[go: up one dir, main page]

PE20190418A1 - Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos - Google Patents

Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos

Info

Publication number
PE20190418A1
PE20190418A1 PE2019000055A PE2019000055A PE20190418A1 PE 20190418 A1 PE20190418 A1 PE 20190418A1 PE 2019000055 A PE2019000055 A PE 2019000055A PE 2019000055 A PE2019000055 A PE 2019000055A PE 20190418 A1 PE20190418 A1 PE 20190418A1
Authority
PE
Peru
Prior art keywords
tim3
binding
antigen
light chain
binds
Prior art date
Application number
PE2019000055A
Other languages
English (en)
Inventor
Xiao Min Schebye
Mark J Selby
Michelle Minhua Han
Christine BEE
Andy X Deng
Anan Chuntharapai
Brigitte Devaux
Huiming Li
Paul O Sherppard
Alan J Korman
Daniel F Ardourel
Ekaterina DEYANOVA
Richard Huang
Guodong Chen
Michelle Kuhne
Hong-An Truong
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of PE20190418A1 publication Critical patent/PE20190418A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], 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
    • C07K16/2818Immunoglobulins [IGs], 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 CD28 or CD152
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], 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
    • C07K16/2827Immunoglobulins [IGs], 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3046Stomach, Intestines
    • G01N33/5759
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507Comprising a combination of two or more separate antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/40Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41Glycosylation, sialylation, or fucosylation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55Fab or Fab'
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/71Decreased effector function due to an Fc-modification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732Antibody-dependent cellular cytotoxicity [ADCC]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734Complement-dependent cytotoxicity [CDC]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/74Inducing cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Peptides Or Proteins (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Hospice & Palliative Care (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Referido a un anticuerpo aislado o una porcion de union al antigeno del mismo, se une a la proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos T (TIM3), con propiedades como: union a TIM3 humana soluble, union a TIM3 humana unida a la membrana, induce o mejora la activacion de linfocitos T; y opcionalmente se une a TIM3 de mono cinomologo soluble; y se une a TIM3 de mono cinomologo de membrana. Tambien se refiere a polinucleotidos que codifican las regiones de las cadenas pesada y/o ligera de los anticuerpos, o porciones de union al antigeno de los mismos, y vectores que comprenden los polinucleotidos que codifican las regiones de las cadenas pesada y/o ligera de los anticuerpos, o porciones de union al antigeno de los mismos. Estos se caracterizan porque el CDR3 de la cadena pesada comprende una secuencia de aminoacidos seleccionados de: SEQ ID NO: 53, 54, 55, entre otros; CDR1 de la cadena ligera comprende X1, X2, X3, X4, X5 y X6, y en donde X1 es S o ninguno; X2 es R o ninguno; X3 es S, R o D, X4 es Y o H; X5 es W o M, y X6 es G, N, S o H. Ademas, se caracteriza por estimular la respuesta inmunitaria antitumoral, y su uso aplicaciones terapeuticas, tales como el tratamiento del cancer.
PE2019000055A 2016-07-14 2017-07-13 Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos PE20190418A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662362541P 2016-07-14 2016-07-14
US201762459499P 2017-02-15 2017-02-15

Publications (1)

Publication Number Publication Date
PE20190418A1 true PE20190418A1 (es) 2019-03-19

Family

ID=59383664

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2019000055A PE20190418A1 (es) 2016-07-14 2017-07-13 Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos

Country Status (19)

