CA2943262A1 - Anti-ox40 antibodies and methods of use - Google Patents

Anti-ox40 antibodies and methods of use Download PDF

Info

Publication number
CA2943262A1
CA2943262A1 CA2943262A CA2943262A CA2943262A1 CA 2943262 A1 CA2943262 A1 CA 2943262A1 CA 2943262 A CA2943262 A CA 2943262A CA 2943262 A CA2943262 A CA 2943262A CA 2943262 A1 CA2943262 A1 CA 2943262A1
Authority
CA
Canada
Prior art keywords
antibody
seq
amino acid
acid sequence
hvr
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.)
Abandoned
Application number
CA2943262A
Other languages
English (en)
French (fr)
Inventor
Changchun DU
Jeong Kim
Jing Zhu
Jack Bevers Iii
Kevin Walsh
Patricia DE ALMEIDA
James Andya
Ye Shen
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.)
Genentech Inc
Original Assignee
Genentech Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52829446&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2943262(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Genentech Inc filed Critical Genentech Inc
Publication of CA2943262A1 publication Critical patent/CA2943262A1/en
Abandoned legal-status Critical Current

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
    • C07K16/2878Immunoglobulins [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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07K2317/33Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • 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
    • C07K2317/75Agonist effect on antigen
    • 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)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA2943262A 2014-03-31 2015-03-30 Anti-ox40 antibodies and methods of use Abandoned CA2943262A1 (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201461973193P 2014-03-31 2014-03-31
US61/973,193 2014-03-31
US201461989448P 2014-05-06 2014-05-06
US61/989,448 2014-05-06
US201462073873P 2014-10-31 2014-10-31
US62/073,873 2014-10-31
US201462080171P 2014-11-14 2014-11-14
US62/080,171 2014-11-14
PCT/US2015/023432 WO2015153513A1 (en) 2014-03-31 2015-03-30 Anti-ox40 antibodies and methods of use

Publications (1)

Publication Number Publication Date
CA2943262A1 true CA2943262A1 (en) 2015-10-08

Family

ID=52829446

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2943262A Abandoned CA2943262A1 (en) 2014-03-31 2015-03-30 Anti-ox40 antibodies and methods of use

Country Status (29)

Country Link
EP (2) EP3126394B1 (Direct)
JP (2) JP6637439B2 (Direct)
KR (1) KR20160145624A (Direct)
CN (1) CN106103486B (Direct)
AU (1) AU2015241037B2 (Direct)
BR (1) BR112016022658A2 (Direct)
CA (1) CA2943262A1 (Direct)
CL (1) CL2016002462A1 (Direct)
CR (1) CR20160500A (Direct)
DK (1) DK3126394T3 (Direct)
EA (1) EA201691974A1 (Direct)
ES (1) ES2763898T3 (Direct)
HR (1) HRP20192285T1 (Direct)
HU (1) HUE046767T2 (Direct)
IL (1) IL247898A0 (Direct)
LT (1) LT3126394T (Direct)
MA (2) MA51552A (Direct)
MX (1) MX2016012781A (Direct)
PE (2) PE20211291A1 (Direct)
PH (1) PH12016501894B1 (Direct)
PL (1) PL3126394T3 (Direct)
PT (1) PT3126394T (Direct)
RS (1) RS59738B1 (Direct)
SG (1) SG11201607969XA (Direct)
SI (1) SI3126394T1 (Direct)
TW (1) TWI680985B (Direct)
UA (1) UA121112C2 (Direct)
WO (1) WO2015153513A1 (Direct)
ZA (1) ZA201606630B (Direct)

