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CARRIER FOR DRUG DELIVERY USE

Foreign code F200010022
File No. (S2018-0655-N0)
Posted date Jan 30, 2020
Country WIPO
International application number 2019JP017921
International publication number WO 2019225296
Date of international filing Apr 26, 2019
Date of international publication Nov 28, 2019
Priority data
  • P2018-099998 (May 24, 2018) JP
Title CARRIER FOR DRUG DELIVERY USE
Abstract A carrier for drug delivery use, comprising a human serum albumin variant in which a mannose-rich sugar chain having 8 or more mannose residues is bonded to a substance capable of interacting with the mannose-rich sugar chain or a binding site in the substance capable of interacting with the mannose-rich sugar chain.
Outline of related art and contending technology BACKGROUND ART
New refractory cancer as a therapeutic target, the characteristic of tumor tissue in the tumor microenvironment interstitial has attracted attention. This is because the growth of cancer the tumor microenvironment, transition, or progression in a cause of drug resistance.
Comprising a target molecule in a variety of anti-cancer drugs in recent years and although the significant progress in the treatment method, a single agent cannot kill the cancer. This is because, in the cancer microenvironment (TAM) and tumor-associated macrophage-associated fibroblasts (CAF) or the like to control the group of cells is yet to be established therapeutic strategy because it does not. M2 TAM is as macrophages, the occurrence of a malignant tumor from the initial to the formation of metastases of course, that is, the growth of cancer cells, invasion, metastasis and involved, treatment of malignant tumor microenvironment is positioned as a resistance factor.
Also, the CAF, proliferation, and excellent mobility, cancer cell proliferation, invasion, metastasis only play an important role in the course but, to promote overgrowth of the extracellular matrix, anti-tumor penetration of the treatment due to the attenuation of the calibration resistance occurs. Further, cancer stem cells and the signaling link and the CAF of cancer stem cells may be important to survival have been reported (for example, see Non-Patent Document 1.).
Interestingly, cancer microenvironment CAF TAM CD280 and high CD206 expression to cancer tissues there are a number of highly expressed, the higher the grade, is a poor prognosis and treatment-resistant depression from the clinical observations have been demonstrated.
However, human serum albumin (hereinafter, referred to as' HSA '.) Is a simple protein, sugar chain does not have. On the other hand, the inventors have found that, previously, the HSA N- coupling type sugar chain binding amino acid sequence to form a site-directed mutagenesis (D63N, A320T, D494N) is introduced, this can be produced in the yeast, yeast expression systems are specific to the HSA high-mannose sugar chain bound to (or less, 'Man-HSA' may be referred to.) Was successful for the first time to produce (for example, see Non-Patent Document 2.) Further, Man-HSA is prepared, the target CD280 and CD206 has the ability, healthy mice and fibrosis model by a mouse has been confirmed.
Scope of claims (In Japanese)[請求項1]
 8個以上のマンノース残基を有する高マンノース糖鎖と、
 前記高マンノース糖鎖と相互作用する物質又は前記高マンノース糖鎖と相互作用する物質の結合部位と、
 が結合した、ヒト血清アルブミン変異体を含む薬物送達用担体。

[請求項2]
 前記高マンノース糖鎖と相互作用する物質が、生体適合性ポリマー又はタンパク質である、請求項1に記載の薬物送達用担体。

[請求項3]
 前記高マンノース糖鎖と相互作用する物質の分子量が、5,000~100,000である、請求項1又は2に記載の薬物送達用担体。

[請求項4]
 前記高マンノース糖鎖と相互作用する物質が生体適合性ポリマーであり、前記生体適合性ポリマーの重量平均分子量が、30,000~50,000である、請求項1~3のいずれか一項に記載の薬物送達用担体。

[請求項5]
 前記高マンノース糖鎖と相互作用する物質がタンパク質であり、前記高マンノース糖鎖と相互作用する物質の結合部位が、前記タンパク質が結合するアミノ酸配列からなる部位である、請求項1~3のいずれか一項に記載の薬物送達用担体。

[請求項6]
 前記ヒト血清アルブミン変異体が、D63N、A320T及びD494Nからなる群より選択される少なくとも1つの変異を有する、請求項1~5のいずれか一項に記載の薬物送達用担体。

[請求項7]
 D63N、A320T及びD494Nからなる群より選択される少なくとも1つの変異を有するヒト血清アルブミン変異体と、N-結合型糖鎖結合アミノ酸配列を有しないヒト血清アルブミンとの融合タンパク質である、請求項6に記載の薬物送達用担体。

[請求項8]
 D63N、A320T及びD494Nからなる群より選択される少なくとも1つの変異を有するヒト血清アルブミン変異体と、抗体定常領域との融合タンパク質である、請求項6に記載の薬物送達用担体。

[請求項9]
 請求項7又は8に記載の薬物送達用担体をコードする核酸。

[請求項10]
 請求項1~9のいずれか一項に記載の薬物送達用担体と、薬物とが結合した、薬物送達システム。

[請求項11]
 癌治療剤、腫瘍微小環境の改善剤又は造影剤である、請求項10に記載の薬物送達システム。

[請求項12]
 8個以上のマンノース残基を有する高マンノース糖鎖と、重量平均分子量が30,000~50,000である生体適合性ポリマーが結合した、ヒト血清アルブミン変異体を含む薬物送達用担体と、抗癌剤とが結合した、癌治療剤。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION KUMAMOTO UNIVERSITY
  • Inventor
  • MARUYAMA Toru
  • WATANABE Hiroshi
  • ISHIMA Yu
  • MAEDA Hitoshi
  • MIZUTA Yuki
  • KINOSHITA Ryo
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 JP 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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