Country Link
US (7) US10077306B2 (es)
EP (2) EP4512829A3 (es)
JP (3) JP7027401B2 (es)
KR (3) KR102493282B1 (es)
CN (2) CN109757103B (es)
AU (1) AU2017297506A1 (es)
BR (1) BR112019000431A2 (es)
CA (1) CA3030765A1 (es)
CL (2) CL2019000100A1 (es)
CO (1) CO2019000372A2 (es)
ES (1) ES3005961T3 (es)
IL (1) IL264011A (es)
MX (1) MX2019000443A (es)
MY (1) MY200602A (es)
PE (1) PE20190418A1 (es)
SG (2) SG10201911972QA (es)
TW (2) TW202244061A (es)
UY (1) UY37325A (es)
WO (1) WO2018013818A2 (es)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3274370T3 (da) 2015-03-23 2020-02-17 Bayer Pharma AG Anti-ceacam6-antistoffer og anvendelser deraf
MD3443009T2 (ro) 2016-04-12 2022-02-28 Symphogen As Anticorpi anti-TIM-3 și compoziții
EP3458485B1 (en) 2016-05-19 2021-12-29 The General Hospital Corporation Tethered interleukin-2 to its receptor il-2rbeta, a platform to enhance natural killer and regulatory t cell activity
MX2019000443A (es) 2016-07-14 2019-06-20 Squibb Bristol Myers Co Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos.
TWI665216B (zh) * 2016-12-29 2019-07-11 財團法人生物技術開發中心 抗人類tim-3抗體及其使用方法
CA3058175A1 (en) 2017-03-31 2018-10-04 Bristol-Myers Squibb Company Methods of treating tumor
CA3058960C (en) 2017-04-05 2023-08-29 Symphogen A/S Combination therapies targeting pd-1, tim-3, and lag-3
EP4098662A1 (en) 2017-05-25 2022-12-07 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
US11787859B2 (en) 2017-08-28 2023-10-17 Bristol-Myers Squibb Company TIM-3 antagonists for the treatment and diagnosis of cancers
JP2020536894A (ja) 2017-10-15 2020-12-17 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 腫瘍処置法
EP3737700A1 (en) 2018-01-12 2020-11-18 Bristol-Myers Squibb Company Antibodies against tim3 and uses thereof
WO2019143607A1 (en) * 2018-01-16 2019-07-25 Bristol-Myers Squibb Company Methods of treating cancer with antibodies against tim3
CN110144011B (zh) * 2018-02-14 2020-06-23 上海洛启生物医药技术有限公司 针对t淋巴细胞免疫球蛋白黏蛋白3的单域抗体
CN110272489B (zh) * 2018-03-15 2023-08-22 上海健信生物医药科技有限公司 一种针对tim-3的全人源化抗体分子, 抗原结合片段及其医药用途
EP3768725A4 (en) 2018-03-20 2021-06-02 Wuxi Biologics Ireland Limited NEW ANTI-TIM-3 ANTIBODIES
WO2019183551A1 (en) 2018-03-23 2019-09-26 Bristol-Myers Squibb Company Antibodies against mica and/or micb and uses thereof
CN111918873B (zh) 2018-03-27 2025-06-24 百时美施贵宝公司 使用紫外线信号实时监测滴度
EP3774911A1 (en) 2018-03-30 2021-02-17 Bristol-Myers Squibb Company Methods of treating tumor
MA52190A (fr) 2018-04-02 2021-02-17 Bristol Myers Squibb Co Anticorps anti-trem-1 et utilisations associées
US11807683B2 (en) 2018-04-12 2023-11-07 Nanjing Leads Biolabs Co., Ltd. Antibody binding TIM-3 and use thereof
CA3104530A1 (en) 2018-07-09 2020-01-16 Five Prime Therapeutics, Inc. Antibodies binding to ilt4
CN118667020A (zh) * 2018-08-21 2024-09-20 阿尔伯特爱因斯坦医学院 针对人tim-3的单克隆抗体
CN109180816B (zh) * 2018-09-17 2021-07-30 北京智仁美博生物科技有限公司 抗人tim-3抗体及其用途
WO2020093023A1 (en) * 2018-11-01 2020-05-07 Merck Patent Gmbh Anti-tim-3 antibodies
CN113348177A (zh) 2018-11-28 2021-09-03 百时美施贵宝公司 包含经修饰的重链恒定区的抗体
CN111253485A (zh) * 2018-11-30 2020-06-09 上海开拓者生物医药有限公司 抗人tim-3单克隆抗体及其应用
EP3894442A4 (en) * 2018-12-12 2022-08-10 Wuxi Biologics Ireland Limited ANTI-TIM-3 ANTIBODIES AND USES THEREOF
SG11202104518WA (en) 2018-12-19 2021-05-28 Bayer Ag Pharmaceutical combination of anti ceacam6 and tim3 antibodies
CA3127236A1 (en) 2019-01-22 2020-07-30 Bristol-Myers Squibb Company Antibodies against il-7r alpha subunit and uses thereof
US20220135619A1 (en) 2019-02-24 2022-05-05 Bristol-Myers Squibb Company Methods of isolating a protein
US20200318200A1 (en) 2019-04-02 2020-10-08 The Brigham And Women's Hospital, Inc. Methods for Identifying Progression of a Primary Melanoma
JP7645198B2 (ja) 2019-05-23 2025-03-13 ブリストル-マイヤーズ スクイブ カンパニー 細胞培養培地をモニターする方法
JP2022534981A (ja) 2019-05-30 2022-08-04 ブリストル-マイヤーズ スクイブ カンパニー 細胞局在化シグネチャーおよび組み合わせ治療
EP3976832A1 (en) 2019-05-30 2022-04-06 Bristol-Myers Squibb Company Methods of identifying a subject suitable for an immuno-oncology (i-o) therapy
KR20220016156A (ko) 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 면역-종양학 요법에의 적합성을 위한 다종양 유전자 시그너쳐
CN110517726B (zh) * 2019-07-15 2023-07-04 西安电子科技大学 一种基于高通量测序数据的微生物成分及浓度检测方法
JP2022548627A (ja) * 2019-09-16 2022-11-21 ノバルティス アーゲー 骨髄線維症の治療のための、高親和性のリガンドを遮断するヒト化抗t細胞免疫グロブリンドメイン及びムチンドメイン3(tim-3)igg4抗体の使用
CN113166264B (zh) * 2019-09-19 2024-02-27 上药生物治疗(香港)有限公司 一种分离的抗原结合蛋白及其用途
WO2021055994A1 (en) 2019-09-22 2021-03-25 Bristol-Myers Squibb Company Quantitative spatial profiling for lag-3 antagonist therapy
CN113214396B (zh) * 2020-07-31 2022-04-19 北京市神经外科研究所 抗tim3的单链抗体及其在制备治疗肿瘤的药物中的用途
PE20230983A1 (es) * 2020-08-07 2023-06-21 Genentech Inc Proteinas de fusion del ligando para flt3 y metodos de uso
AU2021334361A1 (en) 2020-08-31 2023-05-11 Bristol-Myers Squibb Company Cell localization signature and immunotherapy
EP4225770A1 (en) 2020-10-05 2023-08-16 Bristol-Myers Squibb Company Methods for concentrating proteins
CN114539357B (zh) * 2020-11-27 2024-07-30 广州汉腾生物科技有限公司 信号肽在表达glp-1融合蛋白中的应用
WO2022120179A1 (en) 2020-12-03 2022-06-09 Bristol-Myers Squibb Company Multi-tumor gene signatures and uses thereof
TW202237638A (zh) * 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 烏苷酸環化酶c(gcc)抗原結合劑之組成物及其使用方法
DK4267105T3 (da) 2020-12-28 2025-05-19 Bristol Myers Squibb Co Antistofsammensætninger og fremgangsmåder til anvendelse deraf
US20220233689A1 (en) 2020-12-28 2022-07-28 Bristol-Myers Squibb Company Methods of treating tumors
US20240376224A1 (en) 2021-04-02 2024-11-14 The Regents Of The University Of California Antibodies against cleaved cdcp1 and uses thereof
CN117377692A (zh) 2021-04-23 2024-01-09 苏州逻晟生物医药有限公司 Tim-3-靶向抗体及其用途
CA3230117A1 (en) 2021-09-02 2023-03-09 Mark Trautwein Anti-cecam6 antibodies with reduced side-effects
EP4456907A1 (en) 2021-12-30 2024-11-06 NeoImmuneTech, Inc. Method of treating a tumor with a combination of il-7 protein and vegf antagonist
WO2023173011A1 (en) 2022-03-09 2023-09-14 Bristol-Myers Squibb Company Transient expression of therapeutic proteins
EP4493575A1 (en) 2022-03-18 2025-01-22 Bristol-Myers Squibb Company Methods of isolating polypeptides
CN114632156B (zh) * 2022-05-17 2022-08-16 中国人民解放军军事科学院军事医学研究院 Tim-3在预防、治疗或减轻疼痛中的应用
IL317319A (en) 2022-06-02 2025-01-01 Bristol Myers Squibb Co Antibody compounds and methods of using them
EP4615485A1 (en) 2022-11-07 2025-09-17 NeoImmuneTech, Inc. Methods of treating a tumor with an unmethylated mgmt promoter
EP4658687A1 (en) 2023-01-31 2025-12-10 University of Rochester Immune checkpoint blockade therapy for treating staphylococcus aureus infections
CN118496354A (zh) * 2023-02-15 2024-08-16 三优生物医药(上海)有限公司 包含共同轻链的抗体库、其制备方法及其用途
WO2024196952A1 (en) 2023-03-20 2024-09-26 Bristol-Myers Squibb Company Tumor subtype assessment for cancer therapy
WO2025038763A1 (en) 2023-08-15 2025-02-20 Bristol-Myers Squibb Company Ceramic hydroxyapatite chromatography flow through method
US20250215087A1 (en) 2023-12-29 2025-07-03 Bristol-Myers Squibb Company Combination therapy of kras inhibitor and treg depleting agent
EP4658320A1 (en) 2024-02-27 2025-12-10 Bristol-Myers Squibb Company Anti-ceacam5 antibody drug conjugates
WO2025184208A1 (en) 2024-02-27 2025-09-04 Bristol-Myers Squibb Company Anti-ceacam5 antibodies and uses thereof

