JPWO2020077276A5 - - Google Patents

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JPWO2020077276A5
JPWO2020077276A5 JP2021519617A JP2021519617A JPWO2020077276A5 JP WO2020077276 A5 JPWO2020077276 A5 JP WO2020077276A5 JP 2021519617 A JP2021519617 A JP 2021519617A JP 2021519617 A JP2021519617 A JP 2021519617A JP WO2020077276 A5 JPWO2020077276 A5 JP WO2020077276A5
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抗ＰＤ－１結合ドメインを含む組成物であって、前記抗ＰＤ－１結合ドメインが、可変重鎖ドメイン（ＶＨドメイン）および可変軽鎖ドメイン（ＶＬドメイン）を含み、前記ＶＨドメインが、配列番号５と少なくとも９５％のアミノ酸配列同一性を有し、前記ＶＬドメインが、配列番号６と少なくとも９５％のアミノ酸配列同一性を有する、組成物。A composition comprising an anti-PD-1 binding domain, said anti-PD-1 binding domain comprising a variable heavy chain domain (VH domain) and a variable light chain domain (VL domain), wherein said VH domain comprises SEQ ID NO: 5, wherein said VL domain has at least 95% amino acid sequence identity with SEQ ID NO:6. 前記ＶＨドメインが、配列番号５と少なくとも９６％のアミノ酸配列同一性を有し、前記ＶＬドメインが、配列番号６と少なくとも９６％のアミノ酸配列同一性を有する、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain has at least 96% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 96% amino acid sequence identity with SEQ ID NO:6. 前記ＶＨドメインが、配列番号５と少なくとも９７％のアミノ酸配列同一性を有し、前記ＶＬドメインが、配列番号６と少なくとも９７％のアミノ酸配列同一性を有する、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain has at least 97% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 97% amino acid sequence identity with SEQ ID NO:6. 前記ＶＨドメインが、配列番号５と少なくとも９８％のアミノ酸配列同一性を有し、前記ＶＬドメインが、配列番号６と少なくとも９８％のアミノ酸配列同一性を有する、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain has at least 98% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 98% amino acid sequence identity with SEQ ID NO:6. 前記ＶＨドメインが、配列番号５と少なくとも９９％のアミノ酸配列同一性を有し、前記ＶＬドメインが、配列番号６と少なくとも９９％のアミノ酸配列同一性を有する、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain has at least 99% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 99% amino acid sequence identity with SEQ ID NO:6. 前記ＶＨドメインが、アミノ酸置換Ｆ３２Ｌを含み、前記ＶＬドメインが、Ｎ２７ｄＨ、Ｋ３０Ｙ、およびＳ９３Ｔからなる群から選択される１つ以上のアミノ酸置換を含み、付番はＫａｂａｔによる付番である、請求項１に記載の組成物。12. The numbering is according to Kabat, wherein the VH domain comprises the amino acid substitution F32L and the VL domain comprises one or more amino acid substitutions selected from the group consisting of N27dH, K30Y, and S93T. 1. The composition according to 1. 前記ＶＬドメインが、アミノ酸置換Ｎ２７ｄＨ、Ｋ３０Ｙ、およびＳ９３Ｔを含む、請求項６に記載の組成物。7. The composition of claim 6, wherein said VL domain comprises amino acid substitutions N27dH, K30Y, and S93T. 前記ＶＨドメインが、配列番号５であり、前記ＶＬドメインが、配列番号６である、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain is SEQ ID NO:5 and said VL domain is SEQ ID NO:6. 前記ＶＨドメインが、配列番号５であり、前記ＶＬドメインが、配列番号３６８である、請求項１に記載の組成物。