JPH09500867A - 細胞活性を制御するための新規作用薬 - Google Patents
細胞活性を制御するための新規作用薬Info
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- JPH09500867A JPH09500867A JP6520806A JP52080694A JPH09500867A JP H09500867 A JPH09500867 A JP H09500867A JP 6520806 A JP6520806 A JP 6520806A JP 52080694 A JP52080694 A JP 52080694A JP H09500867 A JPH09500867 A JP H09500867A
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Obesity (AREA)
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- Heart & Thoracic Surgery (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.リサイクル性の膜小胞(Recyclable Membrane Vesicle、RMVs) 中の細胞 膜への完全な膜タンパク質類(Integral Membrane Proteins、IMPs)の輸送 を制御することによって細胞の外部環境と細胞の相互作用を制御する本作用薬。 2.細胞膜を通過しての代謝物の輸送に応答するIMPのレベルを制御し、その 結果として、細胞を通って代謝物の輸送をあるいは細胞内の代謝物の有用性を制 御する請求項1の作用薬。 3.細胞膜を通過して細胞内外への代謝物の輸送に応答するIMPのレベルを制 御し、その結果として、細胞を通って代謝物の輸送をあるいは細胞内の代謝物の 有用性を制御する請求項1の作用薬。 4.イオンに対する細胞の原形質膜の選択的透過性に応答するIMPのレベルを 制御し、細胞内イオンの濃度を転調する請求項1の作用薬。 5.信号分子の認識に応答するIMPのレベルを制御し、信号分子の細胞への認 識性を転調する請求項1の作用薬。 6.信号分子の膜への結合につながる細胞膜を通過しての信号の伝達に応答する IMPのレベルを制御し、信号分子への細胞の応答性を転調する請求項1の作用 薬。 7.摂取された抗原から誘導したペプチド断片の細胞表面での描写に応答するI MPのレベルを制御する請求項1の作用薬。 8.標的化細胞タイプに対する標的化特性を有し、作用薬の有効範囲を該細胞タ イプに限定する、前記記載のいずれかの作用薬。 9.下記の方法によって連結した3つのドメインB、TおよびEからなる前記記 載のいずれかの作用薬。 ドメインB--ドメインT--ドメインE ここで ドメインBは、エンドサイトーシスを受ける細胞の結合部位に本作用薬を結合し てエンドソームを生成する結合ドメインである。 ドメインTは、エンドソーム内からエンドソーム膜を通して細胞の細胞質ゾル中 に本作用薬(結合部位とともにもしくは無しに)を輸送する輸送ドメインである 。 ドメインEは、細胞の表面にIMPsを輸送する本RMVsの能力を阻害する効 果ドメインである。 10.下記の方法で互いに連結した3つのドメインB,TそしてEからなる請求 項9の作用薬。 ドメインB--X--ドメインT--X--ドメインE ここでXはスペーサー分子あるいは共有結合、ただし少なくとも一つのXはスペ ーサー分子である。 11.ドメインBが、特殊な細胞タイプに特徴的な結合部位に結合する結合ドメ インである請求項9または10の作用薬。 12.ドメインBがエンドサイトーシスを受け、エンドソームを生成する標的細 胞上の表面抗原に対するモノクローナル抗体からなり、ドメインTが得られたエ ンドソームから細胞の細胞質ゾルへ作用薬を輸送するトキシン分子のドメインま たはドメイン断片からなり、ドメインEが、Zn++依存性タンパク質分解活性で ドメインTと機能的に異なるトキシン分子のドメインまたはドメイン断片からな る、前記のいずれかの請求項に記載の作用薬。 13.ドメインBが、エンドサイトーシスを受け、エンドソームを生成する標的 細胞上の細胞表面受容体へのリガンドからなり、ドメインTが得られたエンドソ ームから細胞の細胞質ゾルへ作用薬を輸送するトキシン分子のドメインまたはド メイン断片からなり、ドメインEが、Zn++依存性タンパク質分解活性でドメイ ンTと機能的に異なるトキシン分子のドメインまたはドメイン断片からなる、前 記のいずれかの請求項に記載の作用薬Q 14.ドメインBがインシュリン様成長因子へのリガンドであり、ドメインTが 細胞膜を通ってトキシンの輸送に応答するボツリヌスニューロトキシン重鎖のド メインまたはドメイン断片であり、ドメインEがZn++依存性メタロプロテアー ゼ活性をもつボツリヌスニューロトキシン軽鎖のドメインまたはドメイン断片で ある、インシュリンに応答における脂肪細胞によるグルコース取り込み速度に影 響する、請求項13の作用薬。 15.ドメインTおよびEがクロストリアルニューロトキシンから得られる請求 項9から14のいずれかに記載の作用薬。 16.下記の方法で3つのドメインB,TおよびEが共有的に結合してなる前記 請求項のいずれかに記載の作用薬製造方法。 