CN114702587A - 用于使蛋白质多聚化的变体结构域及其分离 - Google Patents

用于使蛋白质多聚化的变体结构域及其分离 Download PDF

Info

Publication number
CN114702587A
CN114702587A CN202210393772.0A CN202210393772A CN114702587A CN 114702587 A CN114702587 A CN 114702587A CN 202210393772 A CN202210393772 A CN 202210393772A CN 114702587 A CN114702587 A CN 114702587A
Authority
CN
China
Prior art keywords
region
amino acid
antibody
immunoglobulin
amino acids
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210393772.0A
Other languages
English (en)
Chinese (zh)
Inventor
科内利斯·阿德里安·德克吕夫
彼得·布莱恩·西尔弗曼
理查德·博诺
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merus BV
Original Assignee
Merus BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merus BV filed Critical Merus BV
Publication of CN114702587A publication Critical patent/CN114702587A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/16—Extraction; Separation; Purification by chromatography
    • C07K1/18—Ion-exchange chromatography
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/06—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies from serum
    • C07K16/065—Purification, fragmentation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1282—Clostridium (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/36—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0684—Cells of the urinary tract or kidneys
    • C12N5/0686—Kidney cells
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C07K2317/522—CH1 domain
    • 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
    • C07K2317/524—CH2 domain
    • 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
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/71—Decreased effector function due to an Fc-modification
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Urology & Nephrology (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
CN202210393772.0A 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离 Pending CN114702587A (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP19173633.9 2019-05-09
EP19173633 2019-05-09
CN202080048983.XA CN114430745A (zh) 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离
PCT/NL2020/050298 WO2020226502A2 (en) 2019-05-09 2020-05-08 Variant domains for multimerizing proteins and separation thereof

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN202080048983.XA Division CN114430745A (zh) 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离

Publications (1)

Publication Number Publication Date
CN114702587A true CN114702587A (zh) 2022-07-05

Family

ID=66476558

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202210393772.0A Pending CN114702587A (zh) 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离
CN202080048983.XA Pending CN114430745A (zh) 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202080048983.XA Pending CN114430745A (zh) 2019-05-09 2020-05-08 用于使蛋白质多聚化的变体结构域及其分离

Country Status (16)

Country Link
US (1) US20210054049A1 (https=)
EP (1) EP3966238A2 (https=)
JP (2) JP7760377B2 (https=)
KR (1) KR20220017909A (https=)
CN (2) CN114702587A (https=)
AR (1) AR118898A1 (https=)
AU (2) AU2020268684C1 (https=)
BR (1) BR112021022405A2 (https=)
CA (1) CA3139402A1 (https=)
IL (1) IL287928A (https=)
MA (1) MA55884A (https=)
MX (1) MX2021013646A (https=)
PH (1) PH12021552833A1 (https=)
SG (1) SG11202112399PA (https=)
TW (1) TW202108613A (https=)
WO (1) WO2020226502A2 (https=)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA52212A (fr) * 2018-03-30 2021-02-17 Merus Nv Anticorps multivalent
EP4263597A2 (en) * 2020-12-18 2023-10-25 Kiniksa Pharmaceuticals, Ltd. Protein compositions and methods for producing and using the same
KR20250129720A (ko) 2022-12-27 2025-08-29 메뤼스 엔.페. 이중특이적 단백질을 생성하는 방법
TW202544033A (zh) 2024-04-15 2025-11-16 荷蘭商美勒斯公司 Ｃｄ３結合結構域
WO2025230409A1 (en) 2024-04-30 2025-11-06 Merus N.V. Multispecific antibody-drug conjugates
WO2025230410A1 (en) 2024-04-30 2025-11-06 Merus N.V. Multispecific antibody-drug conjugates
WO2026013015A1 (en) 2024-07-09 2026-01-15 Merus N.V. Multispecific binding moieties comprising calr and cd3 binding domains
WO2026018064A1 (en) 2024-07-16 2026-01-22 Merus N.V. Multispecific multi-drug antibody-drug conjugates

