TR201904385T4 - Optimize Fc varyantları - Google Patents
Optimize Fc varyantları Download PDFInfo
- Publication number
- TR201904385T4 TR201904385T4 TR2019/04385T TR201904385T TR201904385T4 TR 201904385 T4 TR201904385 T4 TR 201904385T4 TR 2019/04385 T TR2019/04385 T TR 2019/04385T TR 201904385 T TR201904385 T TR 201904385T TR 201904385 T4 TR201904385 T4 TR 201904385T4
- Authority
- TR
- Turkey
- Prior art keywords
- variants
- optimized
- region
- parent polypeptide
- variant
- Prior art date
Links
- 229920001184 polypeptide Polymers 0.000 abstract 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 abstract 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 238000012986 modification Methods 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- 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
Abstract
Buluş, bir Fc bölgesi içeren bir parent polipeptidin bir varyantıyla ilgili olup, varyant söz konusu parent polipeptide kıyasla FcRn?ye artan bağlanma sergiler ve Fc bölgesinde en az bir amino asit modifikasyonu içerir.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09305250A EP2233500A1 (en) | 2009-03-20 | 2009-03-20 | Optimized Fc variants |
Publications (1)
Publication Number | Publication Date |
---|---|
TR201904385T4 true TR201904385T4 (tr) | 2019-04-22 |
Family
ID=40578514
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TR2019/04385T TR201904385T4 (tr) | 2009-03-20 | 2010-03-19 | Optimize Fc varyantları |
Country Status (14)
Country | Link |
---|---|
US (3) | USRE46585E1 (tr) |
EP (5) | EP2233500A1 (tr) |
JP (2) | JP5770710B2 (tr) |
KR (3) | KR101757136B1 (tr) |
CN (2) | CN104892762A (tr) |
AU (1) | AU2010224800B2 (tr) |
BR (2) | BR122021019353B1 (tr) |
CA (3) | CA3069425C (tr) |
DK (1) | DK2805969T3 (tr) |
ES (1) | ES2726625T3 (tr) |
IL (2) | IL215041A (tr) |
PL (1) | PL2805969T3 (tr) |
TR (1) | TR201904385T4 (tr) |
WO (1) | WO2010106180A2 (tr) |
Families Citing this family (152)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006106905A1 (ja) | 2005-03-31 | 2006-10-12 | Chugai Seiyaku Kabushiki Kaisha | 会合制御によるポリペプチド製造方法 |
ES2568436T3 (es) | 2006-03-31 | 2016-04-29 | Chugai Seiyaku Kabushiki Kaisha | Procedimiento para controlar la farmacocinética en sangre de anticuerpos |
US9670269B2 (en) | 2006-03-31 | 2017-06-06 | Chugai Seiyaku Kabushiki Kaisha | Methods of modifying antibodies for purification of bispecific antibodies |
EP3689912A1 (en) | 2007-09-26 | 2020-08-05 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in cdr |
SG10201605394SA (en) | 2007-09-26 | 2016-08-30 | Chugai Pharmaceutical Co Ltd | Modified Antibody Constant Region |
EP4238993A3 (en) | 2008-04-11 | 2023-11-29 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
JP5787446B2 (ja) | 2009-03-19 | 2015-09-30 | 中外製薬株式会社 | 抗体定常領域改変体 |
US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
JP5889181B2 (ja) | 2010-03-04 | 2016-03-22 | 中外製薬株式会社 | 抗体定常領域改変体 |
MX341925B (es) * | 2010-03-29 | 2016-09-07 | Zymeworks Inc | Anticuerpos con funcion efectora suprimida o mejorada. |
WO2011124635A1 (en) | 2010-04-07 | 2011-10-13 | Humalys | Binding molecules against chikungunya virus and uses thereof |