ドメインB--ドメインT--ドメインE ここで、ドメインBが、エンドサイトーシスを受けエンドソームを生成する細胞 の結合部位に作用薬を結合する結合ドメインであり、ドメインTが、エンドソー ム内からエンドソーム膜を通して細胞の細胞質ゾル中に本作用薬(結合部位とと もにもしくは無しに)を輸送する輸送ドメインであり、ドメインEは、細胞の表 面にIMPsを輸送するRMVsの能力を阻害する効果ドメインである。 17.下記の方法で3つのドメインB,TおよびEが共有的に結合してなる請求 項16の作用薬製造方法。 ドメインB--X--ドメインT--X--ドメインE ここで、Xはスペーサー分子あるいは共有結合、ただし少なくとも一つのXはス ペーサー分子である。 18.ドメインBが特定の細胞タイプに特徴的である結合部位に結合する結合ド メインである、請求項16または17の製造方法。 19.本作用薬をコードする遺伝的構築物を構築し、宿主生物に前記構築物を組 み込みそして本作用薬を生産するように構築物を発現させる請求項1から28の 請求項にいずれかに記載の作用薬を製造する方法。 20.グルコース代謝疾患の処置のための医薬として前記請求項のいずれかに記 載の作用薬またはそれらの薬理学的に受け入れられる塩の使用。 21.臨床的肥満の処置のための前記請求項のいずれかに記載の作用薬のいずれ かに記載された作用薬またはそれらの薬理学的に受け入れられる塩の使用。 22.高血圧の処置のための前記請求項作用薬のいずれかに記載された作用薬ま たはそれらの薬理学的に受け入れられる塩の使用。 23.炎症疾患の処置のための前記請求項作用薬のいずれかに記載された作用薬 またはそれらの薬理学的に受け入れられる塩の使用。 24.免疫系疾患の処置のための前記請求項作用薬のいずれかに記載された作用 薬またはそれらの薬理学的に受け入れられる塩の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9305735.4 | 1993-03-19 | ||
GB939305735A GB9305735D0 (en) | 1993-03-19 | 1993-03-19 | Novel agent for controlling cell activity |
PCT/GB1994/000558 WO1994021300A1 (en) | 1993-03-19 | 1994-03-18 | Novel agent for controlling cell activity |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007211720A Division JP4740206B2 (ja) | 1993-03-19 | 2007-08-15 | 細胞活性を制御するための新規作用薬 |
Publications (2)
Publication Number | Publication Date |
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JPH09500867A true JPH09500867A (ja) | 1997-01-28 |
JP4300265B2 JP4300265B2 (ja) | 2009-07-22 |
Family
ID=10732382
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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JP52080694A Expired - Lifetime JP4300265B2 (ja) | 1993-03-19 | 1994-03-18 | 細胞活性を制御するための新規作用薬 |
JP2007211720A Expired - Lifetime JP4740206B2 (ja) | 1993-03-19 | 2007-08-15 | 細胞活性を制御するための新規作用薬 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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JP2007211720A Expired - Lifetime JP4740206B2 (ja) | 1993-03-19 | 2007-08-15 | 細胞活性を制御するための新規作用薬 |
Country Status (24)
Country | Link |
---|---|
US (1) | US20080070278A1 (ja) |
EP (1) | EP0689459B1 (ja) |
JP (2) | JP4300265B2 (ja) |
KR (1) | KR960700756A (ja) |
CN (1) | CN1195551C (ja) |
AT (1) | ATE228856T1 (ja) |
AU (1) | AU671203C (ja) |
BR (1) | BR9406232A (ja) |
CA (1) | CA2158647A1 (ja) |
CZ (1) | CZ242695A3 (ja) |
DE (1) | DE69431832T2 (ja) |