2. The composition of claim 1, wherein said VH domain is SEQ ID NO:5 and said VL domain is SEQ ID NO:368. 抗ＰＤ－１結合ドメインが、前記ＶＨドメインおよび前記ＶＬドメインに共有結合して前記ｓｃＦｖドメインを形成するｓｃＦｖリンカーをさらに含むｓｃＦｖである、請求項１に記載の組成物。2. The composition of claim 1, wherein the anti-PD-1 binding domain is a scFv further comprising an scFv linker covalently joining said VH domain and said VL domain to form said scFv domain. 前記ｓｃＦｖリンカーが、（ＧＧＧＧＳ）The scFv linker is (GGGGS) ｎn （配列番号１０）であり、ｎは１～７の整数である、請求項１０に記載の組成物。(SEQ ID NO: 10) and n is an integer from 1-7. 前記ｓｃＦｖリンカーが、（ＧＫＰＧＳ）The scFv linker is (GKPGS) ｎn （配列番号２８）であり、ｎは１～６の整数である、請求項１０に記載の組成物。(SEQ ID NO:28) and n is an integer from 1-6. 請求項１に記載の組成物をコードする、核酸。A nucleic acid encoding the composition of claim 1 . ａ）請求項１に記載のＶＨドメインをコードする第１の核酸と、a) a first nucleic acid encoding the VH domain of claim 1;
ｂ）請求項１に記載のＶＬドメインをコードする第２の核酸とを含む、核酸組成物。b) a second nucleic acid encoding the VL domain of claim 1; 請求項１３に記載の核酸を含む、発現ベクター。An expression vector comprising the nucleic acid of claim 13. ａ）請求項１４に記載の第１の核酸を含む第１の発現ベクターと、a) a first expression vector comprising the first nucleic acid of claim 14;
ｂ）請求項１４に記載の第２の核酸を含む第２の発現ベクターとを含む、発現ベクター組成物。b) a second expression vector comprising the second nucleic acid of claim 14. 請求項１５に記載の発現ベクターまたは請求項１６に記載の発現ベクター組成物を含む、宿主細胞。17. A host cell comprising the expression vector of claim 15 or the expression vector composition of claim 16. 請求項１に記載の組成物を生成する方法であって、請求項１７に記載の宿主細胞を、前記組成物が発現する条件下で培養することと、前記組成物を回収することとを含む、方法。18. A method of producing the composition of claim 1, comprising culturing the host cell of claim 17 under conditions in which said composition is expressed, and recovering said composition. ,Method. 前記組成物が、標的化ＩＬ－１５／ＲαヘテロダイマーＦｃ融合タンパク質である、請求項１に記載の組成物。2. The composition of claim 1, wherein said composition is a targeted IL-15/Rα heterodimeric Fc fusion protein. 標的化ＩＬ－１５／ＲαヘテロダイマーＦｃ融合タンパク質が、
ａ）Ｎ末端からＣ末端に向けて、
ｉ）ＩＬ－１５Ｒαスシドメインタンパク質、
ｉｉ）第１のドメインリンカー、
ｉｉｉ）ＩＬ－１５タンパク質、および
ｉｖ）第１のバリアントＦｃドメインを含む、第１のモノマーと、
ｂ）ＶＨ－ＣＨ１－ヒンジ－ＣＨ２－ＣＨ３を含む重鎖を含む第２のモノマーであって、ＣＨ２－ＣＨ３が第２のバリアントＦｃドメインである、第２のモノマーと、
ｃ）ＶＬ－ＣＬを含む軽鎖を含む第３のモノマーであって、前記ＶＨおよびＶＬドメインが、前記ヒトＰＤ－１についてニボルマブおよび／またはペムブロリズマブと競合しない前記抗原結合ドメインを形成する、第３のモノマーとを含む、請求項１９に記載の組成物。 A targeted IL-15/Rα heterodimeric Fc fusion protein comprising:
a) from the N-terminus to the C-terminus,
i) IL-15Rα sushi domain protein,
ii) a first domain linker,
iii) an IL-15 protein, and iv) a first monomer comprising a first variant Fc domain;
b) a second monomer comprising a heavy chain comprising VH-CH1-hinge-CH2-CH3, wherein CH2-CH3 is a second variant Fc domain;
