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THERAPEUTIC AGENT FOR ARTERIOSCLEROSIS OR ARTERIOSCLEROTIC DISORDERS AND DIAGNOSTIC AGENT FOR ARTERIOSCLEROSIS OR ARTERIOSCLEROTIC DISORDERS

Foreign code F120006750
File No. S2011-0075
Posted date Jun 7, 2012
Country WIPO
International application number 2011JP076132
International publication number WO 2012063955
Date of international filing Nov 8, 2011
Date of international publication May 18, 2012
Priority data
  • P2010-249876 (Nov 8, 2010) JP
  • P2011-153862 (Jul 12, 2011) JP
Title THERAPEUTIC AGENT FOR ARTERIOSCLEROSIS OR ARTERIOSCLEROTIC DISORDERS AND DIAGNOSTIC AGENT FOR ARTERIOSCLEROSIS OR ARTERIOSCLEROTIC DISORDERS
Abstract The present invention ameliorates arteriosclerosis or arteriosclerotic disorders by means of a pharmacological mechanism that reduces the size of arteriosclerotic lesions. The following is included as an active ingredient: a complex comprising an antibody, which binds to folate receptor beta (FRβ), conjugated to a cytotoxin or cytotoxic agent; or said antibody.
Outline of related art and contending technology BACKGROUND ART
And arteriosclerosis, cured and then thickened artery atherosclerosis atherosclerosis means, such as film curing in curing and arterioles are classified into. Among them atherosclerosis atherosclerosis is, to the inside wall of the artery atherosclerosis (plaque) (atherosclerosis) occurs in the raised, thickened artery means that the cured state. In addition, atherosclerotic disease is, various diseases caused by arteriosclerosis. Atherosclerotic disease, cerebral artery in a stroke or cerebral hemorrhage caused by arteriosclerosis, myocardial infarction or angina pectoris due to coronary arteries arteriosclerosis such as ischemic heart disease, aortic aneurysm or arteriosclerosis in the aorta due to aortic dissection, due to the renal artery sclerosis in the renal artery and renal failure caused thereby in a peripheral artery arteriosclerosis due to arteriosclerosis and the like can be exemplified. At present, for the treatment of atherosclerotic disease or arteriosclerosis, or atherosclerosis or atherosclerotic plaque such as reduced to stabilize the therapeutic agent is not efficacy, risk factors (hyperlipidemia, hypertension, obesity, diabetes) is given priority to improve. In addition, treatment of arteriosclerosis, for example of a narrow tube called a catheter through a blood vessel by inserting the instrument 'catheter operation', vascular atherosclerosis periphrastic made to rotate to the path of the 'bypass surgery' such as the surgical method may be employed. In addition, as the arteriosclerosis forming the, oxidized LDL membrane has been penetrated within the vessel undergoing degeneration, or via the macrophage scavenger receptor LDL and takes in the foam cells, macrophages and foam cells in atherosclerotic plaques due to the accumulation of which is assumed to be generated. However, the patent document 1, are involved in the metastasis of cancer growth and plays a central role in the inflammatory response responsible for 'cancer-associated macrophages localized cancerous tissue' targeted solid cancer therapeutic agents is disclosed. In addition, the patent document 1, solid cancer therapeutic agents as an example of the folate receptor (FR β) β cell an antibody which binds to a toxin or cytotoxic agent-conjugated complex disclosed can be used. This is, to localize to cancer tissues and cancer-associated macrophages expressed FR β, normal tissues do not express FR β is little are based on the findings that. In addition, patent document 2, non-patent document 1, and 2 is 3, a mouse monoclonal antibody anti-human FR β genes and the antigen recognition site of a modified form of Pseudomonas exotoxin (Pseudomonas aeruginosa exotoxin) gene fuzed to prepare a recombinant type immunotoxin, in a mouse model of rheumatoid arthritis synovial SCID -, for the selective removal of the immunotoxins FR β is expressed by macrophages, or effective in the treatment of rheumatoid arthritis, rheumatoid arthritis from macrophages observed differentiation into osteoclasts can inhibit angiogenesis and have been reported.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 葉酸受容体β(FRβ)に結合する抗体と細胞毒素又は細胞毒性剤とをコンジュゲートした複合体若しくは当該抗体を有効成分として含む、動脈硬化又は動脈硬化性疾患の治療剤。