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003092630A2 (en) * 2002-05-06 2003-11-13 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Identification of novel broadly cross-reactive neutralizing human monoclonal antibodies using sequential antigen panning of phage display libraries
WO2004016769A2 (en) * 2002-08-19 2004-02-26 Abgenix, Inc. Antibodies directed to monocyte chemo-attractant protein-1 (mcp-1) and uses thereof
EP2009101A1 (en) * 2006-03-31 2008-12-31 Chugai Seiyaku Kabushiki Kaisha Antibody modification method for purifying bispecific antibody
WO2013055809A1 (en) * 2011-10-10 2013-04-18 Xencor, Inc. A method for purifying antibodies
CN104045714A (zh) * 2013-03-14 2014-09-17 南京金斯瑞生物科技有限公司 曲妥珠单抗突变体IgG及其应用
WO2017218698A1 (en) * 2016-06-15 2017-12-21 Sutro Biopharma, Inc. Antibodies with engineered ch2 domains, compositions thereof and methods of using the same

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4801687A (en) 1986-10-27 1989-01-31 Bioprobe International, Inc. Monoclonal antibody purification process using protein A
US5151504A (en) 1989-11-17 1992-09-29 E. R. Squibb & Sons, Inc. Method for purification of monoclonal antibodies
US7135287B1 (en) * 1999-10-02 2006-11-14 Biosite, Inc. Human antibodies
US6680209B1 (en) * 1999-12-06 2004-01-20 Biosite, Incorporated Human antibodies as diagnostic reagents
DK2314629T4 (da) 2002-07-18 2023-02-06 Merus Nv Rekombinant produktion af blandinger af antistoffer
EP1737890A2 (en) * 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
EP1858925A2 (en) * 2005-01-12 2007-11-28 Xencor, Inc. Antibodies and fc fusion proteins with altered immunogenicity
WO2008027236A2 (en) 2006-08-30 2008-03-06 Genentech, Inc. Multispecific antibodies
ES2595638T3 (es) * 2007-09-26 2017-01-02 Chugai Seiyaku Kabushiki Kaisha Método para modificar el punto isoeléctrico de un anticuerpo mediante la sustitución de aminoácidos en una CDR
US20090162359A1 (en) 2007-12-21 2009-06-25 Christian Klein Bivalent, bispecific antibodies
US8242247B2 (en) 2007-12-21 2012-08-14 Hoffmann-La Roche Inc. Bivalent, bispecific antibodies
US9266967B2 (en) 2007-12-21 2016-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
EP2147594B1 (en) 2008-06-27 2013-11-13 Merus B.V. Antibody producing non-human mammals
MY152068A (en) 2009-03-20 2014-08-15 Genentech Inc Bispecific anti-her antibodies
BR112013023918A2 (pt) * 2011-03-25 2016-12-13 Glenmark Pharmaceuticals Sa imunoglobulina hetero-dimérica ou fragmento hetero-dimérico da mesma, método para produzir uma imunoglobulina hetero-dimérica ou fragmento hetero-dimérico da mesma, método para construir uma interface proteína-proteína de um domínio de uma proteína de múltiplos domínios e uso de um domínio doador de um primeiro e de um segundo membro de uma super-família de imunoglobulina de ocorrência natural
TW201817744A (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
CN109134658B (zh) * 2011-10-31 2022-10-14 中外制药株式会社 控制了重链与轻链的缔合的抗原结合分子
US9248181B2 (en) * 2012-04-20 2016-02-02 Merus B.V. Methods and means for the production of Ig-like molecules
JP6594855B2 (ja) * 2013-03-15 2019-10-23 ゼンコア インコーポレイテッド ヘテロ二量体タンパク質
JP6771385B2 (ja) 2014-02-28 2020-10-21 メルス ナムローゼ フェンノートシャップ 二重特異性抗体および医薬組成物
EP3174897B1 (en) * 2014-07-29 2020-02-12 F.Hoffmann-La Roche Ag Multispecific antibodies
MA41375A (fr) * 2015-01-22 2017-11-28 Lilly Co Eli Anticorps igg bispécifiques et leurs procédés de préparation
MY202858A (en) * 2016-06-10 2024-05-25 Eisai R&D Man Co Ltd Lysine conjugated immunoglobulins
CN118027197A (zh) 2017-07-06 2024-05-14 美勒斯公司 调节由细胞表达的生物活性的抗体
MX2020000055A (es) 2017-07-06 2020-08-06 Merus Nv Anticuerpos biespecificos antiproteina 1 de muerte celular programada (pd-1) -anti inmunoglobulina de celulas t y dominio de mucina que contiene -3 (tim-3).
AU2018296067B2 (en) 2017-07-06 2021-06-10 Merus B.V. Binding molecules that modulate a biological activity expressed by a cell
SG11202001050PA (en) 2017-08-09 2020-03-30 Merus Nv Antibodies that bind egfr and cmet
WO2019148412A1 (en) * 2018-02-01 2019-08-08 Merck Sharp & Dohme Corp. Anti-pd-1/lag3 bispecific antibodies
WO2019148410A1 (en) * 2018-02-01 2019-08-08 Merck Sharp & Dohme Corp. Anti-pd-1 antibodies
MA52212A (fr) 2018-03-30 2021-02-17 Merus Nv Anticorps multivalent
CN110272495A (zh) * 2019-06-11 2019-09-24 南京华岩生物技术有限公司 一种能结合两种抗原的双特异性结合的免疫球蛋白及其用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003092630A2 (en) * 2002-05-06 2003-11-13 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Identification of novel broadly cross-reactive neutralizing human monoclonal antibodies using sequential antigen panning of phage display libraries
WO2004016769A2 (en) * 2002-08-19 2004-02-26 Abgenix, Inc. Antibodies directed to monocyte chemo-attractant protein-1 (mcp-1) and uses thereof
EP2009101A1 (en) * 2006-03-31 2008-12-31 Chugai Seiyaku Kabushiki Kaisha Antibody modification method for purifying bispecific antibody
WO2013055809A1 (en) * 2011-10-10 2013-04-18 Xencor, Inc. A method for purifying antibodies
CN104045714A (zh) * 2013-03-14 2014-09-17 南京金斯瑞生物科技有限公司 曲妥珠单抗突变体IgG及其应用
WO2017218698A1 (en) * 2016-06-15 2017-12-21 Sutro Biopharma, Inc. Antibodies with engineered ch2 domains, compositions thereof and methods of using the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAMILLA DE NARDIS等: "A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1", J. BIOL. CHEM., vol. 292, no. 35, 27 June 2017 (2017-06-27) *