c) a third monomer comprising a light chain comprising VL-CL, wherein said VH and VL domains form said antigen binding domain that does not compete with nivolumab and/or pembrolizumab for said human PD-1; 20. The composition of claim 19, comprising 3 monomers. 前記ＶＨドメインがアミノ酸置換Ｆ３２Ｌを含み、前記ＶＬドメインがアミノ酸置換Ｎ２７ｄＨを含む、請求項２０に記載の組成物。 21. The composition of claim 20 , wherein said VH domain comprises the amino acid substitution F32L and said VL domain comprises the amino acid substitution N27dH. 前記ＶＬドメインがアミノ酸置換Ｋ３０Ｙ／Ｓ９３Ｔをさらに含む、請求項２０に記載の組成物。 21. The composition of claim 20, wherein said VL domain further comprises the amino acid substitution K30Y/ S93T . 前記ＩＬ－１５タンパク質が、Ｄ３０Ｎ／Ｅ６４Ｑ／Ｎ６５Ｄ、Ｄ３０Ｎ／Ｎ６５Ｄ、Ｎ１Ｄ、Ｎ４Ｄ、Ｄ８Ｎ、Ｄ３０Ｎ、Ｄ６１Ｎ、Ｅ６４Ｑ、Ｎ６５Ｄ、Ｑ１０８Ｅ、Ｎ１Ｄ／Ｎ４Ｄ／Ｄ８Ｎ、Ｎ１Ｄ／Ｎ４Ｄ／Ｎ６５Ｄ、Ｎ１Ｄ／Ｄ３０Ｎ、Ｎ１Ｄ／Ｄ６１Ｎ、Ｎ１Ｄ／Ｄ６１Ｎ／Ｅ６４Ｑ／Ｑ１０８Ｅ、Ｎ１Ｄ／Ｅ６４Ｑ、Ｎ１Ｄ／Ｎ６５Ｄ、Ｎ１Ｄ／Ｑ１０８Ｅ、Ｎ４Ｄ、Ｎ４Ｄ／Ｄ３０Ｎ、Ｎ４Ｄ／Ｄ６１Ｎ、Ｎ４Ｄ／Ｄ６１Ｎ／Ｎ６５Ｄ、Ｎ４Ｄ／Ｄ６１Ｎ／Ｅ６４Ｑ／Ｑ１０８Ｅ、Ｎ４Ｄ／Ｅ６４Ｑ、Ｎ４Ｄ／Ｎ６５Ｄ、Ｄ８Ｎ／Ｄ６１Ｎ、Ｄ８Ｎ／Ｅ６４Ｑ、Ｄ３０Ｎ／Ｅ６４Ｑ、Ｄ３０Ｎ／Ｑ１８０Ｅ、Ｄ６１Ｎ／Ｅ６４Ｑ／Ｎ６５Ｄ、Ｅ６４Ｑ、Ｅ６４Ｑ／Ｎ６５Ｄ、Ｅ６４Ｑ／Ｑ１０８Ｅ、およびＮ６５Ｄ／Ｑ１０８Ｅの群から選択されるアミノ酸置換（複数可）を含むバリアントＩＬ－１５タンパク質である、請求項２０～２２のいずれか一項に記載の組成物。 said IL-15 protein is D30N/E64Q/N65D, D30N/N65D, N1D, N4D, D8N, D30N, D61N, E64Q, N65D, Q108E, N1D/N4D/D8N, N1D/N4D/N65D, N1D/D30N, N1D /D61N, N1D/D61N/E64Q/Q108E, N1D/E64Q, N1D/N65D, N1D/Q108E, N4D, N4D/D30N, N4D/D61N, N4D/D61N/N65D, N4D/D61N/E64Q/Q108E, N4D/E64Q , N4D/N65D, D8N/D61N, D8N/E64Q, D30N/E64Q, D30N/Q180E, D61N/E64Q/N65D, E64Q, E64Q/N65D, E64Q/Q108E, and N65D/Q108E ( 23. The composition according to any one of claims 20-22 , which is a variant IL-15 protein comprising: 前記バリアントＩＬ－１５タンパク質が、Ｎ４Ｄ／Ｎ６５Ｄ、Ｄ３０Ｎ、Ｄ３０Ｎ／Ｅ６４Ｑ、Ｄ３０Ｎ／Ｎ６５Ｄ、およびＤ３０Ｎ／Ｅ６４Ｑ／Ｎ６５Ｄの群から選択されるアミノ酸置換（複数可）を含む、請求項２０～２３のいずれか一項に記載の組成物。 24. Any of claims 20-23 , wherein said variant IL-15 protein comprises amino acid substitution(s) selected from the group of N4D/N65D, D30N, D30N/E64Q, D30N/N65D, and D30N/E64Q/N65D. or the composition according to claim 1. 前記第１のバリアントＦｃドメインおよび前記第２のバリアントＦｃドメインが、ＥＵ付番に従って、アミノ酸置換Ｌ３６８Ｄ／Ｋ３７０Ｓ：Ｓ３６４Ｋ／Ｅ３５７Ｑを含む、請求項２０～２４のいずれか一項に記載の組成物。 25. The composition of any one of claims 20-24 , wherein said first variant Fc domain and said second variant Fc domain comprise the amino acid substitutions L368D/K370S:S364K/E357Q according to EU numbering. 前記第１のバリアントＦｃドメインおよび前記第２のバリアントＦｃドメインが、各々、ＥＵ付番に従って、アミノ酸置換Ｍ４２８Ｌ／Ｎ３４３Ｓを含む、請求項２０～２５のいずれか一項に記載の組成物。 The composition of any one of claims 20-25 , wherein said first variant Fc domain and said second variant Fc domain each comprise the amino acid substitution M428L/N343S according to EU numbering. ａ）請求項２０～２６のいずれか一項に記載の第１のモノマーをコードする第１の核酸と、
ｂ）請求項２０～２６のいずれか一項に記載の第２のモノマーをコードする第２の核酸と、
ｃ）請求項２０～２６のいずれか一項に記載の第３のモノマーをコードする第３の核酸とをそれぞれ含む、核酸組成物。 a) a first nucleic acid encoding a first monomer according to any one of claims 20-26 ;
b) a second nucleic acid encoding a second monomer according to any one of claims 20-26 ;
c) a third nucleic acid encoding a third monomer according to any one of claims 20-26 , respectively. ａ）請求項２６に記載の第１の核酸を含む第１の発現ベクターと、