Families Citing this family (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003270439B2 (en) 2002-09-11 2009-09-24 Genentech, Inc. Novel composition and methods for the treatment of immune related diseases
PL3208612T3 (pl) 2008-04-09 2020-03-31 Genentech, Inc. Kompozycje i sposoby leczenia chorób o podłożu immunologicznym
CN105229032A (zh) 2013-03-18 2016-01-06 比奥塞罗克斯产品公司 人源化抗cd134(ox40)抗体及其应用
MX384142B (es) 2013-07-16 2025-03-14 Genentech Inc Antagonista de unión al eje pd-1 e inhibidores de tigit para usarse en el tratamiento de cáncer.
CA2943834A1 (en) 2014-03-31 2015-10-08 Genentech, Inc. Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists
JP2017536842A (ja) 2014-11-03 2017-12-14 ジェネンテック, インコーポレイテッド Ox40アゴニスト治療薬の有効性及び評価を予測するための方法及びバイオマーカー
RU2017119009A (ru) 2014-11-03 2018-12-05 Дженентек, Инк. Анализы для обнаружения субпопуляций иммунных т-клеток и способы их применения
CA2963974A1 (en) * 2014-11-06 2016-05-12 Genentech, Inc. Combination therapy comprising ox40 binding agonists and tigit inhibitors
CN115109158A (zh) 2015-05-07 2022-09-27 阿吉纳斯公司 抗ox40抗体及其使用方法
CA2987410A1 (en) 2015-05-29 2016-12-08 Bristol-Myers Squibb Company Antibodies against ox40 and uses thereof
CN107810011A (zh) * 2015-06-08 2018-03-16 豪夫迈·罗氏有限公司 使用抗ox40抗体治疗癌症的方法
HUE069796T2 (hu) 2015-09-25 2025-04-28 Hoffmann La Roche Anti-TIGIT ellenanyagok és alkalmazásukra szolgáló eljárások
WO2017055398A2 (en) 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Bispecific antibodies specific for a costimulatory tnf receptor
US10624974B2 (en) 2015-10-15 2020-04-21 Dingfu Biotarget Co., Ltd. Anti-OX40 antibody and application thereof
MA45488A (fr) 2015-10-22 2018-08-29 Juno Therapeutics Gmbh Procédés, kits et appareil de culture de cellules
WO2017096179A1 (en) * 2015-12-02 2017-06-08 Agenus Inc. Antibodies and methods of use thereof
CA3006963A1 (en) * 2015-12-03 2017-06-08 Ludwig Institute For Cancer Research Ltd. Anti-ox40 antibodies and methods of use thereof
DE102016105069A1 (de) * 2016-03-18 2017-09-21 Eberhard Karls Universität Tübingen Medizinische Fakultät Antivirale Immuntherapie durch Membranrezeptorligation
JP7181091B2 (ja) 2016-05-10 2022-11-30 ジェネンテック, インコーポレイテッド ポリペプチドの組み換え産生中にトリスルフィド結合を減少させる方法
TW201803905A (zh) 2016-06-20 2018-02-01 克馬伯有限公司 用於免疫腫瘤學之多重專一性抗體
JP2019530434A (ja) * 2016-08-05 2019-10-24 ジェネンテック, インコーポレイテッド アゴニスト活性を有する多価及び多重エピトープ抗体ならびに使用方法
EP3497122A2 (en) 2016-08-08 2019-06-19 Sorrento Therapeutics, Inc. Anti-ox40 binding proteins
US11279948B2 (en) 2016-08-31 2022-03-22 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric OX40
CN107815465B (zh) 2016-08-31 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化基因改造动物模型的制备方法及应用
WO2018089628A1 (en) 2016-11-09 2018-05-17 Agenus Inc. Anti-ox40 antibodies, anti-gitr antibodies, and methods of use thereof
MX2019007144A (es) 2016-12-19 2019-10-07 Glenmark Pharmaceuticals Sa Nuevos agonistas de tnfr y sus usos.
WO2018150326A1 (en) 2017-02-15 2018-08-23 Glaxosmithkline Intellectual Property Development Limited Combination treatment for cancer
CN108623686A (zh) 2017-03-25 2018-10-09 信达生物制药(苏州)有限公司 抗ox40抗体及其用途
