JP2022065039A - マクロファージ上のFc受容体結合の破壊による抗SlRPα抗体療法の効果増強 - Google Patents
マクロファージ上のFc受容体結合の破壊による抗SlRPα抗体療法の効果増強 Download PDFInfo
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Abstract
Description
ヒトIgG受容体ファミリーは、hFcγRI、hFcγRIIA、hFcγRIIC、hFcγRIIIA、hFcγRIIB、hFcRIIIBを含む多くの受容体からなる。IgGはまた、IgGの再利用及び輸送に関与するFcRnに結合する。Fc受容体の活性化は、細胞表面において発現及び機能するためにFcRサブユニットを必要とし得る。他のFc受容体は、例えば、FcαRI(CD89)、Fcα/μR、FcεRI等を含む。Fc受容体の発現は、免疫エフェクター細胞間で変動する。hFcγRI(CD64)は、単球/マクロファージ及び樹状細胞(DC)に限定され、誘導されて好中球及び肥満細胞に発現し、hFcγRIIA(CD32A)は、全ての骨髄細胞に発現するがリンパ球に発現せず、hFcγRIIB(CD32B)は、循環B細胞及び好塩基球においてのみ高発現し、組織マクロファージ及びDCにおいて発現するが、肥満細胞において発現せず、hFcγRIIC(CD32C)は、NK細胞、単球、及び好中球において発現し、hFcγRIIIA(CD16A)は、NK細胞及び単球/マクロファージで発現し、hFcγRIIIB(CD16B)は、好中球、及び好塩基球のサブセットで発現する。
抗体のFc領域は、その血清半減期、ならびに補体依存性細胞傷害(CDC)、抗体依存性細胞傷害(ADCC)、及び抗体依存性細胞食作用(ADCP)等のエフェクター機能を媒介する。治療用モノクローナル抗体またはFc融合タンパク質のFc領域を遺伝子操作することは、それらに要求される薬理活性により良好に適した分子の産生を可能にする。IgGの半減期は、新生児受容体FcRnへのそのpH依存性結合に依存する。内皮細胞表面に発現するFcRnは、pH依存性の様式でIgGに結合し、それを分解から保護する。
一態様において、本開示は、ヒトSIRPαに特異的に結合し、1つの細胞(例えば、がん細胞、感染細胞等)上のCD47と別の細胞(例えば、食細胞)上のSIRPαとの間の相互作用を低減する抗体(すなわち、抗SIRPα抗体)(及びそのような抗体を産生する細胞株)に関する。抗体は、(i)SIRPα、例えばヒトSIRPαに特異的に結合する可変領域と、(ii)FcRn以外の1つ以上の、ヒトFcγ受容体を含むFc受容体に対する低減した結合を有するFc領域とを含むか、またはFc領域を欠く。いくつかのそのような実施形態において、Fc領域はヒトFc領域であり、ここでFcは、Fc受容体結合を低減するように1つ以上のアミノ酸の変更によって改変されているか、または遺伝子操作を受けている。特異的な抗SIRPα抗体は、非限定的にKWAR23を含み、この抗体は本明細書において、キメラ及びヒト化のフォーマットで開示されている。
本開示はまた、対象の抗SIRPα抗体(例えば、上述のポリペプチドの任意のものを含む)をコードする単離された核酸、核酸を含むベクター及び宿主細胞、抗体を産生するための組換え技術を提供する。当該技術分野において知られているように、可変領域の配列は、任意の適切な定常領域配列に融合することができる。
本明細書において提供される抗SIRPα抗体は、特にインビボ治療用途のために、食作用の調節(例えば、食作用の誘導)において使用され得る。例えば、本明細書において提供される対象の抗SIRPα抗体は、1つの細胞上のCD47と別のものの上のSIRPαとの相互作用が遮断されるべきである任意の方法において使用することができる。対象の抗SIRPα抗体を使用するための例示的な方法は、米国特許出願第20130142786号、米国特許出願第20120282174号、米国特許出願第20110076683号、米国特許出願第20120225073号、米国特許出願第20110076683号、米国特許出願第20110015090号、米国特許出願第20110014119号、米国特許出願第20100239579号、米国特許出願第20090191202号、米国特許出願第20070238127号、米国特許出願第20070111238号、及び米国特許出願第20040018531号に記載される方法を含むが、こられには限定されない。これらは、参照によりその全ての内容が本明細書に具体的に組み込まれる。例えば、抗体組成物は、CD47を発現しているがん細胞、炎症細胞、及び/または慢性感染細胞の食作用を誘導するために投与され得る。
以下の実施例は、当業者に本発明をいかに作製及び使用するかの完全な開示及び説明を提供するために進められ、本願発明者が自身の発明と見なすものの範囲を限定することを意図するものではなく、また以下の実験が実施された全部または唯一の実験であることを表すことを意図するものでもない。使用される数字(例えば、量、温度等)に関して正確さを確実にするための努力がなされてきたが、いくつかの実験誤差及び偏差が考慮されるべきである。別途示されない限り、部は重量部であり、分子量は重量平均分子量であり、温度は摂氏であり、そして圧力は大気圧または大気圧付近である。
