JP2001508430A - 免疫抑制因子のエンドサイトーシスによる提示のための化合物、組成物及び方法 - Google Patents
免疫抑制因子のエンドサイトーシスによる提示のための化合物、組成物及び方法Info
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- JP2001508430A JP2001508430A JP53040098A JP53040098A JP2001508430A JP 2001508430 A JP2001508430 A JP 2001508430A JP 53040098 A JP53040098 A JP 53040098A JP 53040098 A JP53040098 A JP 53040098A JP 2001508430 A JP2001508430 A JP 2001508430A
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- plp1
- cells
- cell
- plp
- peptide
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Classifications
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
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- C—CHEMISTRY; METALLURGY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.少なくとも1つのFcレセプターリガンドと少なくとも1つの免疫抑制因子 とを含む、脊椎動物の抗原提示細胞の表面に免疫抑制因子をエンドサイトーシス によって提示するための免疫調節剤。 2.前記免疫抑制因子がT細胞レセプターアンタゴニスト、T細胞レセプター アゴニスト及びこれらの組合せからなる群から選択される請求項1に記載の免疫 調節剤。 3.前記免疫抑制因子がペプチドアンタゴニストを含む請求項2に記載の免疫 調節剤。 4.前記ペプチドアンタゴニストが、プロテオリピドタンパク質に対するT細 胞応答を活性化し得るペプチドアゴニストの類似体である請求項3に記載の免疫 調節剤。 5.前記の少なくとも1つのFcレセプターリガンドが免疫グロブリン分子の定 常領域のドメインの少なくとも一部分を含む請求項1に記載の免疫調節剤。 6.前記免疫調節剤がポリペプチドを含む請求項1に記載の免疫調節剤。 7.前記免疫調節剤が抗体-抗原複合体を含む請求項1に記載の免疫調節剤。 8.前記免疫調節剤がキメラ抗体である請求項1に記載の免疫調節剤。 9.前記キメラ抗体がT細胞レセプターアンタゴニストを含む請求項8に記載 の免疫調節剤。 10.前記T細胞レセプターアンタゴニストが少なくとも1つの相補性決定領 域内で発現される請求項9に記載の免疫調節剤。 11.請求項1〜10のいずれか1項に記載の化合物を含む、脊椎動物の抗原 提示細胞の表面に免疫抑制因子をエンドサイトーシスによって提示するための医 薬組成物。 12.免疫疾患の治療を必要としている患者において該疾患の治療用医薬組成 物を製造するための、請求項1〜10のいずれか1項に記載の免疫調節剤の使用 。 13.前記免疫疾患が、自己免疫疾患、アレルギー応答及び移植片拒絶からな る群から選択される疾患を含む請求項12に記載の方法。 14.前記免疫疾患が、多発性硬化症、狼瘡、リウマチ様関節炎、強皮症、イ ンスリン依存性糖尿病及び潰瘍性大陽炎からなる群から選択される自己免疫疾患 を含む請求項13に記載の方法。 15.前記患者が乳児又は新生児である請求項12に記載の方法。 16.T細胞寛容の誘導を必要としている患者においてこの寛容の誘導用医薬 組成物を製造するための、請求項1〜10のいずれか1項に記載の免疫調節剤の 使用。 17.前記T細胞寛容が、多発性硬化症、狼瘡、リウマチ様関節炎、強皮症、 インスリン依存性糖尿病及び潰瘍性大腸炎からなる群から選択される自己免疫疾 患に関係している請求項16に記載の方法。 18.前記患者が乳児又は新生児である請求項16に記載の方法。 19.患者に、生理学的に許容可能な担体又は希釈剤と組み合わせて免疫調節 剤を含む治療的に有効な量の医薬組成物を投与することを含み、前記免疫調節剤 は少なくとも1つのFcレセプターリガンドと少なくとも1つの免疫抑制因子とを 含む免疫疾患の治療方法。 20.前記免疫抑制因子が、T細胞レセプターアンタゴニスト、T細胞レセプ ターアゴニスト及びこれらの組合せからなる群から選択される請求項19に記載 の方法。 21.前記免疫抑制因子がプロテオリピドタンパク質に対するT細胞応答を活 性化し得るペプチドアゴニストの類似体である請求項19に記載の方法。 22.前記免疫抑制因子がミエリン塩基性タンパク質に対するT細胞応答を活 性化し得るペプチドアゴニストの類似体である請求項19に記載の方法。 23.前記Fcレセプターリガンドが免疫グロブリン分子の定常領域の1つのド メインの少なくとも一部分を含む請求項19に記載の方法。 24.前記免疫グロブリン分子がヒトIgG分子である請求項23に記載の方法 。 25.前記免疫調節剤がポリペプチドを含む請求項19に記載の方法。 26.前記免疫調節剤がキメラ抗体を含む請求項25に記載の方法。 27.前記免疫疾患が、自己免疫疾患、アレルギー応答及び移植片拒絶からな る群から選択される疾患を含む請求項19に記載の方法。 28.前記免疫疾患が、多発性硬化症、狼瘡、リウマチ様関節炎、強皮症、イ ンスリン依存性糖尿病及び潰瘍性大腸炎からなる群から選択される自己免疫疾患 を含む請求項27に記載の方法。 29.少なくとも1つのFcレセプターリガンドと少なくとも1つの免疫抑制因 子とを含むポリペプチドをコードするヌクレオチド配列を含む組換えポリヌクレ オチド分子で適当な宿主細胞を形質転換するか又はトランスフェクションし、 前記細胞が組換えポリヌクレオチド分子を発現する条件下で前記の形質転換又 はトランスフェクションした宿主細胞を培養して、免疫調節剤の少なくとも一部 分を含む前記ポリペプチドを産生させ、 前記免疫調節剤を回収する ことを含む、脊椎動物の抗原提示細胞の表面に免疫抑制因子をエンドサイトーシ スによって提示するための免疫調節剤を製造する方法。 