CA2799595C (en) | 2010-05-27 | 2022-08-16 | Merck Sharp & Dohme Corp. | Method for preparing antibodies having improved properties |
CA2806252C (en) | 2010-07-29 | 2019-05-14 | Xencor, Inc. | Antibodies with modified isoelectric points |
MY166429A (en) | 2010-11-17 | 2018-06-26 | Chugai Pharmaceutical Co Ltd | Multi-specific antigen-binding molecule having alternative function to function of blood coagulation factor viii |
SG190727A1 (en) | 2010-11-30 | 2013-07-31 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
KR102147548B1 (ko) | 2011-02-25 | 2020-08-24 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb 특이적 Fc 항체 |
WO2012132067A1 (ja) * | 2011-03-30 | 2012-10-04 | 中外製薬株式会社 | 抗原結合分子の血漿中滞留性と免疫原性を改変する方法 |
EP2707391B1 (en) | 2011-05-13 | 2017-11-08 | Gamamabs Pharma | Antibodies against her3 |
KR20140028013A (ko) | 2011-05-25 | 2014-03-07 | 머크 샤프 앤드 돔 코포레이션 | 개선된 특성을 갖는 Fc-함유 폴리펩티드를 제조하는 방법 |
RU2014101707A (ru) | 2011-06-22 | 2015-07-27 | Инсерм (Энститю Насьональ Де Ля Сантэ Э Де Ля Решерш Медикаль) | АНТИ-Axl АНТИТЕЛА И ИХ ПРИМЕНЕНИЕ |
EP2723376B1 (en) | 2011-06-22 | 2018-12-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
EP2537864B1 (en) * | 2011-06-24 | 2019-08-07 | Laboratoire Français du Fractionnement et des Biotechnologies | Fc variants with reduced effector functions |
UA117901C2 (uk) * | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
KR20200120743A (ko) * | 2011-07-06 | 2020-10-21 | 젠맵 비. 브이 | 항체 변이체 및 그의 용도 |
KR102366029B1 (ko) | 2011-09-30 | 2022-02-23 | 추가이 세이야쿠 가부시키가이샤 | 표적 항원에 대한 면역응답을 유도하는 항원 결합 분자 |
TW201817745A (zh) * | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
TWI827333B (zh) | 2011-09-30 | 2023-12-21 | 日商中外製藥股份有限公司 | 促進抗原消失的抗原結合分子 |
JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
AU2012323287B2 (en) * | 2011-10-10 | 2018-02-01 | Xencor, Inc. | A method for purifying antibodies |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
US11851476B2 (en) | 2011-10-31 | 2023-12-26 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule having regulated conjugation between heavy-chain and light-chain |
WO2013074598A1 (en) * | 2011-11-18 | 2013-05-23 | Merck Sharp & Dohme Corp. | Fc CONTAINING POLYPEPTIDES HAVING INCREASED ANTI-INFLAMMATORY PROPERTIES AND INCREASED FcRN BINDING |
EP3517550A1 (en) | 2011-11-30 | 2019-07-31 | Chugai Seiyaku Kabushiki Kaisha | Drug containing carrier into cell for forming immune complex |
KR102041412B1 (ko) * | 2011-12-30 | 2019-11-11 | 한미사이언스 주식회사 | 면역글로불린 Fc 단편 유도체 |
KR102219987B1 (ko) | 2012-02-24 | 2021-02-25 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIB를 매개로 항원의 소실을 촉진하는 항원 결합 분자 |
JPWO2013180200A1 (ja) | 2012-05-30 | 2016-01-21 | 中外製薬株式会社 | 標的組織特異的抗原結合分子 |
AU2013285355A1 (en) * | 2012-07-06 | 2015-01-29 | Genmab B.V. | Dimeric protein with triple mutations |
EP3632462A1 (en) * | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
DK2869845T3 (da) * | 2012-07-06 | 2019-12-09 | Genmab Bv | Dimert protein med tredobbelte mutationer |
TWI697501B (zh) | 2012-08-24 | 2020-07-01 | 日商中外製藥股份有限公司 | FcγRIIb特異性Fc區域變異體 |
