery, and the increase in the necessity of additional immunosuppressive agents in many cases, the transition to the chronic rejection (non-patent documents 4-5) is also an example. As immunosuppressive agents, calcineurin inhibitors, mTOR inhibitors, corticosteroids, mycophenolate mofetil (MMF) or the like is used. One year from the remaining through surgical and chronic rejection found. Chronic rejection (bronchiolitis obliterans change obstructive of the bronchioles are: BO) often occur, a failure constraint (restrictive allograft syndrome: RAS) may exhibit. Also, in chronic rejection, while the slow non-reversible change in lung pathology kitashi, lung dysfunction graft (Chronic Lung Allograft Dysfunction: CLAD) that causes a condition referred to. This condition is added or increased existing immunosuppressive agents often cannot be controlled, to improve the long term prognosis of lung transplantation prevent a large barrier (non-patent document 6).
Graft (CLAD) lung dysfunction itself is causing fatal bronchiolitis, serious opportunistic infections as well as the risk factors. The use of long-term immunosuppressive agents, anti-tumor immunity through weakening of new malignant tumors increased risk of developing (non-patent document 7). Chronic rejection reaction mechanism is not known yet, a method is effective to suppress the reaction and chronic rejection are not known. Therefore, there is no countermeasure to the CLAD in the current state.
T cell immune controls the main activation path, the calcineurin pathway, mTOR pathway, 3 MAPK path type are known, heretofore, the calcineurin pathway mTOR pathway and immunosuppressive approach has been investigated. MAPK pathways, many malignant tumor can be permanently activated, malignant melanoma are listed in the insurance for the (non-patent document 8) such as MEK trametinib inhibitor has been developed as an anti-tumor agent. However, MAPK pathway itself is very important to the cell for a path, from the viewpoint of the MAPK pathway immunosuppressive approach, leads to a very small risk of adverse events were not considered.
In recent years, the MEK inhibitor, graft versus host disease after bone marrow transplantation (GVHD) antiviral immune while suppressing the effect of anti-tumor immunity and preserve (GVT) have been reported (Non-Patent Document 9 and 10). These reports, the MEK inhibitor, T-cell function in the early stage of cell differentiation (central memoryT naiveT cells and the cells) and to selectively inhibit, the function of differentiation of the T cells to the post stage can be to preserve (effector memoryT cells) are shown.
Scope of claims (In Japanese)[請求項1]
 MEK阻害剤を有効成分とする、慢性移植肺機能不全の改善又は予防薬。

[請求項2]
 前記MEK阻害剤が、トラメチニブ及び/又はコビメチニブである、請求項1に記載の慢性移植肺機能不全の改善又は予防薬。

[請求項3]
 急性免疫拒絶に対する処置を受けた肺移植患者に対して投与される、請求項1又は2に記載の慢性移植肺機能不全の改善又は予防薬。

[請求項4]
 前記急性免疫拒絶に対する処置が、カルシニューリン阻害剤、mTOR阻害剤、副腎皮質ステロイド、及びミコフェノール酸モフェチルからなる群から選択される免疫抑制剤の投与である、請求項3に記載の慢性移植肺機能不全の改善又は予防薬。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KYOTO UNIVERSITY
  • Inventor
  • SHINDO, Takero
  • CHEN, Fengshi
  • TAKAHAGI, Akihiro
  • DATE, Hiroshi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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