ｂ）請求項２６に記載の第２の核酸を含む第２の発現ベクターと、
ｃ）請求項２６に記載の第３の核酸を含む第３の発現ベクターとを含む、発現ベクター組成物。 a) a first expression vector comprising the first nucleic acid of claim 26 ;
b) a second expression vector comprising the second nucleic acid of claim 26 ;
c) a third expression vector comprising the third nucleic acid of claim 26 . 請求項２８に記載の発現ベクター組成物を含む、宿主細胞。 A host cell comprising the expression vector composition of claim 28 . 請求項２０～２６のいずれか一項に記載の組成物を生成する方法であって、請求項２９に記載の宿主細胞を、前記組成物が発現する条件下で培養することと、前記組成物を回収することとを含む、方法。 A method of producing the composition of any one of claims 20-26 , comprising culturing a host cell of claim 29 under conditions in which said composition is expressed; and recovering. ａ）配列番号５５３に示されるアミノ酸配列を含む第１のモノマーと、a) a first monomer comprising the amino acid sequence shown in SEQ ID NO:553;
ｂ）配列番号５５４に示されるアミノ酸配列を含む第２のモノマーと、b) a second monomer comprising the amino acid sequence shown in SEQ ID NO:554;
ｃ）配列番号５５５に示されるアミノ酸配列を含む第３のモノマーとを含む、組成物。c) a third monomer comprising the amino acid sequence shown in SEQ ID NO:555. ａ）請求項３１に記載の第１のモノマーをコードする第１の核酸と、a) a first nucleic acid encoding the first monomer of claim 31;
ｂ）請求項３１に記載の第２のモノマーをコードする第２の核酸と、b) a second nucleic acid encoding the second monomer of claim 31;
ｃ）請求項３１に記載の第３のモノマーをコードする第３の核酸とを含む、核酸組成物。c) a third nucleic acid encoding the third monomer of claim 31; ａ）請求項３２に記載の第１の核酸を含む第１の発現ベクターと、a) a first expression vector comprising the first nucleic acid of claim 32;
ｂ）請求項３２に記載の第２の核酸を含む第２の発現ベクターと、b) a second expression vector comprising the second nucleic acid of claim 32;
ｃ）請求項３２に記載の第３の核酸を含む第３の発現ベクターとを含む、発現ベクター組成物。c) a third expression vector comprising the third nucleic acid of claim 32. 請求項３３に記載の発現ベクター組成物を含む、宿主細胞。34. A host cell comprising the expression vector composition of claim 33. 請求項３１に記載の組成物を生成する方法であって、請求項３４に記載の宿主細胞を、前記組成物が発現する条件下で培養することと、前記組成物を回収することとを含む、方法。32. A method of producing the composition of claim 31, comprising culturing the host cell of claim 34 under conditions in which said composition is expressed, and recovering said composition. ,Method.
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Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110214148A (en) 2016-10-14 2019-09-06 Xencor股份有限公司 Bispecific heterodimer fusion protein containing IL-15/IL-15R α Fc fusion protein and PD-1 antibody fragment
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
CN112437777A (en) 2018-04-18 2021-03-02 Xencor股份有限公司 TIM-3 targeting heterodimeric fusion proteins comprising an IL-15/IL-15RA Fc fusion protein and a TIM-3 antigen binding domain
MX2021004059A (en) 2018-10-12 2021-09-23 Xencor Inc Pd-1 targeted il-15/il-15ralpha fc fusion proteins and uses in combination therapies thereof.