PT2906235T (pt) * | 2012-10-02 | 2017-09-28 | Proclara Biosciences Inc | Utilização de p3 de proteínas de fusão de bacteriófago como agentes ligantes amilóides |
EP2733153A1 (en) | 2012-11-15 | 2014-05-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the preparation of immunoconjugates and uses thereof |
EA201500741A1 (ru) | 2013-01-10 | 2016-01-29 | Генмаб Б.В. | ВАРИАНТЫ Fc-ОБЛАСТИ IGG1 ЧЕЛОВЕКА И ИХ ПРИМЕНЕНИЕ |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
CN110981964B (zh) | 2013-01-14 | 2023-09-15 | Xencor股份有限公司 | 新型异二聚体蛋白 |
US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
AU2014207549B2 (en) | 2013-01-15 | 2018-12-06 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
GB201302878D0 (en) * | 2013-02-19 | 2013-04-03 | Argen X Bv | Modified igG molecules |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
AU2014232416B2 (en) | 2013-03-15 | 2017-09-28 | Xencor, Inc. | Modulation of T Cells with Bispecific Antibodies and FC Fusions |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
WO2014163101A1 (ja) | 2013-04-02 | 2014-10-09 | 中外製薬株式会社 | Fc領域改変体 |
KR101895634B1 (ko) * | 2013-05-31 | 2018-09-05 | 한미약품 주식회사 | 변이된 힌지 영역을 포함하는 IgG4 Fc 단편 |
AU2014273817B2 (en) | 2013-05-31 | 2019-03-14 | Zymeworks Bc Inc. | Heteromultimers with reduced or silenced effector function |
KR102116495B1 (ko) * | 2013-08-28 | 2020-06-03 | 삼성디스플레이 주식회사 | 축합환 화합물을 포함하는 유기 전계 발광 소자 |
JP6668241B2 (ja) | 2013-09-05 | 2020-03-18 | アムジエン・インコーポレーテツド | 予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 |
KR102441231B1 (ko) | 2013-09-27 | 2022-09-06 | 추가이 세이야쿠 가부시키가이샤 | 폴리펩티드 이종 다량체의 제조방법 |
US20160215061A1 (en) * | 2013-10-08 | 2016-07-28 | Merck Sharp & Dohme Corp. | Fc CONTAINING POLYPEPTIDES HAVING INCREASED BINDING TO FcGammaRIIB |
FR3012453B1 (fr) | 2013-10-31 | 2015-11-13 | Lab Francais Du Fractionnement | Proteine chimerique dans le traitement de l’amylose |
US10196455B2 (en) | 2013-11-07 | 2019-02-05 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Neuregulin allosteric anti-HER3 antibody |
WO2015073307A2 (en) * | 2013-11-13 | 2015-05-21 | Merck Sharp & Dohme Corp. | Fc CONTAINING POLYPEPTIDES HAVING INCREASED BINDING TO HUMAN DC-SIGN |
CN112142843A (zh) * | 2013-12-24 | 2020-12-29 | 阿尔金克斯有限公司 | FcRn拮抗剂及使用方法 |
WO2015112597A1 (en) * | 2014-01-21 | 2015-07-30 | Belmont Biosciences, Inc. | Variants of igg fc with limited amine groups that retain functional properties |
KR102497443B1 (ko) | 2014-03-28 | 2023-02-08 | 젠코어 인코포레이티드 | Cd38 및 cd3에 결합하는 이중특이적 항체 |
CN106459191B (zh) * | 2014-06-12 | 2021-12-10 | 豪夫迈·罗氏有限公司 | 选择具有修饰的FcRn相互作用的抗体的方法 |
FR3024453B1 (fr) * | 2014-08-01 | 2018-06-29 | Lab Francais Du Fractionnement | Procede de production de variants ayant un fc presentant une sialylation amelioree |
MA40764A (fr) | 2014-09-26 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | Agent thérapeutique induisant une cytotoxicité |
PE20171103A1 (es) | 2014-11-26 | 2017-08-07 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38 |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
CA2967426A1 (en) | 2014-11-26 | 2016-06-02 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and tumor antigens |
