JP2017524715A - 抗cd40抗体を用いた併用療法 - Google Patents
抗cd40抗体を用いた併用療法 Download PDFInfo
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Abstract
Description
(a)PD−1と結合する免疫療法薬、
(b)CTLA−4と結合する免疫療法薬、
(c)OX40と結合する免疫療法薬、及び
(d)CD137と結合する免疫療法薬からなる群から選択される。
配列表の簡単な説明
方法
T1a:1.0mm未満の原発腫瘍の厚さ、潰瘍形成なし、及び有糸分裂<1/mm2
T1b:1.0mm未満の原発腫瘍の厚さ、潰瘍形成なし、潰瘍形成あり、または有糸分裂≧1/mm2
T2a:1.01〜2.0mmの原発腫瘍の厚さ、潰瘍形成なし
T2b:1.01〜2.0mmの原発腫瘍の厚さ、潰瘍形成あり
T3a:2.01〜4.0mmの原発腫瘍の厚さ、潰瘍形成なし
T3b:2.01〜4.0mmの原発腫瘍の厚さ、潰瘍形成あり
T4a:4.0mmを超える原発腫瘍の厚さ、潰瘍形成なし
T4b:4.0mmを超える原発腫瘍の厚さ、潰瘍形成あり
N1:単一陽性リンパ節
N2:2〜3つの陽性リンパ節または局所皮膚/イン・トランジット(in―transit)転移
N3:4つの陽性リンパ節または1つのリンパ節及び局所皮膚/イン・トランジット転移
M1a:遠隔皮膚転移、正常LDH
M1b:肺転移、正常LDH
M1c:他の遠隔転移またはLDHが上昇した任意の遠隔転移
−対象における固形腫瘍を治療するための方法で使用するための、CD40に特異的に結合し、かつ投与後に腫瘍部位において保持される抗体であって、本方法は、(a)対象に、CD40に特異的に結合する治療有効量の該抗体を投与することと、任意に(b)対象に、治療有効量の追加の治療薬を全身投与することとを含む。ステップ(a)及び(b)は、同時に実施されてもよい。あるいは、ステップ(a)及び(b)は、ステップ(a)がステップ(b)に先行するという条件で、順次に実施されてもよい。ステップ(a)において、該抗CD40抗体は、好ましくは、腫瘍に局所投与される。
−対象における固形腫瘍を治療するための医薬品の製造における、CD40に特異的に結合し、かつ投与後に腫瘍部位において保持される抗体の使用であって、該治療は、(a)腫瘍に、CD40に特異的に結合する治療有効量の該抗体を投与することと、任意に(b)対象に、治療有効量の追加の治療薬を全身投与することとを含む。ステップ(a)及び(b)は、同時に実施されてもよい。あるいは、ステップ(a)及び(b)は、ステップ(a)がステップ(b)に先行するという条件で、順次に実施されてもよい。ステップ(a)において、該抗CD40抗体は、好ましくは、腫瘍に局所投与される。
−対象における固形腫瘍を治療するための方法で同時、別々、または順次に使用するための(1)CD40に特異的に結合し、かつ投与後に腫瘍部位において保持される抗体と、任意に(2)追加の治療薬とを含む、製品であって、本方法は、(a)腫瘍に、CD40に特異的に結合する治療有効量の該抗体を局所投与することと、任意に(b)対象に、治療有効量の追加の治療薬を全身投与することとを含む。ステップ(a)及び(b)は、同時に実施されてもよい。あるいは、ステップ(a)及び(b)は、ステップ(a)がステップ(b)に先行するという条件で、順次に実施されてもよい。ステップ(a)において、該抗CD40抗体は、好ましくは、腫瘍に局所投与される。
ステップ(a)及び(b)のタイミング及び順序
ステップ(a)
ステップ(b)
抗体
概要
CD40に特異的な抗体
(i)細胞の表面上に局在したときにヒトCD40に特異的に結合し、かつ/または
(ii)CD40を発現させる細胞の抗体依存性細胞傷害性(ADCC)媒介溶解を強化し、かつ/または
(iii)CD40を発現させる細胞ノアポトーシスを強化し、かつ/または
(iv)CD40を発現させる細胞の活性を調節することであって、該調節は、該細胞の活性の増加もしくは減少である。
併用療法
キット及び薬学的組成物
(i)抗PD1免疫療法薬、
(ii)抗CTLA−4免疫療法薬、
(iii)抗OX40免疫療法薬、及び/または
(iv)抗CD137免疫療法薬、のうちの1つ以上と組み合わせて使用するための、請求項実施形態SまたはTに記載の抗体またはその抗原結合部分。
(i)抗PD1免疫療法薬、
(ii)抗CTLA−4免疫療法薬、
(iii)抗OX40免疫療法薬、及び/または
(iv)抗CD137免疫療法薬を含む、実施形態EEまたはFFに記載の併用療法組成物。
II.対象における固形腫瘍の治療のための医薬品の調製における、実施形態R〜DDのいずれか1つに記載の抗体またはその抗原結合部分の使用。
抗CD40抗体クローンG12(抗体ADC−1013)
(a)CDR配列(IMGT番号付けに従って定義され、コアCDR配列は、その中で下線が引かれる)
VL CDR1:CTGSSSNIGAGYNVY [配列番号1]、
VL CDR2:GNINRPS [配列番号2]、
VL CDR3:CAAWDKSISGLV [配列番号3]、
VH CDR1:GFTFSTYGMH [配列番号4]、
VH CDR2:GKGLEWLSYISGGSSYIFYADSVRGR [配列番号5]、
VH CDR3:CARILRGGSGMDL [配列番号6]
可変軽鎖(VL)アミノ酸配列−配列番号7
CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGCACTGGGAGCAGCTCCAACATCGGGGCGGGTTACAATGTATACTGGTATCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATGGTAACATCAATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATAAGAGCATTTCTGGTCTGGTTTTCGGCGGAGGAACCAAGCTGACGGTCCTAGGT
