JP7256011B2 - Ｃｄ４０ｌを阻害するポリペプチド - Google Patents
Ｃｄ４０ｌを阻害するポリペプチド Download PDFInfo
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
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| US62/345,967 | 2016-06-06 | ||
| PCT/EP2016/079048 WO2017089618A1 (en) | 2015-11-27 | 2016-11-28 | Polypeptides inhibiting cd40l |
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| JP2019504822A5 JP2019504822A5 (enExample) | 2020-01-16 |
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| CN117164710A (zh) | 2016-12-07 | 2023-12-05 | 埃博灵克斯股份有限公司 | 改进的血清白蛋白结合免疫球蛋白单可变结构域 |
| SG10202108973SA (en) | 2017-01-17 | 2021-09-29 | Ablynx Nv | Improved serum albumin binders |
| ES2991459T3 (es) | 2017-01-17 | 2024-12-03 | Ablynx Nv | Ligantes de albúmina sérica mejorados |
| EP3710480A4 (en) * | 2017-11-17 | 2021-12-15 | Nanjing Legend Biotech Co., Ltd. | SINGLE-DOMAIN ANTIBODIES AND VARIANTS OF THEM DIRECTED AGAINST PD-L1 |
| AU2020400938A1 (en) * | 2019-12-09 | 2022-07-28 | Ablynx Nv | Polypeptides comprising immunoglobulin single variable domains targeting IL-13 and TSLP |
| CN114149508B (zh) * | 2021-11-25 | 2023-04-28 | 苏州普乐康医药科技有限公司 | 一种结合cd40l的融合蛋白及其应用 |
| TW202440614A (zh) | 2022-12-23 | 2024-10-16 | 比利時商艾伯霖克斯公司 | 基於蛋白質的接合載體 |
| TW202448926A (zh) | 2023-02-17 | 2024-12-16 | 比利時商艾伯霖克斯公司 | 結合新生兒fc受體之多肽 |
| US20250236673A1 (en) | 2023-12-22 | 2025-07-24 | Ablynx N.V. | Protein-based carriers for site-specific amine conjugation |
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| WO2025235683A1 (en) | 2024-05-07 | 2025-11-13 | Eledon Pharmaceuticals, Inc. | Methods and compositions for prevention of transplant rejection |
| WO2025235670A1 (en) | 2024-05-07 | 2025-11-13 | Eledon Pharmaceuticals, Inc. | Use of anti-cd40 ligand antibodies for immunosuppression in islet cell transplantation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012167112A (ja) | 2005-05-18 | 2012-09-06 | Ablynx Nv | 腫瘍壊死因子−アルファに対する改良ナノボディ（商標） |
| WO2015143209A1 (en) | 2014-03-19 | 2015-09-24 | Bristol-Myers Squibb Company | Methods of treating transplant rejection using a domain antibody directed against cd40l |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB335768A (en) | 1929-10-24 | 1930-10-02 | Jacoviac Maurice | Improvements in protecting devices for gramophone disc records |
| 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 |
| SE509359C2 (sv) | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
| EP0656946B2 (en) | 1992-08-21 | 2010-03-31 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
| DE69427974T2 (de) | 1993-04-29 | 2001-12-06 | Unilever N.V., Rotterdam | Herstellung von antikörpern oder funktionstüchtig gemachten teilen davon, abgeleitet von schweren ketten von immunglobulinen von camelidae |
| FR2708622B1 (fr) | 1993-08-02 | 1997-04-18 | Raymond Hamers | Vecteur recombinant contenant une séquence d'un gène de lipoprotéine de structure pour l'expression de séquences de nucléotides. |
| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
| CA2258518C (en) | 1996-06-27 | 2011-11-22 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Recognition molecules interacting specifically with the active site or cleft of a target molecule |
| US6329516B1 (en) | 1997-04-28 | 2001-12-11 | Fmc Corporation | Lepidopteran GABA-gated chloride channels |