EP3229836B1 (en) | 2014-12-09 | 2019-11-13 | Institut National de la Sante et de la Recherche Medicale (INSERM) | Human monoclonal antibodies against axl |
TWI808330B (zh) | 2014-12-19 | 2023-07-11 | 日商中外製藥股份有限公司 | 抗肌抑素之抗體、含變異Fc區域之多胜肽及使用方法 |
US10428155B2 (en) | 2014-12-22 | 2019-10-01 | Xencor, Inc. | Trispecific antibodies |
TW202248212A (zh) | 2015-02-05 | 2022-12-16 | 日商中外製藥股份有限公司 | 包含離子濃度依賴之抗原結合域的抗體、Fc區變體、IL-8結合抗體與其用途 |
WO2016135041A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
FR3034420A1 (fr) | 2015-03-31 | 2016-10-07 | Lab Francais Du Fractionnement | Anticorps monoclonaux anti-cd303 |
EP3279216A4 (en) | 2015-04-01 | 2019-06-19 | Chugai Seiyaku Kabushiki Kaisha | PROCESS FOR PREPARING POLYPEPTIDE HETERO OLIGOMER |
FR3035879A1 (fr) * | 2015-05-07 | 2016-11-11 | Lab Francais Du Fractionnement | Mutants fc a activite fonctionnelle modifiee |
US10526415B2 (en) | 2015-05-22 | 2020-01-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies fragments inhibiting both the Cath-D catalytic activity and its binding to the LRP1 receptor |
FR3038517B1 (fr) * | 2015-07-06 | 2020-02-28 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Utilisation de fragments fc modifies en immunotherapie |
FR3039832A1 (fr) * | 2015-08-04 | 2017-02-10 | Univ Francois Rabelais De Tours | Igg1 et leur utilisation therapeutique |
CN108699136B (zh) | 2015-12-07 | 2022-03-18 | Xencor股份有限公司 | 结合cd3和psma的异二聚抗体 |
AU2016381992B2 (en) | 2015-12-28 | 2024-01-04 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
AU2017233658B2 (en) | 2016-03-14 | 2023-09-21 | Chugai Seiyaku Kabushiki Kaisha | Cell injury inducing therapeutic drug for use in cancer therapy |
CN114907483A (zh) | 2016-03-22 | 2022-08-16 | 国家医疗保健研究所 | 人源化抗claudin-1抗体及其用途 |
FR3051794A1 (fr) * | 2016-05-31 | 2017-12-01 | Lab Francais Du Fractionnement | Anticorps pour le traitement de cancers |
RU2022104399A (ru) | 2016-06-14 | 2022-05-05 | Ксенкор, Инк. | Биспецифические антитела-ингибиторы контрольных точек |
AU2017290086A1 (en) | 2016-06-28 | 2019-01-24 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
FR3053688A1 (fr) * | 2016-07-06 | 2018-01-12 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Mutants fc a activite fonctionnelle amelioree |
MA45602A (fr) | 2016-07-08 | 2019-05-15 | Staten Biotechnology B V | Anticorps anti-apoc3 et leurs méthodes d'utilisation |
BR112019001693A2 (pt) | 2016-07-29 | 2019-07-02 | Ct Hospitalier Universitaire Toulouse | anticorpos direcionados a macrófagos associados a tumores e seus usos |
MX2019001458A (es) * | 2016-08-02 | 2019-07-04 | Visterra Inc | Polipeptidos modificados y usos de los mismos. |
EP3494991A4 (en) | 2016-08-05 | 2020-07-29 | Chugai Seiyaku Kabushiki Kaisha | COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATING TO IL-8 |
US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
CN110214148A (zh) | 2016-10-14 | 2019-09-06 | Xencor股份有限公司 | 含有IL-15/IL-15Rα Fc融合蛋白和PD-1抗体片段的双特异性异源二聚体融合蛋白 |
KR101872455B1 (ko) * | 2016-11-30 | 2018-06-28 | 국민대학교 산학협력단 | 신규한 돌연변이를 포함하는 항체 Fc 영역 |
AU2018221731C1 (en) | 2017-02-17 | 2021-11-18 | Denali Therapeutics Inc. | Engineered transferrin receptor binding polypeptides |