CN113438961A (en) 2018-12-20 2021-09-24 Xencor股份有限公司 Targeting heterodimeric Fc fusion proteins containing IL-15/IL-15R α and NKG2D antigen binding domains
TW202128757A (en) 2019-10-11 2021-08-01 美商建南德克公司 Pd-1 targeted il-15/il-15ralpha fc fusion proteins with improved properties
WO2022140797A1 (en) * 2020-12-23 2022-06-30 Immunowake Inc. Immunocytokines and uses thereof
US20220227867A1 (en) * 2020-12-24 2022-07-21 Xencor, Inc. ICOS TARGETED HETERODIMERIC FUSION PROTEINS CONTAINING IL-15/IL-15RA Fc-FUSION PROTEINS AND ICOS ANTIGEN BINDING DOMAINS
CN112851809A (en) * 2021-01-20 2021-05-28 上海交通大学 Antibody for resisting terminal glycosylated protein receptor and application thereof
CA3205670A1 (en) * 2021-01-22 2022-07-28 Kehao Zhao Anti-pd-l1 monoclonal antibodies and fusion proteins with interleukin-15 (il-15), interleukin-15 receptor 15 alpha or interleukin-2
TW202246357A (en) * 2021-03-09 2022-12-01 加拿大商康爾義明生物製藥公司 Bifunctional homodimeric anti-pd-1 and il-15/il-15rα fusion proteins and uses thereof
CA3221886A1 (en) * 2021-06-23 2022-12-29 Cytune Pharma Interleukin-15 based immunocytokines
CN116023503A (en) * 2021-10-25 2023-04-28 上海交通大学 Fusion protein and preparation method and application thereof
WO2023133424A2 (en) * 2022-01-05 2023-07-13 TCR2 Therapeutics Inc. Compositions and methods for tcr reprogramming using fusion proteins and anti-pd-1 fusion peptides
CN115806628A (en) * 2022-08-03 2023-03-17 深圳市先康达生命科学有限公司 Autocrine IL-15 and anti-TIGIT combined fusion protein and application thereof

Family Cites Families (128)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5811097A (en) 1995-07-25 1998-09-22 The Regents Of The University Of California Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling
WO1997041232A1 (en) 1996-04-26 1997-11-06 Beth Israel Deaconess Medical Center Antagonists of interleukin-15
US6451308B1 (en) 1996-04-26 2002-09-17 Beth Israel Deaconess Medical Center Antagonists of interleukin-15
EP0915987A2 (en) 1997-04-21 1999-05-19 Donlar Corporation POLY-($g(a)-L-ASPARTIC ACID), POLY-($g(a)-L-GLUTAMIC ACID) AND COPOLYMERS OF L-ASP AND L-GLU, METHOD FOR THEIR PRODUCTION AND THEIR USE
EP1137436B1 (en) 1998-12-03 2008-06-04 The Regents Of The University Of California Stimulation of T-cells against self antigens using CTLA-4 blocking agents
ES2340745T3 (en) 1998-12-23 2010-06-08 Pfizer Inc. HUMAN MONOCLONAL ANTIBODIES AGAINST CTLA-4.
EE05627B1 (en) 1998-12-23 2013-02-15 Pfizer Inc. Human monoclonal antibodies to CTLA-4
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
MXPA02001417A (en) 1999-08-09 2002-08-12 Lexigen Pharm Corp Multiple cytokine-antibody complexes.
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
US7449443B2 (en) 2000-03-23 2008-11-11 California Institute Of Technology Method for stabilization of proteins using non-natural amino acids
US6586207B2 (en) 2000-05-26 2003-07-01 California Institute Of Technology Overexpression of aminoacyl-tRNA synthetases for efficient production of engineered proteins containing amino acid analogues
ATE395413T1 (en) 2001-12-03 2008-05-15 Amgen Fremont Inc ANTIBODIES CATEGORIZATION BASED ON BINDING PROPERTIES
WO2003073238A2 (en) 2002-02-27 2003-09-04 California Institute Of Technology Computational method for designing enzymes for incorporation of amino acid analogs into proteins
CN101899114A (en) 2002-12-23 2010-12-01 惠氏公司 Anti-PD-1 antibody and uses thereof
JP2006524039A (en) 2003-01-09 2006-10-26 マクロジェニクス，インコーポレーテッド Identification and production of antibody containing mutant Fc region and use thereof
US7960512B2 (en) 2003-01-09 2011-06-14 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
ES2359473T3 (en) 2003-07-21 2011-05-23 Transgene S.A. MULTIFUNCTIONAL CYTOKINS.
WO2005035727A2 (en) 2003-10-09 2005-04-21 Ambrx, Inc. Polymer derivatives
EP1697741A4 (en) 2003-12-04 2008-02-13 Xencor Inc Methods of generating variant proteins with increased host string content and compositions thereof
AU2005211385B2 (en) 2004-02-02 2008-12-11 Ambrx, Inc. Modified human growth hormone polypeptides and their uses
JP5744369B2 (en) 2004-02-27 2015-07-08 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル Specific IL-15 mutant with IL-15 binding site and agonist / antagonist activity for IL15-Rα
EP1737890A2 (en) 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
CU23472A1 (en) 2004-09-17 2009-12-17 Ct Ingenieria Genetica Biotech ANTAGONIST PEPTIDE OF INTERLEUCINE-15
AU2005335714B2 (en) 2004-11-10 2012-07-26 Macrogenics, Inc. Engineering Fc antibody regions to confer effector function
CA2590778A1 (en) 2004-12-13 2006-06-22 Cytos Biotechnology Ag Il-15 antigen arrays and uses thereof
WO2006106905A1 (en) 2005-03-31 2006-10-12 Chugai Seiyaku Kabushiki Kaisha Process for production of polypeptide by regulation of assembly
US20060257361A1 (en) 2005-04-12 2006-11-16 Government Of The Us, As Represented By The Secretary, Department Of Health And Human Services Novel form of interleukin-15, Fc-IL-15, and methods of use
CA2970873C (en) 2005-05-09 2022-05-17 E. R. Squibb & Sons, L.L.C. 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
MX2007014474A (en) 2005-05-17 2008-02-07 Univ Connecticut Compositions and methods for immunomodulation in an organism.