| BR9813276A (pt) | 1997-10-27 | 2000-08-22 | Unilever Nv | Proteìna multivalente de ligação de antìgeno, sequências de nucleotìdeos, vetor de expressão, célula hospedeira, processo para preparação de proteìna multivalente de ligação de antìgeno, e, uso da mesma |
| WO1999037681A2 (en) | 1998-01-26 | 1999-07-29 | Unilever Plc | Method for producing antibody fragments |
| US20020155604A1 (en) | 1998-02-19 | 2002-10-24 | Jeffrey A. Ledbetter | Compositions and methods for regulating lymphocyte activation |
| EP0967284A1 (en) | 1998-05-28 | 1999-12-29 | Pfizer Limited | Phosphodiesterases |
| WO2000040968A1 (en) | 1999-01-05 | 2000-07-13 | Unilever Plc | Binding of antibody fragments to solid supports |
| WO2000043507A1 (en) | 1999-01-19 | 2000-07-27 | Unilever Plc | Method for producing antibody fragments |
| EP1157119A1 (en) | 1999-02-05 | 2001-11-28 | Rijksuniversiteit Leiden | Method of modulating metabolite biosynthesis in recombinant cells |
| DE60035163T2 (de) | 1999-03-15 | 2008-02-21 | University Of British Columbia, Vancouver | Abc1 polypeptide und verfahren und reagenzien zur modulation des cholesterolgehalts |
| CA2370351A1 (en) | 1999-04-22 | 2000-11-02 | Unilever Plc | Inhibition of viral infection using monovalent antigen-binding proteins |
| WO2000078972A2 (en) | 1999-06-18 | 2000-12-28 | Cv Therapeutics, Inc. | Regulation with binding cassette transporter protein abc1 |
| IL147920A0 (en) | 1999-08-02 | 2002-08-14 | Keygene Nv | Method for generating cgmmv resistant plants, genetic constructs, and the obtained cgmmv-resistant plants |
| GB9922124D0 (en) | 1999-09-17 | 1999-11-17 | Pfizer Ltd | Phosphodiesterase enzymes |
| US6479280B1 (en) | 1999-09-24 | 2002-11-12 | Vlaams Interuniversitair Institutuut Voor Biotechnologie Vzw | Recombinant phages capable of entering host cells via specific interaction with an artificial receptor |
| DE19955408A1 (de) | 1999-11-18 | 2001-05-23 | Bayer Ag | GABA-B-Rezeptoren |
| AU1859201A (en) | 1999-11-29 | 2001-06-12 | Unilever Plc | Immobilisation of proteins |
| ATE440111T1 (de) | 1999-11-29 | 2009-09-15 | Bac Ip B V | Immobilisierte antigenbindende moleküle aus einer domäne |
| WO2001045746A2 (en) | 1999-12-24 | 2001-06-28 | Genentech, Inc. | Methods and compositions for prolonging elimination half-times of bioactive compounds |
| ATE428733T1 (de) | 2000-03-14 | 2009-05-15 | Unilever Nv | Variabele domänen der schweren kette eines antikörpers gegen menschliche ernährungslipasen und deren verwendungen |
| GB0006398D0 (en) | 2000-03-16 | 2000-05-03 | Novartis Ag | Organic compounds |
| US20030190598A1 (en) | 2000-05-26 | 2003-10-09 | Jasmid Tanha | Single-domain antigen-binding antibody fragments derived from llama antibodies |
| EP1360207B1 (en) | 2000-12-13 | 2011-06-22 | Bac Ip B.V. | Protein arrays of camelid heavy-chain immunoglobulin variable domains |
| CA2440582A1 (en) | 2001-03-09 | 2002-10-03 | Dyax Corp. | Serum albumin binding moieties |
| DE60237282D1 (de) | 2001-06-28 | 2010-09-23 | Domantis Ltd | Doppelspezifischer ligand und dessen verwendung |
| US20060073141A1 (en) | 2001-06-28 | 2006-04-06 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| JP4213586B2 (ja) | 2001-09-13 | 2009-01-21 | 株式会社抗体研究所 | ラクダ抗体ライブラリーの作製方法 |
| JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
| AU2002351896A1 (en) | 2001-12-11 | 2003-06-23 | Ablynx N.V. | Method for displaying loops from immunoglobulin domains in different contexts |
| AU2002360068B2 (en) | 2001-12-21 | 2009-09-03 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Method for cloning of variable domain sequences |
| JP2005517674A (ja) | 2002-01-03 | 2005-06-16 | フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー | 腫瘍の処置に有用な新規免疫コンジュゲート |
| AU2003284891A1 (en) | 2002-10-23 | 2004-05-13 | Ludwig Institute For Cancer Research | A34 and a33-like 3 dna, proteins, antibodies thereto and methods of treatment using same |
| WO2005044858A1 (en) | 2003-11-07 | 2005-05-19 | Ablynx N.V. | Camelidae single domain antibodies vhh directed against epidermal growth factor receptor and uses therefor |
| EP1558647B1 (en) | 2002-11-08 | 2015-06-10 | Ablynx N.V. | Single domain antibodies directed against tumour necrosis factor-alpha and uses therefor |
| EP3299393A1 (en) | 2002-11-08 | 2018-03-28 | Ablynx N.V. | Single domain antibodies directed against tumour necrosis factor-alpha and uses therefor |
| NZ540771A (en) | 2003-01-10 | 2009-05-31 | Ablynx Nv | Recombinant VHH single domain antibody from camelidae against von willebrand factor (vWF) or against collagen |
| US7461263B2 (en) | 2003-01-23 | 2008-12-02 | Unspam, Llc. | Method and apparatus for a non-revealing do-not-contact list system |
| CA2535550A1 (en) | 2003-08-12 | 2005-03-03 | William M. Yarbrough | Treatment for acne vulgaris and method of use |
| US7563443B2 (en) * | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| BRPI0518151A2 (pt) | 2004-10-13 | 2009-06-16 | Ablynx Nv | polipetìdeos contra amiloide-beta, ácido nucléico que codifica tal polipetìdeo, composição compreendendo tal polipetìdeo, método para produzir um polipetìdeo e uso do mesmo |
| CA2595682A1 (en) | 2005-01-31 | 2006-08-03 | Ablynx N.V. | Method for generating variable domain sequences of heavy chain antibodies |
| CN101213214B (zh) | 2005-05-20 | 2014-06-25 | 埃博灵克斯股份有限公司 | 针对冯威勒布兰特因子的单一结构域vhh抗体 |
| EP2057191A1 (en) | 2006-08-18 | 2009-05-13 | Ablynx N.V. | Amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of deseases and disorders associated with il-6-mediated signalling |
| JP2010511397A (ja) | 2006-12-05 | 2010-04-15 | アブリンクス エン．ヴェー． | 血清タンパク質と結合可能なペプチド |
| JP2010518839A (ja) | 2007-02-21 | 2010-06-03 | アブリンクス エン．ヴェー． | 血管内皮増殖因子に指向性を有するアミノ酸配列、及び過度の及び／もしくは病的な血管形成又は血管新生を特徴とする症状及び疾患を治療するためにこれを含むポリペプチド |
| PL2125894T3 (pl) | 2007-03-22 | 2019-08-30 | Biogen Ma Inc. | Białka wiążące, w tym przeciwciała, pochodne przeciwciał i fragmenty przeciwciał, które swoiście wiążą się z CD154 i ich zastosowania |
| CN101796072B (zh) | 2007-05-24 | 2014-09-24 | 埃博灵克斯股份有限公司 | 用于治疗骨疾病和病症的针对rank-l的氨基酸序列以及包括其的多肽 |
| WO2009127691A1 (en) | 2008-04-17 | 2009-10-22 | Ablynx N.V. | Peptides capable of binding to serum proteins and compounds, constructs and polypeptides comprising the same |
| AU2009256246B2 (en) * | 2008-06-03 | 2013-07-18 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
| US8962807B2 (en) * | 2009-12-14 | 2015-02-24 | Ablynx N.V. | Single variable domain antibodies against OX40L, constructs and therapeutic use |
| WO2012088302A2 (en) * | 2010-12-22 | 2012-06-28 | Abbott Laboratories | Half immunoglobulin binding proteins and uses thereof |
| NZ780183A (en) | 2011-06-23 | 2024-12-20 | Ablynx Nv | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
| EP2723771B1 (en) * | 2011-06-23 | 2019-09-11 | Ablynx NV | Serum albumin binding proteins |