DK (1) | DK0689459T3 (ja) |
ES (1) | ES2183836T3 (ja) |
FI (1) | FI954390A (ja) |
GB (1) | GB9305735D0 (ja) |
HU (1) | HU217220B (ja) |
IL (1) | IL109045A0 (ja) |
IN (1) | IN178499B (ja) |
NO (1) | NO953643L (ja) |
NZ (1) | NZ262484A (ja) |
PL (1) | PL178895B1 (ja) |
PT (1) | PT689459E (ja) |
SG (1) | SG73411A1 (ja) |
SK (1) | SK115595A3 (ja) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002514659A (ja) * | 1998-05-13 | 2002-05-21 | ビオテコン ゲゼルシャフト フュア ビオテヒノロギッシェ エントヴィックルング ウント コンズルティンク エムベーハー | マスト細胞の脱顆粒を阻害するためのハイブリッドタンパク質とその使用 |
JP2003513941A (ja) * | 1999-11-12 | 2003-04-15 | マイクロバイオロジカル リサーチ オーソリティ | 溶菌毒素および毒素結合体の使用 |
JP2007505094A (ja) * | 2003-09-11 | 2007-03-08 | ヘルス プロテクション エージェンシー | リターゲティングされる毒素結合体の設計 |
JP2011074091A (ja) * | 1999-09-23 | 2011-04-14 | Syntaxin Ltd | 非神経細胞からの分泌の阻害 |
JP4740206B2 (ja) * | 1993-03-19 | 2011-08-03 | イプセン ディベロプメンツ リミテッド | 細胞活性を制御するための新規作用薬 |
JP2011522560A (ja) * | 2008-06-12 | 2011-08-04 | シンタクシン リミテッド | 神経内分泌疾患の抑制 |
US8796216B2 (en) | 2008-06-12 | 2014-08-05 | Syntaxin Limited | Suppression of neuroendocrine diseases |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9617671D0 (en) | 1996-08-23 | 1996-10-02 | Microbiological Res Authority | Recombinant toxin fragments |
US7192596B2 (en) * | 1996-08-23 | 2007-03-20 | The Health Protection Agency Ipsen Limited | Recombinant toxin fragments |
DK1531647T3 (da) * | 2003-11-14 | 2010-05-10 | Starhome Gmbh | Styring af indkommende opkald til roamende abonnenter i et cellulært mobiltelefonnet |
US8399400B2 (en) | 2004-12-01 | 2013-03-19 | Syntaxin, Ltd. | Fusion proteins |
US8603779B2 (en) | 2004-12-01 | 2013-12-10 | Syntaxin, Ltd. | Non-cytotoxic protein conjugates |
GB0426394D0 (en) * | 2004-12-01 | 2005-01-05 | Health Prot Agency | Fusion proteins |
US7659092B2 (en) * | 2004-12-01 | 2010-02-09 | Syntaxin, Ltd. | Fusion proteins |
US8512984B2 (en) | 2004-12-01 | 2013-08-20 | Syntaxin, Ltd. | Non-cytotoxic protein conjugates |
US8778634B2 (en) | 2004-12-01 | 2014-07-15 | Syntaxin, Ltd. | Non-cytotoxic protein conjugates |
US9623117B2 (en) * | 2011-04-04 | 2017-04-18 | Wisconsin Alumni Research Foundation | Method for selective targeting and entry of bacterial toxins to cells |
GB201312317D0 (en) | 2013-07-09 | 2013-08-21 | Syntaxin Ltd | Cationic neurotoxins |
US10647750B2 (en) | 2015-01-09 | 2020-05-12 | Ipsen Bioinnovation Limited | Cationic neurotoxins |