CA2614181A1 (en) 2005-07-01 2007-01-11 Medimmune, Inc. An integrated approach for generating multidomain protein therapeutics
CN104356236B (en) 2005-07-01 2020-07-03 E.R.施贵宝&圣斯有限责任公司 Human monoclonal antibodies to programmed death ligand 1(PD-L1)
EP1777294A1 (en) 2005-10-20 2007-04-25 Institut National De La Sante Et De La Recherche Medicale (Inserm) IL-15Ralpha sushi domain as a selective and potent enhancer of IL-15 action through IL-15Rbeta/gamma, and hyperagonist (IL15Ralpha sushi -IL15) fusion proteins
NZ569541A (en) 2006-01-13 2012-05-25 Us Gov Health & Human Serv Codon optimized IL-15 and IL-15R-alpha genes for expression in mammalian cells
EP1999154B1 (en) 2006-03-24 2012-10-24 Merck Patent GmbH Engineered heterodimeric protein domains
ES2606490T3 (en) 2006-05-08 2017-03-24 Philogen S.P.A. Antibody-directed cytokines for therapy
JP2009541275A (en) 2006-06-22 2009-11-26 ノボ・ノルデイスク・エー／エス Production of bispecific antibodies
US9244059B2 (en) 2007-04-30 2016-01-26 Immutep Parc Club Orsay Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease
EP1987839A1 (en) 2007-04-30 2008-11-05 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease
DK2155789T3 (en) 2007-05-01 2013-10-21 Res Dev Foundation Immunoglobulin Fc libraries
CA2690825C (en) 2007-05-11 2019-02-12 Altor Bioscience Corporation Fusion molecules and il-15 variants
JP6071165B2 (en) 2007-05-31 2017-02-01 ゲンマブ エー／エス Stable IgG4 antibody
EP3222634A1 (en) 2007-06-18 2017-09-27 Merck Sharp & Dohme B.V. Antibodies to human programmed death receptor pd-1
NZ599338A (en) 2007-06-27 2013-11-29 Marinepolymer Tech Inc Complexes of il-15 and il-15ralpha and uses thereof
MX2010002683A (en) 2007-09-14 2010-03-26 Amgen Inc Homogeneous antibody populations.
WO2009089004A1 (en) 2008-01-07 2009-07-16 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
EP2262837A4 (en) 2008-03-12 2011-04-06 Merck Sharp & Dohme Pd-1 binding proteins
US9273136B2 (en) 2008-08-04 2016-03-01 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Fully human anti-human NKG2D monoclonal antibodies
AR072999A1 (en) 2008-08-11 2010-10-06 Medarex Inc HUMAN ANTIBODIES THAT JOIN GEN 3 OF LYMPHOCYTARY ACTIVATION (LAG-3) AND THE USES OF THESE
KR20110074850A (en) 2008-08-25 2011-07-04 앰플리뮨, 인크. Pd-1 antagonists and methods of use thereof
WO2010027423A2 (en) 2008-08-25 2010-03-11 Amplimmune, Inc. Compositions of pd-1 antagonists and methods of use
PE20120341A1 (en) 2008-12-09 2012-04-24 Genentech Inc ANTI-PD-L1 ANTIBODIES AND ITS USE TO IMPROVE T-CELL FUNCTION
US8057507B2 (en) 2009-01-16 2011-11-15 Novate Medical Limited Vascular filter
EP2233500A1 (en) 2009-03-20 2010-09-29 LFB Biotechnologies Optimized Fc variants
EP2448972A4 (en) 2009-06-30 2012-11-28 Res Dev Foundation Immunoglobulin fc polypeptides
JP2012532608A (en) 2009-07-08 2012-12-20 アムジェン インコーポレイテッド Design of stable and non-aggregating antibody Fc molecules through CH3 domain interface manipulation
CA2768965C (en) 2009-08-14 2019-06-04 George N. Pavlakis Use of il-15 to increase thymic output and to treat lymphopenia
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
JP2013511281A (en) 2009-11-23 2013-04-04 アムジェン インコーポレイテッド Monomeric antibody Fc
WO2011066342A2 (en) 2009-11-24 2011-06-03 Amplimmune, Inc. Simultaneous inhibition of pd-l1/pd-l2
KR101573109B1 (en) 2009-11-24 2015-12-01 메디뮨 리미티드 Targeted binding agents against b7-h1
TWI667257B (en) 2010-03-30 2019-08-01 中外製藥股份有限公司 Antibodies with modified affinity to fcrn that promote antigen clearance
SG184427A1 (en) 2010-04-20 2012-11-29 Genmab As Heterodimeric antibody fc-containing proteins and methods for production thereof
WO2011143545A1 (en) 2010-05-14 2011-11-17 Rinat Neuroscience Corporation Heterodimeric proteins and methods for producing and purifying them
