JP2007523088A - Il−23活性を調節する方法;関連する試薬 - Google Patents
Il−23活性を調節する方法;関連する試薬 Download PDFInfo
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Abstract
Description
本発明は一般的に、哺乳動物サイトカインの使用に関する。より具体的には、本発明は、インフルエンザウイルスを処置におけるサイトカインの機能を開示する。
免疫系は、個体を感染性因子(例えば、ウイルス、細菌、多細胞生物、および癌)から保護する。この系としては、数種の型のリンパ球系細胞および骨髄性細胞(例えば、単球、マクロファージ、樹状細胞(DC)、好酸球、T細胞、B細胞および好中球)が挙げられる。これらのリンパ球系細胞および骨髄性細胞は、多くの場合、サイトカインとして公知であるシグナル伝達タンパク質を産生する。免疫応答としては、炎症(すなわち、全身的かまたは身体の特定の場所における免疫細胞の蓄積)が挙げられる。感染性因子または外因性の物質に対する応答において、免疫細胞は、サイトカインを分泌し、次に免疫細胞の増殖、発生、分化または遊走を調節する。サイトカインは、多くのウイルス感染に対する免疫応答に関係している(例えば、非特許文献1;非特許文献2;非特許文献3;非特許文献4;非特許文献5;非特許文献6;非特許文献7;非特許文献8;非特許文献9を参照のこと)。
Abbasら(編)「Cellular and Molecular Immunology」、Philadelphia、PA、W.B.Saunders Co.、2000年 OppenheimおよびFeldmann(編)、「Cytokine Reference」、San Diego、CA、Academic Press、2001年 Kaufmannら、「Immunobiol.」、2001年、第204巻、603〜613ページ SaurezおよびSchultz−Cheery、「Dev.Comp.Immunol.」、2000年、第24巻、269〜283ページ van ReethおよびNauwynck、「Vet.Res.」、2000年、第31巻、187〜213ページ Garcia−Sastre、「Virology」、2001年、第279巻、375〜384ページ Katzeら、「Nat.Rev.Immunol.」、2002年、第2巻、675〜687ページ van Reeth、「Vet.Microbiol.」、2000年、第74巻、109〜116ページ Tripp、「Curr.Pharm.Des.」、2003年、第9巻、51〜59ページ Treanor、「New Engl.J.Med.」、2004年、第350巻、218〜220ページ SteinhauerおよびSkehel、「Annu.Rev.Genet.」、2002年、第36巻、305〜332ページ Mozdzanowskaら、「J.Immunol.」、2000年、第164巻、2635〜2643ページ Nicholsonら、「The Lancet」、2003年、第362巻、1733〜1745ページ KaechおよびAhmed、「Science」、2003年、第300巻、263〜265ページ SunおよびBevan、「Science」、2003年、第300巻、339〜342ページ Turnerら、「Immunity」、2003年、第18巻、549〜559ページ Elyら、「J.Immunol.」、2003年、第170巻、1423〜1429ページ Tophamら、2001年、「J.Immunol.」、第167巻、6983〜6990ページ YewellおよびGarcia−Sastre、「Curr.Opin.Microbiol.」、2002年、第5巻、414〜418ページ 「Canadian Medical Assoc.J.」、第168巻、49〜57ページ Nguyenら、「J.Virol.」、2000年、第74巻、5495〜5501ページ Grahamら、「J.Exp.Med.」、1993年、第178巻、1725〜1732ページ WongおよびPamer、「Annu.Rev.Immunol.」、2003年、第21巻、29〜70ページ Croweら、「J.Exp.Med.」、2003年、第198巻、399〜410ページ Julkunenら、「Vaccine」、2001年、第19巻、S32〜S37ページ Webbyら、「Proc.Natl.Acad.Sci.USA」、2003年、第100巻、7235〜7240ページ Turnerら、「J.Immunol.」、2001年、第167巻、2753〜2758ページ Wileyら、「J.Immunol.」、2001年、第167巻、3293〜3299ページ Belzら、「J.Virol.」、2000年、第74巻、3486〜3493ページ Belzら、「Proc.Natl.Acad.Sci.USA」、1998年、第95巻、13812〜13817ページ
本発明は、部分的に、IL−23のアゴニストまたはアンタゴニストが、インフルエンザウイルスに対する免疫応答を調節するという知見に基づく。
添付の特許請求の範囲を含む本明細書において使用される場合、「a」、「an」および「the」のような単語の単数形態は、文脈が明らかにそうでないことを示さない限り、それらの対応する複数形の言及を包含する。
