JP2017523984A - 拮抗性抗ox40l抗体およびそれらの使用方法 - Google Patents
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Abstract
Description
本発明は全体として、医学の分野に関する。より詳細には、本発明は、自己免疫障害および炎症性障害を治療するため、ならびに免疫応答を改変するための薬学的組成物に関する。
自己免疫疾患およびいくつかの炎症性障害は、体内に通常存在する物質および組織に対する身体の異常免疫応答(自己免疫または自己炎症)が原因で起こる。これはある特定の臓器に限局していることも(例えば、自己免疫性甲状腺炎の場合)、または種々の場所にある特定の組織が罹病することもある(例えば、肺および腎臓の両方で基底膜を冒すことがあるグッドパスチャー病)。自己免疫疾患には米国だけでも5000万人にも及ぶ人々が罹患しているが、自己免疫病の原因は未だに不明である。その上、自己免疫病とは関連しておらず、かつ特発性であるかまたは慢性もしくは急性障害と関連している可能性がある、炎症性疾患も数多くある。
シクロスポリン、タクロリムス、メトトレキサートまたは抗TNFa/IL-6などの免疫抑制剤を用いる従来の免疫療法は、宿主において非病原性T細胞を含むT細胞の機能を非特異的に抑制する。このため、これらの免疫抑制剤を用いる治療では、多くの場合、結果として重症感染症の発症がもたらされ、時には致死的な転帰をたどることもある。本明細書に記載の方法および組成物は、OX40-OX40L相互作用の計画的遮断および炎症性T細胞の近時活性化の特異的抑制を対象とする。その結果として、全体的な免疫抑制を伴うことなく、IL-10の誘導およびTNF-a産生阻害によって、炎症性T細胞の分化が調節性T細胞へと転換される。重要なこととして、OX40Lのターゲティングにより、他のT細胞レパートリーの機能を撹乱することなく、抗原特異的T細胞レパートリーのみをモジュレートすることができ、その結果、免疫抑制性副作用の減少がもたらされる。
A.抗体
本開示の方法および組成物は、OX40L阻害物質に関する。「OX40L」という用語は、T細胞抗原提示細胞(APC)相互作用に関与することが見いだされている、あるタンパク質のことを指す。OX40Lはまた、TNFSF4、GP34、CD252、OX40L、TXGP1、およびCD134Lとしても知られている。このタンパク質は、OX40(CD134、TNFRSF4、ACT35、IMD16、およびTXGP1Lとしても知られる)のリガンドである。OX40Lのヒトタンパク質配列は、Genbankアクセッション番号:NP_003317.1、P23510.1、BAB18304.1、およびP43489.1によって表されている。これらのアクセッション番号と関連づけられている配列は、参照により具体的に組み入れられる。
OX40L阻害物質には、OX40L遺伝子および/またはタンパク質の生物活性を低下させるポリヌクレオチドが含まれ、これは例えば、OX40L DNAもしくはmRNAを対象とするmiRNA、siRNA、shRNA、dsRNAもしくはアンチセンスRNA、またはmiRNA、siRNA、shRNA、dsRNAもしくはアンチセンスRNAをコードするポリヌクレオチド、またはそのポリヌクレオチドを含むベクターであってよい。
本発明は、それを必要とする対象においてOX40Lの阻害をするための方法および組成物を含む。本発明による組成物の投与は、典型的には、任意の一般的な経路を介すると考えられる。これには、非経口的、同所性、皮内、皮下、筋肉内、腹腔内、鼻腔内、または静脈内注射によるものが含まれる。ある特定の態様において、ワクチン組成物は吸入されうる(例えば、米国特許第6,651,655号、これは参照により具体的に組み入れられる)。他の投与様式に適するそのほかの製剤には、経口製剤が含まれる。経口製剤は、例えば、薬剤等級のマンニトール、ラクトース、デンプン、ステアリン酸マグネシウム、サッカリンナトリウム、セルロース、炭酸マグネシウムなどのような、通常使用される賦形剤を含む。これらの組成物は、液剤、懸濁剤、錠剤、丸剤、カプセル剤、徐放性製剤、または散剤の形態をとり、活性成分を約10%〜約95%、好ましくは約25%〜約70%含有する。
本発明の方法は、炎症および自己免疫の治療または予防を含む。炎症性T細胞の分化を阻害し、調節T細胞の生成および機能を、IL-10を誘導してTNF-αを阻害することによって促進し、かつ異常なTh2細胞応答を低下させるOX40L阻害物質を投与することによって、炎症を治療することができる。炎症は、自己免疫と関連のない機能不全(例えば、癌、損傷など)の結果としての自己免疫疾患または炎症の構成要素であってもよい。さらに別の場合に、炎症は特発性または原因不明のものであってよい。
