JP2018524373A - 薬物がコンジュゲートされた二重特異性抗原結合コンストラクト - Google Patents

薬物がコンジュゲートされた二重特異性抗原結合コンストラクト Download PDF

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JP2018524373A
JP2018524373A JP2018501976A JP2018501976A JP2018524373A JP 2018524373 A JP2018524373 A JP 2018524373A JP 2018501976 A JP2018501976 A JP 2018501976A JP 2018501976 A JP2018501976 A JP 2018501976A JP 2018524373 A JP2018524373 A JP 2018524373A
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antigen
construct
binding
drug
amino acid
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JP2018524373A5 (https=
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ゴードン イウ コン エング
ゴードン イウ コン エング
レオナード ジー． プレスタ
レオナード ジー． プレスタ
フォン クロイデンシュタイン トマス スプレッター
フォン クロイデンシュタイン トマス スプレッター
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ザイムワークス，インコーポレイテッド
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    • C07—ORGANIC CHEMISTRY
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    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022548145A (ja) * 2019-09-16 2022-11-16 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ 免疫療法の化合物および方法
JP2023506017A (ja) * 2019-12-11 2023-02-14 カリナン オンコロジー インコーポレイテッド 抗ｃｄ１９抗体および多重特異性結合タンパク質
JP2024512957A (ja) * 2021-03-23 2024-03-21 広州凌騰生物医薬有限公司 Ｃｄ３に結合する多重特異性抗原結合タンパク質とその使用方法
JP2024519585A (ja) * 2021-05-13 2024-05-17 ウーシー バイオロジクス アイルランド リミテッド 抗ｐ－カドヘリン抗体を含む抗体コンジュゲートおよびその使用

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107750255B (zh) 2015-04-17 2022-08-30 安进研发（慕尼黑）股份有限公司 用于cdh3和cd3的双特异性抗体构建体
US9708412B2 (en) 2015-05-21 2017-07-18 Harpoon Therapeutics, Inc. Trispecific binding proteins and methods of use
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
KR20180090290A (ko) 2015-12-04 2018-08-10 시애틀 지네틱스, 인크. 사차화 튜불리신 화합물들의 컨쥬게이트들
EP3493844A4 (en) 2016-05-20 2021-03-24 Harpoon Therapeutics Inc. SINGLE DOMAIN SERUM ALBUMIN BINDING PROTEIN
EP3571230A4 (en) * 2017-01-20 2020-12-16 Magenta Therapeutics, Inc. COMPOSITIONS AND METHODS FOR DELETION OF CD137 + CELLS
CN110582509A (zh) 2017-01-31 2019-12-17 诺华股份有限公司 使用具有多特异性的嵌合t细胞受体蛋白治疗癌症
AU2018219887B2 (en) 2017-02-08 2024-08-15 Dragonfly Therapeutics, LLC Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer
CN110944661A (zh) 2017-02-20 2020-03-31 蜻蜓疗法股份有限公司 结合her2、nkg2d和cd16的蛋白质
CN117982673A (zh) * 2017-02-28 2024-05-07 第一三共株式会社 抗her3抗体-药物偶联物的应用
EP3615055A1 (en) 2017-04-28 2020-03-04 Novartis AG Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor
US20200179511A1 (en) 2017-04-28 2020-06-11 Novartis Ag Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor
IL270803B1 (en) * 2017-05-23 2026-02-01 Dragonfly Therapeutics Inc NKG2D, CD16, and tumor-associated antigen binding protein
JP7279026B2 (ja) * 2017-09-20 2023-05-22 メルサナ セラピューティクス インコーポレイテッド Ｎａｐｉ２ｂ標的化療法に対する応答を予測するための組成物および方法
AU2018351050B2 (en) 2017-10-18 2025-09-18 Novartis Ag Compositions and methods for selective protein degradation
CN111787938A (zh) 2017-11-15 2020-10-16 诺华股份有限公司 靶向bcma的嵌合抗原受体、靶向cd19的嵌合抗原受体及组合疗法
US20200371091A1 (en) 2017-11-30 2020-11-26 Novartis Ag Bcma-targeting chimeric antigen receptor, and uses thereof
US12539308B2 (en) 2018-01-08 2026-02-03 The Trustees Of The University Of Pennsylvania Immune-enhancing RNAs for combination with chimeric antigen receptor therapy