CA2806252C (en) 2010-07-29 2019-05-14 Xencor, Inc. Antibodies with modified isoelectric points
WO2012032080A1 (en) 2010-09-07 2012-03-15 F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H Stabilised human fc
KR20140020228A (en) 2010-09-21 2014-02-18 알토 바이오사이언스 코포레이션 Multimeric il-15 soluble fusion molecules and methods of making and using same
JP6167040B2 (en) 2010-11-05 2017-07-19 ザイムワークス，インコーポレイテッド Design of stable heterodimeric antibodies with mutations in the Fc domain
EA201791693A1 (en) 2011-03-25 2018-05-31 Гленмарк Фармасьютикалс С.А. HETERODIMERNY IMMUNOHLOBULINS
EA201892619A1 (en) 2011-04-29 2019-04-30 Роше Гликарт Аг IMMUNOCONJUGATES CONTAINING INTERLEUKIN-2 MUTANT POLYPETIPS
EP2537933A1 (en) 2011-06-24 2012-12-26 Institut National de la Santé et de la Recherche Médicale (INSERM) An IL-15 and IL-15Ralpha sushi domain based immunocytokines
TWI687441B (en) 2011-06-30 2020-03-11 中外製藥股份有限公司 Heterodimerized polypeptide
TWI827333B (en) 2011-09-30 2023-12-21 日商中外製藥股份有限公司 Antigen-binding molecules that promote antigen disappearance
AU2012323287B2 (en) 2011-10-10 2018-02-01 Xencor, Inc. A method for purifying antibodies
LT2785375T (en) 2011-11-28 2020-11-10 Merck Patent Gmbh Anti-pd-l1 antibodies and uses thereof
JP6416628B2 (en) 2012-01-20 2018-10-31 ブイアイビー ブイゼットダブリュＶｉｂ Ｖｚｗ Targeted variant alpha helix bundle cytokine
UY34887A (en) 2012-07-02 2013-12-31 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware OPTIMIZATION OF ANTIBODIES THAT FIX THE LYMPHOCYTE ACTIVATION GEN 3 (LAG-3) AND ITS USES
WO2014079000A1 (en) 2012-11-21 2014-05-30 Wuhan Yzy Biopharma Co., Ltd. Bispecific antibody
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
CN110981964B (en) 2013-01-14 2023-09-15 Xencor股份有限公司 Novel heterodimeric proteins
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
EP3936521A1 (en) 2013-03-15 2022-01-12 Xencor, Inc. Heterodimeric proteins
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
AU2014232416B2 (en) 2013-03-15 2017-09-28 Xencor, Inc. Modulation of T Cells with Bispecific Antibodies and FC Fusions
DK2986312T3 (en) 2013-04-19 2022-02-14 Cytune Pharma CYTOKINE DERIVATIVE TREATMENT WITH REDUCED VASCULAR MEDICAL SYNDROME
JP6329343B2 (en) 2013-06-13 2018-05-23 任天堂株式会社 Image processing system, image processing apparatus, image processing program, and image processing method
US10202433B2 (en) 2013-06-27 2019-02-12 Inserm (Institut National De La Sante Et De La Recherche Medicale) IL-15 mutant polypeptides as IL-15 antagonists and encoding nucleic acids
JP6648890B2 (en) 2013-07-19 2020-02-14 ファイヤーフライ メディカル インコーポレイテッド Movement assist device
KR102457731B1 (en) 2013-08-08 2022-10-21 싸이튠 파마 Combined pharmaceutical composition
US11273204B2 (en) 2013-08-08 2022-03-15 Cytune Pharma IL-15 and IL-15RAPLHA sushi domain based immunocytokines
CA2935599A1 (en) 2014-01-08 2015-07-16 Shanghai Hengrui Pharmaceutical Co., Ltd. Il-15 heterodimeric protein and uses thereof
JOP20200096A1 (en) 2014-01-31 2017-06-16 Children’S Medical Center Corp Antibody molecules to tim-3 and uses thereof
EP2915569A1 (en) 2014-03-03 2015-09-09 Cytune Pharma IL-15/IL-15Ralpha based conjugates purification method
ME03558B (en) 2014-03-14 2020-07-20 Novartis Ag Antibody molecules to lag-3 and uses thereof
KR102497443B1 (en) 2014-03-28 2023-02-08 젠코어 인코포레이티드 Bispecific antibodies that bind to cd38 and cd3
US20150351275A1 (en) 2014-05-30 2015-12-03 Johanson Manufacturing Corporation Thin-Film Radio Frequency Power Terminator
WO2015195163A1 (en) 2014-06-20 2015-12-23 R-Pharm Overseas, Inc. Pd-l1 antagonist fully human antibody
US9925247B2 (en) 2014-06-30 2018-03-27 Altor Bioscience Corporation IL-15-based molecules and methods of use thereof
MX2016017288A (en) 2014-07-16 2017-06-27 Genentech Inc Methods of treating cancer using tigit inhibitors and anti-cancer agents.