KR20200074214A (ko) * 2017-11-01 2020-06-24 브리스톨-마이어스 스큅 컴퍼니 암을 치료하는데 사용하기 위한 면역자극 효능작용 항체
WO2019106605A1 (en) 2017-12-01 2019-06-06 Board Of Regents, The University Of Texas System Combination treatment for cancer
US11142579B2 (en) 2017-12-06 2021-10-12 Sorrento Therapeutics, Inc. Variant antibodies that bind OX40
WO2019129136A1 (zh) 2017-12-27 2019-07-04 信达生物制药(苏州)有限公司 抗pd-l1抗体及其用途
WO2019129137A1 (zh) 2017-12-27 2019-07-04 信达生物制药(苏州)有限公司 抗lag-3抗体及其用途
CN109970856B (zh) 2017-12-27 2022-08-23 信达生物制药(苏州)有限公司 抗lag-3抗体及其用途
CN115925943A (zh) 2017-12-27 2023-04-07 信达生物制药(苏州)有限公司 抗pd-l1抗体及其用途
CN108218990B (zh) 2017-12-29 2021-03-02 南京优迈生物科技有限公司 分离的抗体或其抗原结合片段及其在肿瘤治疗中的应用
SG11202003893UA (en) 2017-12-29 2020-05-28 Ap Biosciences Inc Monospecific and bispecific proteins with immune checkpoint regulation for cancer therapy
CN111393529B (zh) * 2018-01-29 2022-02-22 康源博创生物科技(北京)有限公司 与ox40l非竞争结合的抗ox40抗体
TW202003555A (zh) 2018-03-07 2020-01-16 英商葛蘭素史克智慧財產發展有限公司 用於純化重組多肽之方法
US11242393B2 (en) 2018-03-23 2022-02-08 Bristol-Myers Squibb Company Antibodies against MICA and/or MICB and uses thereof
EP3774840A1 (en) 2018-03-27 2021-02-17 Bristol-Myers Squibb Company Real-time monitoring of protein concentration using ultraviolet signal
MX2020010028A (es) 2018-03-29 2020-10-14 Genentech Inc Actividad lactogenica modulada en celulas de mamifero.
BR112020023026A2 (pt) * 2018-05-11 2021-02-09 WuXi Biologics Ireland Limited anticorpos completamente humanos contra ox40, método para a sua preparação e sua utilização
US12103974B2 (en) 2018-05-23 2024-10-01 Beigene, Ltd. Anti-OX40 antibodies and methods of use
US20210277135A1 (en) 2018-07-13 2021-09-09 Bristol-Myers Squibb Company Ox-40 agonist, pd-1 pathway inhibitor and ctla-4 inhibitor combination for use in a method of treating a cancer or a solid tumor
BR112021001201A2 (pt) 2018-07-25 2021-04-27 Innovent Biologics (Suzhou) Co., Ltd. anticorpo anti-tigit e uso do mesmo
EP3858857A1 (en) 2018-09-26 2021-08-04 Jiangsu Hengrui Medicine Co., Ltd. An anti-ox40 antibody, antigen-binding fragment thereof, and the pharmaceutical use
EP3889180A4 (en) * 2018-11-26 2023-01-04 Nanjing GenScript Biotech Co., Ltd. ANTI-OX40 HUMANIZED MONOCLONAL ANTIBODY, METHOD FOR PREPARATION AND USE
WO2020132857A1 (zh) * 2018-12-25 2020-07-02 杭州翰思生物医药有限公司 抗ox40的单克隆抗体及其应用
US10442866B1 (en) 2019-01-23 2019-10-15 Beijing Mabworks Biotech Co. Ltd Antibodies binding OX40 and uses thereof
WO2020172658A1 (en) 2019-02-24 2020-08-27 Bristol-Myers Squibb Company Methods of isolating a protein
WO2020237221A1 (en) 2019-05-23 2020-11-26 Bristol-Myers Squibb Company Methods of monitoring cell culture media
KR20220016155A (ko) 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법
KR20220016157A (ko) 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 세포 국재화 시그너쳐 및 조합 요법
US20220363760A1 (en) 2019-05-30 2022-11-17 Bristol-Myers Squibb Company Multi-tumor gene signature for suitability to immuno-oncology therapy
CN110172090B (zh) * 2019-06-03 2020-04-03 中山标佳生物科技有限公司 Cd134单克隆抗体及其制备方法和癌症治疗中的应用
CN114040776B (zh) * 2019-06-28 2024-05-14 江苏恒瑞医药股份有限公司 Tlr激动剂与抗ox40抗体或其抗原结合片段联合在制备治疗肿瘤的药物中的用途