AU2019215031C1 (en) 2018-01-31 2026-02-26 Novartis Ag Combination therapy using a chimeric antigen receptor
BR112020015994A2 (pt) 2018-02-08 2020-12-15 Dragonfly Therapeutics, Inc. Terapia de combinação do câncer que envolve proteínas de ligação multiespecíficas que ativam células natural killer
CA3237846A1 (en) 2018-02-08 2019-08-15 Dragonfly Therapeutics, Inc. Antibody variable domains targeting the nkg2d receptor
US20200399383A1 (en) 2018-02-13 2020-12-24 Novartis Ag Chimeric antigen receptor therapy in combination with il-15r and il15
WO2019164930A1 (en) 2018-02-20 2019-08-29 Dragonfly Therapeutics, Inc. Multi-specific binding proteins that bind cd33, nkg2d, and cd16, and methods of use
BR112020023330A2 (pt) 2018-05-14 2021-04-20 Harpoon Therapeutics, Inc. porção de ligação para ativação condicional de moléculas de imunoglobulina
EA202091888A1 (ru) 2018-08-08 2020-10-23 Драгонфлай Терапьютикс, Инк. Вариабельные домены антител, нацеленные на рецептор nkg2d
EP3833392A4 (en) 2018-08-08 2022-05-18 Dragonfly Therapeutics, Inc. MULTISPECIFIC BINDING PROTEINS FOR BINDING CD33, NKG2D AND CD16 AND METHODS OF USE
KR102835308B1 (ko) 2018-08-08 2025-07-21 드래곤플라이 쎄라퓨틱스, 인크. Nkg2d, cd16 및 종양 관련 항원에 결합하는 단백질
EP3844265A2 (en) 2018-08-31 2021-07-07 Novartis AG Methods of making chimeric antigen receptor-expressing cells
EP4635978A2 (en) 2018-08-31 2025-10-22 Novartis AG Methods of making chimeric antigen receptor-expressing cells
US12195544B2 (en) 2018-09-21 2025-01-14 Harpoon Therapeutics, Inc. EGFR binding proteins and methods of use
US10815311B2 (en) * 2018-09-25 2020-10-27 Harpoon Therapeutics, Inc. DLL3 binding proteins and methods of use
WO2020099513A1 (en) * 2018-11-13 2020-05-22 Lipoxen Technologies Limited Glycopolysialylation of blinatumomab
CN114426578B (zh) * 2019-02-14 2025-03-21 美勒斯公司 结合egfr、her2及her3的结合部分的组合
US20220152150A1 (en) 2019-02-25 2022-05-19 Novartis Ag Mesoporous silica particles compositions for viral delivery
CN109776683B (zh) * 2019-03-19 2020-04-07 益科思特(北京)医药科技发展有限公司 一种双特异性抗体及其制备方法与应用
EP3942025A1 (en) 2019-03-21 2022-01-26 Novartis AG Car-t cell therapies with enhanced efficacy
EP3953455A1 (en) 2019-04-12 2022-02-16 Novartis AG Methods of making chimeric antigen receptor-expressing cells
EP3959320A1 (en) 2019-04-24 2022-03-02 Novartis AG Compositions and methods for selective protein degradation
TWI911155B (zh) * 2019-04-25 2026-01-11 瑞士商赫孚孟拉羅股份公司 藉由多肽鏈交換活化之治療性多特異性多肽
WO2020232247A1 (en) 2019-05-14 2020-11-19 Provention Bio, Inc. Methods and compositions for preventing type 1 diabetes
JP7489407B2 (ja) 2019-05-21 2024-05-23 ノバルティス アーゲー Ｃｄ１９結合分子及びその使用
CN110423723A (zh) * 2019-07-18 2019-11-08 南方医科大学南方医院 一种外周血b细胞系的构建方法及其应用
IL293215A (en) 2019-11-26 2022-07-01 Novartis Ag Chimeric antigen receptors that bind bcma and cd19 and their uses
JP7392145B2 (ja) * 2019-12-20 2023-12-05 山東博安生物技術股▲ふん▼有限公司 免疫療法のためのｔ細胞二重特異性抗体の作製における最適化された抗ｃｄ３アーム
CN115397460A (zh) 2020-02-27 2022-11-25 诺华股份有限公司 制备表达嵌合抗原受体的细胞的方法
JP2023515196A (ja) * 2020-02-27 2023-04-12 フェインズ セラピューティクス，インコーポレーテッド 脂肪酸分子とコンジュゲートされた抗体及びその使用
EP4110376A2 (en) 2020-02-27 2023-01-04 Novartis AG Methods of making chimeric antigen receptor-expressing cells
MX2023013382A (es) 2020-04-04 2024-01-30 Janux Therapeutics Inc Composiciones y metodos relacionados con anticuerpos activados contra tumores dirigidos a egfr y antigenos de celulas efectoras.