GB201517450D0 (en) | 2015-10-02 | 2015-11-18 | Ipsen Biopharm Ltd | Method |
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US4664911A (en) * | 1983-06-21 | 1987-05-12 | Board Of Regents, University Of Texas System | Immunotoxin conjugates employing toxin B chain moieties |
US5668255A (en) * | 1984-06-07 | 1997-09-16 | Seragen, Inc. | Hybrid molecules having translocation region and cell-binding region |
EP0329184A3 (en) * | 1988-02-19 | 1990-05-23 | Neorx Corporation | Antimers and antimeric conjugation |
US5045451A (en) * | 1988-10-26 | 1991-09-03 | Board Of Regents | Methods for screening antibodies for use as immunotoxins |
WO1990010692A1 (en) * | 1989-03-15 | 1990-09-20 | University Of Florida | Monoclonal antibody for use in detection and treatment of childhood leukemia |
US5300496A (en) * | 1991-09-30 | 1994-04-05 | The University Of British Columbia | Complexed vanadium for the treatment of diabetes mellitus |
US5877295A (en) * | 1992-09-30 | 1999-03-02 | The Center For Blood Research | Antibodies which bind a subpopulation of Mac-1 (CD11b/CD18) molecules which mediate neutrophil adhesion to ICAM-1 and fibrinogen |
GB9305735D0 (en) * | 1993-03-19 | 1993-05-05 | North John R | Novel agent for controlling cell activity |
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JP4740206B2 (ja) * | 1993-03-19 | 2011-08-03 | イプセン ディベロプメンツ リミテッド | 細胞活性を制御するための新規作用薬 |
JP2002514659A (ja) * | 1998-05-13 | 2002-05-21 | ビオテコン ゲゼルシャフト フュア ビオテヒノロギッシェ エントヴィックルング ウント コンズルティンク エムベーハー | マスト細胞の脱顆粒を阻害するためのハイブリッドタンパク質とその使用 |
JP2011074091A (ja) * | 1999-09-23 | 2011-04-14 | Syntaxin Ltd | 非神経細胞からの分泌の阻害 |
JP2011184459A (ja) * | 1999-09-23 | 2011-09-22 | Syntaxin Ltd | 非神経細胞からの分泌の阻害 |
JP2014037429A (ja) * | 1999-09-23 | 2014-02-27 | Syntaxin Ltd | 非神経細胞からの分泌の阻害 |
JP2003513941A (ja) * | 1999-11-12 | 2003-04-15 | マイクロバイオロジカル リサーチ オーソリティ | 溶菌毒素および毒素結合体の使用 |
JP2007505094A (ja) * | 2003-09-11 | 2007-03-08 | ヘルス プロテクション エージェンシー | リターゲティングされる毒素結合体の設計 |
JP2012139222A (ja) * | 2003-09-11 | 2012-07-26 | Syntaxin Ltd | リターゲティングされる毒素結合体の設計 |
JP2011522560A (ja) * | 2008-06-12 | 2011-08-04 | シンタクシン リミテッド | 神経内分泌疾患の抑制 |
US8796216B2 (en) | 2008-06-12 | 2014-08-05 | Syntaxin Limited | Suppression of neuroendocrine diseases |
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