可変重鎖(VH)ヌクレオチド配列−配列番号10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTACTTATGGCATGCACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGCTTTCATATATTAGTGGTGGTAGTAGTTACATTTTCTACGCAGACTCAGTGAGGGGCCGATTCACCATCTCCAGAGACAACTCCGAGAACGCGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAATATTAAGAGGCGGGAGCGGTATGGACCTCTGGGGCCAAGGTACACTGGTCACCGTGAGCTCA
ヒトIgラムダ軽鎖C2領域(NCBI AAA59107.1)−配列番号11
QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
ヒトIgガンマ−1重鎖定常領域(Uniprot P01857.1)−配列番号12
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
ヒトCD40配列−配列番号13
>gi|117606560|gb|ABK41937.1|CD40分子、TNF受容体スーパーファミリーメンバー5[ホモ・サピエンス]
MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCVLHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTNKTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ
実施例2−局所または全身投与後のバイオアベイラビリティ
材料及び方法
結果及び結論
実施例3−インビボマウス黒色腫モデル
材料及び方法
結果及び結論
実施例4−インビボマウス膀胱癌モデル
材料及び方法
結果及び結論
実施例5−併用療法Iのインビボ効果
材料及び方法
結果及び結論
実施例6−併用療法IIのインビボ効果
材料及び方法
結果及び結論
実施例7−マウスにおける野生型B16黒色腫に対するADC−1013の効果
材料及び方法
結果及び結論
実施例8−リンパ腫モデル(A20)におけるADC−1013の効果
材料及び方法
結果及び結論
実施例9−肺癌モデル(LLC−1)におけるADC−1013の効果
材料及び方法
結果及び結論
実施例10−ADC−1013の局所投与の遠位効果
材料及び方法
結果及び結論
実施例11−ADC−1013の全身(iv)投与の効果
材料及び方法
結果及び結論
実施例12−併用療法IIIのインビボ効果
材料及び方法
結果及び結論
Claims (43)
- (a)CD40に特異的に結合する抗体またはその抗原結合部分と、(b)癌の治療において有効性を有するさらなる免疫療法薬であって、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、免疫療法薬と、を含む、対象における固形腫瘍を治療する方法で使用するための併用療法であって、
CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合し、
前記さらなる免疫療法薬は、CD40以外の免疫チェックポイント分子に特異的に結合する、併用療法。 - 前記固形腫瘍は、腺腫、芽腫、癌腫、類腱腫、線維形成性小円形細胞腫瘍、内分泌腺腫瘍、胚細胞腫瘍、リンパ腫、肉腫、ウィルムス腫瘍、肺腫瘍、結腸腫瘍、リンパ腫瘍、乳房腫瘍、及び黒色腫からなる群から選択される、請求項1に記載の併用療法。
- 前記固形腫瘍は、黒色腫、好ましくは転移性黒色腫である、請求項1または2に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、無傷抗体を含むか、またはそれからなる、請求項1〜3のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、Fvフラグメント(一本鎖Fvフラグメントまたはジスルフィド結合Fvフラグメントなど)、及びFab様フラグメント(Fabフラグメント、Fab’フラグメント、またはF(ab)2フラグメントなど)からなる群から選択される、抗原結合フラグメントを含むか、またはそれからなる、請求項1〜3のいずれか1項に記載の併用療法。
- 前記抗体またはその抗原結合部分は、ヒトまたはヒト化である、請求項1〜5のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、配列番号1、2、3、4、5、及び6から選択される少なくとも1つのCDRを含む、請求項1〜6のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、配列番号1、2、及び3、ならびに/または配列番号4、5、及び6のCDR配列を含む、請求項1〜7のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、配列番号7の軽鎖可変領域及び/または配列番号8の重鎖可変領域を含む、請求項1〜8のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、配列番号11の軽鎖定常領域及び/または配列番号12の重鎖定常領域を含む、請求項1〜9のいずれか1項に記載の併用療法。
- CD40に特異的に結合する前記抗体またはその抗原結合部分は、配列番号7及び配列番号11の軽鎖、ならびに/または配列番号8及び配列番号12の重鎖を含むか、またはそれからなる、請求項1〜10のいずれか1項に記載の併用療法。
- 前記さらなる免疫療法薬は、
(a)PD−1と結合する免疫療法薬、
(b)CTLA−4と結合する免疫療法薬、
(c)OX40と結合する免疫療法薬、及び
