JP4943161B2 - 新規抗il13モノクローナル抗体での癌の処置 - Google Patents
新規抗il13モノクローナル抗体での癌の処置 Download PDFInfo
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Description
IL13は、CD4+T−ヘルパー2型細胞ならびにNKT細胞、好塩基球、および肥満細胞によって優勢的に産生される多面発現的なTh2サイトカインである(非特許文献1)。喘息、線維症、慢性肺閉塞性疾患および潰瘍性大腸炎におけるその病因学的役割(非特許文献2;非特許文献3;非特許文献4)に加え、IL13はまた、腫瘍増殖(非特許文献5;非特許文献6)および腫瘍免疫の改変(非特許文献7;非特許文献8)で重要な役割を演じていることが知られている。従って、IL13およびそのレセプターは、癌に対する可能な治療標的である。
Hershey、GKK、J Allergy Clin Immunol.(2003)111:677〜90 Wynn、TA、Annu Rev Immunol.(2003)21:425〜56 Wynn TA.、Nat Rev Immunol.(2004)4:583〜94 Heller Fら、Immunity(2002)17:629〜38 Kapp Uら、J Exp Med.(1999)189:1939〜4 Trieu Yら、Cancer Res.2004;64:3271〜5 Terabe Mら、Cancer Immunol Immunother.2004;53:79〜85 Terabe Mら、Nat Immunol.2000;1:515〜20 Debinski Wら、J Biol Chem.(1995)270:16775〜80 Puri RKら、Blood(1966)87:4333〜9 Maini Aら、J Urol.(1997)158:948〜53 Debinski Wら、Clin Cancer Res.(1995)1:1253〜8 Kornmann Mら、Anticancer Res.(1999)19:125〜31 Husain SRら、Blood(2000)95:3506〜13 Kawakami Kら、Cancer Res.(2001)61:6194〜6200
本出願は、新規抗IL13モノクローナル抗体を用いた、IL13を発現する癌および/または腫瘍の処置に関する。本発明で有用な抗体は、グリコシル化および非グリコシル化ヒトIL13の両方に特異的かつ高親和性で結合し;マウスIL13には結合せず、そして約1:2のモル比(MAb:IL13)でヒトIL13活性を中和する新規抗IL13抗体を含む。本発明にまた含まれるのは、上記抗体の軽鎖可変領域および/または重鎖可変領域由来の抗原結合性領域を含む抗体である。本発明の抗体はモノクローナル抗体であり得、そしてモノクローナル抗体は、ヒト抗体、キメラ抗体、またはヒト化抗体であり得る。
本発明は、本明細書中に記載される特定の方法、プロトコール、細胞株、ベクター、または試薬に限定されない。なぜなら、それらは変動し得るからである。さらに、本明細書中で用いられる用語法は、特定の実施形態のみを記載する目的のために用いられ、そして本発明の範囲を制限することは意図されない。本明細書および添付の請求項で用いられるとき、単数形「a」、「an」、および「the」は、文脈が明瞭にそうでないことを指示しなければ、複数の参照を含み、例えば、「宿主細胞」への参照は、複数のこのような宿主細胞を含む。
含む分子をいう。本発明の免疫グロブリン分子は、免疫グロブリン分子の任意のタイプ(例えば、IgG、IgE、IgM、IgD、IgAおよびIgY)、クラス(例えば、IgG1、IgG2、IgG3、IgG4、IgA1およびIgA2)またはサブクラスであり得る。さらに、用語「抗体」(Ab)または「モノクローナル抗体」(mAb)は、タンパク質に特異的に結合し得る、インタクトな分子および抗体フラグメント(例えば、FabおよびF(ab’)2フラグメント)を含むことを意味する。FabおよびF(ab’)2フラグメントは、インタクトな抗体のFcフラグメントを欠き、動物または植物の循環からより迅速にクリアされ、そしてインタクトな抗体より少ない非特異的組織結合を有し得る(Wahlら、J.Nucl.Med.24:316〜325(1983))。
組換えIL13を用いてマウスを免疫化し、本発明のモノクローナル抗体を産生するハイブリドーマを生成した。組換えIL13は、多くの供給元から市販される(例えば、R&D Systems、Minneapolis、MN、PetproTech、Inc.、NJ、およびSanofi Bio−Industries、Inc.、Tervose、PA.を参照のこと)。あるいは、IL13をコードする遺伝子またはcDNAは、プラスミドまたはその他の発現ベクター中にクローン化され、そして当業者に周知の方法に従って、多くの発現システムのいずれかで発現され得る。IL13およびIL13の核酸配列をクローニングし、そして発現するする方法は周知である(例えば、米国特許第5,652,123号を参照のこと)。遺伝子コードの縮重のため、IL13ポリペプチドをコードする複数のヌクレオチド配列が産生され得る。可能なコドン選択に基づいて組み合わせを選択することにより、ヌクレオチド配列を改変し得る。これらの組み合わせは、天然に存在するIL13ポリペプチドをコードするヌクレオチド配列に適用されるような標準的なトリプレット遺伝子コードに従ってなされ得、そしてすべてのそのような改変が考慮されるべきである。これらポリペプチドの任意の1つが、IL13に結合する抗体を生成するために動物の免疫化において用いられ得る。
本発明の抗体は、当該分野で公知の任意の適切な方法によって生成され得る。本発明の抗体は、ポリクローナル抗体を含み得る。ポリクローナル抗体を調製する方法は、当業者に公知である(Harlowら、Antibodies:a Laboratory Manual、(Cold spring Harbor Laboratory Press、第2版(1988))、これは、その全体が参考として本明細書中に援用される)。
本発明は、IL13の作用を阻害および中和するアンタゴニストモノクローナル抗体を提供する。特に、本発明の抗体は、IL13に結合し、そしてIL13レセプター複合体の活性化を阻害する。本発明の抗体としては、228B/C−1、228A−4、227−26、および227−43と称される抗体が挙げられ、そして228B/C−1のヒト化クローンが開示される。本発明としてはまた、モノクローナル抗体228B/C−1のと同じエピトープに結合する抗体が挙げられる。
別の局面では、本発明は、本発明の抗体をコードするヌクレオチド配列を含むベクター構築物、およびこのようなベクターを含む宿主細胞を提供する。クローニングおよび形質転換のための標準的な技法が、本発明の抗体を発現する細胞株の調製で用いられ得る。
本発明は、本発明の抗体およびそのフラグメントをコードするヌクレオチド配列を含む、ポリヌクレオチドをさらに提供する。本発明はまた、本発明の抗体をコードするポリヌクレオチドに、ストリンジェントまたはより低いストリンジェンシーハイブリダイゼーション条件下でハイブリダイズするポリヌクレオチドを包含する。
本発明の抗体は、抗体の合成のための当該技術分野で公知の任意の方法、特に化学的合成または好ましくは、組換え発現技法により産生され得る。
本発明の抗体は、改変されている、すなわち、抗体への任意のタイプの分子の共有結合による誘導体を含み、この共有結合は、IL13への結合を妨害しない。例えば、制限するのではなく、この抗体誘導体としては、例えば、ビオチン化、HRP、または任意のその他の検出可能成分によって改変された抗体が挙げられる。
抗体に結合体化された治療成分と一緒にまたはなしで、抗体は、単独でまたは細胞傷害性因子または細胞分裂阻害因子(単数または複数)と組み合わせて、治療薬として用いられ得る。本発明は、抗体を基礎にした治療に関し、これは、本発明の抗体を、IL13が媒介する疾患、傷害、または状態を、動物、哺乳動物、またはヒトに投与する工程を含む。IL13に対して惹起された抗体は、動物において腫瘍または癌細胞増殖を阻害するために有用であり、この動物としては、ウシ、ブタ、ウマ、ニワトリ、ネコ、イヌ、非ヒト霊長類など、およびヒトが挙げられるが、これらに限定されない。例えば、治療的に受容可能な用量の本発明の抗体(もしくは複数の抗体)または本発明の抗体のカクテル、または種々の供給源のその他の抗体との組み合わせを投与することにより、癌または腫瘍が、処置された哺乳動物において減少またはなくされ得る。
(IL13免疫グロブリンの調製:変異された不活性ヒトIL13/Fc(MT−IL13/Fc))
(A.MT−IL13/Fcのための発現プラスミドのクローニングおよび構築)
等しいかまたはより高い親和性をもつ、IL13Rα1に結合したアミノ酸残基番号13における変異(グルタミン酸からリンジンへ)をもつヒトIL13は、しかし、IL13Rα1保持細胞を活性化する能力を失ったことが報告された(Thompsonら、J.Biol.Chem.、274:29944(1999))。この変異した不活性なIL13(MT−IL13と示される)を、ヒト胎児腎細胞293−T中で発現した。この精製された組換えタンパク質を、本発明における免疫原として用い、抗IL−13モノクローナル抗体を生成した。2つのオリゴヌクレオチドプライマーは:
MT−IL13/Fcの一時的発現のために、精製されたプラスミドDNAを、製造業者のプロトコールに従って、Lipofectamine 2000(Invitrogen)によって293T細胞中にトランスフェクトした。トランスフェンション72時間後、トランスフェクトされた細胞からの培養上清液を精製のために収集した。MT−IL13/Fcの安定な発現のために、細胞株を、Flp−In 293T細胞株(Invitrogen)を用いて樹立した。発現を確認するために、細胞上清液を、ドデシル硫酸ナトリウムポリアクリルアミドゲル電気泳動(SDS−PAGE)によって分析した。分離されたタンパク質を、ニトロセルロースメンブレンに移し、そして西洋ワサビペルオキシダーゼ(HRP)結合体化マウス抗ヒトIgG(Fc)モノクローナル抗体(Sigma、St.Louis、MO)またはポリクローナルヤギ抗−IL13抗体(R&D Systems、Minneapolis、MN)との反応より検出し、これらは次いでHRP−ロバ抗ヤギIgG(Jackson ImmunoResearch Laboratories、West Grove、PA)で検出された。免疫反応性タンパク質を、増幅化学発光検出(Supersignal West Pico Chemiluminescent Substrate、Pierce、Rockford、IL)を用いて、フィルム上で同定した。
MT−IL13/Fcは、リン酸緩衝化生理食塩水(PBS)で平衡化されたハイパー−DプロテインAアフィニティーカラム(Invitrogen)で精製した。このカラムに細胞培養上清液を付与した後、樹脂を20カラム容量を超える量のPBSで洗浄した。次いで、この樹脂をSCC緩衝液(0.05Mクエン酸ナトリウム、0.5M塩化ナトリウム、pH6.0)で洗浄し、非結合のタンパク質を除去した。IL13融合タンパク質を、次いで、溶出し(005Mクエン酸ナトリウム、0.15M塩化ナトリウム、pH3.0)、そしてPBS中で透析した。
(抗IL13モノクローナル抗体の生成)
