JP6276701B2 - 血漿交換療法によるガレクチン−3レベルの低減 - Google Patents
血漿交換療法によるガレクチン−3レベルの低減 Download PDFInfo
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Description
本出願は、2011年12月8日に提出された米国仮特許出願第61/568,210号の優先権の恩典を主張し、これは参照によりその全体が組み入れられる。
発明の分野
本発明は、1つ以上のガレクチンによって少なくとも部分的に媒介される疾病および生物学的容態の処置に関する。ガレクチンは、レクチン(糖結合タンパク質)のファミリーであり、これは、β−ガラクトシドに対する親和性を有する少なくとも1つの糖認識ドメイン(CRD)を有することによって特徴付けられる。これらのタンパク質は、最近になってやっとファミリーとして認識されたが、動物界全体に見られ、そして哺乳動物、鳥類、両生類、魚類、海綿動物、線形動物およびさらには真菌にも見られる。本出願は、哺乳動物、特にヒトにおけるガレクチンに焦点を当てる。本明細書の発明は、コンパニオン動物(例えばイヌおよびネコのようなペット)および商業用動物(例えばウシ、ブタおよびヒツジ)の両方と共に使用され得るが、本明細書で記載された方法および対象は、特に、ヒトの処置に焦点が当てられている。
本出願は、2011年6月6日に提出された米国特許出願第13/153,648号に関する。本出願は、同様に、2006年7月6日に提出された米国特許出願第11/485,955号の優先権の恩典を主張する。これらの両方の特許出願の内容は、明確に本明細書に参照により組み入れられる。米国特許出願第13/153,648号(米国特許公開公報第US−2011−0294755A1)において、細胞増殖容態、炎症および悪化した線維症を処置する方法が開示され、この方法は、循環gal−3に結合することのできる薬剤(例えば、改変シトラスペクチン(modified citrus pectin)、すなわちMCP、すなわち2万(20,000)ダルトン以下、好ましくは1万(10,000)ダルトンなどの減少した分子量を有するシトラスペクチン)の投与を含む。MCPは、EcoNugenics of Santa Rosa, Californiaから市販されており、そして米国特許第6,274,566号および第6,462,029号に考察されている。
Gal−3は、約30kDaであり、そして全てのガレクチンと同様に、β−ガラクトシドとの特異的な結合を可能とする約130個のアミノ酸の糖認識結合ドメイン(CRD)を含む。Gal−3は、第14番染色体q21−q22の遺伝子座に位置する単一の遺伝子LGALS3によってコードされている。このタンパク質は、多数の生物学的プロセスに関与していることが示された。本明細書で示されたリストは単なる例示である。なぜならgal−3に関する新たな状況および役割が次々と判明しているからである。gal−3によって少なくとも部分的に媒介されていると示された細胞レベルでの生物学的プロセスには、細胞接着、細胞遊走、細胞侵入、細胞活性化および化学誘引、細胞増殖および細胞分化、細胞周期、およびアポトーシスがある。
本発明は、血漿交換療法による哺乳動物の循環からの生物学的に活性なgal−3の除去に存する。哺乳動物は、ヒト、霊長類、モデル、例えばラットもしくはマウス、商業用動物、例えばウシもしくはブタもしくはヤギ、またはコンパニオン動物、例えばイヌもしくはネコであり得る。処置のための非ヒト哺乳動物としては、循環からのgal−3の除去により利点が得られる処置および介入のためのモデルとしておよび試験台としての霊長類が挙げられる。除去は、自己免疫疾患などを患うヒトの循環から抗体を除去するために伝統的に開発および使用されるプロセスである血漿交換療法によって達成される。
1.循環gal−3の直接的な減少;および
2.組織レベルでgal−3をより良好に標的化する能力。
A.循環gal−3を低減することによって、より大きな勾配差を通して組織中のgal−3をより多く排出することができ、これにより炎症の低減、線維症の低減および組織レベルでのリモデリングがもたらされる。
B.IL−6、TNFα、TNFκβおよびその他などの二次炎症誘発性サイトカインの減少。
C.それは、一般的に循環中の種々のgal−3遮断剤、特にMCPおよび40Kダルトン以下のポリウロニドのより大きな効力を可能とし得る。
D.それは、過剰な循環gal−3によって阻害される他の療法の効力を増加させ得る。
Claims (10)
- 炎症を低減するための、哺乳動物の血液を血漿交換するシステムであって、
哺乳動物の血液から血漿を得る手段;哺乳動物の炎症の容態を少なくとも部分的に媒介する循環ガレクチン−3を選択的に除去する手段;及び血漿から循環ガレクチン−3を選択的に除去したのちに血漿を哺乳動物の血液へ戻すための手段を備え、
得られた血漿中の、哺乳動物の炎症の容態を少なくとも部分的に媒介する循環ガレクチン−3を選択的に除去する手段が、哺乳動物の血清中の循環ガレクチン−3のレベルを少なくとも10%低減させるレベルに相当する量の循環ガレクチン−3を選択的に除去する、哺乳動物の血液を血漿交換するシステム。 - 循環ガレクチン−3レベルを、少なくとも25%低減する、請求項1に記載のシステム。
- 循環ガレクチン−3レベルを、50%低減する、請求項1に記載のシステム。
- 循環ガレクチン−3レベルを、少なくとも75%低減する、請求項1に記載のシステム。
- 前記血漿を得る手段が、血液から赤血球を取り出すことにより血漿を分離し、前記循環ガレクチン−3を選択的に除去する手段が、血漿を、循環ガレクチン−3と結合する抗体と接触させ、並びにあらゆるこのような抗体およびこれらと結合した循環ガレクチン−3を、前記の分離された残りの血漿から分離して、低下したレベルの循環ガレクチン−3を有する血漿を得る、請求項1に記載のシステム。
- 前記循環ガレクチン−3と結合する抗体が、前記抗体とそれに結合したあらゆる循環ガレクチン−3の、前記の分離された血漿からの分離をより容易にするエレメントにコンジュゲートしている、請求項5に記載のシステム。
- 前記エレメントが、前記抗体が付着しているカラム、足場(その上に前記抗体のアレイが付着している)、磁気で誘引することのできる粒子(そこに抗体が付着される)、およびその混合物である、請求項6に記載のシステム。
- 前記炎症が、分解不可能な病原体、自己免疫反応、アレルギー、電離放射線、核照射、糖尿病、心臓病および心機能不全、アテローム性動脈硬化症、気管支炎、腸潰瘍、腸の小腸炎、肝炎、肝硬変を伴う肝炎、寄生虫感染を伴う炎症、ウイルス感染を伴う炎症、真菌感染を伴う炎症、細菌感染を伴う炎症、関節炎を伴う炎症、器質的な精神疾患または脳疾患を伴う炎症、多発性硬化症および乾癬に関連している、請求項1に記載のシステム。
- 前記哺乳動物が、前記哺乳動物に投与しようとする医薬品の有効性を向上させるために、前記哺乳動物への医薬品の投与後に循環ガレクチン−3のレベルの低減を必要とする哺乳動物である、請求項1に記載のシステム。
- 前記医薬品が、スタチン系薬剤、抗腫瘍化学療法剤、抗炎症剤、TNF遮断剤、またはTNFα活性の促進剤である、請求項9に記載のシステム。