| PE20141522A1 (es) | 2011-08-17 | 2014-11-17 | Glaxo Group Ltd | Proteinas y peptidos modificados |
| SMT202000091T1 (it) | 2011-10-13 | 2020-05-08 | Bristol Myers Squibb Co | Polipeptidi anticorpali che antagonizzano cd40l |
| AU2014326674B2 (en) | 2013-09-26 | 2020-03-12 | Ablynx Nv | Bispecific nanobodies |
| TN2018000021A1 (en) | 2015-07-14 | 2019-07-08 | Immunext Inc | ANTl-CD154 ANTIBODY HAVING IMPROVED BINDING, FUNCTIONAL AND SAFETY CHARACTERISTICS AND USE IN HUMAN IMMUNOTHERAPY. |
| CA2994825A1 (en) | 2015-08-05 | 2017-02-09 | Janssen Biotech, Inc. | Anti-cd154 antibodies and methods of using them |
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2016
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- 2016-11-28 MA MA043302A patent/MA43302A/fr unknown
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- 2016-11-28 CN CN201680068704.XA patent/CN108473561B/zh active Active
- 2016-11-28 EP EP21179221.3A patent/EP3932945A1/en not_active Withdrawn
- 2016-11-28 SG SG11201803976VA patent/SG11201803976VA/en unknown
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- 2016-11-28 KR KR1020187018169A patent/KR20180080337A/ko not_active Withdrawn
- 2016-11-28 MX MX2018006377A patent/MX2018006377A/es unknown
- 2016-11-28 SG SG10201913503VA patent/SG10201913503VA/en unknown
- 2016-11-28 WO PCT/EP2016/079048 patent/WO2017089618A1/en not_active Ceased
- 2016-11-28 TN TNP/2018/000180A patent/TN2018000180A1/en unknown
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- 2016-11-28 RU RU2018122255A patent/RU2018122255A/ru unknown
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2018
- 2018-05-09 IL IL259249A patent/IL259249A/en unknown
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- 2018-06-08 CO CONC2018/0005921A patent/CO2018005921A2/es unknown
- 2018-06-21 EC ECSENADI201846820A patent/ECSP18046820A/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012167112A (ja) | 2005-05-18 | 2012-09-06 | Ablynx Nv | 腫瘍壊死因子−アルファに対する改良ナノボディ（商標） |
| WO2015143209A1 (en) | 2014-03-19 | 2015-09-24 | Bristol-Myers Squibb Company | Methods of treating transplant rejection using a domain antibody directed against cd40l |
Non-Patent Citations (1)
| Title |
|---|
| ＴＨＥ ＪＯＵＲＮＡＬ ＯＦ ＩＭＭＵＮＯＬＯＧＹ，２０１４，Ｖｏｌ．１９２，Ｎｏ．９，ｐ．１－１０ |
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| BR112018010802A2 (pt) | 2018-11-27 |
| CO2018005921A2 (es) | 2018-06-20 |
| RU2018122255A (ru) | 2019-12-19 |
| PE20181956A1 (es) | 2018-12-17 |
| WO2017089618A1 (en) | 2017-06-01 |
| RU2018122255A3 (enExample) | 2020-04-06 |
| IL259249A (en) | 2018-07-31 |
| CA3006398A1 (en) | 2017-06-01 |
| CN108473561A (zh) | 2018-08-31 |
| AU2016360987A1 (en) | 2018-06-07 |
| MA43302A (fr) | 2021-03-17 |
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| TN2018000180A1 (en) | 2019-10-04 |
| SG10201913503VA (en) | 2020-03-30 |
| ECSP18046820A (es) | 2018-07-31 |
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| US11248055B2 (en) | 2022-02-15 |
| PH12018501114A1 (en) | 2019-01-28 |
| EP3380517A1 (en) | 2018-10-03 |
| SG11201803976VA (en) | 2018-06-28 |
| CL2018001400A1 (es) | 2018-10-26 |
| MX2018006377A (es) | 2018-09-05 |
| JP2019504822A (ja) | 2019-02-21 |
| CN108473561B (zh) | 2022-12-16 |
| DOP2018000128A (es) | 2018-09-30 |
| KR20180080337A (ko) | 2018-07-11 |
| EP3932945A1 (en) | 2022-01-05 |
| US20180355050A1 (en) | 2018-12-13 |
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