WO2021098749A1 (en) * 2019-11-21 2021-05-27 Beigene (Beijing) Co., Ltd. Methods of cancer treatment with anti-ox40 antibody in combination with radiation
CN114729050A (zh) * 2019-11-21 2022-07-08 百济神州有限公司 使用抗OX40抗体与PI3激酶δ抑制剂组合治疗癌症的方法
BR112022011949A2 (pt) 2019-12-17 2022-11-22 Amgen Inc Dupla de interleucina-2/agonista do receptor tnf para uso em terapia
EP4130039A4 (en) * 2020-03-23 2024-07-31 Bio-Thera Solutions, Ltd. DEVELOPMENT AND APPLICATION OF AN IMMUNE CELL ACTIVATOR
TW202144005A (zh) * 2020-03-25 2021-12-01 大陸商江蘇恆瑞醫藥股份有限公司 一種抗ox40抗體醫藥組成物及其用途
US12098365B2 (en) 2020-03-26 2024-09-24 Genentech, Inc. Modified mammalian cells
AR121706A1 (es) 2020-04-01 2022-06-29 Hoffmann La Roche Moléculas de unión a antígeno biespecíficas dirigidas a ox40 y fap
WO2021209019A1 (en) 2020-04-17 2021-10-21 Hutchison Medipharma Limited Anti-ox40 antibody and uses thereof
IL299161A (en) 2020-06-24 2023-02-01 Genentech Inc Cell lines resistant to apoptosis
CN114106173A (zh) * 2020-08-26 2022-03-01 上海泰槿生物技术有限公司 抗ox40抗体、其药物组合物及应用
TW202227625A (zh) 2020-08-28 2022-07-16 美商建南德克公司 宿主細胞蛋白質之CRISPR/Cas9多重剔除
AU2021334361A1 (en) 2020-08-31 2023-05-11 Bristol-Myers Squibb Company Cell localization signature and immunotherapy
JP2023544410A (ja) 2020-10-05 2023-10-23 ブリストル-マイヤーズ スクイブ カンパニー タンパク質を濃縮するための方法
AU2021361083A1 (en) * 2020-10-13 2023-05-11 Almirall, S.A. Bispecific molecules and methods of treatment using the same
CN114515335A (zh) * 2020-11-19 2022-05-20 百奥泰生物制药股份有限公司 抗ox40抗体在治疗肿瘤或癌症中的应用
WO2022120179A1 (en) 2020-12-03 2022-06-09 Bristol-Myers Squibb Company Multi-tumor gene signatures and uses thereof
PL4267105T3 (pl) 2020-12-28 2025-06-30 Bristol-Myers Squibb Company Kompozycje przeciwciał i metody ich stosowania
WO2022146948A1 (en) 2020-12-28 2022-07-07 Bristol-Myers Squibb Company Subcutaneous administration of pd1/pd-l1 antibodies
US20240026019A1 (en) 2021-02-04 2024-01-25 Innovent Biologics (Suzhou) Co., Ltd. Anti-tnfr2 antibody and use thereof
US20240376224A1 (en) 2021-04-02 2024-11-14 The Regents Of The University Of California Antibodies against cleaved cdcp1 and uses thereof
IL307501A (en) 2021-04-19 2023-12-01 Hoffmann La Roche Modified mammalian cells
EP4341385A1 (en) 2021-05-21 2024-03-27 Genentech, Inc. Modified cells for the production of a recombinant product of interest
CN115403670A (zh) 2021-05-26 2022-11-29 安徽瀚海博兴生物技术有限公司 抗cd40抗体及其用途
CN115611983A (zh) 2021-07-14 2023-01-17 三优生物医药(上海)有限公司 Cldn18.2结合分子及其用途
TW202323280A (zh) * 2021-10-15 2023-06-16 新加坡商創響私人有限公司 包含抗-ox40單株抗體的藥物製劑
US20250188152A1 (en) 2022-03-09 2025-06-12 Bristol-Myers Squibb Company Transient expression of therapeutic proteins
CN118871451A (zh) 2022-03-18 2024-10-29 百时美施贵宝公司 分离多肽的方法
CN119562830A (zh) 2022-06-02 2025-03-04 百时美施贵宝公司 抗体组合物及其使用方法
WO2024054992A1 (en) 2022-09-09 2024-03-14 Bristol-Myers Squibb Company Methods of separating chelator
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
WO2025145207A1 (en) 2023-12-29 2025-07-03 Bristol-Myers Squibb Company Combination therapy of kras inhibitor and treg-depleting agent