JP7512394B2 (ja) 2020-05-06 2024-07-08 ドラゴンフライ セラピューティクス， インコーポレイテッド Ｎｋｇ２ｄ、ｃｄ１６及びｃｌｅｃ１２ａに結合するタンパク質
JP2023529211A (ja) 2020-06-11 2023-07-07 ノバルティス アーゲー Ｚｂｔｂ３２阻害剤及びその使用
IL298999A (en) 2020-06-11 2023-02-01 Provention Bio Inc Methods and compositions for the prevention of type 1 diabetes
CN111840571B (zh) * 2020-08-03 2022-09-20 杭州皓阳生物技术有限公司 一种抗体药物偶联物及其用途
US11124568B1 (en) * 2020-08-19 2021-09-21 Vitruviae LLC CD3/CD25 antibodies for neuro-immune diseases
US11197910B1 (en) 2020-08-19 2021-12-14 Vitruviae LLC Fusion proteins for the diagnosis, prophylaxis and treatment of infectious diseases
MX2023002107A (es) 2020-08-21 2023-03-15 Novartis Ag Composiciones y metodos para la generacion in vivo de celulas que expresan car.
WO2022109404A1 (en) * 2020-11-20 2022-05-27 Actinium Pharmaceuticals, Inc. Her3 radioimmunotherapy for the treatment of solid cancers
EP4259202A4 (en) * 2020-12-09 2025-01-15 Janux Therapeutics, Inc. COMPOSITIONS AND METHODS RELATED TO TUMOR-ACTIVATED ANTIBODIES AGAINST TROP2 AND EFFECTOR CELL ANTIGENS
JP2024506022A (ja) * 2021-02-08 2024-02-08 シンアフィックス ビー．ブイ． 多機能性抗体
EP4301774A4 (en) 2021-03-03 2025-08-13 Dragonfly Therapeutics Inc METHODS OF TREATING CANCER USING MULTI-SPECIFIC BINDING PROTEINS THAT BIND TO NKG2D, CD16, AND A TUMOR-ASSOCIATED ANTIGEN
WO2022229853A1 (en) 2021-04-27 2022-11-03 Novartis Ag Viral vector production system
US20240254241A1 (en) * 2021-05-11 2024-08-01 Janux Therapeutics, Inc. Antibodies targeting egfr and cd3 and uses thereof
JP2024520444A (ja) 2021-05-24 2024-05-24 プロヴェンション・バイオ・インコーポレイテッド １型糖尿病を治療するための方法
EP4388000A1 (en) 2021-08-20 2024-06-26 Novartis AG Methods of making chimeric antigen receptor?expressing cells
MX2024009740A (es) * 2022-02-11 2024-08-19 Shenzhen Enduring Biotech Ltd Conjugado de anticuerpo-farmaco pegilado que contiene grupos hidroxilo.
AU2023369684A1 (en) 2022-10-26 2025-04-17 Novartis Ag Lentiviral formulations
TW202434307A (zh) 2023-01-18 2024-09-01 大陸商泰勵生物科技（上海）有限公司 抗體偶聯藥物及其用途
EP4680648A1 (en) * 2023-03-17 2026-01-21 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Anti-her3 and anti-met antibodies and uses thereof
WO2024193682A1 (en) * 2023-03-23 2024-09-26 Xadcera Biopharmaceutical (Suzhou) Co., Ltd. Anti-tpbg/met antibodies and uses thereof
WO2025099489A1 (en) * 2023-11-10 2025-05-15 Ligachem Biosciences Inc. Antibody-drug conjugate comprising bispecific antibody specifically binding to cd20 and cd22 and uses thereof
CN120285217A (zh) * 2024-01-11 2025-07-11 成都百利多特生物药业有限责任公司 双特异性抗体-奥瑞他汀类药物偶联物及其用途
TW202546005A (zh) * 2024-01-11 2025-12-01 美商西雅圖免疫公司 抗體-奧瑞他汀藥物偶聯物以及其製造及使用方法
WO2025223455A1 (en) 2024-04-24 2025-10-30 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Anti-ptk7/b7h3 antibodies and uses thereof
CN119431525B (zh) * 2024-10-08 2025-04-11 北京溯本源和生物科技有限公司 狂犬病毒g蛋白重组抗原、单克隆抗体及其制备方法和应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010126137A1 (ja) * 2009-05-01 2010-11-04 国立大学法人 東京大学 抗カドヘリン抗体
WO2012022814A1 (en) * 2010-08-20 2012-02-23 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
WO2012143524A2 (en) * 2011-04-20 2012-10-26 Genmab A/S Bispecific antibodies against her2 and cd3
WO2015006749A2 (en) * 2013-07-12 2015-01-15 Zymeworks Inc. Bispecific cd3 and cd19 antigen binding contructs
US20150044216A1 (en) * 2013-08-06 2015-02-12 Bio-Thera Solutions, Ltd. Bispecific antibodies