(d)CD137と結合する免疫療法薬からなる群から選択される、請求項1〜11のいずれか1項に記載の併用療法。 - 前記さらなる免疫療法薬は、PD1阻害剤である、請求項12に記載の併用療法。
- 前記PD1阻害剤は、PD1機能を阻害することが可能な抗PD1抗体またはその抗原結合フラグメントを含むか、またはそれからなる、請求項1〜13のいずれか1項に記載の併用療法。
- 前記抗PD1抗体は、ニボルマブ、ペンブロリズマブ、ランブロリズマブ、ピディリズマブ、及びAMP−224からなる群から選択される、請求項14に記載の併用療法。
- 前記PD1阻害剤は、PD1機能を阻害することが可能な抗PD−L1抗体またはその抗原結合フラグメントを含むか、またはそれからなる、請求項1〜15のいずれか1項に記載の併用療法。
- 前記抗PD−L1抗体は、MEDI−4736及びMPDL3280Aからなる群から選択される、請求項16に記載の併用療法。
- 前記さらなる免疫療法薬は、抗CD137抗体またはその抗原結合部分である、請求項12に記載の併用療法。
- 前記さらなる免疫療法薬は、抗OX40抗体またはその抗原結合部分である、請求項12に記載の併用療法。
- 前記さらなる免疫療法薬は、抗CTLA−4抗体またはその抗原結合部分である、請求項12に記載の併用療法。
- 癌の治療において有効性を有する第3の免疫療法薬をさらに含む、請求項1〜20のいずれか1項に記載の併用療法。
- (a)CD40に特異的に結合する抗体またはその抗原結合部分と、(b)PD1またはPD−L1に特異的に結合する抗体またはその抗原結合部分と、(c)CTLA−4に特異的に結合する抗体またはその抗原結合部分と、を含む、請求項21に記載の併用療法。
- 固形腫瘍を治療する方法で使用するための、CD40に特異的に結合する抗体またはその抗原結合部分であって、
CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合し、
CD40に特異的に結合する前記抗体またはその抗原結合部分は、癌の治療において有効性を有するさらなる免疫療法薬と併用するためのものであり、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、抗体またはその抗原結合部分。 - 前記抗体またはその抗原結合部分は、請求項4〜11のいずれか1項で定義される通りである、請求項23に記載の抗体またはその抗原結合部分。
- 癌の治療において有効性を有する前記さらなる免疫療法薬は、請求項12〜20のいずれか1項で定義される通りである、請求項23または24に記載の抗体またはその抗原結合部分。
- 固形腫瘍を治療するための医薬品の調製における、CD40に特異的に結合する抗体またはその抗原結合部分の使用であって、
CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合し、
CD40に特異的に結合する前記抗体またはその抗原結合部分は、癌の治療において有効性を有するさらなる免疫療法薬と併用するためのものであり、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、使用。 - 前記抗体またはその抗原結合部分は、請求項4〜11のいずれか1項で定義される通りである、請求項26に記載の使用。
- 癌の治療において有効性を有する前記さらなる免疫療法薬は、請求項12〜20のいずれか1項で定義される通りである、請求項26または27に記載の使用。
- (a)CD40に特異的に結合する抗体またはその抗原結合部分と、(b)癌の治療において有効性を有するさらなる免疫療法薬であって、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、さらなる免疫療法薬と、を含む、薬学的組成物であって、CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合する、薬学的組成物。
- 前記抗体またはその抗原結合部分は、請求項4〜11のいずれか1項で定義される通りである、請求項29に記載の薬学的組成物。
- 癌の治療において有効性を有する前記さらなる免疫療法薬は、請求項12〜20のいずれか1項で定義される通りである、請求項29または30に記載の薬学的組成物。
- (a)CD40に特異的に結合する抗体またはその抗原結合部分と、(b)癌の治療において有効性を有するさらなる免疫療法薬であって、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、さらなる免疫療法薬と、を含む、固形腫瘍を治療するためのキットであって、CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合する、キット。
- 前記抗体またはその抗原結合部分は、請求項4〜11のいずれか1項で定義される通りである、請求項32に記載のキット。
- 癌の治療において有効性を有する前記さらなる免疫療法薬は、請求項12〜20のいずれか1項で定義される通りである、請求項32または33に記載のキット。
- 対象における固形腫瘍を治療するための方法であって、前記方法は、前記対象に、治療有効量の(a)前記対象に、CD40に特異的に結合する治療有効量の抗体またはその抗原結合部分を投与することと、(b)前記対象に、癌の治療において有効性を有する治療有効量のさらなる免疫療法薬であって、その薬剤は、抗CD40抗体またはその抗原結合フラグメントではない、さらなる免疫療法薬を投与することと、を投与することを含み、CD40に特異的に結合する前記抗体またはその抗原結合部分は、ヒトCD40への結合に対して、配列番号7の軽鎖可変領域及び配列番号8の重鎖可変領域を含む抗体と競合する、方法。
- 前記抗体またはその抗原結合部分は、請求項4〜11のいずれか1項で定義される通りである、請求項35に記載の方法。
- 癌の治療において有効性を有する前記さらなる免疫療法薬は、請求項12〜20のいずれか1項で定義される通りである、請求項35または36に記載の方法。