Family Cites Families (137)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CU22545A1 (es) 1994-11-18 1999-03-31 Centro Inmunologia Molecular Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4943533A (en) 1984-03-01 1990-07-24 The Regents Of The University Of California Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
DE3883899T3 (de) 1987-03-18 1999-04-22 Sb2, Inc., Danville, Calif. Geänderte antikörper.
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
ATE102631T1 (de) 1988-11-11 1994-03-15 Medical Res Council Klonierung von immunglobulin sequenzen aus den variabelen domaenen.
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
CA2066428C (en) 1989-09-08 2000-11-28 Bert Vogelstein Structural alterations of the egf receptor gene in human gliomas
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
EP0564531B1 (en) 1990-12-03 1998-03-25 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
AU675916B2 (en) 1991-06-14 1997-02-27 Genentech Inc. Method for making humanized antibodies
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
US7018809B1 (en) 1991-09-19 2006-03-28 Genentech, Inc. Expression of functional antibody fragments
FI941572L (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
AU661533B2 (en) 1992-01-20 1995-07-27 Astrazeneca Ab Quinazoline derivatives
ATE419355T1 (de) 1992-02-06 2009-01-15 Novartis Vaccines & Diagnostic Marker für krebs und biosynthetisches bindeprotein dafür
WO1994011026A2 (en) 1992-11-13 1994-05-26 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
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
GB9314893D0 (en) 1993-07-19 1993-09-01 Zeneca Ltd Quinazoline derivatives
PT659439E (pt) 1993-12-24 2002-04-29 Merck Patent Gmbh Imunoconjugados
IL112249A (en) 1994-01-25 2001-11-25 Warner Lambert Co Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
IL112248A0 (en) 1994-01-25 1995-03-30 Warner Lambert Co Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them
US5679683A (en) 1994-01-25 1997-10-21 Warner-Lambert Company Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
DE69507956T2 (de) 1994-07-21 1999-09-09 Akzo Nobel N.V. Zyklische keton peroxyde zubereitungen
US5804396A (en) 1994-10-12 1998-09-08 Sugen, Inc. Assay for agents active in proliferative disorders
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
ES2161290T3 (es) 1995-03-30 2001-12-01 Pfizer Derivados de quinazolina.
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
GB9508538D0 (en) 1995-04-27 1995-06-14 Zeneca Ltd Quinazoline derivatives
GB9508565D0 (en) 1995-04-27 1995-06-14 Zeneca Ltd Quiazoline derivative
US5747498A (en) 1996-05-28 1998-05-05 Pfizer Inc. Alkynyl and azido-substituted 4-anilinoquinazolines
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
CA2222231A1 (en) 1995-06-07 1996-12-19 Imclone Systems Incorporated Antibody and antibody fragments for inhibiting the growth of tumors
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
WO1997002266A1 (en) 1995-07-06 1997-01-23 Novartis Ag Pyrrolopyrimidines and processes for the preparation thereof
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
US5760041A (en) 1996-02-05 1998-06-02 American Cyanamid Company 4-aminoquinazoline EGFR Inhibitors
GB9603095D0 (en) 1996-02-14 1996-04-10 Zeneca Ltd Quinazoline derivatives
GB9603256D0 (en) 1996-02-16 1996-04-17 Wellcome Found Antibodies
ES2174250T5 (es) 1996-04-12 2010-04-21 Warner-Lambert Company Llc Inhibidores irreversibles de tirosina quinasas.
WO1998002434A1 (en) 1996-07-13 1998-01-22 Glaxo Group Limited Fused heterocyclic compounds as protein tyrosine kinase inhibitors
ID18494A (id) 1996-10-02 1998-04-16 Novartis Ag Turunan pirazola leburan dan proses pembuatannya
UA73073C2 (uk) 1997-04-03 2005-06-15 Уайт Холдінгз Корпорейшн Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція
US6002008A (en) 1997-04-03 1999-12-14 American Cyanamid Company Substituted 3-cyano quinolines
US6235883B1 (en) 1997-05-05 2001-05-22 Abgenix, Inc. Human monoclonal antibodies to epidermal growth factor receptor