「活性化」、「刺激」および「処置」とは、細胞またはレセプターに対して適用される場合、文脈によってそうでないことが示されないか、または明示的にそうでないことが示されない限り、同じ意味(例えば、リガンドでの細胞またはレセプターの活性化、刺激または処置)を有し得る。「リガンド」は、天然リガンドおよび合成リガンド(例えば、サイトカイン、サイトカイン改変体、アナログ、ムテイン、および抗体由来の結合組成物)を包含する。「リガンド」はまた、低分子(例えば、サイトカインのペプチド模倣体、および抗体のペプチド模倣体)も包含する。「活性化」は、内部機構ならびに外部機構または環境因子によって調節される場合の細胞の活性化について言及し得る。例えば、細胞、組織、器官または生物の「応答」は、生化学的挙動または生理学的挙動(例えば、生物学的画分内の濃度、密度、接着または移動、遺伝子発現の速度、あるいは分化の状態)の変化を包含し、ここで、この変化は、活性化、刺激または処置、あるいは遺伝的プログラミングのような内部機構と相関する。
(1)疎水性:ノルロイシン、Ile、Val、Leu、Phe、CysまたはMet;
(2)中性で親水性:Cys、Ser、Thr;
(3)酸性:Asp、Glu;
(4)塩基性:Asn、Gln、His、Lys、Arg;
(5)鎖の配向に影響する残基:Gly、Pro;
(6)芳香性:Trp、Tyr、Phe;
(7)低分子アミノ酸:Gly、Ala、Ser。
本発明は、IL−23ヘテロダイマー、IL−23のp19サブユニット、IL−23およびIL−12のp40サブユニット、IL−23レセプターヘテロダイマー、IL−23RサブユニットまたはIL−12Rβ1サブユニットの、ポリペプチド、核酸、改変体、ムテインおよび模倣体を使用するウイルスまたはウイルス感染に対する免疫応答を調節する方法を提供する。ハイパーカイン(hyperkine)(すなわち、例えば、p40サブユニットに結合されたp19サブユニットを含む融合タンパク質)ならびにハイパーカインをコードする核酸を使用するための方法もまた提供される(Oppmannら(前出);Fischerら(1997)Nature Biotechnol.15:142−145;Rakemannら(1999)J.Biol.Chem.274:1257−1266;およびPetersら(1998)J.Immunol.161:3575−3581)。
本発明は、IL−23のアゴニストおよびアンタゴニストを使用する方法を提供する。IL−23のアゴニストは、例えば、IL−23、IL−23改変体、ムテイン、ハイパーカイン(hyperkine)、またはそれらに対するペプチド模倣体、IL−23Rに対するアゴニスト性抗体、およびこれらのアゴニストをコードする核酸を包含する。IL−23のアンタゴニストとしては、例えば、IL−23に対する抗体、IL−23Rに対するブロッキング抗体、IL−23Rのサブユニットの細胞外領域に基づいた可溶性レセプター、それらに対するペプチド模倣体、およびこれらのアンタゴニストをコードする核酸が挙げられる。
本発明は、ウイルス感染を処置または予防するための方法を提供する。これらの方法は、ワクチン(例えば、不活化インフルエンザ、生きた弱毒化インフルエンザワクチン、および粘膜ワクチン)、または低分子(例えば、アマンタジンおよびリマンタジンのようなイオンチャネルブロッカー、ならびにザナミビルおよびオセルタミビルのようなノイラミニダーゼインヒビター)と組み合わせて使用され得る。家庭用ブタ(domestic pig)、家畜、または家禽と同様に、農業において使用するために、呼吸器ウイルス(インフルエンザウイルスを含む)を処置および診断するための方法が、提供される(例えば、van Ginkelら(2000)Emerging Infectious Diseases 6:123−132;SidwellおよびSmee(2000)Antiviral Res.48:1−16;Couch(2000)New Engl.J.Med.343:1178−1787;YewdellおよびGarcia−Sastre(2002)Curr.Opinion Microbiol.5:414−418;Prober(2002)Semin.Pediatr.Infect.Dis.13:31−39;EllisおよびZambon(2002)Rev.Med.Virol.12:375−389;Zambon(2001)Rev.Med.Virol.11:227−241;Ulmer(2002)Vaccine 20(補遺2):S74−S76;TollisおよびDi Trani(2002)The Veterinary J.164:202−215を参照のこと)。
抗体、核酸ハイブリダイゼーション、およびPCR方法に基づいたインフルエンザの診断方法が、記載される。ウイルス(呼吸器ウイルスおよび粘膜ウイルス(例えば、インフルエンザ)を含む)に関連する試験および診断のための方法としては、酵素ベースのアッセイ(例えば、インフルエンザウイルスノイラミニダーゼインヒビター)、例えば、Madin Darbyイヌ腎細胞を使用した細胞ベースのアッセイ、および動物モデル(例えば、インフルエンザ感染についてのフェレット、マウス、およびニワトリの動物モデル)が挙げられる。