Also Published As

Publication number Publication date
AR118898A1 (es) 2021-11-10
MX2021013646A (es) 2022-01-31
CA3139402A1 (en) 2020-11-12
JP2022534674A (ja) 2022-08-03
TW202108613A (zh) 2021-03-01
AU2020268684B2 (en) 2025-07-03
JP7760377B2 (ja) 2025-10-27
CN114430745A (zh) 2022-05-03
SG11202112399PA (en) 2021-12-30
WO2020226502A9 (en) 2022-03-03
PH12021552833A1 (en) 2023-01-16
KR20220017909A (ko) 2022-02-14
WO2020226502A3 (en) 2021-02-04
US20210054049A1 (en) 2021-02-25
BR112021022405A2 (pt) 2022-04-19
MA55884A (fr) 2022-03-16
AU2020268684C1 (en) 2026-04-02
IL287928A (en) 2022-01-01
AU2025208511A1 (en) 2025-08-14
JP2025120179A (ja) 2025-08-15
NZ782091A (en) 2025-08-29
EP3966238A2 (en) 2022-03-16
WO2020226502A2 (en) 2020-11-12
AU2020268684A1 (en) 2021-12-09

Similar Documents

Publication Publication Date Title
CN114702587A (zh) 用于使蛋白质多聚化的变体结构域及其分离
JP6904902B2 (ja) ドメイン交換抗体
JP2024056829A (ja) Ｃｈ３ドメインに基づくヘテロダイマー分子、その調製方法及び用途
KR102269650B1 (ko) Ig-유사 분자의 제조방법 및 제조수단
CN111936514A (zh) 多价抗体
CN109415435B (zh) 新型抗体形式
TW202208425A (zh) 製造類ｉｇ分子之方法及手段
TW202346337A (zh) Ilt3及cd3結合劑以及其使用方法
JP2024507693A (ja) 二重特異性抗体
JP2024507693A5 (https=)
JP7734075B2 (ja) 疑似ｆａｂベースの多重特異性結合タンパク質
Jung et al. Engineering an aglycosylated Fc variant for enhanced FcγRI engagement and pH-dependent human FcRn binding
JP2024547221A (ja) 抗イヌインターロイキン－３１－受容体ａ（ｉｌ－３１ｒａ）抗体及びその使用
KR20210126699A (ko) 2개 이상의 항체를 포함하는 조성물의 제조
KR20260047593A (ko) 최적화된 Fc 분자
CN114409798A (zh) 制备包含两种或更多种抗体的组合物
CN113439090A (zh) 制备包含两种或更多种抗体的组合物

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination