DK2841456T3 - Human cd30-ligand-antigenbindende proteiner - Google Patents
Human cd30-ligand-antigenbindende proteiner Download PDFInfo
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- DK2841456T3 DK2841456T3 DK13720714.8T DK13720714T DK2841456T3 DK 2841456 T3 DK2841456 T3 DK 2841456T3 DK 13720714 T DK13720714 T DK 13720714T DK 2841456 T3 DK2841456 T3 DK 2841456T3
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- Prior art keywords
- seq
- cd30l
- antigen binding
- ser
- thr
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Claims (12)
- HUMAN CD30-LIGAND-ANTIGENBINDENDE PROTEINER Patentkrav1. Isoleret antistof, der binder human CD30L, omfattende en CDRH1, en CDRH2, en CDRH3, en CDRL1, en CDRL2 og en CDRL3, hvor a) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 14, 19, 25, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 1, 7 og 11, eller b) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 15, 21, 26, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 2, 8 og 12, eller c) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 15, 21, 26, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 3, 8 og 12, eller d) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 16, 22, 27, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 4, 9 og 12, eller e) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 17, 23, 28, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 5, 8 og 13, eller f) CDRH1, CDRH2 og CDRH3 er identificeret ved henholdsvis SEQ ID NO: 18, 24, 29, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 6,10 og 12.
- 2. Isoleret antistof ifølge krav 1, hvor antistoffet binder en C-terminal region af human CD30L defineret ved AA 201-234.
- 3. Isoleret antistof ifølge krav 2, hvor antistoffet binder en yderligere region af human CD30L defineret ved AA 75-95.
- 4. Isoleret antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet har mindst en egenskab udvalgt fra gruppen bestående af: a) hæmmer hCD30/hCD30L-interaktion; b) hæmmer hCD30L-induceret IL-8-induktion; c) kryds-konkurrerer med et af de antistoffer, der er defineret under punkt a) til og med f) i krav 1 om binding til human CD30L og d) har en dissociationskonstant over for human CD30L på højst 70 pM.
- 5. Isoleret antistof ifølge et hvilket som helst af kravene 1-3, hvor antistoffet binder sig til human CD30L med samme eller lavere Kd som et af følgende antistoffer: A) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 36 og en variabel tungkæderegion defineret ved SEQ ID NO: 50; B) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 38 og en variabel tungkæderegion defineret ved SEQ ID NO: 64; C) omfattende en variabel letkæderegion defineret ved SEQ ID NO 40: og en variabel tungkæderegion defineret ved SEQ ID NO: 66; D) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 42 og en variabel tungkæderegion defineret ved SEQ ID NO: 68; E) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 44 og en variabel tungkæderegion defineret ved SEQ ID NO: 70; eller F) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 46 og en variabel tungkæderegion defineret ved SEQ ID NO: 72.
- 6. Isoleret antistof ifølge et hvilket som helst af kravene 1-4, hvor antistoffet konkurrerer med et Fab af et eller flere af følgende antistoffer: A) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 36 og en variabel tungkæderegion defineret ved SEQ ID NO: 50; B) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 38 og en variabel tungkæderegion defineret ved SEQ ID NO: 64; C) omfattende en variabel letkæderegion defineret ved SEQ ID NO 40 og en variabel tungkæderegion defineret ved SEQ ID NO 66; D) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 42 og en variabel tungkæderegion defineret ved SEQ ID NO: 68; E) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 44 og en variabel tungkæderegion defineret ved SEQ ID NO: 70; og F) omfattende en variabel letkæderegion defineret ved SEQ ID NO: 46 og en variabel tungkæderegion defineret ved SEQ ID NO: 72 til binding til human CD30L
- 7. Isoleret antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet er af IgGl-, lgG2- lgG3- eller lgG4-typen.
- 8. Isoleret antistof ifølge et hvilket som helst af kravene 1-3, hvor CDRFI1, CDRFI2 og CDRFI3 er identificeret ved henholdsvis SEQ ID NO: 14, 19, 25, og CDRL1, CDRL2 og CDRL3 er identificeret ved henholdsvis SEQ ID NO: 1, 7 og 11.
- 9. Isoleret antistof ifølge et hvilket som helst af kravene 1-3 omfattende en variabel tungkæderegion af SEQ ID NO: 48 og en variabel letkæderegion af SEQ ID NO: 36.
- 10. Farmaceutisk sammensætning omfattende mindst et antistof ifølge et hvilket som helst af de foregående krav og et farmaceutisk acceptabelt hjælpestof.