atica)、性腺機能低下症、局部性回腸炎、白血球減少症、伝染性単球増加症、横移動脊髄炎、原発性特発性粘液水腫、ネフローゼ、交感神経眼炎(ophthalmia symphatica)、精巣炎肉芽腫症、膵炎、急性多発性神経根炎、壊疽性膿皮症、ケルヴァン甲状腺炎、後天性脾臓萎縮、非悪性胸腺腫、白斑、毒素性ショック症候群、食中毒、T細胞の浸潤を伴う状態、白血球接着不全症、サイトカインおよびTリンパ球によって媒介される急性及び遅発性過敏症関連免疫応答、白血球血管外遊出を伴う疾患、多器官損傷症候群、抗原-抗体複合体媒介性疾患、抗糸球体基底膜疾患、アレルギー性神経炎、自己免疫多腺性内分泌障害、卵巣炎、原発性粘液水腫、自己免疫萎縮性胃炎、交感性眼炎、リウマチ性疾患、ネフローゼ症候群、膵島炎、多内分泌性不全、自己免疫性多腺性症候群I型、成人発症型特発性副甲状腺機能低下症(AOIH)、心筋症、例えば、拡張型心筋症など、後天性表皮水疱症(EBA)、ヘモクロマトーシス、心筋炎、ネフローゼ症候群、原発性硬化性胆管炎、化膿性または非化膿性副鼻腔炎、急性または慢性副鼻腔炎、篩骨、正面、上顎骨または蝶形骨副鼻腔炎、好酸球関連疾患、例えば、好酸球増加症、肺浸潤好酸球増加症、好酸球増加症-筋肉痛症候群、レフラー症候群、慢性好酸性肺炎、熱帯肺好酸球増加症など、気管支肺炎アスペルギルス症、アスペルギローム、または好酸球性を含有する肉芽腫、アナフィラキシー、血清陰性脊椎関節炎、多内分泌性自己免疫性疾患、硬化性胆管炎、強膜、上強膜、慢性皮膚粘膜カンジダ症、ブラットン症候群、乳児期の一過性低ガンマグロブリン血症、ウィスコット-アルドリッチ症候群、毛細血管拡張運動失調症候群、血管拡張症、膠原病と関係する自己免疫障害、リウマチ、神経病学的疾患、リンパ節炎、血圧応答の低下、血管機能不全、組織損傷、心血管乏血、痛覚過敏、腎虚血、脳虚血、および脈管化を伴う疾患、アレルギー性過敏症疾患、糸球体腎炎、再灌流障害、虚血性再灌流障害、心筋または他の組織の再灌流障害、リンパ腫気管気管支炎、炎症性皮膚病、急性炎症性成分を有する皮膚病、多臓器不全、水疱性疾患、腎皮質壊死、急性化膿性髄膜炎または他の中枢神経系炎症障害、眼および眼窩の炎症性障害、顆粒球輸血関連症候群、サイトカイン誘導性毒性、ナルコレプシー、急性の重篤な炎症、慢性難治性炎症、腎盂炎、動脈内過形成、消化性潰瘍、弁膜炎、移植片対宿主病、接触過敏症、喘息気道反応性亢進、重症筋無力症、免疫性血小板減少性紫斑病、抗好中球細胞質自己抗体媒介性疾患、IgA媒介性血管炎、Ig4関連障害、ならびに子宮内膜症。
本明細書において用いる場合、インビトロ投与という用語は、培養下の細胞を非限定的に含む、対象から取り出されたかまたは対象の外部の細胞に対して行われる操作のことを指す。エクスビボ投与という用語は、インビトロで操作され、続いて対象に投与される細胞のことを指す。インビボ投与という用語は、投与を含む対象内で行われるすべての操作を含む。
本発明の組成物および関連する方法、特にOX40L抗体または抗原結合性断片の投与を、従来の治療法の投与と組み合わせて用いることもできる。これらには、免疫抑制性または免疫調節性の治療法または治療の適用が非限定的に含まれる。
以下の実施例は、本発明の好ましい態様を実証するために含められる。以下の実施例において開示される手法は、本発明の実施において十分に機能すると本発明者によって見いだされた技術を表しており、それ故にその実施のための好ましい態様であると見なしうることが当業者に認識されるべきである。しかし、当業者は、本開示に鑑みて、本発明の趣旨および範囲から逸脱することなく、開示される特定の態様に多くの変更を施すことができ、それでもなお同様または類似の結果を得ることができることを認識すべきである。
OX40L抗体である5C6(AB104_105.5C6.3F9とも表示される)、19A3(AB104_105.19A3.2C4とも表示される)および44F3(AB104_105.44F3.2F7とも表示される)を、それらがmDCと共培養したナイーブT細胞によるサイトカイン産生を促進する能力について、以下のアッセイ法を用いて試験した。mDC培養物の増殖および生存率に対するOX40L抗体の効果についても、本実施例に記載しているアッセイ法を用いて試験した。
全身性エリテマトーデス(SLE)は、核抗原に対する寛容の破綻を特徴とする、慢性の全身炎症性自己免疫疾患である(Tsokos, 2011)。SLEは臨床症状発現および疾患経過の点でかなりの多様性を示す。SLE病態のより包括的な理解が長く待ち望まれている;これまでの50年で、SLE治療のために承認された新薬は1つしかない(Murphy et al., 2013;Stohl et al., 2012)。ゲノムワイド関連研究(GWAS)により、SLEに関する多くの感受性遺伝子座が同定され、SLE患者がdisplay素因となる遺伝要因を示すことが確かめられた(Cunninghame Graham et al., 2008;Delgado-Vega et al., 2009;Gateva et al., 2009;Han et al., 2009;International Consortium for Systemic Lupus Erythematosus et al., 2008)。SLEでは、素因を有する免疫系と環境要因との相互作用が、抗原提示細胞(APC)およびリンパ球の機能の変化を引き起こす。樹状細胞(DC)を含むAPCがSLE患者では異常に活性化されており、自己反応性T細胞およびB細胞の活性化を促進する(Blanco et al., 2001;Blanco et al., 2008)。生じた自己反応性形質細胞が、核成分を対象とする病原性自己抗体を産生して、組織傷害を引き起こす。