US9763705B2 (en) 2014-10-03 2017-09-19 Globus Medical, Inc. Orthopedic stabilization devices and methods for installation thereof
EP3206713A4 (en) 2014-10-14 2018-06-27 Armo Biosciences, Inc. Interleukin-15 compositions and uses thereof
CU20170052A7 (en) 2014-10-14 2017-11-07 Dana Farber Cancer Inst Inc ANTIBODY MOLECULES THAT JOIN PD-L1
US10208120B2 (en) 2014-11-05 2019-02-19 Genentech, Inc. Anti-FGFR2/3 antibodies and methods using same
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
PE20171103A1 (en) 2014-11-26 2017-08-07 Xencor Inc HETERODIMERIC ANTIBODIES THAT BIND TO CD3 AND CD38
US20160176969A1 (en) 2014-11-26 2016-06-23 Xencor, Inc. Heterodimeric antibodies including binding to cd8
CA2967426A1 (en) 2014-11-26 2016-06-02 Xencor, Inc. Heterodimeric antibodies that bind cd3 and tumor antigens
CN106459219B (en) 2014-12-19 2019-01-08 江苏恒瑞医药股份有限公司 Interleukin 15 albumen composition and application thereof
EP3916017A1 (en) * 2014-12-22 2021-12-01 PD-1 Acquisition Group, LLC Anti-pd-1 antibodies
MA40662B1 (en) 2014-12-23 2020-12-31 Bristol Myers Squibb Co Antibodies against tigit
US10227411B2 (en) 2015-03-05 2019-03-12 Xencor, Inc. Modulation of T cells with bispecific antibodies and FC fusions
EP3064507A1 (en) 2015-03-06 2016-09-07 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Fusion proteins comprising a binding protein and an interleukin-15 polypeptide having a reduced affinity for IL15ra and therapeutic uses thereof
TWI715587B (en) 2015-05-28 2021-01-11 美商安可美德藥物股份有限公司 Tigit-binding agents and uses thereof
KR20200087283A (en) 2015-09-25 2020-07-20 제넨테크, 인크. Anti-tigit antibodies and methods of use
CA2999294A1 (en) 2015-09-25 2017-03-30 Altor Bioscience Corporation Interleukin-15 superagonist significantly enhances graft-versus-tumor activity
RU2022104399A (en) 2016-06-14 2022-05-05 Ксенкор, Инк. BISPECIFIC ANTIBODIES-CHECKPOINT INHIBITORS
WO2018007919A1 (en) 2016-07-05 2018-01-11 Novartis Ag New process for early sacubitril intermediates
CN110214148A (en) 2016-10-14 2019-09-06 Xencor股份有限公司 Bispecific heterodimer fusion protein containing IL-15/IL-15R α Fc fusion protein and PD-1 antibody fragment
SG11201903306SA (en) 2016-10-21 2019-05-30 Altor Bioscience Corp Multimeric il-15-based molecules
JP7178999B2 (en) * 2016-11-18 2022-11-28 シムフォゲン・アクティーゼルスカブ Anti-PD-1 Antibodies and Compositions
MA49517A (en) 2017-06-30 2020-05-06 Xencor Inc TARGETED HETERODIMERIC FC FUSION PROTEINS CONTAINING IL-15 / IL-15RA AND AREAS OF ANTIGEN BINDING
EP3749363A1 (en) 2018-02-08 2020-12-16 Amgen Inc. Low ph pharmaceutical antibody formulation
PE20201342A1 (en) 2018-02-28 2020-11-25 Pfizer VARIANTS OF IL-15 AND USES OF THE SAME
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
WO2019204592A1 (en) 2018-04-18 2019-10-24 Xencor, Inc. Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof
MX2021004059A (en) 2018-10-12 2021-09-23 Xencor Inc Pd-1 targeted il-15/il-15ralpha fc fusion proteins and uses in combination therapies thereof.
CN113438961A (en) 2018-12-20 2021-09-24 Xencor股份有限公司 Targeting heterodimeric Fc fusion proteins containing IL-15/IL-15R α and NKG2D antigen binding domains

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