- 11. Isoleret nukleinsyremolekyle, der koder for et antistof ifølge et hvilket som helst af de foregående krav.
- 12. Værtscelle omfattende nukleinsyremolekylet ifølge krav 11.
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Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL307989A (en) * | 2012-04-27 | 2023-12-01 | Novo Nordisk As | Human CD30 ligand antigen-binding proteins |
US20150315566A1 (en) * | 2014-04-30 | 2015-11-05 | The Board Of Trustees Of The University Of Illinois | Method for generating high affinity, bivalent binding agents |
US11473080B2 (en) | 2014-04-30 | 2022-10-18 | The Board Of Trustees Of The University Of Illinois | Method for generating high affinity, bivalent binding agents for sandwich assays |
CA3056630A1 (en) | 2017-03-15 | 2018-09-20 | Pandion Therapeutics, Inc. | Targeted immunotolerance |
US10676516B2 (en) | 2017-05-24 | 2020-06-09 | Pandion Therapeutics, Inc. | Targeted immunotolerance |
US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
US10174092B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
CN112368301A (zh) * | 2018-04-30 | 2021-02-12 | 西达-赛奈医疗中心 | 用于选择和治疗炎性疾病患者的方法和系统 |
WO2020096046A1 (ja) * | 2018-11-09 | 2020-05-14 | 国立大学法人大阪大学 | 老化関連t細胞を標的とした糖代謝異常の予防または治療用ワクチン |
CN113227147B (zh) * | 2018-12-24 | 2022-07-19 | 信达生物制药(苏州)有限公司 | 全人源的抗cd30单链抗体及其应用 |
KR20220035333A (ko) | 2019-05-20 | 2022-03-22 | 팬디온 오퍼레이션스, 인코포레이티드 | Madcam 표적 면역관용 |
US11981715B2 (en) | 2020-02-21 | 2024-05-14 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a CD39 effector |
CA3207893A1 (en) | 2021-01-15 | 2022-07-21 | Seagen Inc. | Immunomodulatory antibody-drug conjugates |
JP2024506300A (ja) | 2021-02-03 | 2024-02-13 | シージェン インコーポレイテッド | 免疫刺激化合物及びコンジュゲート体 |
WO2022177963A1 (en) * | 2021-02-17 | 2022-08-25 | Prometheus Biosciences, Inc. | Anti-cd30l antibodies and uses thereof |
WO2023215740A1 (en) | 2022-05-06 | 2023-11-09 | Seagen Inc. | Immunomodulatory antibody-drug conjugates |
WO2024026271A1 (en) * | 2022-07-25 | 2024-02-01 | Prometheus Biosciences, Inc. | Anti-cd30l antibodies, formulations therefor, and uses thereof |
WO2024030577A1 (en) | 2022-08-03 | 2024-02-08 | Seagen Inc. | Immunostimulatory anti-pd-l1-drug conjugates |
EP4321522A1 (en) | 2022-08-12 | 2024-02-14 | Seagen Inc. | Cytotoxic compounds and conjugates thereof |
Family Cites Families (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4740461A (en) | 1983-12-27 | 1988-04-26 | Genetics Institute, Inc. | Vectors and methods for transformation of eucaryotic cells |
US4751180A (en) | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
WO1987005330A1 (en) | 1986-03-07 | 1987-09-11 | Michel Louis Eugene Bergh | Method for enhancing glycoprotein stability |
US4959455A (en) | 1986-07-14 | 1990-09-25 | Genetics Institute, Inc. | Primate hematopoietic growth factors IL-3 and pharmaceutical compositions |
WO1988001649A1 (en) | 1986-09-02 | 1988-03-10 | Genex Corporation | Single polypeptide chain binding molecules |
US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US4912040A (en) | 1986-11-14 | 1990-03-27 | Genetics Institute, Inc. | Eucaryotic expression system |
US5011912A (en) | 1986-12-19 | 1991-04-30 | Immunex Corporation | Hybridoma and monoclonal antibody for use in an immunoaffinity purification system |
US4965195A (en) | 1987-10-26 | 1990-10-23 | Immunex Corp. | Interleukin-7 |
US4968607A (en) | 1987-11-25 | 1990-11-06 | Immunex Corporation | Interleukin-1 receptors |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