Family Cites Families (250)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4634665A (en) 1980-02-25 1987-01-06 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US5179017A (en) 1980-02-25 1993-01-12 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
DE3572982D1 (en) 1984-03-06 1989-10-19 Takeda Chemical Industries Ltd Chemically modified lymphokine and production thereof
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
GB8601597D0 (en) 1986-01-23 1986-02-26 Wilson R H Nucleotide sequences
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US4881175A (en) 1986-09-02 1989-11-14 Genex Corporation Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US5260203A (en) 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
EP0307434B2 (en) 1987-03-18 1998-07-29 Scotgen Biopharmaceuticals, Inc. Altered antibodies
US5013653A (en) 1987-03-20 1991-05-07 Creative Biomolecules, Inc. Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage
US5132405A (en) 1987-05-21 1992-07-21 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US5091513A (en) 1987-05-21 1992-02-25 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
JPH02500329A (ja) 1987-05-21 1990-02-08 クリエイテイブ・バイオマリキユールズ・インコーポレーテツド ターゲット化多機能蛋白質
US5258498A (en) 1987-05-21 1993-11-02 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
GB8717430D0 (en) 1987-07-23 1987-08-26 Celltech Ltd Recombinant dna product
US5677425A (en) 1987-09-04 1997-10-14 Celltech Therapeutics Limited Recombinant antibody
GB8809129D0 (en) 1988-04-18 1988-05-18 Celltech Ltd Recombinant dna methods vectors and host cells
US5476996A (en) 1988-06-14 1995-12-19 Lidak Pharmaceuticals Human immune system in non-human animal
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
EP0401384B1 (en) 1988-12-22 1996-03-13 Kirin-Amgen, Inc. Chemically modified granulocyte colony stimulating factor
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
ES2284161T3 (es) 1990-01-12 2007-11-01 Amgen Fremont Inc. Generacion de anticuerpos xenogenicos.
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
DE69133476T2 (de) 1990-08-29 2006-01-05 GenPharm International, Inc., Palo Alto Transgene Mäuse fähig zur Produktion heterologer Antikörper
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
WO1993012227A1 (en) 1991-12-17 1993-06-24 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
ES2341666T3 (es) 1991-12-02 2010-06-24 Medimmune Limited Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos.
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
CA2118508A1 (en) 1992-04-24 1993-11-11 Elizabeth S. Ward Recombinant production of immunoglobulin-like domains in prokaryotic cells
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
JPH08511420A (ja) 1993-06-16 1996-12-03 セルテック・セラピューテイクス・リミテッド 抗 体
WO1995017886A1 (en) 1993-12-27 1995-07-06 Baxter International Inc. Water soluble non-immunogenic polyamide cross-linking agents
US6066322A (en) 1995-03-03 2000-05-23 Millennium Pharmaceuticals, Inc. Methods for the treatment of immune disorders
US6121022A (en) 1995-04-14 2000-09-19 Genentech, Inc. Altered polypeptides with increased half-life
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
US6410690B1 (en) 1995-06-07 2002-06-25 Medarex, Inc. Therapeutic compounds comprised of anti-Fc receptor antibodies
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
EP0904107B1 (en) 1996-03-18 2004-10-20 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US5922845A (en) 1996-07-11 1999-07-13 Medarex, Inc. Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
US6277375B1 (en) 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
AU6703198A (en) 1997-03-21 1998-10-20 Brigham And Women's Hospital Immunotherapeutic ctla-4 binding peptides
DE69833755T2 (de) 1997-05-21 2006-12-28 Biovation Ltd. Verfahren zur herstellung von nicht-immunogenen proteinen
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
DK1071700T3 (da) 1998-04-20 2010-06-07 Glycart Biotechnology Ag Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet
CZ303703B6 (cs) 1998-12-23 2013-03-20 Pfizer Inc. Monoklonální protilátka nebo její antigen-vázající fragment, farmaceutická kompozice obsahující tuto protilátku nebo fragment, bunecná linie produkující tuto protilátku nebo fragment, zpusob prípravy této protilátky, izolovaná nukleová kyselina kóduj
KR100887482B1 (ko) 1999-01-15 2009-03-10 제넨테크, 인크. 효과기 기능이 변화된 폴리펩티드 변이체
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
ES2569919T3 (es) 1999-04-09 2016-05-13 Kyowa Hakko Kirin Co., Ltd. Procedimiento para controlar la actividad de una molécula inmunofuncional