雄のA/Jマウス(Harlan、Indianapolis、IN)、8〜12週齢に、200μLのPBS(pH7.4)で完全フロイントアジュバント(Difco Laboratories、Detroit、MI)中の20μgのMT−IL13/Fcを皮下注射した。2週間の間隔で、マウスを、不完全フロイントアジュバント中の20μgのMT−IL13/Fcで2度皮下注射した。次いで、2週間後、そして屠殺の3日前に、マウスに、PBS中の20μgの同じ免疫原で腹腔内注射した。1匹以上の抗原免疫化マウスから単離された脾臓細胞を、融合のために用いた。免疫化および融合の類似の手順もまた、免疫原としてのE.coli発現ヒトIL13(R&D Systems)とともに用いた。
(ELISAにおける、抗IL13モノクローナル抗体とヒトおよびマウスIL13との反応性)
種々の抗IL13モノクローナル抗体の反応性を、ELISAによって試験した。96ウェルマイクロテストプレートの異なるウェルを、E.coli発現非グリコシル化ヒトIL13(R&D Systems)、293T細胞発現グリコシル化MT−IL13/Fc、またはE.coli発現マウスIL13(R&D Systems)のいずれかで、PBS中の100μLの0.1μg/mL IL13タンパク質の添加によりコーティングした。室温で一晩インキュベーション後、これらウェルを、PBSTB(2%BSAを含むPBST)で処理し、残りの結合部位を飽和した。これらウェルを次いでPBSTで洗浄した。
(JES10−5A2によるヒトIL13への228B/C−1−HRP結合の競合の欠如)
JES10−5A2および228B/C−1が、ヒトIL13上の同じエピトープに結合するか否かを取り扱うために、競合ELISAを用いて、E.coli発現ヒトIL13への228B/C−1−HRP結合に対するJES10−5A2の影響を試験した。96ェルマイクロテストプレートの96ウェルの各ウェルを、100μLのPBS中0.1μg/mLのIL13タンパク質とともにインキュベートした。室温で一晩のインキュベーションの後、これらウェルを、PBSTB(2%BSAを含むPBST)で処理し、残りの結合部位を飽和した。これらウェルを、次いで、PBSTで洗浄した。50マイクロリットルの2倍系列希釈の228B/C−1およびJES10−5A2(最終濃度20μg/mL〜9.76ng/mL)を、50μLの予備滴定した228B/C−1−HRPと(1:6,400希釈で)混合した。その混合物を、次いで、ウェルに添加し、そして室温で1時間インキュベートした。次いで、上記のように、発色のためにペルオキシダーゼ基質溶液を添加した。OD450を、ELISAリーダーを用いて測定した。
(L−1236およびHDLM−2細胞を用いるIL13自己分泌依存性増殖アッセイによる抗IL13中和モノクローナル抗体のスクリーニング)
L−1236およびHDLM−2は、German Collection of Miroorganisms and Cell Culture(DSMZ、Brauschweig、Germany)から得られるホジキンリンパ腫細胞株である。これら細胞株はIL13を産生し、これは、次いで、自己分泌様式でそれらの細胞増殖を活性化する(Kapp Uら、J.Exp.Med.189:1939(1999))。細胞を、異なる抗IL13MAb(0.2、0.02および0.002μg/mL)の存在または不在下で、5%CO2中37℃で3〜5日間培養した(25,000細胞/ウェル)。次いで、細胞増殖を、テトラゾリウム化合物MTS(Promega、Madison、WI)を用いるアッセイによるか(OD490における読み取り値)、または3H−チミジン(Amersham Bioscience、Piscataway、NJ)の取り込みによるかいずれかにより測定した。
(原発性ヒト単球上のIL13制御CD14およびCD23発現に対するアッセイ)
IL13は、ヒト単球におけるCD14発現の抑制およびCD23発現の上方制御を誘導する(de Waal Malefytら、J.Immunol.、151:6370(1993)、Chomaratら、Int.Rev.Immunol.、17:1(1998))。末梢血白血球(PBL)を、健常なヒトドナーの新鮮に収集したヘパリン処理全血から、Histopaque−1077(Sigma)中の密度勾配遠心分離によって単離した。5%ウシ胎仔血清を含むRPMI−1640培地(Invitrogen)中に懸濁されたPBL(1.5×106)を、組換えIL13(最終10ng/mL=0.813nM)および抗IL13モノクローナル抗体または無関係の抗体(3倍系列希釈、最終12μg/mL=80nMから)を含む96ウェルの組織培養プレートの各ウェルに添加した。単球上のCD14発現またはCD23発現は、イキュベートする培地に0.813nMのヒトIL13の添加により、それぞれ抑制または上方制御された。培地のコントロールは、組換えIL13なしのRPMI−1640/FBS培地を含んだ。
その細胞を、5%CO2中37℃で2日間インキュベートした。その細胞を、抗CD14−FITCまたは抗CD23−PE(BD Biosciences−Pharmingen)での染色のために回収した。単球集団におけるCD14およびCD23の発現レベルは、フローサイトメトリーによって測定され、そして中間値蛍光強度(MFI)によって表した。
(THP−1細胞におけるIL13誘導STAT6リン酸化アッセイ)
IL13は、骨髄細胞株THP−1(ATCC、Manassas、VA)を活性化し得、IL13のシグナル伝達経路における重要なステップであるSTAT6のリン酸化を誘導する(Murata Tら、Int.Immunol.10:1103〜1110(1998))。上記抗IL13MAbを、このアッセイでIL13の阻害について試験した。
(抗IL13モノクローナル抗体をコードする重鎖および軽鎖遺伝子の分子クローニング)
QIAGENキット(Valencia、CA)を用いて、総RNAをハイブリドーマ細胞から単離した。逆転写(第1鎖cDNA)反応を、以下のように実施した:1〜1.5mgの総RNAを、1mlの10mM dNTP、50ngのランダムヘキサマー、およびRNaseを含まない12mLの最終容量の水と混合した。
(エピトープマッピング)
抗IL13 MAb 228B/C−1は、立体配座エピトープに結合し、そしてカニクイザルIL13に、それがヒトIL13に結合するのと同じ高い親和性で結合する。しかし、228B/Cは、マウスIL13には結合しない。そこで、エピトープマッピングのために工夫された戦略は、このサルIL13の小部分を、対応するマウスIL13配列と交換することであった。重複するオリゴヌクレオチドを図18に示されるように合成した。2ラウンドのPCRを実施し、IL13ハイブリッド構築物を、サルIL13の一部が、マウスIL13からの対応する配列によって置換されるようにアセンブルした(図18)。最終のPCR増幅されたIL13コード領域を、TOPOクローニングキット(Invitrogen)を用いて、pcDNA3.1ベクター中にV5タグとインフレームでクローニングした。すべてのPCR増幅された領域は、配列決定により、所望のドメインがスワップしている変異のみを含み、そしてこの発現ベクター中にさらなる所望されない変異が含まれないことが確認された。
(抗IL13 MAbのADCCアッセイ)
PBMCは、Ficoll−paqueを用いる標準的な遠心分離技法によって、新鮮なヘパリン処理血液サンプルから単離する(50mlバフィコートは、約300×106PBMCを与える)。このPBMCは、RPMI1640/10%FCSで、24時間、37℃で5%CO2中、IL2(10U/ml)で刺激する(20×106PBMC)。
細胞溶解%=(Cpm試験(test)−Cpm自発(spont))/(Cpm最大(max)−Cpm自発)×100%
[さらなるADCCの情報については、例えば、L.M.Weinerら、Cancer Res.、48:2568〜2573(1988);P.Herseyら、Cancer Res.、46:6083〜6090(1988);およびC.J.Hansikら、Proc.Natl.Acad.Sci.、83:7893〜97(1986)を参照のこと。]
(実施例11)
(補体媒介細胞傷害性(CMC)のアッセイ)
腫瘍細胞(50μLのDMEM培養培地中5×104)、正常ヒト血清(50μLの培地中1:1希釈)、および種々の濃度のヒト化抗IL13 MAb(IgG1)(100μLの培地中)を、96ウェルの平底プレートにおいて、2時間37℃で5%CO2中でインキュベートし得る。無関係のアイソタイプ一致抗体を、ネガティブコントロールとして用い得る。細胞増殖試薬WST−1(15μL;Roche Diagnostics、Basel、Switzerland)を添加し、そして5時間37℃でインキュベートする。発色反応の吸光度を、450nmでELISAプレートリーダーを用いて読み取る。抗IL13 MAbによるCMCの阻害%=100×(ODs/a−ODs)/(ODns−ODs);血清および抗体で処理されたウェルについてODs/a=OD;血清で処理されたウェルについてODs=OD;血清および抗体なしで処理されたウェルについてODns=OD。
以下の培養物は、American Type Culture Collection、10801 University Boulevard、Manassas Va.20110−2209 USA(ATCC)に寄託されている:
Claims (34)
- 癌の処置における使用のための、抗IL13抗体を含む薬学的組成物であって、該抗IL13抗体はヒトIL13に特異的に結合し、該抗体は、ハイブリドーマ228B/C−1(PTA−5657)によって産生される抗体が特異的に結合するヒトIL13エピトープに、特異的に結合する、薬学的組成物。
- 癌の処置における使用のための、ヒトIL−13に特異的に結合する抗IL13抗体を含む薬学的組成物であって、該抗IL13抗体が、アミノ酸配列ESLINVSGまたはYCAALESLINVSを有するエピトープに結合する、薬学的組成物。
- 前記抗IL13抗体は、10−10M〜10−12Mの解離定数(KD)を有する親和性でヒトIL13に結合する、請求項1または2に記載の薬学的組成物。
- 前記抗IL13抗体が、配列番号99のアミノ酸配列を有するCDR1、配列番号104のアミノ酸配列を有するCDR2、および配列番号115のアミノ酸配列を有するCDR3を含む可変軽(VL)鎖領域を含む、請求項1または3に記載の薬学的組成物。
- 前記抗IL13抗体が、配列番号117のアミノ酸配列を有するCDR1、配列番号123のアミノ酸配列を有するCDR2、および配列番号135のアミノ酸配列を有するCDR3を含む可変重(VH)鎖領域を含む、請求項1〜4のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体が、
(a)配列番号3のアミノ酸配列を含むVL鎖領域、および配列番号4のアミノ酸配列を含むVH鎖領域;
(b)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号143のアミノ酸配列を含むVH鎖領域;
(c)配列番号144のアミノ酸配列を含むVL鎖領域、および配列番号145のアミノ酸配列を含むVH鎖領域;
(d)配列番号150のアミノ酸配列を含むVL鎖領域、および配列番号151のアミノ酸配列を含むVH鎖領域;