- ステップ(a)及び(b)は、同時に実施されるか、またはステップ(b)は、ステップ(a)の24時間〜2週間後、ステップ(a)の24時間〜1週間後、ステップ(a)の24時間〜72時間後、もしくはステップ(a)の24時間〜48時間後に実施される、請求項35〜37のいずれか1項に記載の方法。
- ステップ(a)は、前記腫瘍部位への前記抗体の局所投与を含む、請求項35〜38のいずれか1項に記載の方法。
- ステップ(a)において投与される抗体の量の少なくとも30%が、投与の4時間後に前記腫瘍部位において保持され、好ましくは、前記量の少なくとも40%が、投与の4時間後に前記腫瘍部位において保持される、請求項35〜39のいずれか1項に記載の方法。
- ステップ(b)の前記追加の治療薬は、全身投与に好適な組成物として、少なくとも1つの薬学的に許容される希釈剤または担体と共に製剤化される、請求項35〜40のいずれか1項に記載の方法。
- ステップ(a)は、複数の別々の時機に実施され、ステップ(b)は、前記追加の治療薬への前記対象の曝露が前記方法の継続時間にわたって連続的であるように実施される、請求項35〜41のいずれか1項に記載の方法。
- 前記対象は、ヒトである、請求項35〜42のいずれか1項に記載の方法。
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Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG194701A1 (en) | 2011-04-29 | 2013-12-30 | Apexigen Inc | Anti-cd40 antibodies and methods of use |
DK2953634T3 (da) | 2013-02-07 | 2021-08-30 | Massachusetts Gen Hospital | Fremgangsmåder til udvidelse eller udtømning af regulerende t-celler |
AR097584A1 (es) | 2013-09-12 | 2016-03-23 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra el csf-1r humano y anticuerpos contra el pd-l1 humano |
US10344090B2 (en) | 2013-12-12 | 2019-07-09 | Shanghai Hangrui Pharmaceutical Co., Ltd. | PD-1 antibody, antigen-binding fragment thereof, and medical application thereof |
MY189018A (en) | 2015-11-18 | 2022-01-19 | Merck Sharp & Dohme | Pd1 and/or lag3 binders |
WO2017106061A1 (en) | 2015-12-14 | 2017-06-22 | Macrogenics, Inc. | Bispecific molecules having immunoreactivity with pd-1 and ctla-4, and methods of use thereof |
KR102410778B1 (ko) * | 2016-05-13 | 2022-06-21 | 더 제너럴 하스피탈 코포레이션 | 길항성 항-종양 괴사 인자 수용체 슈퍼패밀리 항체 |
WO2017220988A1 (en) | 2016-06-20 | 2017-12-28 | Kymab Limited | Multispecific antibodies for immuno-oncology |
EP3484922A1 (en) * | 2016-07-14 | 2019-05-22 | Genmab A/S | Multispecific antibodies against cd40 and cd137 |
EP3504239A1 (en) | 2016-08-25 | 2019-07-03 | H. Hoffnabb-La Roche Ag | Intermittent dosing of an anti-csf-1r antibody in combination with macrophage activating agent |
WO2018078620A1 (en) | 2016-10-25 | 2018-05-03 | Urogen Pharma Ltd. | Immunomodulating treatments of body cavities |
AU2017353852A1 (en) * | 2016-11-02 | 2019-05-23 | Apexigen, Inc. | Anti-CD40 antibodies in combination and methods of use |
CN110072553B (zh) | 2016-12-22 | 2023-09-15 | 豪夫迈·罗氏有限公司 | 在抗pd-l1/pd1治疗失败之后抗csf-1r抗体与抗pd-l1抗体组合对肿瘤的治疗 |
ES2902670T3 (es) * | 2017-01-13 | 2022-03-29 | Taizhou Hanzhong Biopharmaceutics Inc | Anticuerpo monoclonal contra PD-1 y aplicaciones del mismo |
EP3589324A1 (en) * | 2017-03-03 | 2020-01-08 | Janssen Biotech, Inc. | Co-therapy comprising a small molecule csf-1r inhibitor and an agonistic antibody that specifically binds cd40 for the treatment of cancer |