本発明は、粘膜ウイルス、呼吸器ウイルス、オルソミクソファミリーのウイルス、インフルエンザウイルス、麻疹ウイルス、ライノウイルス、コロナウイルス、エンテロウイルス、アデノウイルス、パラインフルエンザウイルス(PIV)、RSウイルス(RSV)、およびヘルペスウイルスを診断、予防、および処置するためのIL−23およびIL−23レセプターのアゴニストならびにアンタゴニストを使用する方法を提供する(例えば、Mackie(2003)Paediatr.Respir.Rev.4:84−90;Wilsonおよびvon Itzstein(2003)Curr.Drug Targets 4:389−408;Coxら(2004)Scand.J.Immunol.59:1−15;Wileyら(2001)J.Immunol 167:3293−3299;Ninomiyaら(2002)Vaccine 20:3123−3129;CroweおよびWilliams(2003)Paediatric Respiratory Revs.4:112−119;O’Hagan(1998)J.Pharm.Pharmacol.50:1−10を参照のこと)。
ウイルスの特徴付け、遺伝的操作によるウイルスの改変、ならびにウイルス感染の処置および診断のための標準的な技術が利用可能である(例えば、MahyおよびKango(1996)Virology Methods Manual,Academic Press,San Diego,CA;Flintら(2003)Principles of Virology:Molecular Biology,Pathogenesis,and Control of Animal Viruses,Am.Soc.Microbiol.,Wash.D.C.;Fieldsら(編)(2001)Virology,Lippincott,Williams,and Wilkins,NY,NY;Cann(2001)Principles of Molecular Virology,Academic Press,San Diego,CA;WhiteおよびFenner(1994)Medical Virology,第4版,Academic Press,San Diego,CA;Murphyら(1999)Veterinary Virology,第3版,Academic Press,San Diego,CA;Richmanら(編)(2002)Clinical Virology,第2版,Am.Soc.Microbiol.,Wash.D.C.を参照のこと)。
細胞障害アッセイ、細胞内IFNγアッセイ、抗原特異的CD8+T細胞を同定するための四量体方法のためのプロトコルおよびマウスを感染させるためのプロトコルが、提供される(例えば、Leanderら(2002)Mechanisms Ageing Devel.123:1167−1181;Halsteadら(2002)Nature Immunol.3:536−541を参照のこと)。CD8+T細胞は、パーフォリン/グランザイム機構によってか、またはFas媒介性細胞障害性によって、ウイルスに感染した細胞の細胞死を媒介する。51C放出アッセイ(5h)は、パーフォリン/グランザイム機構に対してのみ感受性である(Belzら(2000)J.Virol.74:3486−3493)。インフルエンザウイルスにマウスを感染させる研究は、比較的軽い株であるHKx31(H3N2としてもまた公知)、およびより毒性のPR8株(Flynnら(1998)Immunity 8:683−691;Belzら(2000)J.Virol.74:3486−3493)の使用を包含する。
インフルエンザA型ウイルスによる二次感染を、野生型マウス、p35KOマウス、およびp40KOマウスにおいて研究した。二次感染のためのプロトコルは、0日目にインフルエンザウイルスのPR8株を腹腔内に用いてプライミングし、30日目にインフルエンザウイルスのX31株を鼻腔内に再チャレンジする工程を包含する。35日目、すなわちX31ウイルスに曝露した5日後に、組織を収集した(表2)。
以下に記載するように、間隔を置いて、IL−23またはIL−12をマウスに投与(i.p.)した。一次感染の試験において、鼻腔内接種時にサイトカインの投与を開始した(表3)。二次感染の試験において、再チャレンジ時にサイトカインの投与を開始した(表4)。記憶応答についての試験において、最初のプライミング時にサイトカインの投与を開始したが、再チャレンジ時にはサイトカインを投与しなかった(表5)。
Claims (19)
- ウイルス、ウイルス性抗原またはウイルス感染に対するCD8+T細胞応答を調節する方法であって、該方法は、有効量の以下:
a)p19、IL−23またはIL−23Rのアゴニスト;あるいは
b)p19、IL−23またはIL−23Rのアンタゴニスト
を投与する工程を包含する、方法。 - 前記アンタゴニストが、以下:
a)p19、IL−23またはIL−23Rに特異的に結合する抗体由来の結合組成物;
b)IL−23に特異的に結合するIL−23R由来の可溶性レセプター;
c)p19またはIL−23Rをコードするポリヌクレオチドに特異的にハイブリダイズする、核酸;あるいは
d)低分子
を含む、請求項1に記載の方法。 - 前記抗体由来の結合組成物が、以下:
a)ポリクローナル抗体;
b)モノクローナル抗体;
c)ヒト化抗体、またはそのフラグメント;
d)Fabフラグメント、Fvフラグメント、またはF(ab’)2フラグメント;
e)抗体のペプチド模倣体;あるいは
f)検出可能な標識
を含む、請求項2に記載の方法。 - 前記核酸が、以下:
a)アンチセンス核酸;または
b)低分子干渉RNA(siRNA)
を含む、請求項2に記載の方法。 - 有効量の以下:
a)p35、IL−12、p40、IL−12Rβ1またはIL−12Rβ2のアゴニスト;あるいは
b)p35、IL−12、p40、IL−12Rβ1またはIL−12Rβ2のアンタゴニスト