[請求項2]
 前記動脈硬化は、アテローム性粥状動脈硬化である、請求項1記載の治療剤。

[請求項3]
 前記動脈硬化性疾患は、脳梗塞、脳出血、虚血性心疾患、大動脈瘤、大動脈解離、腎硬化症、腎不全及び閉塞性動脈硬化症からなる群から選ばれる一種であることを特徴とする請求項1記載の治療剤。

[請求項4]
 前記複合体は、リコンビナントイムノトキシンである、請求項1記載の治療剤。

[請求項5]
 前記抗体は、葉酸受容体αに結合しない、請求項1記載の治療剤。

[請求項6]
 前記抗体は、キメラ抗体、ヒト化抗体又はヒト抗体である、請求項1記載の治療剤。

[請求項7]
 前記抗体は、抗ヒト葉酸受容体βマウスモノクローナル抗体又は抗マウス葉酸受容体βラットモノクローナル抗体のいずれかの重鎖(H鎖)可変領域及び/又は軽鎖(L鎖)可変領域の各アミノ酸配列中の少なくとも1つの相補性決定領域(CDR)を含むアミノ酸配列を含む、請求項1記載の治療剤。

[請求項8]
 前記細胞毒素は、緑膿菌外毒素(Pseudomonas aeruginosa exotoxin)リシンA鎖(ricin A chain)、脱糖鎖リシンA鎖(deglycosylated ricin A chain)、リボゾーム不活性化タンパク質(a ribosome inactivating protein)、アルファサルシン(alpha-sarcin)、ゲロニン(gelonin)、アスペルギリン(aspergillin)、リストリクトシン(restrictocin)、リボヌクレアーゼ(ribonuclease)、エポドフィロトキシン(epidophyllotoxin)、ジフテリアトキシン(diphtheria toxin)からなる群から選択されるものである、請求項1記載の治療剤。

[請求項9]
 葉酸受容体β(FRβ)に結合する抗体を有効成分として含む、動脈硬化又は動脈硬化性疾患の診断薬。

[請求項10]
 前記動脈硬化としてアテローム性粥状動脈硬化を診断することを特徴とする、請求項9記載の診断薬。

[請求項11]
 前記動脈硬化性疾患として脳梗塞、脳出血、虚血性心疾患、大動脈瘤、大動脈解離、腎硬化症、腎不全及び閉塞性動脈硬化症からなる群から選ばれる一種を診断することを特徴とする請求項9記載の診断薬。

[請求項12]
 前記抗体は、葉酸受容体αに結合しない、請求項9記載の診断薬。

[請求項13]
 前記抗体は、キメラ抗体、ヒト化抗体又はヒト抗体である、請求項9記載の診断薬。

[請求項14]
 前記抗体は、抗ヒト葉酸受容体βマウスモノクローナル抗体又は抗マウス葉酸受容体βラットモノクローナル抗体のいずれかの重鎖(H鎖)可変領域及び/又は軽鎖(L鎖)可変領域の各アミノ酸配列中の少なくとも1つの相補性決定領域(CDR)を含むアミノ酸配列を含む、請求項9記載の診断薬。

[請求項15]
 動脈硬化病巣のうち不安定プラーク部位を判別する、請求項9記載の診断薬。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KAGOSHIMA UNIVERSITY
  • Inventor
  • TEI, Chuwa
  • MIYATA, Masaaki
  • FURUSYO, Yuko
  • MATSUYAMA, Takami
  • NAGAI, Taku
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW 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 MD 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 ML MR NE SN TD TG
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