CD47-SIRPα経路の遮断は、がん細胞の食作用を媒介し、がんを標的とするモノクローナル抗体と相乗的に作用する。遮断剤は、例えば、CD47に特異的に結合する抗体、及びSIRPαに特異的に結合する抗体を含む。後者は、SIRPαの発現がCD47よりも限定されているので、治療用途において、ある特定の利点を有し得る。これは、薬物動態学及び毒物学プロファイルに影響を与える可能性がある。
インビトロにおいてリツキシマブと組み合わされた、ヒトマクロファージによるNHL細胞の食作用のための低減したFcγR結合を有する抗SIRPα抗体に関して、実施例1で述べたように、遺伝子操作されたFc領域を含む抗ヒトSIRPα抗体を、インビトロでヒトマクロファージによるヒトNHL細胞株、初代培養NHL細胞、及び正常末梢血(NPB)細胞の食作用を可能にする能力について評価する。NHL細胞をIgG1アイソタイプ対照または抗CD45 IgG1抗体の存在下でインキュベートし、リツキシマブの存在下で、野生型または遺伝子操作を受けたN297A Fc領域を有するヒト化抗SIRPα抗体の存在下での活性を比較する。これらの条件下における腫瘍細胞の食作用が測定される。
バーキットリンパ腫細胞株(Raji)及びDLBCL細胞株(SUDHL4)は、アメリカ合衆国培養細胞系統保存機関から取得されるか、または研究室で樹立される。NHL17*細胞株は、バルク細胞を、10%ヒトAB血清を補充したIMDMによって1.5ヶ月間インビトロで培養することによってDLBCLを有する患者から樹立される。
正常ヒト末梢血及びヒトNHL試料は、IRB承認プロトコルに従ってインフォームドコンセントを得て、または地域倫理委員会(REK)承認プロトコルに従ってノルウェーラジウム病院(ノルウェー、オスロ)からインフォームドコンセントを得て取得される。胚中心B細胞解析のための正常扁桃腺は、同意された小児患者からの廃棄された扁桃摘出標本から得られる。
正常末梢血球、胚中心B細胞、及び初代NHL細胞の解析のために、CD19、CD20、CD3、CD10、CD45、CD5、CD38(Invitrogen, Carlsbad, CA, USA and BD Biosciences, San Jose, CA, USA)の抗体を使用した。CD47発現の解析は、抗ヒトCD47FITC抗体(クローンB6H12.2、BD Biosciences)によって実施した。細胞染色及びフローサイトメトリー解析は、以前に記載されたように実施した。
リツキシマブ(anti-CD20、ヒトIgG1)は、スタンフォード大学メディカルセンターより得られ、マウス抗ヒトCD20,IgG2aは、Beckman Coulter(Miami, FL, USA)より得られる。
示された抗体、抗CD20 IgG2a、またはリツキシマブを単独で、または1μg/ml~10μg/mlの濃度で組み合わせてインキュベートされたNHL細胞によってインビトロ食作用アッセイを実施する。規定された単剤効果(食作用指数)を生じるために必要とされる各々の抗体の濃度は、各細胞型について決定される。次いで、この同一の食作用指数を達成するために組み合わせた2つの抗体の濃度をアイソボログラムにプロットし、そして組み合わせ指数(CI)を決定する。CIは、式CI=(d1/D1)+(d2/D2)から計算され、ここで、d1=食作用指数を達成するための組み合わせでの薬物1の用量、d2=食作用指数を達成するための組み合わせでの薬物2の用量、D1=食作用指数を達成するための薬物1単独の用量、D2=食作用指数を達成するための薬物2単独の用量である。1未満、1に等しい、及び1を超えるCIは、それぞれ相乗作用、相加性、及び拮抗作用を示す。
インビトロにおいて抗EGFRと組み合わされた、ヒトマクロファージによる結腸直腸がん細胞の食作用のための低減したFcγR結合を有する抗SIRPα抗体がん細胞
DLD1細胞(ATCC)、HT29細胞(ATCC)、SW620細胞(ATCC)、SW48細胞(ATCC)、LS174T細胞(ATCC)、HCT116細胞(ATCC)、及びCACO-2細胞(ATCC)は、10%ウシ胎仔血清(Omega Scientific)、100U/mLペニシリン、及び100μg/mLストレプトマイシン(ThermoFisher S)を補充した、RPMI(ThermoFisher S.)(DLD1)、EMEM(ThermoFisher S.)(CACO-2、LS174T)、McCoy’s 5A(ThermoFisher S.)(HT29、HCT116)、またはLeibovitz’s L-15(ThermoFisher S.)(SW48、SW 620)において培養される。GFP-ルシフェラーゼ+DLD1細胞株は、eGFP-ルシフェラーゼ2(pgl4)融合タンパク質を発現するよう遺伝子操作を受けたpCDH-CMV-MCS-EF1 puro HIVに基づくレンチウイルスベクター(Systems Biosciences)を用いて形質導入することによって樹立された。安定な株は、FACSAria IIセルソーター(BD Biosciences)でGFP発現についてソーティングすることによって作製された。腫瘍細胞は、6μg/mLのポリブレンを含む培地中で、レンチウイルスによって一晩形質導入された。次の日に、細胞を繰り返し洗浄してポリブレンと細胞外のレンチウイルスを除去した。形質導入された(GFP+)細胞は、後に、FACSによって移植腫瘍から単離された。