EP1074563A1 (en) 1999-08-02 2001-02-07 F. Hoffmann-La Roche Ag Chimeric polypeptides enhancing dimer formation through electrostatic interactions and disulfide bond, method for production and uses thereof
AU784062B2 (en) 1999-08-23 2006-01-19 Dana-Farber Cancer Institute, Inc. Novel B7-4 molecules and uses therefor
EP1212422B1 (en) 1999-08-24 2007-02-21 Medarex, Inc. Human ctla-4 antibodies and their uses
ES2629683T3 (es) 1999-11-30 2017-08-14 Mayo Foundation For Medical Education And Research B7-H1, una nueva molécula inmunorreguladora
WO2001058957A2 (en) 2000-02-11 2001-08-16 Lexigen Pharmaceuticals Corp. Enhancing the circulating half-life of antibody-based fusion proteins
US6725230B2 (en) 2000-07-18 2004-04-20 Aegis Analytical Corporation System, method and computer program for assembling process data of multi-database origins using a hierarchical display
IL155977A0 (en) 2000-11-30 2003-12-23 Medarex Inc Transgenic transchromosomal rodents for making human antibodies
JP2004532038A (ja) 2001-05-17 2004-10-21 ディヴァーサ コーポレイション 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法
US7129261B2 (en) 2001-05-31 2006-10-31 Medarex, Inc. Cytotoxic agents
US7838220B2 (en) 2001-06-29 2010-11-23 The Board Of Trustees Of The Leland Stanford Junior University T cell regulatory genes associated with immune disease
US8709412B2 (en) 2001-06-29 2014-04-29 The Board Of Trustees Of The Leland Stanford Junior University Modulation of TIM receptor activity in combination with cytoreductive therapy
JP4572276B2 (ja) 2001-06-29 2010-11-04 ザ ボード オブ トラスティーズ オブ ザ リランド スタンフォード ジュニア ユニヴァーシティ T細胞調節遺伝子およびその使用方法
PL213948B1 (pl) 2001-10-25 2013-05-31 Genentech Inc Kompozycje zawierajace glikoproteine, czasteczka kwasu nukleinowego kodujaca te glikoproteine, komórka gospodarza, sposób wytwarzania glikoproteiny, kompozycja do zastosowania do leczenia, zastosowanie kompozycji i zestaw zawierajacy kompozycje
EP3020413A1 (en) 2002-01-30 2016-05-18 The Brigham and Women's Hospital, Inc. Compositions and methods related to TIM-3, a TH1-specific cell surface molecule
US20040002587A1 (en) 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
WO2003074679A2 (en) 2002-03-01 2003-09-12 Xencor Antibody optimization
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US20040014194A1 (en) 2002-03-27 2004-01-22 Schering Corporation Beta-secretase crystals and methods for preparing and using the same
IL149820A0 (en) 2002-05-23 2002-11-10 Curetech Ltd Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency
PT1534335E (pt) 2002-08-14 2012-02-28 Macrogenics Inc Anticorpos específicos de fcγriib e processos para a sua utilização
EP3321282A1 (en) 2002-09-27 2018-05-16 Xencor, Inc. Optimized fc variants and methods for their generation
JP4768439B2 (ja) 2002-10-15 2011-09-07 アボット バイオセラピューティクス コーポレイション 変異誘発による抗体のFcRn結合親和力又は血清半減期の改変
US7355008B2 (en) 2003-01-09 2008-04-08 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
CN1753693A (zh) 2003-02-13 2006-03-29 辉瑞产品公司 抗-胰岛素样生长因子ⅰ受体抗体的用途
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
WO2005044853A2 (en) 2003-11-01 2005-05-19 Genentech, Inc. Anti-vegf antibodies
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
EP1685159B1 (en) 2003-10-03 2012-08-01 Brigham & Women's Hospital Tim-3 polypeptides
GB0324368D0 (en) 2003-10-17 2003-11-19 Univ Cambridge Tech Polypeptides including modified constant regions
WO2005070963A1 (en) 2004-01-12 2005-08-04 Applied Molecular Evolution, Inc Fc region variants
EP1737890A2 (en) 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
BRPI0509139A (pt) 2004-03-24 2007-08-28 Telos Fharmaceuticals Inc composição, e, método de estimulação de uma resposta imune em um indivìduo, de tratamento profilático de uma doença, de melhoramento de um sinal ou sintoma associado com uma doença, de alvejamento de um tumor, de inibição do crescimento de tumor, e de detecção de um tumor
NZ550934A (en) 2004-05-19 2010-05-28 Medarex Inc Chemical linkers and conjugates thereof
US7691962B2 (en) 2004-05-19 2010-04-06 Medarex, Inc. Chemical linkers and conjugates thereof
DK2213683T3 (da) 2004-08-04 2013-09-02 Mentrik Biotech Llc VARIANT-Fc-REGIONER
TWI380996B (zh) 2004-09-17 2013-01-01 Hoffmann La Roche 抗ox40l抗體
EA010654B1 (ru) 2004-11-23 2008-10-30 Пи Ай Пи Ко., Лтд. Вмонтированная в стену распределительная коробка водоснабжения
EP1866338B1 (en) 2005-03-23 2016-09-21 Genmab A/S Antibodies against cd38 for treatment of multiple myeloma
AU2006230099B2 (en) 2005-03-25 2012-04-19 Gitr, Inc. GITR binding molecules and uses therefor
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