(e)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号145のアミノ酸配列を含むVH鎖領域;
(f)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号146のアミノ酸配列を含むVH鎖領域;
(g)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号147のアミノ酸配列を含むVH鎖領域;
(h)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号148のアミノ酸配列を含むVH鎖領域;または
(i)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号149のアミノ酸配列を含むVH鎖領域
を含む、請求項1〜5のいずれか1項に記載の薬学的組成物。 - 前記抗IL13抗体が、配列番号142に記載の配列を含むVL鎖領域、および配列番号143に記載の配列を含むVH鎖領域を含む、請求項6に記載の薬学的組成物。
- 前記抗IL13抗体が、
(a)配列番号100のアミノ酸配列を有するVL CDR1、配列番号104のアミノ酸配列を有するVL CDR2、および配列番号116のアミノ酸配列を有するVL CDR3を含むVL鎖領域;ならびに、配列番号117のアミノ酸配列を有するVH CDR1、 配列番号123のアミノ酸配列を有するVH CDR2、および配列番号137のアミノ酸配列を有するVH CDR3を含むVH鎖領域;
(b)配列番号100のアミノ酸配列を有するVL CDR1、配列番号104のアミノ酸配列を有するVL CDR2、および配列番号115のアミノ酸配列を有するVL CDR3を含むVL鎖領域;ならびに、配列番号118のアミノ酸配列を有するVH CDR1、配列番号123のアミノ酸配列を有するVH CDR2、および配列番号139のアミノ酸配列を有するVH CDR3を含むVH鎖領域;または
(c)配列番号100のアミノ酸配列を有するVL CDR1、配列番号104のアミノ酸配列を有するVL CDR2、および配列番号116のアミノ酸配列を有するVL CDR3を含むVL鎖領域;ならびに、配列番号118のアミノ酸配列を有するVH CDR1、配列番号123のアミノ酸配列を有するVH CDR2、および配列番号137のアミノ酸配列を有するVH CDR3を含むVH鎖領域
を含む、請求項1または2に記載の薬学的組成物。 - 前記抗IL13抗体が、(i)配列番号3に記載の配列に少なくとも95%相同なVL鎖領域、および(ii)配列番号4に記載の配列に少なくとも95%相同なVH鎖領域
を含む、請求項1または2のいずれか1項に記載の薬学的組成物。 - 前記抗IL13抗体がモノクローナル抗体である、請求項1〜9のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体がIgG抗体である、請求項1〜10のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体が、IgG1、IgG2、IgG3またはIgG4抗体である、請求項11に記載の薬学的組成物。
- 前記抗IL13抗体は、ヒト抗体、キメラ抗体もしくはヒト化抗体、または抗原結合性抗体フラグメントである、請求項1〜12のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体は、一価抗体、多特異性抗体、単鎖抗体またはFabフラグメントである、請求項1〜13のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体は、二重特異的抗体である多特異的抗体である、請求項14に記載の薬学的組成物。
- 前記抗IL13抗体は、抗体依存性細胞媒介細胞傷害性および/または補体媒介細胞傷害性による腫瘍細胞殺傷を媒介する、請求項1〜15のいずれか1項に記載の薬学的組成物。
- 生理学的に受容可能なキャリア、希釈剤、賦形剤および/または安定化剤をさらに含む、請求項1〜16のいずれか1項に記載の薬学的組成物。
- 吸入、ボーラス注射、または注入によって投与されるものであることを特徴とする、請求項1〜17のいずれか1項に記載の薬学的組成物。
- 前記癌が、ホジキンリンパ腫、皮膚癌、胃癌、結腸癌、乳癌、膵臓癌、肝癌、前立腺癌、肺癌、頭頸部癌、腎臓細胞癌、扁平上皮癌、AIDS関連カポジ肉腫、または脳腫瘍である、請求項1〜18のいずれか1項に記載の薬学的組成物。
- 前記抗IL13抗体は、細胞傷害性因子に結合体化される、請求項1〜19のいずれか1項に記載の薬学的組成物。
- 前記細胞傷害性因子が、放射線性同位元素または化学療法剤である、請求項20に記載の薬学的組成物。
- 生物学的サンプルでの癌または腫瘍の診断における使用のための、抗IL13抗体を含む組成物であって、該癌および/または腫瘍がIL13を過剰発現し、該抗IL13抗体はヒトIL13に特異的に結合し、該抗IL13抗体は、ハイブリドーマ228B/C−1(PTA−5657)によって産生される抗体が特異的に結合するヒトIL13エピトープに特異的に結合する、組成物。
- 生物学的サンプルでの癌または腫瘍の診断における使用のための、ヒトIL13に特異的に結合する抗IL13抗体を含む組成物であって、該癌または腫瘍がIL13を過剰発現し、該抗IL13抗体が、アミノ酸配列ESLINVSGまたはYCAALESLINVSを有するエピトープに結合する、組成物。
- 前記抗IL13抗体が、配列番号99のアミノ酸配列を有するCDR1、配列番号104のアミノ酸配列を有するCDR2、および配列番号115のアミノ酸配列を有するCDR3を含むVL鎖領域を含む、請求項22または23に記載の組成物。
- 前記抗IL13抗体が、配列番号117のアミノ酸配列を有するCDR1、配列番号123のアミノ酸配列を有するCDR2、および配列番号135のアミノ酸配列を有するCDR3を含むVH鎖領域を含む、請求項22〜24のいずれか1項に記載の組成物。
- 前記抗IL13抗体が、
(a)配列番号3のアミノ酸配列を含むVL鎖領域、および配列番号4のアミノ酸配列を含むVH鎖領域;
(b)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号143のアミノ酸配列を含むVH鎖領域;
(c)配列番号144のアミノ酸配列を含むVL鎖領域、および配列番号145のアミノ酸配列を含むVH鎖領域;
(d)配列番号150のアミノ酸配列を含むVL鎖領域、および配列番号151のアミノ酸配列を含むVH鎖領域;
(e)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号145のアミノ酸配列を含むVH鎖領域;
(f)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号146のアミノ酸配列を含むVH鎖領域;
(g)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号147のアミノ酸配列を含むVH鎖領域;
(h)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号148のアミノ酸配列を含むVH鎖領域;または
(i)配列番号142のアミノ酸配列を含むVL鎖領域、および配列番号149のアミノ酸配列を含むVH鎖領域
を含む、請求項22または23に記載の組成物。 - 前記抗IL13抗体が、10−10M〜10−12Mの解離定数(KD)を有する親和性でヒトIL−13に結合する、請求項22〜25のいずれか1項に記載の組成物。
- 前記抗IL13抗体が、配列番号142に記載の配列を含むVL鎖領域、および配列番号143に記載の配列を含むVH鎖領域を含む、請求項26に記載の組成物。
- 癌を処置するための医薬の製造における、請求項1〜16のいずれか1項に記載の抗IL13抗体の使用。
- 前記医薬が、吸入、ボーラス注射、または注入によって投与される、請求項29に記載の使用。
- 前記癌が、ホジキンリンパ腫、皮膚癌、胃癌、結腸癌、乳癌、膵臓癌、肝癌、前立腺癌、肺癌、頭頸部癌、腎臓細胞癌、扁平上皮癌、AIDS関連カポジ肉腫、または脳腫瘍である、請求項29または30に記載の使用。
- 前記抗IL13抗体は、細胞傷害性因子に結合体化される、請求項29〜31のいずれか1項に記載の使用。
- 前記細胞傷害性因子が、放射線性同位元素または化学療法剤である、請求項32に記載の使用。
- 生物学的サンプルでの癌または腫瘍の診断のための医薬の製造における、請求項22〜28のいずれか1項に記載の抗IL13抗体の使用であって、該癌および/または腫瘍は、IL13を過剰発現する、使用。
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Families Citing this family (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7883704B2 (en) * | 1999-03-25 | 2011-02-08 | Abbott Gmbh & Co. Kg | Methods for inhibiting the activity of the P40 subunit of human IL-12 |
US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
GB0407315D0 (en) | 2003-07-15 | 2004-05-05 | Cambridge Antibody Tech | Human antibody molecules |
CA2550651C (en) * | 2003-12-23 | 2018-01-23 | Tanox, Inc. | Novel anti-il 13 antibodies and uses thereof |
US20050186146A1 (en) * | 2004-02-12 | 2005-08-25 | Nektar Therapeutics | Interleukin-13 antagonist powders, spray-dried particles, and methods |
DK1716181T3 (da) | 2004-02-19 | 2010-03-01 | Genentech Inc | CDR-reparerede antistoffer |
AR049390A1 (es) | 2004-06-09 | 2006-07-26 | Wyeth Corp | Anticuerpos contra la interleuquina-13 humana y usos de los mismos |
US20090098142A1 (en) * | 2004-06-09 | 2009-04-16 | Kasaian Marion T | Methods and compositions for treating and monitoring treatment of IL-13-associated disorders |
US7501121B2 (en) | 2004-06-17 | 2009-03-10 | Wyeth | IL-13 binding agents |
DE602005025525D1 (de) | 2004-11-17 | 2011-02-03 | Amgen Inc | Vollständige humane monoklonale antikörper gegen il-13 |