末梢血単核細胞を密度勾配遠心分離によって濃縮し、単球を抗CD14マイクロビーズ(Miltenyi)で精製し、10%AB-ヒト血清(Invitrogen)ならびに100U/mLペニシリン及び100μg/mLストレプトマイシン(Invitrogen)を補充したIMDM+GlutaMax(Invitrogen)中で7~10日間培養することによってマクロファージに分化させる。食作用アッセイは、50,000のマクロファージと100,000のGFP+腫瘍細胞との2時間の共培養によって実施され、その後、ハイスループットサンプラー(BD Biosciences)を備えたLSRFortessa細胞分析装置を用いて解析される。処理に使用された抗体は、IgG1アイソタイプ対照、活性の、または機能しないFc領域を有する抗SIRPα、及び抗EGFRセツキシマブ(Bristoll-Myers Squibb)を含む。マクロファージは抗CD206抗体を用いてフローサイトメトリーで同定される。死細胞は、DAPI(Sigma)による染色によって解析より排除された。食作用は、GFP+マクロファージのパーセンテージによって評価され、各々の細胞株に対する各々の独立したドナーによる最大応答に対して標準化された。
進行悪性腫瘍において抗SIRPαと併用したアベルマブ
上述のアッセイを用いて、野生型または機能しないFcを有する抗SIRPα抗体の、抗PD-L1抗体であるアベルマブ(MSB0010718C)と組み合わせた組み合わせを、進行性または転移性固形腫瘍(例えば、非小細胞肺がん(NSCLC)、黒色腫、及び頭頸部扁平上皮がん(SCCHN))の、インビトロでの食作用及び/または細胞媒介細胞溶解について試験する。
個体の応答における変動
マウスFc配列を有する抗SIRPα KWAR23の可変領域を用いて(mKWARと命名)、ヒトFcγRとの相互作用を無効にするためのN297A変異を含むヒトFc配列とのキメラ(chKWAR-dead-Fcと命名)、野生型ヒトIgG1 Fcとのキメラ(chKWAR-IgG1と命名)、及びヒトIgG4 Fc領域とのキメラ(chKWAR-IgG4と命名)の抗体を作製した。
さらなる抗SIRPα抗体
ヒトSIRPαに対するさらなる抗体が、マウスをヒトタンパク質で免疫して、SIRPaに結合した抗体をスクリーニングすることによって作製された。2つのモノクローナル抗体のクローンは、それぞれ9B11及び7E11と名付けられた。マウス可変領域をヒトIgG4 Fc領域(7E11-G4または9B11-G4と命名)にキメラとして結合するか、またはヒトFcγRとの相互作用を無効にするためのN297A変異を含むヒトIgG1 Fc領域にキメラとして結合した(7E11-G1または9B11-G1と命名)。
F(ab)2 フラグメント
Fcγ受容体に対する低減した親和性を有するヒトFc領域を含む抗体の使用の代替として、例えばF(ab′)2 フラグメントを産生することによってFc配列を欠くように抗体を遺伝子操作することができる。
ヒト化KWAR抗体
例えば、参照により本明細書に具体的に組み込まれる米国特許出願US-2017-0073414-A1に開示される抗SIRPα抗体KWAR23は、マウス抗ヒト抗体として最初に開発された。
マウスKWAR23可変重鎖(VH)(CDRに下線を付す)
EVQLVQSGAEVKKPGATVKISCKVSGFNIKDYYIHWVQQAPGKGLEWIGRIDPEDGETKYAPKFQDRATITADTSTDTAYMELSSLRSEDTAVYYCARWGAYWGQGTLVTVSS
ヒト化KWAR23可変軽鎖(VL)、配列番号2:
QIVLTQSPPTLSLSPGERVTLTCSASSSVSSSYLYWYQQKPGQAPKLWIYSTSNLASGVPARFSGSGSGTSYTLTISSLQPEDFAVYFCHQWSSYPRTFGAGTKLEIK
CDR-H1:DYYIH(配列番号3)
CDR-H2:RIDPEDGETKYAPKFQD(配列番号4)
CDR-H3:WGAY(配列番号5)
CDR-L1:SASSSVSSSYLY(配列番号6)
CDR-L2:STSNLAS(配列番号7)
CDR-L3:HQWSSYPRT(配列番号8)
本願は、2016年8月3日に出願された米国仮特許出願第62/370,422号の権益を主張し、その出願は、参照によりその全体が本明細書に組み込まれる。
Claims (1)
- 単離された治療用の抗体であって、
(i)ヒトSIRPαに特異的に結合する可変領域と、
(ii)FcRn以外のヒトFc受容体に対する結合を低減する改変を含むヒトFc領域と
を含む、抗体。
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PCT/US2017/043935 WO2018026600A1 (en) | 2016-08-03 | 2017-07-26 | Disrupting fc receptor engagement on macrophages enhances efficacy of anti-sirpalpha antibody therapy |
JP2019505387A JP7369620B2 (ja) | 2016-08-03 | 2017-07-26 | マクロファージ上のFc受容体結合の破壊による抗SlRPα抗体療法の効果増強 |
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Families Citing this family (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JOP20190009A1 (ar) | 2016-09-21 | 2019-01-27 | Alx Oncology Inc | أجسام مضادة ضد بروتين ألفا منظم للإشارات وطرق استخدامها |