US20200237860A1 (en) | 2017-08-31 | 2020-07-30 | Multimmune Gmbh | Hsp70 based combination therapy |
KR20210038839A (ko) * | 2018-03-13 | 2021-04-08 | 히버셀, 인크. | 베타 글루칸 및 cd40 효능제 조합 면역요법 |
US20210386856A1 (en) * | 2018-06-12 | 2021-12-16 | Biontech Us Inc. | Combination therapy with neoantigen vaccine |
WO2019241730A2 (en) | 2018-06-15 | 2019-12-19 | Flagship Pioneering Innovations V, Inc. | Increasing immune activity through modulation of postcellular signaling factors |
AU2019383548A1 (en) | 2018-11-23 | 2021-06-24 | Strike Pharma Ab | Bi-specific conjugates |
AU2019389354A1 (en) * | 2018-11-30 | 2021-07-15 | Jiangsu Hengrui Medicine Co., Ltd. | Anti-CD40 antibody, antigen binding fragment and pharmaceutical use thereof |
MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
CN113939535A (zh) * | 2019-05-28 | 2022-01-14 | 詹森生物科技公司 | 提供抗cd40抗体的安全施用的方法 |
EP4027998A1 (en) | 2019-09-09 | 2022-07-20 | Basilea Pharmaceutica International AG | Pharmaceutical combinations comprising a furazanobenzimidazoles and a cd40 agonist for use in the treatment of neoplastic diseases |
EP4076434A1 (en) | 2019-12-17 | 2022-10-26 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
EP4083210A1 (en) * | 2019-12-27 | 2022-11-02 | Interoligo Corporation | Anti-cancer immunotherapeutic composition for treating cancer |
GB202008003D0 (en) | 2020-05-28 | 2020-07-15 | Quine Medical Ab | Anti-CD40 antibody |
CN116096906A (zh) | 2020-06-29 | 2023-05-09 | 旗舰创业创新五公司 | 工程化以促进萨诺传递的病毒及其在治疗癌症中的用途 |
WO2022036495A1 (en) | 2020-08-17 | 2022-02-24 | Utc Therapeutics Inc. | Lymphocytes-antigen presenting cells co-stimulators and uses thereof |
US20220325287A1 (en) | 2021-03-31 | 2022-10-13 | Flagship Pioneering Innovations V, Inc. | Thanotransmission polypeptides and their use in treating cancer |
WO2023278641A1 (en) | 2021-06-29 | 2023-01-05 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
WO2023064878A1 (en) * | 2021-10-15 | 2023-04-20 | The Rockefeller University | Combination of anti-cd40 antibody and il-15 for treating cancer |
WO2023247050A1 (en) | 2022-06-23 | 2023-12-28 | Alligator Bioscience Ab | Combination therapies |
WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6051228A (en) | 1998-02-19 | 2000-04-18 | Bristol-Myers Squibb Co. | Antibodies against human CD40 |
WO2001083755A2 (en) | 2000-04-28 | 2001-11-08 | La Jolla Institute For Allergy And Immunology | Human anti-cd40 antibodies and methods of making and using same |
PT1341909E (pt) | 2000-12-12 | 2005-10-31 | Alligator Bioscience Ab | Metodo para a evolucao molecular in vitro da funcao de proteina |