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6129914A (en) 1992-03-27 2000-10-10 Protein Design Labs, Inc. Bispecific antibody effective to treat B-cell lymphoma and cell line
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US6294170B1 (en) 1997-08-08 2001-09-25 Amgen Inc. Composition and method for treating inflammatory diseases
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
US7951917B1 (en) 1997-05-02 2011-05-31 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
US7183387B1 (en) 1999-01-15 2007-02-27 Genentech, Inc. Polypeptide variants with altered effector function
US20080260731A1 (en) * 2002-03-01 2008-10-23 Bernett Matthew J Optimized antibodies that target cd19
US7332580B2 (en) 2002-04-05 2008-02-19 The Regents Of The University Of California Bispecific single chain Fv antibody molecules and methods of use thereof
JP2008501621A (ja) 2003-05-31 2008-01-24 マイクロメット アクツィエン ゲゼルシャフト Ｂ細胞関連疾患を処置するための二重特異性抗ｃｄ３、抗ｃｄ１９抗体構築物を含む薬学的組成物
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
EP1701979A2 (en) * 2003-12-03 2006-09-20 Xencor, Inc. Optimized antibodies that target the epidermal growth factor receptor
AU2005274905B2 (en) 2004-08-04 2010-12-23 Mentrik Biotech, Llc Variant Fc regions
JP2009514537A (ja) 2005-11-03 2009-04-09 ジェネンテック・インコーポレーテッド 治療的抗ｈｅｒ２抗体融合ポリペプチド
EP1820513A1 (en) 2006-02-15 2007-08-22 Trion Pharma Gmbh Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies
ES2469676T3 (es) 2006-05-25 2014-06-18 Bayer Intellectual Property Gmbh Complejos moleculares dim�ricos
RU2495882C2 (ru) 2006-09-08 2013-10-20 Медиммун, Ллк. Гуманизированные антитела к cd19 и их применение для лечения онкологического, связанного с трансплантацией и аутоиммунного заболевания
WO2008140493A2 (en) 2006-11-21 2008-11-20 The Regents Of The University Of Californina Anti-egfr family antibodies, bispecific anti-egfr family antibodies and methods of use thereof
RS53008B2 (sr) * 2007-04-03 2022-12-30 Amgen Res Munich Gmbh Interspecijski specifičan cd3-epsilon vezujući domen
US8435749B2 (en) * 2008-06-30 2013-05-07 Oncotherapy Science, Inc. Anti-CDH3 antibodies labeled with radioisotope label and uses thereof
EP2352765B1 (en) 2008-10-01 2018-01-03 Amgen Research (Munich) GmbH Cross-species-specific single domain bispecific single chain antibody
RS54655B2 (sr) 2009-10-27 2021-04-29 Amgen Res Munich Gmbh Dozni režim za primenu cd19xcd3 bispecifičnog antitela
EP2496598B1 (en) 2009-11-04 2017-08-02 Affibody AB Her3 binding polypeptides
US20130129723A1 (en) 2009-12-29 2013-05-23 Emergent Product Development Seattle, Llc Heterodimer Binding Proteins and Uses Thereof
CA2785907A1 (en) 2009-12-29 2011-07-28 Emergent Product Development Seattle, Llc Ron binding constructs and methods of use thereof
JP2013528357A (ja) 2010-03-29 2013-07-11 ザイムワークス，インコーポレイテッド 強化又は抑制されたエフェクター機能を有する抗体
CA2800769C (en) 2010-05-27 2021-11-02 Genmab A/S Monoclonal antibodies against her2 epitope
ES2758994T3 (es) 2010-11-05 2020-05-07 Zymeworks Inc Diseño anticuerpo heterodimérico estable con mutaciones en el dominio Fc
EA026075B1 (ru) 2010-11-10 2017-02-28 Эмджен Рисерч (Мьюник) Гмбх Предотвращение неблагоприятных эффектов, вызванных cd3-специфическими связывающими доменами
AU2012222833B2 (en) 2011-03-03 2017-03-16 Zymeworks Inc. Multivalent heteromultimer scaffold design and constructs