GB2430883B (en) * | 2005-09-30 | 2008-03-19 | Cambridge Antibody Tech | Interleukin-13 antibody composition |
US20070202106A1 (en) * | 2005-10-06 | 2007-08-30 | Baylor Research Institute | Compositions and methods for the treatment of cancer |
US20070237763A1 (en) * | 2005-10-06 | 2007-10-11 | Baylor Research Institute | Compositions and methods for the treatment of cancer |
WO2007045477A2 (en) | 2005-10-21 | 2007-04-26 | Novartis Ag | Human antibodies against il-13 and therapeutic uses |
RU2432362C2 (ru) | 2005-11-30 | 2011-10-27 | Эбботт Лэборетриз | Моноклональные антитела и их применения |
GB0600488D0 (en) * | 2006-01-11 | 2006-02-22 | Glaxo Group Ltd | Immunoglobulins |
AU2007209202A1 (en) * | 2006-01-24 | 2007-08-02 | Domantis Limited | Ligands that bind IL-4 and/or IL-13 |
EP2471816A1 (en) | 2006-08-30 | 2012-07-04 | Genentech, Inc. | Multispecific antibodies |
ES2817756T3 (es) * | 2006-09-08 | 2021-04-08 | Abbvie Bahamas Ltd | Proteínas de unión a interleuquina-13 |
AU2008205512B2 (en) | 2007-01-16 | 2014-06-12 | Abbvie Inc. | Methods for treating psoriasis |
TW200848429A (en) * | 2007-04-23 | 2008-12-16 | Wyeth Corp | Methods and compositions for treating and monitoring treatment of IL-13-associated disorders |
WO2008140455A1 (en) * | 2007-05-15 | 2008-11-20 | Tanox, Inc. | Treatment of radiation and chemo-therapy induced fibrosis using novel anti-il 13 monoclonal antibodies |
US8183982B2 (en) | 2007-08-14 | 2012-05-22 | Infineon Technologies Ag | System including reply signal that at least partially overlaps request |
JP5641599B2 (ja) * | 2007-08-24 | 2014-12-17 | 学校法人慶應義塾 | 腫瘍細胞による免疫抑制の解除剤とそれを用いた抗腫瘍剤 |
EP2050764A1 (en) | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
EP2274333A4 (en) | 2008-03-18 | 2011-06-15 | Abbott Lab | PROCESS FOR TREATING PSORIASIS |
NZ601815A (en) * | 2008-03-31 | 2014-10-31 | Genentech Inc | Compositions and methods for treating and diagnosing asthma |
MX2011001909A (es) | 2008-08-20 | 2011-03-21 | Centocor Ortho Biotech Inc | Anticuerpos anti-interleucina-13 modificados, composiciones, metodos y usos. |
CA2734905A1 (en) | 2008-09-03 | 2010-03-11 | Jenny M. Bostrom | Multispecific antibodies |
KR20110092328A (ko) * | 2008-11-26 | 2011-08-17 | 글락소 그룹 리미티드 | Il-13에 결합하는 리간드 |
GB0904214D0 (en) | 2009-03-11 | 2009-04-22 | Ucb Pharma Sa | Biological products |
CN102946906B (zh) | 2010-04-23 | 2015-07-15 | 弗·哈夫曼-拉罗切有限公司 | 生产异源多聚体蛋白质 |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
EP2857499A1 (en) | 2010-10-01 | 2015-04-08 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
MY188365A (en) | 2010-12-16 | 2021-12-06 | Genentech Inc | Diagnosis and treatments relating to th2 inhibition |
EP3604339B1 (en) | 2011-01-14 | 2021-03-10 | The Regents Of The University Of California | Therapeutic antibodies against ror-1 protein and methods for use of same |
US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
RU2013140685A (ru) | 2011-02-04 | 2015-03-10 | Дженентек, Инк. | ВАРИАНТЫ Fc, СПОСОБЫ ИХ ПОЛУЧЕНИЯ |
JP2014510730A (ja) | 2011-03-16 | 2014-05-01 | サノフイ | デュアルv領域抗体様タンパク質の使用 |
EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
SG10201602654SA (en) | 2011-10-03 | 2016-05-30 | Moderna Therapeutics Inc | Modified nucleosides,nucleotides,and nucleic acids,and uses thereof |
RU2665810C2 (ru) * | 2011-10-31 | 2018-09-04 | Дженентек, Инк. | Содержащие антитела составы |
KR101483335B1 (ko) | 2011-11-01 | 2015-01-15 | 울산대학교 산학협력단 | 골 손실 진단 마커로서의 피브리노겐의 용도 |
CA3018046A1 (en) | 2011-12-16 | 2013-06-20 | Moderna Therapeutics, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
MX370486B (es) * | 2012-03-27 | 2019-12-16 | Genentech Inc | Composiciones, métodos y usos para asistir en el diagnóstico, pronóstico y tratamiento de la fibrosis pulmonar idiopática. |
AU2013243950A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9303079B2 (en) | 2012-04-02 | 2016-04-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
WO2013158279A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Protein purification methods to reduce acidic species |
WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
WO2013176754A1 (en) | 2012-05-24 | 2013-11-28 | Abbvie Inc. | Novel purification of antibodies using hydrophobic interaction chromatography |
IN2014DN10889A (ja) * | 2012-07-13 | 2015-09-11 | Univ Pennsylvania | |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
PT2922554T (pt) | 2012-11-26 | 2022-06-28 | Modernatx Inc | Arn modificado nas porções terminais |
AU2013381687A1 (en) | 2013-03-12 | 2015-09-24 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
CA2905223A1 (en) * | 2013-04-05 | 2014-10-09 | Genentech, Inc. | Anti-il-4 antibodies and bispecific antibodies and uses thereof |
BR112016004413A2 (pt) | 2013-09-13 | 2017-10-17 | Genentech Inc | composições, preparação de anticorpo e método de purificação de um polipeptídeo recombinante e de tratamento de um distúrbio |
BR112016004437A2 (pt) | 2013-09-13 | 2017-10-17 | Genentech Inc | métodos de imunoteste e de seleção de linhagem de células, anticorpos e kit |
WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
US10323076B2 (en) | 2013-10-03 | 2019-06-18 | Modernatx, Inc. | Polynucleotides encoding low density lipoprotein receptor |
EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9085618B2 (en) * | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
WO2015127405A2 (en) | 2014-02-21 | 2015-08-27 | Genentech, Inc. | Anti-il-13/il-17 bispecific antibodies and uses thereof |
BR112016023238A2 (pt) * | 2014-04-11 | 2017-10-17 | Novartis Ag | processos de tratamento seletivo de asma usando antagonistas de il-13 |
WO2015195758A1 (en) * | 2014-06-18 | 2015-12-23 | Medimmune, Llc | Cell culture methods and media comprising n-acetylcysteine |
WO2016073794A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
MX2017005930A (es) | 2014-11-05 | 2017-06-30 | Genentech Inc | Metodo de produccion de proteinas de cadena doble en bacterias. |
JP6929771B2 (ja) | 2014-11-10 | 2021-09-01 | ジェネンテック, インコーポレイテッド | 抗インターロイキン−33抗体及びその使用 |
CN107109494B (zh) | 2014-11-10 | 2023-10-27 | 豪夫迈·罗氏有限公司 | Il-33介导型疾病的治疗方法和诊断方法 |
WO2016149276A1 (en) | 2015-03-16 | 2016-09-22 | Genentech, Inc. | Methods of detecting and quantifying il-13 and uses in diagnosing and treating th2-associated diseases |
EP3286227A2 (en) | 2015-04-24 | 2018-02-28 | F. Hoffmann-La Roche AG | Multispecific antigen-binding proteins |
EP3286315B1 (en) | 2015-04-24 | 2021-05-26 | F. Hoffmann-La Roche AG | Methods of identifying bacteria comprising binding polypeptides |
SI3528838T1 (sl) | 2016-09-23 | 2023-10-30 | F. Hoffmann-La Roche Ag | Uporabe IL-13 antagonistov za zdravljenje atopijskega dermatitisa |
EP3551034A1 (en) | 2016-12-07 | 2019-10-16 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
CA3051700A1 (en) | 2017-02-10 | 2018-08-16 | Genentech, Inc. | Anti-tryptase antibodies, compositions thereof, and uses thereof |
WO2018183932A1 (en) | 2017-03-30 | 2018-10-04 | Progenity Inc. | Treatment of a disease of the gastrointestinal tract with a il-13 inhibitor |
WO2018195388A1 (en) * | 2017-04-21 | 2018-10-25 | Kindred Biosciences, Inc. | Il4/il13 receptor molecule for veterinary use |
US11053309B2 (en) | 2017-08-04 | 2021-07-06 | Regeneron Pharmaceuticals, Inc. | Methods for treating active eosinophilic esophagitis |
CN109776677B (zh) * | 2017-11-15 | 2023-11-03 | 尚华科创投资管理(江苏)有限公司 | 一种人源化抗il-13抗体及其制备方法和应用 |
CN113101364B (zh) | 2018-05-29 | 2023-12-01 | 康诺亚生物医药科技(成都)有限公司 | 一种自免疫抑制剂的开发和应用 |
EP3866924A4 (en) * | 2018-06-29 | 2022-07-06 | Krystal Biotech, Inc. | COMPOSITIONS AND METHODS OF ANTIBODY DELIVERY |
US20210220471A1 (en) * | 2018-07-13 | 2021-07-22 | Memorial Sloan Kettering Cancer Center | Methods of using pharmacologic inhibitors of type 2 cytokine signaling to treat or prevent pancreatic cancer |
US20220249814A1 (en) | 2018-11-19 | 2022-08-11 | Progenity, Inc. | Methods and devices for treating a disease with biotherapeutics |
WO2020180727A1 (en) | 2019-03-06 | 2020-09-10 | Regeneron Pharmaceuticals, Inc. | Il-4/il-13 pathway inhibitors for enhanced efficacy in treating cancer |
CN113597328A (zh) | 2019-03-21 | 2021-11-02 | 瑞泽恩制药公司 | 用于治疗过敏症的il-4/il-13途径抑制剂和浆细胞消融的组合 |
EP3966244A1 (en) * | 2019-05-09 | 2022-03-16 | F. Hoffmann-La Roche AG | Methods of making antibodies |
US20200352958A1 (en) * | 2019-05-10 | 2020-11-12 | The Trustees Of The University Of Pennsylvania | Methods And Compositions For Targeting Retinoic Acid For Solid Tumor Immunotherapy |
CA3154522A1 (en) | 2019-10-15 | 2021-04-22 | Christopher Carl Frye | Recombinantly engineered, lipase/esterase-deficient mammalian cell lines |
US11707610B2 (en) | 2019-12-13 | 2023-07-25 | Biora Therapeutics, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
CN115605507A (zh) | 2020-03-13 | 2023-01-13 | 基因泰克公司(Us) | 抗白介素-33抗体及其用途 |
TW202317191A (zh) | 2021-07-16 | 2023-05-01 | 美商德米拉股份有限公司 | 用於治療異位性皮炎之il-13抗體 |
TW202323291A (zh) | 2021-08-13 | 2023-06-16 | 美商德米拉股份有限公司 | 用於治療異位性皮膚炎之il-13抗體 |
IL311027A (en) | 2021-09-15 | 2024-04-01 | Dermira Inc | IL-13 inhibitors for the treatment of PRURIGO NODULARIS |
WO2023130010A1 (en) | 2021-12-30 | 2023-07-06 | Regeneron Pharmaceuticals, Inc. | Methods for attenuating atopic march by administering an il-4/il-13 antagonist |
US20230357381A1 (en) * | 2022-04-26 | 2023-11-09 | Novartis Ag | Multispecific antibodies targeting il-13 and il-18 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6468528B1 (en) * | 1999-02-01 | 2002-10-22 | Amgen Canada Inc. | Materials and methods to inhibit Hodgkin and Reed Sternberg cell growth |
JP2007161724A (ja) * | 2003-12-23 | 2007-06-28 | Tanox Inc | 新規抗il13抗体およびその使用 |
Family Cites Families (150)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
US4714681A (en) | 1981-07-01 | 1987-12-22 | The Board Of Reagents, The University Of Texas System Cancer Center | Quadroma cells and trioma cells and methods for the production of same |
DE3127674A1 (de) | 1981-07-14 | 1983-02-24 | Rheinmetall GmbH, 4000 Düsseldorf | Verfahren und vorrichtung zum belegen einer zielflaeche mit munition |