を同時投与する工程をさらに包含する、請求項1に記載の方法。 - 前記p19、IL−23またはIL−23Rのアゴニストが、以下:
a)ウイルス性抗原特異的CD8+T細胞であるCD8+T細胞の割合;
b)IFNγ産生ウイルス性抗原特異的CD8+T細胞であるCD8+T細胞の割合;または
c)ウイルス性抗原特異的CD8+T細胞の細胞毒性
を減少する、請求項1に記載の方法。 - 前記p19、IL−23またはIL−23Rのアンタゴニストが、以下:
a)ウイルス性抗原特異的CD8+T細胞であるCD8+T細胞の割合;
b)IFNγ産生ウイルス性抗原特異的CD8+T細胞であるCD8+T細胞の割合;または
c)ウイルス性抗原特異的CD8+T細胞の細胞毒性
を増大する、請求項1に記載の方法。 - 前記p19、IL−23またはIL−23Rのアンタゴニストが、二次ウイルス感染に対する免疫応答の間に、CD8+T細胞の総数を増大する、請求項1に記載の方法。
- 前記CD8+T細胞の総数が、以下:
a)肺;
b)気管支肺胞洗浄(BAL);
c)脾臓;または
d)リンパ節
に由来する、請求項8に記載の方法。 - 有効量のp35、IL−12、IL−12β2またはp40のアンタゴニストを当時投与する工程をさらに包含する、請求項8に記載の方法。
- 前記ウイルスが、以下:
a)呼吸器ウイルス;
b)粘膜のウイルス;または
c)インフルエンザウイルス
である、請求項1に記載の方法。 - 前記インフルエンザウイルスが、以下:
a)インフルエンザA型;
b)インフルエンザB型;または
c)インフルエンザC型
である、請求項11に記載の方法。 - 前記ウイルス性抗原が、インフルエンザウイルス抗原を含む、請求項1に記載の方法。
- 前記インフルエンザウイルス抗原が、以下:
a)ウイルス性核タンパク質;
b)ウイルス性酸性ポリメラーゼ
に由来する、請求項13に記載の方法。 - 前記ウイルス感染が、以下:
a)呼吸症候群;または
b)肺炎
を含む、請求項1に記載の方法。 - a)ワクチン;または
b)アジュバント
を投与する工程をさらに包含する、請求項1に記載の方法。 - インフルエンザA型ウイルス感染を処置する方法であって、該方法は、有効量の請求項1に記載のアゴニストまたはアンタゴニストを投与する工程を包含する、方法。
- ウイルス感染を診断する方法であって、該方法は、以下:
結合組成物を生物学的サンプルに接触させる工程であって、ここで、該結合組成物は、以下:
a)p19、IL−23またはIL−23R;あるいは
b)p19またはIL−23Rをコードする核酸
に特異的に結合する、工程;および
該結合組成物の、該生物学的サンプルへの特異的結合を測定または決定する工程
を包含する、方法。 - ウイルス感染の診断をするためのキットであって、該キットは、以下:
コンパートメント;および
結合組成物であって、以下:
a)p19、IL−23またはIL−23R;あるいは
b)p19またはIL−23Rをコードする核酸
に特異的に結合する、結合組成物
を備える、キット。
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JP2009506041A (ja) * | 2005-08-25 | 2009-02-12 | イーライ リリー アンド カンパニー | 抗il−23抗体 |
JP2020527153A (ja) * | 2017-07-17 | 2020-09-03 | シュ ド ナント − セントレ ホスピタリエ ユニヴェルシテール ド ナント − | 二次疾患の治療における使用のためのインターロイキン12(il12)又はその誘導体 |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020137890A1 (en) * | 1997-03-31 | 2002-09-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
DK1576011T3 (da) | 2002-10-30 | 2009-11-30 | Genentech Inc | Inhibering af IL-17 produktion |
EP3501537A1 (en) | 2005-06-30 | 2019-06-26 | Janssen Biotech, Inc. | Anti-il23 antibodies, compositions, methods and uses |
PL1971366T3 (pl) | 2005-12-29 | 2015-01-30 | Janssen Biotech Inc | Ludzkie przeciwciała skierowane przeciw IL-23, kompozycje, sposoby i zastosowanie |
US7910703B2 (en) * | 2006-03-10 | 2011-03-22 | Zymogenetics, Inc. | Antagonists to IL-17A, IL-17F, and IL-23P19 and methods of use |
US7790862B2 (en) * | 2006-06-13 | 2010-09-07 | Zymogenetics, Inc. | IL-17 and IL-23 antagonists and methods of using the same |