CN110392697A (zh) | 2017-03-02 | 2019-10-29 | 国家医疗保健研究所 | 对nectin-4具有特异性的抗体及其用途 |
FR3064007A1 (fr) | 2017-03-20 | 2018-09-21 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Anticorps pour le traitement de cancers |
KR101792205B1 (ko) | 2017-04-13 | 2017-10-31 | 재단법인 오송첨단의료산업진흥재단 | 혈중 지속성 연장을 위한 항체 Fc 변이체들 |
AU2018249796B2 (en) * | 2017-04-07 | 2021-03-11 | Kookmin University Industry Academy Cooperation Foundation | Antibody Fc variants for improving blood half-life |
KR101913743B1 (ko) * | 2017-04-07 | 2018-11-01 | 국민대학교 산학협력단 | 혈중 반감기 연장을 위한 항체 Fc 변이체들 |
CA3059133A1 (en) | 2017-04-21 | 2018-10-25 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
MA49517A (fr) | 2017-06-30 | 2020-05-06 | Xencor Inc | Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène |
EP3456737B1 (en) * | 2017-09-19 | 2024-02-14 | Tillotts Pharma Ag | Antibody variants |
EP3456736B1 (en) | 2017-09-19 | 2021-04-07 | Tillotts Pharma Ag | Antibody variants |
MX2020003945A (es) * | 2017-10-18 | 2020-11-09 | Regenxbio Inc | Tratamiento de enfermedades oculares y cancer de colon metastasico con vegf-trap humano modificado post-traduccionalmente . |
US10538583B2 (en) | 2017-10-31 | 2020-01-21 | Staten Biotechnology B.V. | Anti-APOC3 antibodies and compositions thereof |
CA3080103A1 (en) | 2017-10-31 | 2019-05-09 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
JP2021502100A (ja) | 2017-11-08 | 2021-01-28 | ゼンコア インコーポレイテッド | 新規抗pd−1配列を用いた二重特異性および単一特異性抗体 |
US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
EP3498293A1 (en) | 2017-12-15 | 2019-06-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Treatment of monogenic diseases with an anti-cd45rc antibody |
FR3075200B1 (fr) * | 2017-12-15 | 2022-12-23 | Lab Francais Du Fractionnement | Variants avec fragment fc ayant une affinite augmentee pour fcrn et une affinite augmentee pour au moins un recepteur du fragment fc |
JP2021506291A (ja) | 2017-12-19 | 2021-02-22 | ゼンコア インコーポレイテッド | 改変されたil−2 fc融合タンパク質 |
FR3076294B1 (fr) | 2017-12-29 | 2022-01-28 | Lab Francais Du Fractionnement | Procede de purification d'anticorps a partir de lait brut |
CN108101992B (zh) * | 2017-12-31 | 2021-03-26 | 武汉班科生物技术股份有限公司 | 与新生的Fc受体结合增强的CH2结构域突变体及其制备方法与应用 |
MA51666A (fr) * | 2018-01-24 | 2020-12-02 | Genmab Bv | Variants polypeptidiques et leurs utilisations |
JP2018138022A (ja) * | 2018-02-23 | 2018-09-06 | ゲンマブ ビー.ブイ. | ヒトIgG1 Fc領域変異体およびその使用 |
TWI827585B (zh) | 2018-03-15 | 2024-01-01 | 日商中外製藥股份有限公司 | 對茲卡病毒具有交叉反應性的抗登革病毒抗體及其使用方法 |
CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
CN112437777A (zh) | 2018-04-18 | 2021-03-02 | Xencor股份有限公司 | 包含IL-15/IL-15RA Fc融合蛋白和TIM-3抗原结合结构域的靶向TIM-3的异源二聚体融合蛋白 |
EP3781599A1 (en) | 2018-04-18 | 2021-02-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
GB201809341D0 (en) * | 2018-06-07 | 2018-07-25 | Ucb Biopharma Sprl | Multi-domain proteins with increased native state colloidal stability |
US11358999B2 (en) | 2018-10-03 | 2022-06-14 | Xencor, Inc. | IL-12 heterodimeric Fc-fusion proteins |
MX2021004059A (es) | 2018-10-12 | 2021-09-23 | Xencor Inc | Proteínas de fusión de il-15/il-15ralfa-fc dirigidas a pd-1 y usos de las mismas en terapias combinadas. |