AU2006244885B2 (en) 2005-05-09 2011-03-31 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
PL1879573T3 (pl) 2005-05-10 2013-05-31 Incyte Holdings Corp Modulatory 2,3-dioksygenazy indoloaminy i sposoby ich zastosowania
CN101248089A (zh) 2005-07-01 2008-08-20 米德列斯公司 抗程序性死亡配体1(pd-l1)的人单克隆抗体
ES2416136T3 (es) 2005-09-26 2013-07-30 Medarex, Inc. Conjugados de anticuerpo-fármaco y su uso
DK1940789T3 (da) 2005-10-26 2012-03-19 Medarex Inc Fremgangsmåder og forbindelser til fremstilling af CC-1065-analoger
WO2007059404A2 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
ES2540561T3 (es) 2005-12-20 2015-07-10 Incyte Corporation N-hidroxiamidinoheterociclos como moduladores de indolamina 2,3-dioxigenasa
US20080125470A1 (en) 2006-09-19 2008-05-29 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
CL2007002650A1 (es) 2006-09-19 2008-02-08 Incyte Corp Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras.
US20100061992A1 (en) 2006-11-15 2010-03-11 The Brigham And Women's Hospital, Inc. Therapeutic uses of tim-3 modulators
TWI412367B (zh) 2006-12-28 2013-10-21 Medarex Llc 化學鏈接劑與可裂解基質以及其之綴合物
JP2010519310A (ja) 2007-02-21 2010-06-03 メダレックス インコーポレイテッド 単一のアミノ酸を有する化学リンカーおよびその複合体
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
JP2008278814A (ja) 2007-05-11 2008-11-20 Igaku Seibutsugaku Kenkyusho:Kk アゴニスティック抗ヒトgitr抗体による免疫制御の解除とその応用
WO2009014708A2 (en) 2007-07-23 2009-01-29 Cell Genesys, Inc. Pd-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof
DE102007036200A1 (de) 2007-08-02 2009-02-05 Knorr-Bremse Systeme für Nutzfahrzeuge GmbH Induktiver Weg- oder Drehwinkelsensor mit zwischen zwei Spulen angeordnetem Abschirmblech
EP2044949A1 (en) 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
US9416165B2 (en) 2007-10-26 2016-08-16 The Regents Of The University Of California Methods of inhibiting viral replication and improving T cell function employing soluble Tim-3 inhibitors
JP2011503000A (ja) 2007-11-02 2011-01-27 セントコア・オーソ・バイオテツク・インコーポレーテツド 半合成GLP−1ペプチド−Fc融合コンストラクト、その方法及び使用
WO2009073620A2 (en) 2007-11-30 2009-06-11 Newlink Genetics Ido inhibitors
EP2252319A2 (en) 2008-01-29 2010-11-24 The Brigham and Women's Hospital, Inc. Methods for modulating a population of myeloid-derived suppressor cells and uses thereof
US8168757B2 (en) 2008-03-12 2012-05-01 Merck Sharp & Dohme Corp. PD-1 binding proteins
WO2009120899A2 (en) 2008-03-26 2009-10-01 Cellerant Therapeutics, Inc. G coupled protein receptors associated with myelogenous haematological proliferative disorders and uses thereof
KR20110013421A (ko) 2008-05-29 2011-02-09 생-고뱅 생트레 드 레체르체 에 데투드 유로삐엔 알루미늄 티타네이트 함유 다공질 구조물
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
HUE034832T2 (hu) 2008-12-09 2021-12-28 Hoffmann La Roche Anti-PD-L1 antitestek és alkalmazásuk T-sejt-funkció fokozására
JP5569946B2 (ja) 2009-01-26 2014-08-13 国立大学法人 岡山大学 免疫抑制剤および自己免疫疾患の予防および治療剤
JP5748653B2 (ja) 2009-04-10 2015-07-15 協和発酵キリン株式会社 抗tim−3抗体を用いた血液腫瘍治療法
US20110007023A1 (en) 2009-07-09 2011-01-13 Sony Ericsson Mobile Communications Ab Display device, touch screen device comprising the display device, mobile device and method for sensing a force on a display device
AU2010289677B2 (en) 2009-09-03 2014-07-31 Merck Sharp & Dohme Llc Anti-GITR antibodies
WO2011056652A1 (en) 2009-10-28 2011-05-12 Newlink Genetics Imidazole derivatives as ido inhibitors
SI3279215T1 (sl) 2009-11-24 2020-07-31 Medimmune Limited Usmerjena vezavna sredstva proti B7-H1
RU2565541C2 (ru) 2009-12-10 2015-10-20 Ф.Хоффманн-Ля Рош Аг Антитела, связывающиеся преимущественно с внеклеточным доменом 4 человеческого csf-1r, и их применение
CN110079550A (zh) 2009-12-10 2019-08-02 瑞泽恩制药公司 生产重链抗体的小鼠
JP5955781B2 (ja) 2010-02-08 2016-07-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. 共通の軽鎖のマウス
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
HUE045487T2 (hu) 2010-03-04 2019-12-30 Macrogenics Inc B7-H3-ra reaktív antitestek, immunológiailag aktív fragmenseik és alkalmazásaik
US9221910B2 (en) 2010-03-05 2015-12-29 Hoffmann-La Roche Inc. Antibodies against human CSF-1R
CA2789076C (en) 2010-03-05 2017-11-21 F. Hoffmann-La Roche Ag Antibodies against human colony stimulating factor-1 receptor and uses thereof
CN107011438B (zh) 2010-05-04 2020-11-20 戊瑞治疗有限公司 结合csf1r的抗体
KR101846590B1 (ko) 2010-06-11 2018-04-09 교와 핫꼬 기린 가부시키가이샤 항 tim-3 항체
WO2011159877A2 (en) 2010-06-18 2011-12-22 The Brigham And Women's Hospital, Inc. Bi-specific antibodies against tim-3 and pd-1 for immunotherapy in chronic immune conditions
MY195217A (en) 2010-06-22 2023-01-11 Regeneron Pharma MICE Expressing An Immunoglobulin Hybrid Light Chain
US8907053B2 (en) 2010-06-25 2014-12-09 Aurigene Discovery Technologies Limited Immunosuppression modulating compounds
JP6105470B2 (ja) 2010-09-09 2017-03-29 ファイザー・インク 4−1bb結合分子
GB201016266D0 (en) 2010-09-28 2010-11-10 Fujifilm Mfg Europe Bv Polymers and membranes
HRP20180421T1 (hr) * 2010-11-17 2018-04-20 Chugai Seiyaku Kabushiki Kaisha Višestruko specifične molekule za vezanje na antigen koje imaju alternativnu funkciju u odnosu na funkciju faktora viii zgrušavanja krvi
NO2694640T3 (es) 2011-04-15 2018-03-17
PL2699264T3 (pl) 2011-04-20 2018-08-31 Medimmune, Llc Przeciwciała i inne cząsteczki wiążące B7-H1 i PD-1
DK2714738T3 (en) * 2011-05-24 2019-01-28 Zyngenia Inc MULTIVALENT AND MONOVALENT MULTISPECIFIC COMPLEXES AND THEIR APPLICATIONS
WO2013006490A2 (en) 2011-07-01 2013-01-10 Cellerant Therapeutics, Inc. Antibodies that specifically bind to tim3
US8790651B2 (en) * 2011-07-21 2014-07-29 Zoetis Llc Interleukin-31 monoclonal antibody
BR112014012819B1 (pt) 2011-11-28 2022-08-16 Merck Patent Gmbh Anticorpo anti-pd-l1 ou fragmento de ligação ao antígeno do mesmo e composição
CN102492038B (zh) 2011-12-09 2014-05-28 中国人民解放军军事医学科学院基础医学研究所 抗人Tim-3的中和性单克隆抗体L3D及其用途
CN104159921B (zh) 2011-12-15 2018-05-04 霍夫曼-拉罗奇有限公司 针对人csf-1r的抗体及其用途
EP2812355A4 (en) 2012-02-06 2016-03-02 Hoffmann La Roche COMPOSITIONS AND METHODS OF USE OF CSF1R INHIBITORS
MX2014010016A (es) 2012-02-21 2015-06-05 Inst Nat Sante Rech Med Receptores de mucina de inmunoglobulina de celula t (tim) como co-factores de entrada del virus.
MX2014010015A (es) 2012-02-21 2015-06-05 Inst Nat Sante Rech Med Receptores de tyro3/axl/mer (tam) como cofactores de entrada de virus.
AR090263A1 (es) 2012-03-08 2014-10-29 Hoffmann La Roche Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma
JP2015513912A (ja) 2012-04-02 2015-05-18 モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. タンパク質の産生のための修飾ポリヌクレオチド
EP3539984A1 (en) 2012-05-11 2019-09-18 Five Prime Therapeutics, Inc. Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r)
CA2873402C (en) 2012-05-15 2023-10-24 Bristol-Myers Squibb Company Cancer immunotherapy by disrupting pd-1/pd-l1 signaling
UY34887A (es) 2012-07-02 2013-12-31 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos
JP2015525781A (ja) 2012-07-31 2015-09-07 ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドThe Brigham and Women’s Hospital, Inc. 免疫応答の調節
TWI713436B (zh) 2012-08-31 2020-12-21 美商戊瑞治療有限公司 用結合群落刺激因子1受體(csf1r)之抗體治療病狀之方法
CA2907181C (en) * 2013-03-15 2023-10-17 Viktor Roschke Multivalent and monovalent multispecific complexes and their uses
US20150000806A1 (en) * 2013-06-28 2015-01-01 Octavia A. VILORIO Carry bag with attachment accessory
DE102013215334A1 (de) 2013-08-05 2015-02-05 Tridonic Gmbh & Co Kg Dimmbare LED-Leuchtmittelstrecke
TW201605896A (zh) 2013-08-30 2016-02-16 安美基股份有限公司 Gitr抗原結合蛋白
US10570204B2 (en) 2013-09-26 2020-02-25 The Medical College Of Wisconsin, Inc. Methods for treating hematologic cancers
BR112016010224A2 (pt) 2013-11-05 2018-05-02 Cognate Bioservices, Inc. combinações de inibidores do ponto de verificação e produtos terapêuticos para tratar o câncer.
CN103721255A (zh) 2014-01-07 2014-04-16 苏州大学 共同阻断pd-1和tim-3信号通路在抗胃癌治疗中的用途
CN104072615B (zh) 2014-01-26 2016-08-24 中国人民解放军军事医学科学院基础医学研究所 一种能阻断Tim-3信号通路的人Tim-3融合蛋白
CN103936853B (zh) 2014-01-26 2016-08-17 中国人民解放军军事医学科学院基础医学研究所 一种检测tim-3试剂盒及其使用方法
JOP20200096A1 (ar) 2014-01-31 2017-06-16 Children’S Medical Center Corp جزيئات جسم مضاد لـ tim-3 واستخداماتها
ES2851451T3 (es) 2014-05-13 2021-09-07 Bavarian Nordic As Terapia de combinación para tratar cáncer con un poxvirus que expresa un antígeno de tumor y un anticuerpo monoclonal contra TIM-3
SG11201609721WA (en) 2014-05-28 2016-12-29 Agenus Inc Anti-gitr antibodies and methods of use thereof
DK3151921T3 (da) 2014-06-06 2019-12-02 Bristol Myers Squibb Co Antistoffer mod glucocorticoid-induceret tumornekrosefaktor- receptorer (gitr) og anvendelser deraf
WO2016007513A1 (en) 2014-07-07 2016-01-14 Dana-Farber Cancer Institute, Inc. Methods of treating cancer
US10463732B2 (en) 2014-10-03 2019-11-05 Dana-Farber Cancer Institute, Inc. Glucocorticoid-induced tumor necrosis factor receptor (GITR) antibodies and methods of use thereof
MA41044A (fr) 2014-10-08 2017-08-15 Novartis Ag Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer
CN106973568B (zh) 2014-10-08 2021-07-23 诺华股份有限公司 预测针对嵌合抗原受体疗法的治疗应答性的生物标志及其用途
JP6709215B2 (ja) 2014-10-27 2020-06-10 エージェンシー フォー サイエンス,テクノロジー アンド リサーチ 抗tim−3抗体
GB201419094D0 (en) 2014-10-27 2014-12-10 Agency Science Tech & Res Anti-TIM-3-antibodies