TWI426918B (zh) * | 2007-02-12 | 2014-02-21 | Merck Sharp & Dohme | Il-23拮抗劑於治療感染之用途 |
US8119133B2 (en) * | 2007-02-28 | 2012-02-21 | Schering Corporation | Engineered anti-IL-23R antibodies |
CN101970490A (zh) | 2007-11-27 | 2011-02-09 | 埃博灵克斯股份有限公司 | 针对异二聚体细胞因子和/或其受体的氨基酸序列以及包括所述氨基酸序列的多肽 |
KR20170023209A (ko) | 2008-05-05 | 2017-03-02 | 노비뮨 에스 에이 | 항-il-17a/il-17f 교차-반응성 항체 및 그의 사용 방법 |
CN104974250A (zh) * | 2009-05-05 | 2015-10-14 | 诺维莫尼公司 | 抗il-17f抗体及其使用方法 |
EP2480251A1 (en) | 2009-09-21 | 2012-08-01 | Peptinov SAS | Carrier conjugates of il-23-peptides and their induced antibodies |
JP6126532B2 (ja) | 2010-11-04 | 2017-05-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗il−23抗体 |
MX368653B (es) | 2012-05-03 | 2019-10-10 | Boehringer Ingelheim Int | Anticuerpos anti-il-23p19. |
UA117466C2 (uk) | 2012-12-13 | 2018-08-10 | Мерк Шарп Енд Доме Корп. | СТАБІЛЬНИЙ СКЛАД У ВИГЛЯДІ РОЗЧИНУ АНТИТІЛА ДО IL-23p19 |
CN103837687A (zh) * | 2014-03-10 | 2014-06-04 | 青岛康立泰药业有限公司 | 使用具有白细胞介素-12受体的细胞检测重组人白细胞介素-12体外活性的方法及应用 |
US10507241B2 (en) | 2014-07-24 | 2019-12-17 | Boehringer Ingelheim International Gmbh | Biomarkers useful in the treatment of IL-23A related diseases |
TWI711629B (zh) | 2014-09-03 | 2020-12-01 | 德商包林格因蓋爾漢國際股份有限公司 | 靶向IL-23A與TNF-α之化合物及其用途 |
KR101873499B1 (ko) | 2015-02-10 | 2018-07-03 | 주식회사 원메디칼 | 혈관 질환 진단용 바이오 마커 및 이의 용도 |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
US11845798B2 (en) | 2017-05-02 | 2023-12-19 | Merck Sharp & Dohme Llc | Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies |
EP3634465A4 (en) * | 2017-05-25 | 2021-01-20 | The Broad Institute, Inc. | LYMPHOCYTE ANTIGEN CD5 SIMILAR (CD5L) MONOMER, HOMODIMER AND INTERLEUKIN 12B (P40) HETERODIMER ANTAGONISTS AND METHOD OF USE THEREOF |
EP3883607A4 (en) | 2018-11-20 | 2022-08-17 | Janssen Biotech, Inc. | SAFE AND EFFECTIVE PROCESS FOR TREATING PSORIASIS WITH A SPECIFIC ANTI-IL-23 ANTIBODY |
CN113874073A (zh) | 2019-05-23 | 2021-12-31 | 詹森生物科技公司 | 用针对IL-23和TNFα的抗体的联合疗法治疗炎性肠病的方法 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6132764A (en) | 1994-08-05 | 2000-10-17 | Targesome, Inc. | Targeted polymerized liposome diagnostic and treatment agents |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
US6326482B1 (en) | 1999-04-23 | 2001-12-04 | Genentech, Inc. | SH2 domain-containing peptides |
US7422743B2 (en) * | 2000-05-10 | 2008-09-09 | Schering Corporation | Mammalian receptor protein DCRS5;methods of treatment |