WO1990005183A1 (en) | 1988-10-31 | 1990-05-17 | Immunex Corporation | Interleukin-4 receptors |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US6713610B1 (en) | 1990-01-12 | 2004-03-30 | Raju Kucherlapati | Human antibodies derived from immunized xenomice |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
SG48759A1 (en) | 1990-01-12 | 2002-07-23 | Abgenix Inc | Generation of xenogenic antibodies |
AU651596B2 (en) | 1990-06-05 | 1994-07-28 | Immunex Corporation | Type II interleukin-1 receptors |
US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of 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 |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US5462990A (en) * | 1990-10-15 | 1995-10-31 | Board Of Regents, The University Of Texas System | Multifunctional organic polymers |
AU2249592A (en) | 1991-06-14 | 1993-01-12 | Dnx Corporation | Production of human hemoglobin in transgenic pigs |
DE69224906T2 (de) | 1991-07-08 | 1998-10-29 | Univ Massachusetts | Thermotropes flüssig-kristallines segment-blockcopolymer |
US5262522A (en) | 1991-11-22 | 1993-11-16 | Immunex Corporation | Receptor for oncostatin M and leukemia inhibitory factor |
ATE311895T1 (de) * | 1992-05-26 | 2005-12-15 | Immunex Corp | Neue zytokine die cd30 binden |
WO1994002602A1 (en) | 1992-07-24 | 1994-02-03 | Cell Genesys, Inc. | Generation of xenogeneic antibodies |
PT672141E (pt) | 1992-10-23 | 2003-09-30 | Immunex Corp | Metodos de preparacao de proteinas oligomericas soluveis |
US5457035A (en) | 1993-07-23 | 1995-10-10 | Immunex Corporation | Cytokine which is a ligand for OX40 |
KR100654645B1 (ko) | 1995-04-27 | 2007-04-04 | 아브게닉스, 인크. | 면역화된 제노마우스 유래의 인간 항체 |
KR20080059467A (ko) | 1996-12-03 | 2008-06-27 | 아브게닉스, 인크. | 복수의 vh 및 vk 부위를 함유하는 사람 면역글로불린유전자좌를 갖는 형질전환된 포유류 및 이로부터 생성된항체 |
CA2196496A1 (en) | 1997-01-31 | 1998-07-31 | Stephen William Watson Michnick | Protein fragment complementation assay for the detection of protein-protein interactions |
US6342220B1 (en) | 1997-08-25 | 2002-01-29 | Genentech, Inc. | Agonist antibodies |
JP2002517181A (ja) | 1998-02-06 | 2002-06-18 | キュラサイト・アクチェンゲゼルシャフト | 細胞の活性化を調節するために提供される核酸 |
AU770555B2 (en) | 1998-08-17 | 2004-02-26 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
US6652854B2 (en) | 2000-08-08 | 2003-11-25 | Immunex Corporation | Methods for treating autoimmune and chronic inflammatory conditions using antagonists of CD30 or CD30L |
AU2006202590A1 (en) * | 2000-08-08 | 2006-07-06 | Immunex Corporation | Methods for treating autoimmune and inflammatory conditions using antagonists of CD30 or CD30L |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
US7090843B1 (en) * | 2000-11-28 | 2006-08-15 | Seattle Genetics, Inc. | Recombinant anti-CD30 antibodies and uses thereof |
EP1478740A2 (en) * | 2001-07-27 | 2004-11-24 | Human Genome Sciences, Inc. | Heteromultimeric tnf ligand family members |
JP2005021110A (ja) * | 2003-07-04 | 2005-01-27 | Toyama Chem Co Ltd | Cd30リガンドおよび/またはcd30の発現誘導剤、アポトーシス誘導剤ならびにそれらを含有する医薬組成物。 |
JP5427027B2 (ja) * | 2006-05-03 | 2014-02-26 | ザ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・コロラド,ア・ボディー・コーポレイト | Cd40アゴニスト抗体/i型インターフェロン相乗性アジュバントの結合体、それを含む複合体、および細胞性免疫を強化する治療としてのその使用 |
US7982016B2 (en) * | 2007-09-10 | 2011-07-19 | Amgen Inc. | Antigen binding proteins capable of binding thymic stromal lymphopoietin |
EP2694550B1 (en) * | 2011-04-01 | 2019-11-27 | Universität Stuttgart | Recombinant tnf ligand family member polypeptides with antibody binding domain and uses thereof |
IL307989A (en) * | 2012-04-27 | 2023-12-01 | Novo Nordisk As | Human CD30 ligand antigen-binding proteins |
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