DK3212233T3 (da) 2014-10-31 2020-07-27 Oncomed Pharm Inc Kombinationsterapi til behandling af sygdom
RS59664B1 (sr) * 2014-11-06 2020-01-31 Hoffmann La Roche Anti-tim3 antitela i postupci upotrebe
PT3221346T (pt) 2014-11-21 2020-10-23 Bristol Myers Squibb Co Anticorpos compreendendo regiões constantes de cadeia pesada modificadas
WO2016111947A2 (en) 2015-01-05 2016-07-14 Jounce Therapeutics, Inc. Antibodies that inhibit tim-3:lilrb2 interactions and uses thereof
ES2929532T3 (es) 2015-01-29 2022-11-30 Univ Pennsylvania Combinaciones de inhibidores de puntos de control y vacunas y su uso en inmunoterapia
CN104592388B (zh) 2015-03-02 2017-05-31 中国人民解放军总医院 一种抗人Tim‑3的单克隆抗体的抗原结合部分
JP6917896B2 (ja) 2015-03-05 2021-08-18 フレッド ハッチンソン キャンサー リサーチ センター 免疫調節性融合タンパク質およびその使用
CA2978892A1 (en) 2015-03-06 2016-09-15 Sorrento Therapeutics, Inc. Antibody therapeutics that bind tim3
US10508149B2 (en) 2015-04-01 2019-12-17 Anaptysbio, Inc. Antibodies directed against T cell immunoglobulin and mucin protein 3 (TIM-3)
WO2016166139A1 (en) 2015-04-14 2016-10-20 Eberhard Karls Universität Tübingen Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells
KR102740444B1 (ko) 2015-04-17 2024-12-10 브리스톨-마이어스 스큅 컴퍼니 항-pd-1 항체 및 또 다른 항체의 조합물을 포함하는 조성물
PT3283508T (pt) 2015-04-17 2021-06-21 Alpine Immune Sciences Inc Proteínas imuno modulatórias com afinidades afináveis
US20180298095A1 (en) 2015-04-24 2018-10-18 The Brigham And Women's Hospital, Inc. Interactions between ceacam and tim family members
US20180153986A1 (en) 2015-04-24 2018-06-07 The Brigham And Women's Hospital, Inc. Interactions between ceacam and tim family members
WO2016179194A1 (en) 2015-05-04 2016-11-10 Jounce Therapeutics, Inc. Lilra3 and method of using the same
WO2016179472A2 (en) 2015-05-07 2016-11-10 University Of Maryland, Baltimore Modulation of natural killer cell tolerance
EP3316902A1 (en) 2015-07-29 2018-05-09 Novartis AG Combination therapies comprising antibody molecules to tim-3
JO3620B1 (ar) 2015-08-05 2020-08-27 Amgen Res Munich Gmbh مثبطات نقطة فحص مناعية للاستخدام في علاج سرطانات محمولة عبر الدم
EP3337826A1 (en) 2015-08-20 2018-06-27 Sutro Biopharma, Inc. Anti-tim-3 antibodies, compositions comprising anti-tim-3 antibodies and methods of making and using anti-tim-3 antibodies
KR101785155B1 (ko) 2015-09-22 2017-10-16 국립암센터 Tim-3을 표적으로 하는 뇌손상 질환 치료용 조성물 및 이의 스크리닝 방법
JP6734919B2 (ja) 2015-10-02 2020-08-05 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft 同時結合を測定するための細胞ベースのfretアッセイ法
US10287352B2 (en) 2015-10-02 2019-05-14 Hoffman-La Roche Inc. Bispecific antibodies specific for PD1 and TIM3
CN108697791B (zh) 2015-11-03 2022-08-23 詹森生物科技公司 特异性结合pd-1的抗体及其用途
MD3443009T2 (ro) 2016-04-12 2022-02-28 Symphogen As Anticorpi anti-TIM-3 și compoziții
WO2017205721A1 (en) 2016-05-27 2017-11-30 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
MX2019000443A (es) 2016-07-14 2019-06-20 Squibb Bristol Myers Co Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos.
JOP20190013A1 (ar) 2016-08-25 2019-01-31 Lilly Co Eli أجسام مضادة لـ (تي آي ام -3)
EA201990594A1 (ru) 2016-08-26 2019-08-30 Бейджин, Лтд. Анти-tim-3 антитела и их применение
JP2019534322A (ja) 2016-09-26 2019-11-28 アドバンテイジーン インコーポレイテッド Tim−3の上昇を処置する方法
MA46113A (fr) 2016-11-01 2019-07-10 Anaptysbio Inc Anticorps dirigés contre l'immunoglobuline de lymphocyte t et la protéine 3 de mucine (tim-3)
WO2018106529A1 (en) 2016-12-08 2018-06-14 Eli Lilly And Company Anti-tim-3 antibodies for combination with anti-pd-l1 antibodies
JOP20190133A1 (ar) 2016-12-08 2019-06-02 Innovent Biologics Suzhou Co Ltd أجسام مضادة لـ Tim-3 لمزجها بأجسام مضادة لـ PD-1
CN106632675A (zh) 2016-12-15 2017-05-10 常州格露康生物医药科技有限公司 一种抗人Tim‑3单克隆抗体8E11及其制备方法
TWI665216B (zh) 2016-12-29 2019-07-11 財團法人生物技術開發中心 抗人類tim-3抗體及其使用方法
EP3565598A4 (en) 2017-01-03 2020-10-28 Trellis Bioscience, LLC NATIVE HUMAN ANTIBODIES FOR TIM-3 AND B7-H3 IMMUNE CHECKPOINT MODULATION TARGETS
CA3058960C (en) 2017-04-05 2023-08-29 Symphogen A/S Combination therapies targeting pd-1, tim-3, and lag-3
JOP20190222A1 (ar) 2017-04-11 2019-09-24 Zymeworks Inc الأجسام المضادة ثنائية النوعية المضادة لـ pd-l1 والمضادة لـ tim-3
US11787859B2 (en) * 2017-08-28 2023-10-17 Bristol-Myers Squibb Company TIM-3 antagonists for the treatment and diagnosis of cancers
KR20200089286A (ko) 2017-11-16 2020-07-24 노파르티스 아게 조합 요법
EP3737700A1 (en) 2018-01-12 2020-11-18 Bristol-Myers Squibb Company Antibodies against tim3 and uses thereof
WO2019143607A1 (en) 2018-01-16 2019-07-25 Bristol-Myers Squibb Company Methods of treating cancer with antibodies against tim3