AU6135101A (en) * | 2000-05-10 | 2001-11-20 | Schering Corp | Mammalian receptor proteins; related reagents and methods |
US6902734B2 (en) * | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
US6811780B2 (en) * | 2002-05-01 | 2004-11-02 | Regeneron Pharmaceuticals, Inc. | Methods of using cytokine antagonists to treat HIV infection and AIDS |
DK1576011T3 (da) * | 2002-10-30 | 2009-11-30 | Genentech Inc | Inhibering af IL-17 produktion |
ATE515514T1 (de) * | 2002-12-23 | 2011-07-15 | Schering Corp | Verwendungen von säuger-cytokin il-23 ; verwandte reagenzien |
ATE506987T1 (de) * | 2002-12-31 | 2011-05-15 | Schering Corp | Il-27 et il-2 pour le traitement du cancer |
US20040219150A1 (en) * | 2003-02-06 | 2004-11-04 | Cua Daniel J. | Uses of mammalian cytokine; related reagents |
AU2004219625B9 (en) * | 2003-03-10 | 2010-12-23 | Merck Sharp & Dohme Corp. | Uses of IL-23 agonists and antagonists; related reagents |
AU2004229527B2 (en) * | 2003-04-11 | 2009-08-20 | Medimmune, Llc | Methods of preventing or treating respiratory conditions |
AU2004239288B2 (en) * | 2003-05-09 | 2010-01-28 | Centocor, Inc. | IL-23p40 specific immunoglobulin derived proteins, compositions, methods and uses |
-
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Non-Patent Citations (1)
Title |
---|
JPN6010066605, HA,S.J. et al, "IL−23 induces stronger sustained CTL and Th1 immune responses than IL−12 in hepatitis C virus envelo", J Immunol, 200401, Vol.172, No.1, p.525−31 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009506041A (ja) * | 2005-08-25 | 2009-02-12 | イーライ リリー アンド カンパニー | 抗il−23抗体 |
JP2020527153A (ja) * | 2017-07-17 | 2020-09-03 | シュ ド ナント − セントレ ホスピタリエ ユニヴェルシテール ド ナント − | 二次疾患の治療における使用のためのインターロイキン12(il12)又はその誘導体 |
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BRPI0507794A (pt) | 2007-07-17 |
NZ548897A (en) | 2009-07-31 |
US8263080B2 (en) | 2012-09-11 |
ATE533502T1 (de) | 2011-12-15 |
CN1942201B (zh) | 2012-06-20 |
AU2005215527B2 (en) | 2011-04-07 |
JP2012092117A (ja) | 2012-05-17 |
WO2005079837A1 (en) | 2005-09-01 |
US20050208052A1 (en) | 2005-09-22 |
CA2556425A1 (en) | 2005-09-01 |
AU2005215527A1 (en) | 2005-09-01 |
EP1901768A1 (en) | 2008-03-26 |
JP4903061B2 (ja) | 2012-03-21 |
NO20064194L (no) | 2006-11-16 |
CN1942201A (zh) | 2007-04-04 |
EP1901768B1 (en) | 2011-11-16 |
ZA200606620B (en) | 2008-02-27 |
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