KR102345943B1 (ko) 2011-04-28 2021-12-31 암젠 리서치 (뮌헨) 게엠베하 잠재적 유해 효과의 위험에 처한 환자에게 cd19xcd3 이중특이적 항체를 투여하기 위한 투여 요법
TWI687439B (zh) 2011-06-30 2020-03-11 中外製藥股份有限公司 異源二聚化多胜肽
NO2748201T3 (https=) 2011-08-23 2018-05-12
BR112014010580B1 (pt) 2011-11-04 2021-01-12 Zymeworks, Inc. constructo de fc heteromultimérico isolado, composição, uso de um constructo de fc heteromultimérico isolado, composição de ácido nucléico e método para expressar o constructo de fc heteromultimérico isolado
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
KR20150008171A (ko) 2012-05-10 2015-01-21 자임워크스 인코포레이티드 단일군 일가 항체 구조물 및 그의 용도
AU2013258834B2 (en) 2012-05-10 2017-09-07 Zymeworks Bc Inc. Heteromultimer constructs of immunoglobulin heavy chains with mutations in the Fc domain
US9499634B2 (en) 2012-06-25 2016-11-22 Zymeworks Inc. Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells
WO2014012082A2 (en) 2012-07-13 2014-01-16 Zymeworks Inc. Multivalent heteromultimer scaffold design an constructs
AU2013289883B2 (en) 2012-07-13 2018-11-01 Zymeworks Bc Inc. Bispecific asymmetric heterodimers comprising anti-CD3 constructs
IN2015DN01299A (https=) 2012-07-23 2015-07-03 Zymeworks Inc
US9382329B2 (en) * 2012-08-14 2016-07-05 Ibc Pharmaceuticals, Inc. Disease therapy by inducing immune response to Trop-2 expressing cells
CN105026430B (zh) 2012-11-28 2025-03-25 酵活英属哥伦比亚有限公司 工程化免疫球蛋白重链-轻链对及其用途
KR102211837B1 (ko) * 2013-01-14 2021-02-03 젠코어 인코포레이티드 신규한 이형이량체 단백질
US9605084B2 (en) * 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
WO2014182970A1 (en) 2013-05-08 2014-11-13 Zymeworks Inc. Bispecific her2 and her3 antigen binding constructs
AU2014357292B2 (en) 2013-11-27 2020-06-25 Zymeworks Bc Inc. Bispecific antigen-binding constructs targeting HER2
RU2016132863A (ru) * 2014-01-15 2018-02-20 Займворкс Инк. БИСПЕЦИФИЧЕСКИЕ CD3 и CD19 АНТИГЕНСВЯЗЫВАЮЩИЕ КОНСТРУКЦИИ
WO2016001810A1 (en) 2014-07-01 2016-01-07 Pfizer Inc. Bispecific heterodimeric diabodies and uses thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010126137A1 (ja) * 2009-05-01 2010-11-04 国立大学法人 東京大学 抗カドヘリン抗体
WO2012022814A1 (en) * 2010-08-20 2012-02-23 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
WO2012143524A2 (en) * 2011-04-20 2012-10-26 Genmab A/S Bispecific antibodies against her2 and cd3
WO2015006749A2 (en) * 2013-07-12 2015-01-15 Zymeworks Inc. Bispecific cd3 and cd19 antigen binding contructs
US20150044216A1 (en) * 2013-08-06 2015-02-12 Bio-Thera Solutions, Ltd. Bispecific antibodies

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022548145A (ja) * 2019-09-16 2022-11-16 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ 免疫療法の化合物および方法
JP7773152B2 (ja) 2019-09-16 2025-11-19 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ 免疫療法の化合物および方法
JP2023506017A (ja) * 2019-12-11 2023-02-14 カリナン オンコロジー インコーポレイテッド 抗ｃｄ１９抗体および多重特異性結合タンパク質
JP7780434B2 (ja) 2019-12-11 2025-12-04 カリナン セラピューティクス インコーポレイテッド 抗ｃｄ１９抗体および多重特異性結合タンパク質
JP2024512957A (ja) * 2021-03-23 2024-03-21 広州凌騰生物医薬有限公司 Ｃｄ３に結合する多重特異性抗原結合タンパク質とその使用方法
JP7708453B2 (ja) 2021-03-23 2025-07-15 広州凌騰生物医薬有限公司 Ｃｄ３に結合する多重特異性抗原結合タンパク質とその使用方法
JP2024519585A (ja) * 2021-05-13 2024-05-17 ウーシー バイオロジクス アイルランド リミテッド 抗ｐ－カドヘリン抗体を含む抗体コンジュゲートおよびその使用

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