WO2020114616A1 (en) | 2018-12-07 | 2020-06-11 | Tillotts Pharma Ag | Topical treatment of immune checkpoint inhibitor induced diarrhoea, colitis or enterocolitis using antibodies and fragments thereof |
CN113438961A (zh) | 2018-12-20 | 2021-09-24 | Xencor股份有限公司 | 含有IL-15/IL-15Rα和NKG2D抗原结合结构域的靶向异二聚体Fc融合蛋白 |
WO2020148207A1 (en) | 2019-01-14 | 2020-07-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies binding to hla-a2 |
BR112021014574A2 (pt) | 2019-01-23 | 2021-10-05 | Encefa | Competidores cd31 e usos dos mesmos |
CA3132185A1 (en) | 2019-03-01 | 2020-09-10 | Xencor, Inc. | Heterodimeric antibodies that bind enpp3 and cd3 |
MA56102A (fr) | 2019-06-07 | 2022-04-13 | Argenx Bvba | Formulations pharmaceutique d'inhibiteurs de fcrn appropriées pour une administration par voie sous-cutanée |
WO2021009263A1 (en) | 2019-07-16 | 2021-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity for cd38 and uses thereof |
TW202128757A (zh) | 2019-10-11 | 2021-08-01 | 美商建南德克公司 | 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白 |
EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
CN114867532A (zh) | 2019-12-18 | 2022-08-05 | 豪夫迈·罗氏有限公司 | 双特异性抗ccl2抗体 |
EP4149558A1 (en) | 2020-05-12 | 2023-03-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
KR102607909B1 (ko) | 2020-08-19 | 2023-12-01 | 젠코어 인코포레이티드 | 항-cd28 조성물 |
CA3212665A1 (en) | 2021-03-09 | 2022-09-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cldn6 |
KR20230154311A (ko) | 2021-03-10 | 2023-11-07 | 젠코어 인코포레이티드 | Cd3 및 gpc3에 결합하는 이종이량체 항체 |
EP4347647A1 (en) | 2021-06-01 | 2024-04-10 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Use of b cell depleting agents for the treatment of rheumatic heart disease |
KR20240021859A (ko) | 2021-06-18 | 2024-02-19 | 에프. 호프만-라 로슈 아게 | 이중특이적 항-ccl2 항체 |
KR20240019034A (ko) * | 2022-08-02 | 2024-02-14 | 주식회사 파노로스바이오사이언스 | 변형된 융합 단백질 및 이의 용도 |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
WO2024061930A1 (en) | 2022-09-22 | 2024-03-28 | Institut National de la Santé et de la Recherche Médicale | New method to treat and diagnose peripheral t-cell lymphoma (ptcl) |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2228904A (en) | 1939-05-10 | 1941-01-14 | Bjorkman Hugo Leonard | Wrench |
US2228908A (en) | 1939-07-12 | 1941-01-14 | Blaw Knox Co | Ferrous alloy mill roll |
US4666884A (en) | 1984-04-10 | 1987-05-19 | New England Deaconess Hospital | Method of inhibiting binding of von Willebrand factor to human platelets and inducing interaction of platelets with vessel walls |
EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
WO1988007089A1 (en) * | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
AU654811B2 (en) | 1990-03-20 | 1994-11-24 | Trustees Of Columbia University In The City Of New York, The | Chimeric antibodies with receptor binding ligands in place of their constant region |
WO1993022332A2 (en) | 1992-04-24 | 1993-11-11 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
US5747035A (en) | 1995-04-14 | 1998-05-05 | Genentech, Inc. | Polypeptides with increased half-life for use in treating disorders involving the LFA-1 receptor |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