US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
JP2532858B2 (ja) | 1985-04-01 | 1996-09-11 | セルテツク リミテツド | 形質転換したミエロ―マ細胞系 |
US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
WO1989004838A1 (en) | 1987-11-25 | 1989-06-01 | Immunex Corporation | Interleukin-1 receptors |
DE68921982T4 (de) | 1988-06-14 | 1996-04-25 | Cetus Oncology Corp | Kupplungsmittel und sterisch gehinderte, mit disulfid gebundene konjugate daraus. |
US4925648A (en) | 1988-07-29 | 1990-05-15 | Immunomedics, Inc. | Detection and treatment of infectious and inflammatory lesions |
US5601819A (en) | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
US5359037A (en) * | 1988-09-12 | 1994-10-25 | Yeda Research And Development Co. Ltd. | Antibodies to TNF binding protein I |
WO1990005183A1 (en) * | 1988-10-31 | 1990-05-17 | Immunex Corporation | Interleukin-4 receptors |
WO1990005144A1 (en) | 1988-11-11 | 1990-05-17 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
ZA902949B (en) | 1989-05-05 | 1992-02-26 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
US5011778A (en) * | 1989-05-23 | 1991-04-30 | Otsuka Pharmaceutical Co., Ltd. | Monoclonal antibodies directed to IL-1 activated endothelial cells and medicaments employing the monoclonal antibodies |
AU641673B2 (en) | 1989-06-29 | 1993-09-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US5436146A (en) | 1989-09-07 | 1995-07-25 | The Trustees Of Princeton University | Helper-free stocks of recombinant adeno-associated virus vectors |
CZ283050B6 (cs) | 1989-12-20 | 1997-12-17 | Schering Corporation | Polypeptid, jeho subsekvence a jejich použití |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
ES2087997T3 (es) | 1990-01-12 | 1996-08-01 | Cell Genesys Inc | Generacion de anticuerpos xenogenicos. |
US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
EP0521985B1 (en) | 1990-03-20 | 1997-09-24 | The Trustees Of Columbia University In The City Of New York | Chimeric antibodies with receptor binding ligands in place of their constant region |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
EP0546073B1 (en) | 1990-08-29 | 1997-09-10 | GenPharm International, Inc. | production and use of transgenic non-human animals capable of producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
CA2092323A1 (en) | 1990-10-01 | 1992-04-02 | George Y. Wu | Targeting viruses and cells for selective internalization by cells |
EP0553244B8 (en) | 1990-10-05 | 2005-06-08 | Celldex Therapeutics, Inc. | Targeted immunostimulation with bispecific reagents |
AU8727291A (en) | 1990-10-29 | 1992-06-11 | Cetus Oncology Corporation | Bispecific antibodies, method of production, and uses thereof |
ES2178635T3 (es) | 1990-11-09 | 2003-01-01 | Stephen D Gillies | Inmunoconjugados de citoquinas. |
ES2054601T3 (es) * | 1991-03-29 | 1996-04-01 | Sanofi Sa | Proteina con actividad de tipo citoquina, adn recombinante codante para esta proteina, celulas y microorganismos transformados. |
HUT66753A (en) | 1991-04-26 | 1994-12-28 | Surface Active Ltd | Novel antibodies and methods for their use |
CA2103064A1 (en) | 1991-05-14 | 1992-11-15 | George Y. Wu | Targeted delivery of genes encoding immunogenic proteins |
DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
CA2103371C (en) | 1991-06-05 | 2003-09-16 | George Y. Wu | Targeted delivery of genes encoding secretory proteins |
US5994514A (en) * | 1991-08-14 | 1999-11-30 | Genentech, Inc. | Immunoglobulin variants |
US5965709A (en) * | 1991-08-14 | 1999-10-12 | Genentech, Inc. | IgE antagonists |
US6329509B1 (en) * | 1991-08-14 | 2001-12-11 | Genentech, Inc. | Anti-IgE antibodies |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
ATE408012T1 (de) | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
WO1993014188A1 (en) | 1992-01-17 | 1993-07-22 | The Regents Of The University Of Michigan | Targeted virus |
AU3658093A (en) | 1992-02-10 | 1993-09-03 | Seragen, Inc. | Desensitization to specific allergens |
AU3737893A (en) | 1992-03-05 | 1993-10-05 | Board Of Regents, The University Of Texas System | Diagnostic and/or therapeutic agents, targeted to neovascular endothelial cells |
WO1993020221A1 (en) | 1992-04-03 | 1993-10-14 | Young Alexander T | Gene therapy using targeted viral vectors |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
US5318564A (en) | 1992-05-01 | 1994-06-07 | Hemostatic Surgery Corporation | Bipolar surgical snare and methods of use |
ES2136664T3 (es) | 1992-06-09 | 1999-12-01 | Hoppe Ag | Sistema de cierre y conjunto de cerradura. |
US5397703A (en) * | 1992-07-09 | 1995-03-14 | Cetus Oncology Corporation | Method for generation of antibodies to cell surface molecules |
US5596072A (en) * | 1992-08-21 | 1997-01-21 | Schering Corporation | Method of refolding human IL-13 |
CN1085953A (zh) * | 1992-08-21 | 1994-04-27 | 先灵公司 | 人白细胞介素13 |
JPH07508179A (ja) | 1992-08-21 | 1995-09-14 | シェリング・コーポレーション | ヒトインターロイキン−13 |
EP0749475A4 (en) | 1992-08-26 | 1997-05-07 | Harvard College | USE OF THE CYTOKIN IP-10 AS AN ANTI-TUMOR AGENCY |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