EP2011802A3 (en) | 2001-04-27 | 2009-04-15 | Kyowa Hakko Kirin Co., Ltd. | Anti-CD40 monoclonal antibody |
AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
US7432063B2 (en) | 2002-02-14 | 2008-10-07 | Kalobios Pharmaceuticals, Inc. | Methods for affinity maturation |
US20040110226A1 (en) | 2002-03-01 | 2004-06-10 | Xencor | Antibody optimization |
US7262012B2 (en) | 2002-05-17 | 2007-08-28 | Alligator Bioscience Ab | Method for in vitro molecular evolution of protein function using varied exonuclease digestion in two polynucleotide populations |
CN101001872A (zh) * | 2004-04-16 | 2007-07-18 | 宏观基因有限公司 | FcγRIIB-特异性抗体及其使用方法 |
RU2006141632A (ru) | 2004-04-27 | 2008-06-10 | Новартис Вэксинес Энд Дайэгностикс, Инк. (Us) | Антагонистические моноклональные анти-cd40-антитела и способы их применения |
CA2607147C (en) | 2005-05-09 | 2018-07-17 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
CA2609269C (en) | 2005-05-26 | 2014-08-05 | Seattle Genetics, Inc. | Humanized anti-cd40 antibodies and their methods of use |
GB0620894D0 (en) * | 2006-10-20 | 2006-11-29 | Univ Southampton | Human immune therapies using a CD27 agonist alone or in combination with other immune modulators |
AU2009206506B2 (en) | 2008-01-23 | 2013-01-10 | Xencor, Inc. | Optimized CD40 antibodies and methods of using the same |
US20110311525A1 (en) | 2008-08-29 | 2011-12-22 | Academisch Ziekenhuis Leiden H.O.D.N. Lumc | Delivery of a cd40 agonist to a tumor draining lymph node of a subject |
WO2013019906A1 (en) | 2011-08-01 | 2013-02-07 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors |
GB201115280D0 (en) * | 2011-09-05 | 2011-10-19 | Alligator Bioscience Ab | Antibodies, uses and methods |
AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
WO2014121099A1 (en) * | 2013-01-31 | 2014-08-07 | Thomas Jefferson University | Agonist fusion protein for cd40 ox40 and uses thereof |
EP3082857B1 (en) | 2013-12-20 | 2018-07-25 | F. Hoffmann-La Roche AG | Combination therapy with an anti-ang2 antibody and a cd40 agonist |
TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
RS60753B1 (sr) | 2015-04-17 | 2020-10-30 | Bristol Myers Squibb Co | Kompozicije koje sadrže kombinaciju ipilimumaba i nivolumaba |
AR104809A1 (es) | 2015-05-29 | 2017-08-16 | Abbvie Inc | Anticuerpos anti-cd40 y usos de los mismos |
EA035268B1 (ru) | 2015-06-29 | 2020-05-22 | Бристол-Маерс Сквибб Компани | Антитела к cd40 |
EP3313886A1 (en) | 2015-06-29 | 2018-05-02 | The Rockefeller University | Antibodies to cd40 with enhanced agonist activity |
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