WO1997043316A1 (en) | 1996-05-10 | 1997-11-20 | Beth Israel Deaconess Medical Center, Inc. | Physiologically active molecules with extended half-lives and methods of using same |
BR9908226A (pt) | 1998-02-25 | 2000-10-24 | Lexigen Pharm Corp | Melhoramento da meia vida de circulação de proteìnas de fusão com base em anticorpo |
DK1068241T3 (da) * | 1998-04-02 | 2008-02-04 | Genentech Inc | Antistofvarianter og fragmenter deraf |
PT1071700E (pt) | 1998-04-20 | 2010-04-23 | Glycart Biotechnology Ag | Modificação por glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
CA2341029A1 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
ES2694002T3 (es) * | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
US7183387B1 (en) | 1999-01-15 | 2007-02-27 | Genentech, Inc. | Polypeptide variants with altered effector function |
PT1914244E (pt) | 1999-04-09 | 2013-07-26 | Kyowa Hakko Kirin Co Ltd | Processo para regular a actividade de moléculas funcionais sob o ponto de vista imunológico |
JP4668498B2 (ja) | 1999-10-19 | 2011-04-13 | 協和発酵キリン株式会社 | ポリペプチドの製造方法 |
FR2807767B1 (fr) | 2000-04-12 | 2005-01-14 | Lab Francais Du Fractionnement | Anticorps monoclonaux anti-d |
CA2785941C (en) | 2000-10-06 | 2017-01-10 | Kyowa Hakko Kirin Co., Ltd. | Antibody composition-producing cell |
AU2001294175A1 (en) | 2000-10-06 | 2002-04-22 | Kyowa Hakko Kogyo Co. Ltd. | Method of purifying antibody |
FR2816319B1 (fr) | 2000-11-08 | 2004-09-03 | Millegen | Utilisation d'adn polymerase mutagene pour la creation de mutations aleatoires |
ES2649037T3 (es) | 2000-12-12 | 2018-01-09 | Medimmune, Llc | Moléculas con semividas prolongadas, composiciones y usos de las mismas |
KR20030033007A (ko) | 2001-05-31 | 2003-04-26 | 코울터 파머수티컬, 인코포레이티드 | 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제 |
CN101124245A (zh) * | 2003-11-12 | 2008-02-13 | 比奥根艾迪克Ma公司 | 新生儿Fc受体(FcRn)-结合多肽变体、二聚体Fc结合蛋白及其相关方法 |
EP1697415A1 (en) * | 2003-11-12 | 2006-09-06 | Biogen Idec MA Inc. | NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
DK1817340T3 (da) * | 2004-11-12 | 2012-08-13 | Xencor Inc | Fc-varianter med ændret binding til fcrn |
FR2879204B1 (fr) | 2004-12-15 | 2007-02-16 | Lab Francais Du Fractionnement | Anticorps cytotoxique dirige contre les proliferations hematopoietiques lymphoides de type b. |
FR2894983B1 (fr) | 2005-12-16 | 2012-08-17 | Lab Francais Du Fractionnement | Test de caracterisation des anticorps. |
KR100932915B1 (ko) | 2007-12-11 | 2009-12-21 | 한국전자통신연구원 | 방사방향 제어장치 및 방법 |
EP2352521B1 (en) * | 2008-10-14 | 2020-09-16 | Genentech, Inc. | Immunoglobulin variants and uses thereof |
US20100113929A1 (en) | 2008-10-31 | 2010-05-06 | National Tsing Hua University | High-frequency ultrasonic imaging system and method |
US10817851B2 (en) | 2009-12-23 | 2020-10-27 | Aristocrat Technologies Australia Pty Limited | System and method for cashless gaming |
US11392902B2 (en) | 2017-06-06 | 2022-07-19 | United Parcel Service Of America, Inc. | Systems, methods, apparatuses and computer program products for providing notification of items for pickup and delivery |
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