WO1994008598A1 (en) | 1992-10-09 | 1994-04-28 | Advanced Tissue Sciences, Inc. | Liver reserve cells |
EP0911413A3 (en) | 1992-12-03 | 2000-11-15 | Genzyme Corporation | Minimal adenovirus-based gene therapy vector |
US5441050A (en) | 1992-12-18 | 1995-08-15 | Neoprobe Corporation | Radiation responsive surgical instrument |
EP0604693A1 (en) | 1992-12-29 | 1994-07-06 | Schering-Plough | Monoclonal antibodies against the human interleukin-4 receptor and hybridomas producing the same |
DK0698097T3 (da) | 1993-04-29 | 2001-10-08 | Unilever Nv | Produktion af antistoffer eller (funktionaliserede) fragmenter deraf afledt af Camelidae-immunoglobuliner med tung kæde |
CN1127351C (zh) * | 1993-09-02 | 2003-11-12 | 达特茅斯学院理事 | 诱导抗原特异性t细胞耐受的方法 |
RU2162711C2 (ru) * | 1993-09-07 | 2001-02-10 | Смитклайн Бичам Корпорейшн | Рекомбинантные il4-антитела, используемые для лечения нарушений, связанных с действием il4 |
EP0659766A1 (en) | 1993-11-23 | 1995-06-28 | Schering-Plough | Human monoclonal antibodies against human cytokines and methods of making and using such antibodies |
GB9415379D0 (en) * | 1994-07-29 | 1994-09-21 | Smithkline Beecham Plc | Novel compounds |
IT1270662B (it) * | 1994-10-13 | 1997-05-07 | Applied Research Systems | Antagonista della interleuchina-1 |
US5705154A (en) * | 1995-03-08 | 1998-01-06 | Schering Corporation | Humanized monoclonal antibodies against human interleukin-4 |
US6037453A (en) * | 1995-03-15 | 2000-03-14 | Genentech, Inc. | Immunoglobulin variants |
US6518061B1 (en) * | 1995-03-15 | 2003-02-11 | The United States Of America As Represented By The Department Of Health And Human Services | IL-13 receptor specific chimeric proteins and uses thereof |
US6165463A (en) | 1997-10-16 | 2000-12-26 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
ES2317646T3 (es) | 1995-09-08 | 2009-04-16 | Genzyme Corporation | Vectores aav mejorados para terapia genica. |
CA2238080C (en) | 1995-10-23 | 2012-03-13 | Amrad Operations Pty. Ltd. | A novel haemopoietin receptor and genetic sequences encoding same |
US6911530B1 (en) * | 1995-10-23 | 2005-06-28 | Amrad Operations, Pty., Ltd. | Haemopoietin receptor and genetic sequences encoding same |
FR2742156A1 (fr) | 1995-12-06 | 1997-06-13 | Sanofi Sa | Polypeptide recepteur de l'il-13 |
RO123028B1 (ro) | 1996-02-09 | 2010-07-30 | Abbott Laboratories (Bermuda) Ltd. | Anticorpi umani, care leagă tnf alpha uman |
US7078494B1 (en) * | 1996-03-01 | 2006-07-18 | Genetics Institute, Llc | Antibodies to human IL-13bc and methods of their use in inhibiting IL-13 binding |
US6664227B1 (en) * | 1996-03-01 | 2003-12-16 | Genetics Institute, Llc | Treatment of fibrosis by antagonism of IL-13 and IL-13 receptor chains |
US5710023A (en) | 1996-03-01 | 1998-01-20 | Genetics Institute, Inc. | IL-13 cytokine receptor chain |
WO1997033899A1 (en) | 1996-03-14 | 1997-09-18 | Human Genome Sciences, Inc. | Apoptosis inducing molecule i |
KR20030096450A (ko) | 1996-03-22 | 2003-12-31 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 고사 유도 분자 ⅱ |
WO1997047742A1 (en) | 1996-06-12 | 1997-12-18 | Smithkline Beecham Corporation | Hr-1 receptor |
WO1998010638A1 (en) | 1996-09-10 | 1998-03-19 | Amrad Operations Pty. Ltd. | Therapeutic molecules |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
PT942968E (pt) | 1996-12-03 | 2008-03-27 | Amgen Fremont Inc | Anticorpos totalmente humanos que se ligam ao egfr |
US6743604B1 (en) * | 1996-12-13 | 2004-06-01 | Smithkline Beecham Corporation | Substances and their uses |
GB9625899D0 (en) * | 1996-12-13 | 1997-01-29 | Glaxo Group Ltd | Substances and their uses |
KR20000070034A (ko) | 1997-01-10 | 2000-11-25 | 아스트루 마이클 제이 | 항 cd40l 화합물로 신염성 루푸스를 치료하는 방법 |
WO1998031394A2 (en) * | 1997-01-22 | 1998-07-23 | Board Of Regents, The University Of Texas System | Tissue factor methods and compositions for coagulation and tumor treatment |
AU742045B2 (en) | 1997-04-14 | 2001-12-13 | Amgen Research (Munich) Gmbh | Novel method for the production of anti-human antigen receptors and uses thereof |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US6642051B1 (en) | 1997-10-21 | 2003-11-04 | Targeted Genetics Corporation | Amplifiable adeno-associated virus(AAV) packaging cassettes for the production of recombinant AAV vectors |
CA2309541C (en) | 1997-11-03 | 2011-01-11 | Human Genome Sciences, Inc. | Vegi, an inhibitor of angiogenesis and tumor growth |
US6576232B1 (en) * | 1998-04-03 | 2003-06-10 | The Penn State Research Foundation | IL13 mutants |
US6482403B1 (en) | 1998-05-29 | 2002-11-19 | Heska Corporation | Caniney IL-13 immunoregulatory proteins and uses thereof |
US6299875B1 (en) * | 1998-06-04 | 2001-10-09 | Panacea Pharmaceuticals, Llc | Methods to block IGE binding to cell surface receptors of mast cells |
US6222971B1 (en) | 1998-07-17 | 2001-04-24 | David Slobodin | Small inlet optical panel and a method of making a small inlet optical panel |
GB9820014D0 (en) | 1998-09-14 | 1998-11-04 | Cancer Res Campaign Tech | Receptor antagonists and uses thereof |