CA3044684A1 (en) | 2016-12-09 | 2018-06-14 | Alector Llc | Anti-sirp-alpha antibodies and methods of use thereof |
US10851164B2 (en) | 2017-04-13 | 2020-12-01 | Aduro Biotech Holdings, Europe B.V. | Anti-SIRPα antibodies |
WO2018210793A2 (en) | 2017-05-16 | 2018-11-22 | Synthon Biopharmaceuticals B.V. | ANTI-SIRPα ANTIBODIES |
SG11202000658PA (en) | 2017-07-26 | 2020-02-27 | Forty Seven Inc | Anti-sirp-alpha antibodies and related methods |
CN117771364A (zh) | 2017-10-18 | 2024-03-29 | 四十七公司 | 基于抗cd47剂的卵巢癌疗法 |
CN108484774B (zh) * | 2018-03-09 | 2021-11-05 | 上海高菲生物科技有限公司 | 一种SIRPα融合蛋白及其制备方法和用途 |
KR20200133376A (ko) | 2018-03-21 | 2020-11-27 | 알렉소 온콜로지 인크. | 신호-조절 단백질 알파에 대한 항체 및 사용 방법 |
MA52753A (fr) | 2018-05-25 | 2021-04-21 | Alector Llc | Anticorps anti-sirpa et leurs procédés d'utilisation |
CN112673023B (zh) | 2018-07-10 | 2023-09-12 | 国立大学法人神户大学 | 抗SIRPα抗体 |
CA3108795A1 (en) * | 2018-08-08 | 2020-02-13 | Orionis Biosciences, Inc. | Sirp1a targeted chimeric proteins and uses thereof |
BR112021005585A2 (pt) * | 2018-09-27 | 2021-06-29 | Celgene Corporation | proteínas de ligação a sirpa e métodos de uso das mesmas |
US11591390B2 (en) | 2018-09-27 | 2023-02-28 | Celgene Corporation | SIRP-α binding proteins and methods of use thereof |
MX2021005761A (es) | 2018-11-15 | 2021-08-11 | Byondis Bv | Anticuerpos anti-proteína alfa reguladora de señal (anti-sirpalfa) humanizados. |
US20200400662A1 (en) | 2019-06-07 | 2020-12-24 | ALX Oncology Inc. | Methods and reagents for reducing the interference of drugs that bind cd47 in serological assays |
CA3142513A1 (en) | 2019-06-25 | 2020-12-30 | Gilead Sciences, Inc. | Flt3l-fc fusion proteins and methods of use |
JP2022545300A (ja) * | 2019-08-20 | 2022-10-27 | エルピサイエンス(スーチョウ)・バイオファーマ,リミテッド | 新規の抗sirpa抗体 |
US20230136228A1 (en) | 2019-09-18 | 2023-05-04 | Lamkap Bio Alpha AG | Bispecific antibodies against ceacam5 and cd3 |
AU2020365113A1 (en) | 2019-10-18 | 2022-04-07 | Forty Seven, Inc. | Combination therapies for treating myelodysplastic syndromes and acute myeloid leukemia |
MX2022005123A (es) | 2019-10-31 | 2022-05-30 | Forty Seven Inc | Tratamiento basado en anti-cd47 y anti-cd20 para cancer hematologico. |
JP2023503943A (ja) | 2019-11-27 | 2023-02-01 | エーエルエックス オンコロジー インコーポレイテッド | がんを治療するための組み合わせ療法 |