患者試料‐米国リウマチ学会(American College of Rheumatology)によるSLEの改訂基準(Hochberg, 1997)に適合する成人SLE患者(計61人:女性53人と男性8人)および小児SLE患者(計38人:女性34人および男性4人)を組み入れた。患者のすべての臨床情報および生物学的に意義のある情報を以下の表1および2に示している。臨床的な疾患活動性は、SLE疾患活動性指数(SLEDAI)を用いて評価した。活動性患者は、SLEDAIスコアが6以上であると定義した。成人SLE試料については、インフォームドコンセントが得られた後に、通常の検査分析による血液試料を用いた。小児SLE試料については、試験がBaylor Research Instituteの施設内審査委員会(Institutional Review Board)の承認を受けた上で、すべての参加者またはその親からインフォームドコンセントを得た。対照PBMCは、成人志願者からのバフィーコート試料、採血試料、またはアフェレーシス血液試料から得た。
略号: F:女性、M:男性、A:関節、C:皮膚、D:消化器、H:血液、M:心筋、N:神経、P:胸膜心膜、R:腎臓、V:血管、APS:抗リン脂質症候群、HCQ:ヒドロキシクロロキン、AZA:アザチオプリン、CYC:シクロホスファミド、MMF:ミコフェノール酸モフェチル、MPA:ミコフェノール酸、MTX:メトトレキサート、RTX:リツキシマブ。
OX40Lは炎症性扁桃において大量に発現される‐本出願人らは以前に、真皮CD14+ DCがインビトロでTfh様細胞の生成を選好的に誘導することを実証した(Klechevsky et al., 2008)。真皮CD14+ DCを含む皮膚DCサブセットは所属リンパ節内に遊走して(Segura et al., 2012)、T細胞ゾーンでT細胞と相互作用する。遊走性真皮CD14+ DCの対応物と提唱されている、リンパ節内のCD206+ DCは、Tfh細胞によって大量に発現されるケモカインである(Bentebibel et al., 2011;Kim et al., 2004)CXCL13を産生するように、ナイーブTh細胞を促進する(Segura et al., 2012)。これらの観察所見は、皮膚の所属リンパ節におけるTfh細胞の生成および抗体応答における、真皮CD14+ DCの関与を示唆する。しかし、扁桃などの炎症性リンパ系器官におけるTfh応答と関連のあるAPCの表現型は明らかにされていない。
有害作用を伴わずに同種移植片が生着することが、移植の究極的な目標である。これまで数十年にわたって、多岐にわたる免疫抑制剤が開発され、移植手術を受ける患者に対して用いられてきた。しかし、そのような免疫抑制薬は、臓器、組織、および造血幹細胞(HPSC)の移植を受ける患者において長期にわたる同種反応の予防を保証するものではなかった。その結果、患者は、移植片宿主病(GVHD)のほか、生涯にわたって続く免疫抑制による重篤な副作用のために死亡する。
Claims (66)
- それを必要とする対象において移植片対宿主病または移植片拒絶を治療または予防するための方法であって、該対象にOX40L阻害物質の治療的有効量を投与する段階を含む、方法。
- 前記対象が、移植組織を受け入れる予定であるかまたは受け入れている対象である、請求項1に記載の方法。
- 前記対象が前記移植組織による合併症を有しており、該合併症が移植片拒絶またはGVHDである、請求項2に記載の方法。
- それを必要とする対象において自己免疫疾患、炎症、および/または自己免疫疾患に関連する炎症を治療または予防するための方法であって、該対象にOX40L阻害物質の治療的有効量を投与する段階を含む、方法。
- それを必要とする対象において炎症性Th2細胞応答および/または病原性Tfh細胞応答を低下させるための方法であって、該対象にOX40L阻害物質の治療的有効量を投与する段階を含む、方法。
- 前記対象が、アレルギー性疾患喘息、アトピー性皮膚炎、実験的自己免疫性脳脊髄炎、炎症性腸疾患、接触過敏症、喘息性気道反応亢進、自己免疫性糖尿病、アテローム性動脈硬化症、全身性エリテマトーデス、関節リウマチ、多発性硬化症、潰瘍性大腸炎、移植片対宿主病、移植片拒絶反応、および多発性筋炎の群より選択される自己免疫疾患を有する、請求項4または5に記載の方法。
- 前記自己免疫疾患が全身性エリテマトーデスである、請求項6に記載の方法。
- 前記対象がヒトである、請求項1〜7のいずれか一項に記載の方法。
- 前記OX40L阻害物質が、siRNA、dsRNA、miRNA、リボザイム、分子阻害物質、小分子、抗体、または抗原結合性断片より選択される、請求項1〜8のいずれか一項に記載の方法。
- 前記OX40L阻害物質がOX40L抗体またはその抗原結合性断片である、請求項9に記載の方法。