DE19848026A1 (de) | 1998-10-17 | 2000-04-20 | Bayer Ag | Verfahren zur Herstellung von Bis(4-hydroxyaryl)alkanen |
US7553487B2 (en) * | 1998-12-14 | 2009-06-30 | Genetics Institute, Llc | Method and compositions for treating asthma |
BR9916209A (pt) | 1998-12-14 | 2001-12-26 | Genetics Inst | Cadeia de receptor de citocina |
US6567436B1 (en) | 1999-01-26 | 2003-05-20 | California Institute Of Technology | Opto-electronic oscillators having optical resonators |
JP2003511019A (ja) * | 1999-10-06 | 2003-03-25 | ザ ペン ステート リサーチ ファウンデーション | Il13変異体 |
AU1599301A (en) | 1999-11-11 | 2001-06-06 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Modulating IL-13 activity using mutated IL-13 molecules that are antagonists or agonists of IL-13 |
US7422376B2 (en) | 1999-12-07 | 2008-09-09 | Molex Incorporated | Self-contained fiber optic connector module |
EP1270595B1 (en) | 2000-03-03 | 2008-07-23 | Kyowa Hakko Kogyo Co., Ltd. | Anti ccr4 antibody and its fragment |
CN1323812A (zh) | 2000-05-16 | 2001-11-28 | 上海博德基因开发有限公司 | 一种新的多肽——人白细胞介素-13(il-13)受体11和编码这种多肽的多核苷酸 |
WO2002033073A1 (fr) | 2000-10-20 | 2002-04-25 | Chugai Seiyaku Kabushiki Kaisha | Anticorps agoniste degrade |
EP2027867A1 (en) | 2000-10-20 | 2009-02-25 | Genetics Institute, LLC | Method and composition for inhibition of tumor growth and enhancing an immune response |
PT1449850E (pt) * | 2001-08-31 | 2011-02-02 | Kyowa Hakko Kirin Co Ltd | Anticorpos humanos enxertados em rdc¿s e fragmentos desses anticorpos |
US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
EP1578912A4 (en) | 2001-10-26 | 2007-12-26 | Centocor Inc | IL-13 MUTEIN PROTEINS, ANTIBODIES, COMPOSITIONS, METHODS AND USES |
CA2466492A1 (en) | 2001-11-07 | 2003-05-15 | Cytos Biotechnology Ag | Antigen arrays presenting il-5, il-13 or eotaxin for treatment of allergic eosinophilic diseases |
US7541040B2 (en) * | 2001-12-04 | 2009-06-02 | The United States Of America As Represented By The Department Of Health And Human Serivces | Chimeric molecule for the treatment of th2-like cytokine mediated disorders |
US20030170724A1 (en) * | 2002-03-08 | 2003-09-11 | Anderson David C. | Methods of identifying target polypeptides |
WO2003075859A2 (en) * | 2002-03-08 | 2003-09-18 | Rigel Pharmaceuticals, Inc. | COMPOUNDS THAT MODULATE PROCESSES ASSOCIATED WITH IgE PRODUCTION AND METHODS AND KITS FOR IDENTIFYING AND USING THE SAME |
AU2003223497A1 (en) * | 2002-04-05 | 2003-10-27 | Centocor, Inc. | Asthma-related anti-il-13 immunoglobulin derived proteins, compositions, methods and uses |
ATE503233T1 (de) | 2002-06-14 | 2011-04-15 | Us Gov Health & Human Serv | Verfahren zur behandlung und prävention von kolitis, an der il-13 und nk-t zellen beteiligt sind |
US7374894B2 (en) * | 2002-07-16 | 2008-05-20 | Rigel Pharmaceuticals, Inc. | Methods of identifying compounds that modulate IL-4 receptor-mediated IgE synthesis utilizing a chloride intracellular channel 1 protein |
US20060147417A1 (en) | 2002-08-30 | 2006-07-06 | Claire Ashman | Immunogenic composition comprising an il-13 element and t cell epitopes, and its therapeutic use |
CA2496948A1 (en) | 2002-08-30 | 2004-03-11 | Glaxo Group Limited | Il-14 vaccine for the treatment of asthma and atopic disorders |
EP1572946B1 (en) * | 2002-09-06 | 2012-03-14 | Amgen, Inc. | Therapeutic human anti-il-1r1 monoclonal antibody |
EP1592776A4 (en) | 2003-02-01 | 2008-06-04 | Tanox Inc | ANTI-HUMAN IGE ANTIBODIES WITH HIGH AFFINITY |
DK1471057T3 (da) * | 2003-04-25 | 2006-05-15 | Actimis Pharmaceuticals Inc | Pyrimidinyleddikesyrederivater, der er egnede til behandlingen af sygdomme medieret af CRTH2 |
GB0407315D0 (en) * | 2003-07-15 | 2004-05-05 | Cambridge Antibody Tech | Human antibody molecules |
US7501121B2 (en) | 2004-06-17 | 2009-03-10 | Wyeth | IL-13 binding agents |
AR049390A1 (es) | 2004-06-09 | 2006-07-26 | Wyeth Corp | Anticuerpos contra la interleuquina-13 humana y usos de los mismos |
TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
GB2430883B (en) | 2005-09-30 | 2008-03-19 | Cambridge Antibody Tech | Interleukin-13 antibody composition |
WO2007045477A2 (en) | 2005-10-21 | 2007-04-26 | Novartis Ag | Human antibodies against il-13 and therapeutic uses |
WO2008140455A1 (en) | 2007-05-15 | 2008-11-20 | Tanox, Inc. | Treatment of radiation and chemo-therapy induced fibrosis using novel anti-il 13 monoclonal antibodies |
NZ601815A (en) | 2008-03-31 | 2014-10-31 | Genentech Inc | Compositions and methods for treating and diagnosing asthma |
MY188365A (en) | 2010-12-16 | 2021-12-06 | Genentech Inc | Diagnosis and treatments relating to th2 inhibition |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6468528B1 (en) * | 1999-02-01 | 2002-10-22 | Amgen Canada Inc. | Materials and methods to inhibit Hodgkin and Reed Sternberg cell growth |
JP2007161724A (ja) * | 2003-12-23 | 2007-06-28 | Tanox Inc | 新規抗il13抗体およびその使用 |
JP2008500024A (ja) * | 2003-12-23 | 2008-01-10 | タノックス インコーポレイテッド | 新規抗il13抗体およびその使用 |
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