Also Published As

Publication number Publication date
CA3030765A1 (en) 2018-01-18
EP3484920B1 (en) 2024-12-11
US10077306B2 (en) 2018-09-18
SG10201911972QA (en) 2020-02-27
JP7027401B2 (ja) 2022-03-01
JP7387776B2 (ja) 2023-11-28
MY200602A (en) 2024-01-04
TW202244061A (zh) 2022-11-16
JP2024023302A (ja) 2024-02-21
US20250326841A1 (en) 2025-10-23
BR112019000431A2 (pt) 2019-07-09
EP4512829A3 (en) 2025-06-11
JP2022078102A (ja) 2022-05-24
EP4512829A2 (en) 2025-02-26
KR102899060B1 (ko) 2025-12-12
US20240209083A1 (en) 2024-06-27
CN109757103A (zh) 2019-05-14
KR20230020562A (ko) 2023-02-10
ES3005961T3 (en) 2025-03-17
KR20190027384A (ko) 2019-03-14
EP4512829A8 (en) 2025-04-16
CO2019000372A2 (es) 2019-01-18
US20190248893A1 (en) 2019-08-15
IL264011A (en) 2019-01-31
EP3484920A2 (en) 2019-05-22
US20200190186A1 (en) 2020-06-18
US10533052B2 (en) 2020-01-14
WO2018013818A3 (en) 2018-02-22
US12312403B2 (en) 2025-05-27
CL2019000100A1 (es) 2019-05-10
SG11201900026TA (en) 2019-01-30
UY37325A (es) 2018-01-31
US20180298097A1 (en) 2018-10-18
CN109757103B (zh) 2024-01-02
US11591392B2 (en) 2023-02-28
KR20250177404A (ko) 2025-12-23
WO2018013818A2 (en) 2018-01-18
CL2021000698A1 (es) 2021-08-13
KR102493282B1 (ko) 2023-02-01
US20230382992A1 (en) 2023-11-30
TW201811829A (zh) 2018-04-01
JP2019533981A (ja) 2019-11-28
MX2019000443A (es) 2019-06-20
TWI780057B (zh) 2022-10-11
US20180016336A1 (en) 2018-01-18
AU2017297506A1 (en) 2019-02-21
CN117683135A (zh) 2024-03-12

Similar Documents

Publication Publication Date Title
PE20190418A1 (es) Anticuerpos contra proteina 3 que contiene el dominio de mucina e inmunoglobulina de linfocitos t (tim3) y sus usos
PE20220495A1 (es) Receptores antigenicos quimericos y agentes de union dirigidos a dll3
UY37698A (es) Proteínas de unión a antígenos trem2 y usos de estas
PE20200384A1 (es) Metodo de fabricacion de anticuerpos bispecificos, anticuerpos bispecificos y uso terapeutico de dichos anticuerpos
UY37928A (es) Anticuerpos anti-cd38 y métodos de uso
PE20190975A1 (es) Novela cd47 anticuerpos monoclonales y sus usos
PE20191648A1 (es) Nuevos receptores de celulas t y terapia inmunologica que los utiliza
MX2022002018A (es) Anticuerpos de union a cd3.
PE20171336A1 (es) Anticuerpos contra tau y sus usos
EA201891435A1 (ru) Гуманизированные моноклональные антитела, моноклональные антитела мыши или химерные моноклональные антитела против cd47
PE20171790A1 (es) Anticuerpos anti-ceacam6 y sus usos
UY36687A (es) Anticuerpos contra ox40 y sus usos
PE20240111A1 (es) Moleculas de union a pd-1 y metodos de uso de las mismas
MX395074B (es) Anticuerpos anti-axl, fragmentos de anticuerpos y sus inmunoconjugados y usos de los mismos
PE20250415A1 (es) Composiciones y metodos de inhibicion del masp-3 para el tratamiento de diversas enfermedades y trastornos
PE20181054A1 (es) Anticuerpos anti-cd19 humano humanizados y metodos de utilizacion
PE20201149A1 (es) Anticuerpos de union a hla-a2/wt1
PE20190737A1 (es) Anticuerpos anti-cd27
EA202091054A1 (ru) Слитые молекулы на основе антитела против pd-l1 и ил-7
AR109683A1 (es) Anticuerpos contra el factor xi y sus usos
PE20191404A1 (es) Proteinas de union al receptor de glucagon y metodos para usarlas
MX2021015356A (es) Anticuerpos y fragmentos de anticuerpos anti-epcam condicionalmente activos, sus inmunoconjugados y usos de estos.
EA202192488A1 (ru) Антитела против tsg-6 и их применения
CL2023003005A1 (es) Polipéptido de unión a gucy2c y usos del mismo.
PE20090981A1 (es) Moleculas aglutinantes de nogo-a mejoradas y uso farmaceutico de las mismas