- 前記OX40L抗体またはその抗原結合性断片が、3つの相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインを含み、該CDRの1つまたは複数が、SEQ ID NO:5〜7、19〜21、33〜35より選択されるアミノ酸配列またはそれらの等価物を含む、請求項10に記載の方法。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:5〜7のアミノ酸配列またはそれらの等価物を含む、請求項11に記載の方法。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:19〜21のアミノ酸配列またはそれらの等価物を含む、請求項11に記載の方法。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:33〜35のアミノ酸配列またはそれらの等価物を含む、請求項11に記載の方法。
- 前記抗OX40L抗体またはその抗原結合性断片が、3つの相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインをさらに含み、該CDRの1つまたは複数が、SEQ ID NO:12〜14、26〜28、40〜42より選択されるアミノ酸配列またはそれらの等価物を含む、請求項10〜14のいずれか一項に記載の方法。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:12〜14のアミノ酸配列またはそれらの等価物を含む、請求項15に記載の方法。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:26〜28のアミノ酸配列またはそれらの等価物を含む、請求項15に記載の方法。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:40〜42のアミノ酸配列またはそれらの等価物を含む、請求項15に記載の方法。
- 前記抗OX40L抗体またはその抗原結合性断片がヒトOX40Lまたはその等価物と結合する、請求項10〜18のいずれか一項に記載の方法。
- 前記抗OX40L抗体が中和性である、請求項10〜19のいずれか一項に記載の方法。
- 前記抗体が、ヒト抗体、ヒト化抗体、組換え抗体、キメラ抗体、抗体誘導体、ベニア抗体(veneered antibody)、ダイアボディ、モノクローナル抗体、またはポリクローナル抗体である、請求項10〜20のいずれか一項に記載の方法。
- 前記抗体がヒト化抗体である、請求項21に記載の方法。
- 前記抗体またはその抗原結合性断片が改変を含む、請求項10〜22のいずれか一項に記載の方法。
- 前記改変が、VHおよび/またはVLのCDR1領域内、CDR2領域内、および/またはCDR3領域内の保存的アミノ酸突然変異である、請求項23に記載の方法。
- 前記改変が、Fcヒンジ領域内の保存的アミノ酸突然変異である、請求項23に記載の方法。
- 前記改変がペグ化である、請求項23に記載の方法。
- 前記改変が血清タンパク質とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変がヒト血清アルブミンとのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が、検出可能な標識とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が診断剤とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が酵素とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が、蛍光物質、発光物質、または生物発光物質とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が放射性物質とのコンジュゲーションである、請求項23に記載の方法。
- 前記改変が治療剤とのコンジュゲーションである、請求項23に記載の方法。
- 3つの相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインを含む単離された抗OX40L抗体またはその抗原結合性断片を含み、該CDRの1つまたは複数が、SEQ ID NO:5〜7、19〜21、もしくは33〜35より選択されるアミノ酸配列またはそれらの等価物を含む、薬学的組成物。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:5〜7のアミノ酸配列またはそれらの等価物を含む、請求項35に記載の薬学的組成物。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:19〜21のアミノ酸配列またはそれらの等価物を含む、請求項35に記載の薬学的組成物。
- 前記重鎖可変ドメインCDRが、SEQ ID NO:33〜35のアミノ酸配列またはそれらの等価物を含む、請求項35に記載の薬学的組成物。
- 前記抗OX40L抗体またはその抗原結合性断片が、3つの相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインをさらに含み、該CDRの1つまたは複数が、SEQ ID NO:12〜14、26〜28、40〜42より選択されるアミノ酸配列またはそれらの等価物を含む、請求項35〜38のいずれか一項に記載の薬学的組成物。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:12〜14のアミノ酸配列またはそれらの等価物を含む、請求項39に記載の薬学的組成物。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:26〜28のアミノ酸配列またはそれらの等価物を含む、請求項39に記載の薬学的組成物。
- 前記軽鎖可変ドメインCDRが、SEQ ID NO:40〜42のアミノ酸配列またはそれらの等価物を含む、請求項39に記載の薬学的組成物。
- 前記抗OX40L抗体またはその抗原結合性断片がヒトOX40Lまたはその等価物と結合する、請求項35〜42のいずれか一項に記載の薬学的組成物。
- 前記抗OX40L抗体が中和性である、請求項35〜43のいずれか一項に記載の薬学的組成物。
- 前記抗体が、ヒト抗体、ヒト化抗体、組換え抗体、キメラ抗体、抗体誘導体、ベニア抗体、ダイアボディ、モノクローナル抗体、またはポリクローナル抗体である、請求項35〜44のいずれか一項に記載の薬学的組成物。
- 前記抗体がヒト化抗体である、請求項45に記載の薬学的組成物。
- 前記抗体またはその抗原結合性断片が改変を含む、請求項35〜46のいずれか一項に記載の薬学的組成物。
- 前記改変が、VHおよび/またはVLのCDR1領域内、CDR2領域内、および/またはCDR3領域内の保存的アミノ酸突然変異である、請求項47に記載の薬学的組成物。
- 前記改変が、Fcヒンジ領域内の保存的アミノ酸突然変異である、請求項47に記載の薬学的組成物。
- 前記改変がペグ化である、請求項47に記載の薬学的組成物。
- 前記改変が血清タンパク質とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変がヒト血清アルブミンとのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が、検出可能な標識とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が診断剤とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が酵素とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が、蛍光物質、発光物質、または生物発光物質とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が放射性物質とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 前記改変が治療剤とのコンジュゲーションである、請求項47に記載の薬学的組成物。
- 担体をさらに含む、請求項35〜58のいずれか一項に記載の薬学的組成物。
- SEQ ID NO:4、SEQ ID NO:5、およびSEQ ID NO:6の相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインとSEQ ID NO:10、SEQ ID NO:11、およびSEQ ID NO:12の相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインとを含む単離されたヒト化IgG抗OX40L抗体またはその抗原結合性断片を含む、薬学的組成物。
- SEQ ID NO:17、SEQ ID NO:18、およびSEQ ID NO:19の相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインとSEQ ID NO:24、SEQ ID NO:25、およびSEQ ID NO:26の相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインとを含む単離されたヒト化IgG抗OX40L抗体またはその抗原結合性断片を含む、薬学的組成物。
- SEQ ID NO:31、SEQ ID NO:32、およびSEQ ID NO:33の相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインとSEQ ID NO:38、SEQ ID NO:39、およびSEQ ID NO:40の相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインとを含む単離されたヒト化IgG抗OX40L抗体またはその抗原結合性断片を含む、薬学的組成物。
- 3つの相補性決定領域(CDR)アミノ酸配列を含む重鎖可変ドメインを含む抗OX40L抗体またはその抗原結合性断片のポリペプチド鎖をコードする核酸配列を含み、該CDRの1つまたは複数が、SEQ ID NO:5〜7、19〜21、もしくは33〜35より選択されるアミノ酸配列またはそれらの等価物を含む、単離されたポリヌクレオチド。
- 3つの相補性決定領域(CDR)アミノ酸配列を含む軽鎖可変ドメインを含む抗OX40L抗体またはその抗原結合性断片のポリペプチド鎖をコードする核酸配列を含み、該CDRの1つまたは複数が、SEQ ID NO:12〜14、26〜28、もしくは40〜42より選択されるアミノ酸配列またはそれらの等価物を含む、単離されたポリヌクレオチド。