30.前記免疫抑制因子が、T細胞レセプターアンタゴニスト、T細胞レセプ ターアゴニスト及びこれらの組合せからなる群から選択される請求項29に記載 の方法。 31.前記免疫抑制因子がミエリン塩基性タンパク質に対するT細胞応答を活 性化し得るペプチドアゴニストの類似体である請求項29に記載の方法。 32.前記Fcレセプターリガンドが免疫グロブリン分子の定常領域の1つのド メインの少なくとも一部分を含む請求項29に記載の方法。 33.前記免疫調節剤がキメラ抗体を含む請求項29に記載の方法。 34.前記キメラ抗体が、少なくとも1つの相補性決定領域がT細胞レセプタ ーアンタゴニストで置換されているH鎖を含む請求項33に記載の方法。 35.Fcレセプターリガンドに相当する少なくとも1つのヌクレオチド配列と 免疫抑制因子に相当する少なくとも1つのヌクレオチド配列とを含む、ポリペプ チドをコードする組換えポリヌクレオチド分子。 36.前記免疫抑制因子が、T細胞レセプターアンタゴニスト、T細胞レセプ ターアゴニスト及びこれらの組合せからなる群から選択される請求項35に記載 のポリヌクレオチド分子。 37.前記ポリヌクレオチド分子が、免疫グロブリン分子の定常領域の1つの ドメインの少なくとも一部分に相当する配列を含む請求項35に記載のポリヌク レオチド分子。 38.前記免疫グロブリン分子がヒトIgG分子である請求項37に記載のポリ ヌクレオチド分子。 39.前記ポリヌクレオチド分子が、相補性決定領域が少なくとも部分的に欠 失しておりそしてT細胞レセプターアンタゴニストに相当するヌクレオチド配列 で置換されている免疫グロブリンH鎖に相当するヌクレオチド配列をコードする 請求項35に記載のポリヌクレオチド分子。 40.請求項35〜39のいずれか1項に記載の組換えポリヌクレオチド分子 を含む、トランスフェクションされるか又は形質転換された細胞。 41.Fcレセプターを発現する複数の抗原提示細胞を含む培地を提供し、 前記培地を、少なくとも1つのFcレセプターリガンド及び少なくとも1つの免 疫抑制因子を有する免疫調節剤並びに適合担体を含む免疫調節剤含有組成物と組 み合わせる ことを含む、免疫抑制因子をインビトロでエンドサイトーシスによって効果的に 提示する方法。 42.前記Fcレセプターリガンドが免疫グロブリン分子の定常領域の1つのド メインの少なくとも一部分を含む請求項41に記載の方法。 43.前記免疫調節剤がポリペプチドを含む請求項41に記載の方法。
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US08/779,767 US6737057B1 (en) | 1997-01-07 | 1997-01-07 | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
US08/779,767 | 1997-01-07 | ||
PCT/US1998/000520 WO1998030706A1 (en) | 1997-01-07 | 1998-01-07 | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
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US (2) | US6737057B1 (ja) |
EP (1) | EP1012308A1 (ja) |
JP (1) | JP2001508430A (ja) |
AU (1) | AU744885B2 (ja) |
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US20020081298A1 (en) * | 1997-01-07 | 2002-06-27 | Habib Zaghouani | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
EP1093464A2 (en) * | 1998-07-06 | 2001-04-25 | The University Of Tennessee Research Corporation | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
AU5474399A (en) * | 1998-08-10 | 2000-03-06 | Chiron Corporation | Engineered antigen-presenting cells expressing an array of antigens and uses thereof |
SK782002A3 (en) * | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
EP1598370A3 (en) * | 1999-10-27 | 2006-05-10 | Cel-Sci Corporation | Methods of preparation and composition of peptide constructs useful for treatment of autoimmune and transplant related host versus graft conditions |
EP1223958A4 (en) * | 1999-10-27 | 2004-07-21 | Cel Sci Corp | PREPARATION METHODS AND COMPOUNDS OF PEPTIDE CONSTRUCTIONS CONCERNING THE TREATMENT OF AUTOIMMUNE AND. TRANSPLANTATION-RELATED "HOST VERSUS GRAFT" PATHOGENESE PROPERTIES |
AU2001265417A1 (en) * | 2000-06-05 | 2002-04-08 | University Of Tennessee Corporation | Compositions and methods for the endocytic presentation of immunosuppressive factors |
US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
US7744876B2 (en) * | 2002-04-09 | 2010-06-29 | The Curators Of The University Of Missouri | Methods and compositions for treatment, prevention, suppression, and/or delaying the onset of type 1 diabetes |
US8603471B2 (en) * | 2002-04-09 | 2013-12-10 | The Curators Of The University Of Missouri | Methods and compositions for preventing the onset of type 1 diabetes |
AU2003230830A1 (en) | 2002-04-09 | 2003-10-27 | The Curators Of The University Of Missouri | Treatment of type 1 diabetes before and after expression of predisposition markers |
US8609091B2 (en) | 2002-04-09 | 2013-12-17 | The Curators Of The University Of Missouri | Method for endocytic presentation of an immunosuppressive for the treatment of type 1 diabetes |
US8603472B2 (en) * | 2002-04-09 | 2013-12-10 | The Curators Of The University Of Missouri | Methods and compositions reversing pre-diabetes using fusion proteins comprising a GAD peptide |
EP1507548B1 (en) * | 2002-05-27 | 2014-10-01 | CanImGuide Therapeutics AB | Method for determining immune system affecting compounds |
EA011859B9 (ru) | 2004-01-05 | 2013-07-30 | Емд Лексиген Ресерч Сентер Корп. | Соединения для адресной доставки препарата к ткани или органу-мишени |
SE0402536D0 (sv) | 2004-10-20 | 2004-10-20 | Therim Diagnostica Ab | Immunoregulation in cancer, chronic inflammatory and autoimmune diseases |
US8110347B2 (en) * | 2005-04-15 | 2012-02-07 | Canimguide Therapeutics Ab | Diagnostic method for detecting cancer by measuring amount of cytokine like IL-6 |
EP3636667A3 (en) | 2007-05-08 | 2020-07-29 | CanImGuide Therapeutics AB | Immunoregulatory structures from normally occurring proteins |
CA2759333A1 (en) | 2009-04-22 | 2010-10-28 | Merck Patent Gmbh | Antibody fusion proteins with modified fcrn binding sites |
US9850296B2 (en) | 2010-08-10 | 2017-12-26 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
CN108117586A (zh) | 2010-08-10 | 2018-06-05 | 洛桑聚合联合学院 | 红细胞结合性治疗剂 |
US9517257B2 (en) | 2010-08-10 | 2016-12-13 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
JP6744227B2 (ja) | 2014-02-21 | 2020-08-19 | エコール・ポリテクニーク・フェデラル・ドゥ・ローザンヌ(ウペエフエル)Ecole Polytechnique Federale de Lausanne (EPFL) | 糖標的化治療剤 |
US10046056B2 (en) | 2014-02-21 | 2018-08-14 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
US10953101B2 (en) | 2014-02-21 | 2021-03-23 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
US10946079B2 (en) | 2014-02-21 | 2021-03-16 | Ecole Polytechnique Federale De Lausanne | Glycotargeting therapeutics |
CA2971288A1 (en) | 2015-02-02 | 2016-08-11 | The University Of Birmingham | Targeting moiety peptide epitope complexes having a plurality of t-cell epitopes |
WO2018232176A1 (en) | 2017-06-16 | 2018-12-20 | The University Of Chicago | Compositions and methods for inducing immune tolerance |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4954617A (en) | 1986-07-07 | 1990-09-04 | Trustees Of Dartmouth College | Monoclonal antibodies to FC receptors for immunoglobulin G on human mononuclear phagocytes |
AU616338B2 (en) | 1989-02-02 | 1991-10-24 | Mato Maschinen- Und Metallwarenfabrik Curt Matthaei Gmbh & Co Kg | Belt skimming device |
JP3355351B2 (ja) * | 1989-02-24 | 2002-12-09 | ユーロジェン・ホールディング・ソシエテ・アノニム | 遺伝的に工作されたイムノグロブリン |
US5612035A (en) | 1989-03-21 | 1997-03-18 | The Immune Response Corporation | Vaccination against diseases resulting from pathogenic responses by specific T cell populations |
GB8928874D0 (en) * | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US5969109A (en) * | 1990-02-28 | 1999-10-19 | Bona; Constantin | Chimeric antibodies comprising antigen binding sites and B and T cell epitopes |
WO1992005793A1 (en) | 1990-10-05 | 1992-04-16 | Medarex, Inc. | Targeted immunostimulation with bispecific reagents |
WO1993006135A1 (en) | 1991-09-23 | 1993-04-01 | Genentech, Inc. | Diagnosing and treating autoimmune disorders |
US5474771A (en) | 1991-11-15 | 1995-12-12 | The Trustees Of Columbia University In The City Of New York | Murine monoclonal antibody (5c8) recognizes a human glycoprotein on the surface of T-lymphocytes, compositions containing same |
WO1993010220A1 (en) | 1991-11-19 | 1993-05-27 | Anergen, Inc. | Soluble mhc molecules and their uses |
GB9223377D0 (en) | 1992-11-04 | 1992-12-23 | Medarex Inc | Humanized antibodies to fc receptors for immunoglobulin on human mononuclear phagocytes |
WO1994014847A1 (en) | 1992-12-24 | 1994-07-07 | The Regents Of The University Of California | Genetically engineered immunoglobulins |
US5885573A (en) | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
US5820866A (en) | 1994-03-04 | 1998-10-13 | National Jewish Center For Immunology And Respiratory Medicine | Product and process for T cell regulation |
US6329499B1 (en) | 1994-11-18 | 2001-12-11 | Neurocrine Biosciences, Inc. | Methods for treatment of multiple sclerosis using peptide analogues of human myelin basic protein |
KR100682350B1 (ko) | 1995-05-02 | 2008-11-06 | 알렉시온 파마슈티칼스, 인코오포레이티드 | 변형된미엘린단백질분자 |
US20020081298A1 (en) * | 1997-01-07 | 2002-06-27 | Habib Zaghouani | Compounds, compositions and methods for the endocytic presentation of immunosuppressive factors |
AU5428598A (en) | 1997-08-19 | 1999-03-08 | Mount Sinai School Of Medicine Of The City University Of New York, The | Epitope-bearing major histocompatibility complex class II element/immunoglobulin chimeric molecules |
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CA2277582A1 (en) | 1998-07-16 |
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