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PCT/US2012/057749 WO2013085604A1 (en) | 2011-12-08 | 2012-09-28 | Reduction of galectin-3 levels by plasmapheresis |
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US9549953B2 (en) | 2011-12-08 | 2017-01-24 | Eliaz Therapeutics, Inc. | Galectin-3 plasmapheresis therapy |
WO2014106803A1 (en) * | 2013-01-07 | 2014-07-10 | Eliaz, Isaac | Galectin-3 plasmapheresis therapy |
RU2680677C2 (ru) * | 2013-12-27 | 2019-02-25 | Элиаз Терапьютикс, Инк. | Устройство для плазмафереза |
JP2018509994A (ja) * | 2015-03-27 | 2018-04-12 | エリアス・セラピューティクス・インコーポレイテッドEliaz Therapeutics,Inc. | 患者選択的アフェレシス |
CN106370835A (zh) * | 2016-08-29 | 2017-02-01 | 中山大学孙逸仙纪念医院 | 皮肤离体样本的免疫组织化学染色检测galectin‑3 辅助诊断银屑病的方法 |
CN106645752B (zh) * | 2016-12-27 | 2018-02-16 | 中南大学湘雅医院 | Galectin‑10及其特异性抗体在制备检测鼻咽癌试剂盒中的应用 |
CN113711036A (zh) | 2019-01-30 | 2021-11-26 | 真和制药有限公司 | 抗gal3抗体及其用途 |
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US6245038B1 (en) | 1997-01-07 | 2001-06-12 | Helmut Borberg | Method for treatment of ophthalmological diseases |
US6627151B1 (en) | 1997-06-13 | 2003-09-30 | Helmut Borberg | Method for treatment diseases associated with a deterioration of the macrocirculation, microcirculation and organ perfusion |
US20020159995A1 (en) * | 1997-07-30 | 2002-10-31 | Renal Tech International | Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood, generated as a result of extracorporeal blood processing |
US6274566B1 (en) | 1999-02-23 | 2001-08-14 | Econugenics, Inc. | Methods for treating mammals with modified alginates and pectins |
US6462029B1 (en) | 1999-02-23 | 2002-10-08 | Econugenics | Compositions and methods for treating mammals with modified alginates and modified pectins |
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US20040223971A1 (en) * | 2003-04-07 | 2004-11-11 | Glycogenesys, Inc. | Composition and uses of galectin antagonists |
JP2006522163A (ja) * | 2003-04-07 | 2006-09-28 | グリコジェネシス, インク. | ガレクチンアンタゴニストの組成物と使用 |
EP1522857A1 (en) * | 2003-10-09 | 2005-04-13 | Universiteit Maastricht | Method for identifying a subject at risk of developing heart failure by determining the level of galectin-3 or thrombospondin-2 |
US9427449B2 (en) | 2005-08-26 | 2016-08-30 | Econugenics, Inc. | Binding of galectin-3 by low molecular weight pectin |
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DE112009001564A5 (de) * | 2008-07-14 | 2011-03-31 | Schaeffler Technologies Gmbh & Co. Kg | Trockenkupplung |
WO2010065765A2 (en) * | 2008-12-04 | 2010-06-10 | Aethlon Medical, Inc. | Affinity capture of circulating biomarkers |
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CA2858601C (en) | 2020-11-17 |
EP3151009A1 (en) | 2017-04-05 |
MX355213B (es) | 2018-04-10 |
BR112014012823A2 (pt) | 2015-09-29 |
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CN104011544A (zh) | 2014-08-27 |
DK2788761T3 (en) | 2018-04-30 |
JP2016175925A (ja) | 2016-10-06 |
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CA3036327A1 (en) | 2013-06-13 |
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JP6248138B2 (ja) | 2017-12-13 |
CA3036327C (en) | 2021-10-19 |
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