CA3165735A1 (en) | 2019-12-24 | 2021-07-01 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
KR20220119473A (ko) * | 2019-12-24 | 2022-08-29 | 라노바 메디신즈 리미티드 컴파니 | 항-SIRPα 단클론성 항체 및 그것의 용도 |
BR112022014623A2 (pt) | 2020-02-14 | 2022-09-13 | Jounce Therapeutics Inc | Anticorpos e proteínas de fusão que se ligam a ccr8 e usos dos mesmos |
MX2022010515A (es) | 2020-02-28 | 2022-11-14 | Tallac Therapeutics Inc | Conjugacion mediada por transglutaminasa. |
KR20230018475A (ko) | 2020-06-01 | 2023-02-07 | 알렉소 온콜로지 인크. | 암 치료용 저메틸화제를 포함하는 병용 요법 |
US20230414778A1 (en) | 2020-11-11 | 2023-12-28 | Daiichi Sankyo Company, Limited | COMBINATION OF ANTIBODY-DRUG CONJUGATE WITH ANTI-SIRPalpha ANTIBODY |
WO2022120286A1 (en) | 2020-12-06 | 2022-06-09 | ALX Oncology Inc. | Multimers for reducing the interference of drugs that bind cd47 in serological assays |
CN112574310B (zh) | 2020-12-11 | 2023-05-05 | 浙江博锐生物制药有限公司 | 抗SIRPα抗体及其用途 |
EP4322937A1 (en) * | 2021-04-14 | 2024-02-21 | Institut National de la Santé et de la Recherche Médicale (INSERM) | New method to improve the anti-tumoral activity of macrophages |
TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
IL308400A (en) | 2021-05-13 | 2024-01-01 | Alx Oncology Inc | Combined therapies for cancer treatment |
TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用FLT3L—Fc融合蛋白之方法 |
CA3220923A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
US11926628B2 (en) | 2021-06-23 | 2024-03-12 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
US11976072B2 (en) | 2021-06-23 | 2024-05-07 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
AU2022298639A1 (en) | 2021-06-23 | 2023-12-07 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
AU2022304582A1 (en) | 2021-06-29 | 2024-02-01 | Seagen Inc. | Methods of treating cancer with a combination of a nonfucosylated anti-cd70 antibody and a cd47 antagonist |
CN116472351A (zh) | 2021-08-17 | 2023-07-21 | 杭州九源基因工程有限公司 | 靶向SIRPα的单克隆抗体及其用途 |
WO2023076983A1 (en) | 2021-10-28 | 2023-05-04 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
AU2022376954A1 (en) | 2021-10-29 | 2024-05-02 | Gilead Sciences, Inc. | Cd73 compounds |
WO2023122581A2 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
US20230242508A1 (en) | 2021-12-22 | 2023-08-03 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
TW202346277A (zh) | 2022-03-17 | 2023-12-01 | 美商基利科學股份有限公司 | Ikaros鋅指家族降解劑及其用途 |