- 請求項63または64に記載のポリヌクレオチドを含む発現ベクター。
- 調節配列に機能的に連結された請求項63または64に記載のポリヌクレオチドを含む宿主細胞。
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US9512229B2 (en) | 2015-03-03 | 2016-12-06 | Kymab Limited | Synergistic combinations of OX40L antibodies for the treatment of GVHD |
US9434785B1 (en) | 2015-04-30 | 2016-09-06 | Kymab Limited | Anti-human OX40L antibodies and methods of treating graft versus host disease with the same |
US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
WO2018170764A1 (zh) * | 2017-03-22 | 2018-09-27 | 深圳市博奥康生物科技有限公司 | 一种用于 RNAi 的载体及其应用 |
CN108458964A (zh) * | 2017-10-31 | 2018-08-28 | 天津协和华美医学诊断技术有限公司 | 一种抗体组合物及其在淋巴浆细胞性淋巴瘤微小残留检测中的应用 |
AR126749A1 (es) * | 2021-08-10 | 2023-11-08 | Kymab Ltd | Tratamiento de la dermatitis atópica |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11180893A (ja) * | 1997-09-25 | 1999-07-06 | Mitsui Chem Inc | gp34結合阻害物を有効成分として含有する医薬組成物 |
JP2009518005A (ja) * | 2005-11-25 | 2009-05-07 | 協和発酵キリン株式会社 | ヒトモノクローナル抗体ヒトcd134(ox40)ならびにその作製および使用方法 |
US8551477B1 (en) * | 2002-09-11 | 2013-10-08 | La Jolla Institute For Allergy And Immunology | Methods of treating OX40 mediated recall immune responses using OX40L antibodies and agents useful for identifying same |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI380996B (zh) * | 2004-09-17 | 2013-01-01 | Hoffmann La Roche | 抗ox40l抗體 |
KR20080080639A (ko) * | 2005-12-16 | 2008-09-04 | 제넨테크, 인크. | 항-ox40l 항체 및 그의 사용 방법 |
WO2011073180A1 (en) * | 2009-12-14 | 2011-06-23 | Ablynx N.V. | Single variable domain antibodies against ox40l, constructs and therapeutic use |
US20120020960A1 (en) | 2010-07-26 | 2012-01-26 | Baylor Research Institute | Thymic Stromal Lymphopoietin (TSLP) and OX40 Ligand in Cancer |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11180893A (ja) * | 1997-09-25 | 1999-07-06 | Mitsui Chem Inc | gp34結合阻害物を有効成分として含有する医薬組成物 |
US8551477B1 (en) * | 2002-09-11 | 2013-10-08 | La Jolla Institute For Allergy And Immunology | Methods of treating OX40 mediated recall immune responses using OX40L antibodies and agents useful for identifying same |
JP2009518005A (ja) * | 2005-11-25 | 2009-05-07 | 協和発酵キリン株式会社 | ヒトモノクローナル抗体ヒトcd134(ox40)ならびにその作製および使用方法 |
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