US20230355796A1 (en) | 2022-03-24 | 2023-11-09 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
TW202400138A (zh) | 2022-04-21 | 2024-01-01 | 美商基利科學股份有限公司 | Kras g12d調節化合物 |
WO2023235754A1 (en) | 2022-06-01 | 2023-12-07 | ALX Oncology Inc. | Combination therapies for treating urothelial carcinoma |
US20240116928A1 (en) | 2022-07-01 | 2024-04-11 | Gilead Sciences, Inc. | Cd73 compounds |
US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013541522A (ja) * | 2010-09-16 | 2013-11-14 | バリオファルム・アクチェンゲゼルシャフト | 抗huTNFR1抗体 |
JP2014519338A (ja) * | 2011-06-16 | 2014-08-14 | ノバルティス アーゲー | 治療薬として使用される可溶性タンパク質 |
WO2015138600A2 (en) * | 2014-03-11 | 2015-09-17 | The Board Of Trustees Of The Leland Stanford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
US20090042291A1 (en) * | 2002-03-01 | 2009-02-12 | Xencor, Inc. | Optimized Fc variants |
AU2003273542A1 (en) | 2002-05-31 | 2003-12-19 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of identifying and isolating stem cells and cancer stem cells |
JP4970948B2 (ja) | 2003-12-05 | 2012-07-11 | ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ | 癌幹細胞の同定、単離、および除去の方法 |
US7371381B2 (en) * | 2003-12-12 | 2008-05-13 | Amgen Inc. | Anti-galanin antibodies and uses thereof |
CN104072614B (zh) * | 2005-07-08 | 2017-04-26 | 生物基因Ma公司 | 抗-αvβ6 抗体及其用途 |
US20090191202A1 (en) | 2005-09-29 | 2009-07-30 | Jamieson Catriona Helen M | Methods for manipulating phagocytosis mediated by CD47 |
US7514229B2 (en) | 2005-09-29 | 2009-04-07 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for diagnosing and evaluating treatment of blood disorders |
WO2007055916A2 (en) | 2005-11-07 | 2007-05-18 | The Rockefeller University | Reagents, methods and systems for selecting a cytotoxic antibody or variant thereof |
EP3456351A1 (en) | 2006-04-05 | 2019-03-20 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
US8377448B2 (en) | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
JP2011518313A (ja) | 2008-01-15 | 2011-06-23 | ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ | 急性骨髄性白血病幹細胞のマーカー |
ES2740823T3 (es) | 2008-01-15 | 2020-02-06 | Univ Leland Stanford Junior | Métodos para manipular fagocitosis mediada por CD47 |
PL2477648T3 (pl) | 2009-09-15 | 2022-11-07 | The Board Of Trustees Of The Leland Stanford Junior University | Synergistyczna terapia anty-cd47 dla nowotworów hematologicznych |
WO2011041453A1 (en) | 2009-09-29 | 2011-04-07 | The Board Of Trustees Of The Leland Stanford Junior University | Isolation and use of melanoma cancer stem cells |
WO2011123489A2 (en) * | 2010-03-31 | 2011-10-06 | Boehringer Ingelheim International Gmbh | Anti-cd40 antibodies |
DK3789038T3 (da) | 2010-05-14 | 2022-10-17 | Univ Leland Stanford Junior | Humaniserede og kimære monoklonale antistoffer mod cd47 |
WO2013056352A1 (en) | 2011-10-19 | 2013-04-25 | University Health Network | Antibodies and antibody fragments targeting sirp-alpha and their use in treating hematologic cancers |
CN103665165B (zh) | 2013-08-28 | 2016-02-24 | 江苏匡亚生物医药科技有限公司 | 一种靶向人CD47-SIRPα信号通路的双特异性抗体及其制备方法和用途 |
ES2765483T3 (es) | 2013-09-18 | 2020-06-09 | Univ Leland Stanford Junior | Modulación de las vías de eferocitosis para el tratamiento de una enfermedad aterosclerótica |
ES2822561T3 (es) | 2014-09-15 | 2021-05-04 | Univ Leland Stanford Junior | Direccionamiento a enfermedad por aneurisma modulando las vías de fagocitosis |
ES2941387T3 (es) | 2015-02-27 | 2023-05-22 | Univ Leland Stanford Junior | Terapia de combinación para el tratamiento de la ateroesclerosis |
WO2017109544A1 (fr) | 2015-12-22 | 2017-06-29 | Arcelormittal | Procede de preparation d'une tole pre-revetue, avec enlevement du revetement a l'aide d'un faisceau laser incline; tôle correspondante |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013541522A (ja) * | 2010-09-16 | 2013-11-14 | バリオファルム・アクチェンゲゼルシャフト | 抗huTNFR1抗体 |
JP2014519338A (ja) * | 2011-06-16 | 2014-08-14 | ノバルティス アーゲー | 治療薬として使用される可溶性タンパク質 |
WO2015138600A2 (en) * | 2014-03-11 | 2015-09-17 | The Board Of Trustees Of The Leland Stanford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
Non-Patent Citations (2)
Title |
---|
REVIEW INVIVOGEN, JPN6021015808, 2011, ISSN: 0004996572 * |
SHIELDS RL ET AL, J BIOL CHEM, vol. 276, no. 9, JPN6021015807, 2001, pages 6591 - 6604, ISSN: 0004996571 * |
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CA3031034A1 (en) | 2018-02-08 |
JP7369620B2 (ja) | 2023-10-26 |
US10611842B2 (en) | 2020-04-07 |
KR20190036528A (ko) | 2019-04-04 |
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US20180037652A1 (en) | 2018-02-08 |
WO2018026600A1 (en) | 2018-02-08 |
JP2019534845A (ja) | 2019-12-05 |
CN109862910A (zh) | 2019-06-07 |
AU2017307198A1 (en) | 2019-01-31 |
KR20230142658A (ko) | 2023-10-11 |
EP3493845A4 (en) | 2020-04-15 |
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