CA2288705C (en) 1997-05-06 2008-03-18 American Cyanamid Company Use of quinazoline compounds for the treatment of polycystic kidney disease
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
ES2244066T3 (es) 1997-06-24 2005-12-01 Genentech, Inc. Procedimiento y composiciones de glicoproteinas galactosiladas.
ZA986732B (en) 1997-07-29 1999-02-02 Warner Lambert Co Irreversible inhibitiors of tyrosine kinases
ZA986729B (en) 1997-07-29 1999-02-02 Warner Lambert Co Irreversible inhibitors of tyrosine kinases
TW436485B (en) 1997-08-01 2001-05-28 American Cyanamid Co Substituted quinazoline derivatives
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
CA2307166A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
KR20010031813A (ko) 1997-11-06 2001-04-16 윌리암 에이취 캘넌, 에곤 이 버그 결장 폴립 치료용 티로신 키나제 억제제로서의 퀴나졸린유도체의 용도
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
WO1999029888A1 (en) 1997-12-05 1999-06-17 The Scripps Research Institute Humanization of murine antibody
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
ES2292236T3 (es) 1998-04-02 2008-03-01 Genentech, Inc. Variantes de anticuerpos y sus fragmentos.
DK1071700T3 (da) 1998-04-20 2010-06-07 Glycart Biotechnology Ag Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet
HUP0104211A3 (en) 1998-11-19 2003-01-28 Warner Lambert Co N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases and pharmaceutical composition containing it
EP2364997A3 (en) 1999-01-15 2012-07-04 Genentech, Inc. Polypeptide variants with altered effector function
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
ES2420835T3 (es) 1999-04-09 2013-08-27 Kyowa Hakko Kirin Co., Ltd. Procedimiento para controlar la actividad de las moléculas inmunofuncionales
ES2248127T3 (es) 1999-10-04 2006-03-16 Medicago Inc. Metodo para regular la transcripcion de genes foraneos en presencia de nigtrogeno.
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
AU7950400A (en) 1999-10-19 2001-04-30 Kyowa Hakko Kogyo Co. Ltd. Process for producing polypeptide
IL149809A0 (en) 1999-12-15 2002-11-10 Genentech Inc Shotgun scanning, a combinatorial method for mapping functional protein epitopes
EP1242438B1 (en) 1999-12-29 2006-11-08 Immunogen, Inc. Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use
MXPA02010011A (es) 2000-04-11 2003-04-25 Genentech Inc Anticuerpos multivalentes y usos para los mismos.
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
EP3263702A1 (en) 2000-10-06 2018-01-03 Kyowa Hakko Kirin Co., Ltd. Cells producing antibody compositions
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7041870B2 (en) 2000-11-30 2006-05-09 Medarex, Inc. Transgenic transchromosomal rodents for making human antibodies
KR20100018071A (ko) 2001-08-03 2010-02-16 글리카트 바이오테크놀로지 아게 항체 의존적 세포 독성이 증가된 항체 글리코실화 변이체
MXPA04003798A (es) 2001-10-25 2004-07-30 Genentech Inc Composiciones de glicoproteina.
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
CA2481920A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
EP1500698B1 (en) 2002-04-09 2011-03-30 Kyowa Hakko Kirin Co., Ltd. Cell with depression or deletion of the activity of protein participating in gdp-fucose transport
JPWO2003085118A1 (ja) 2002-04-09 2005-08-11 協和醗酵工業株式会社 抗体組成物の製造方法
EP1502603A4 (en) 2002-04-09 2006-12-13 Kyowa Hakko Kogyo Kk AN ANTIBODY COMPOSITION CONTAINING MEDICAMENT FOR PATIENTS WITH Fc gamma RIIIa POLYMORPHISM
CA2481658A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Method of enhancing of binding activity of antibody composition to fcy receptor iiia
JPWO2003085107A1 (ja) 2002-04-09 2005-08-11 協和醗酵工業株式会社 ゲノムが改変された細胞
EP1513879B1 (en) 2002-06-03 2018-08-22 Genentech, Inc. Synthetic antibody phage libraries
CA2489004C (en) * 2002-06-13 2013-01-08 Crucell Holland B.V. Agonistic binding molecules to the human ox40 receptor
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
PL212899B1 (pl) 2002-12-16 2012-12-31 Genentech Inc Humanizowane przeciwcialo, kompozycja zawierajaca to przeciwcialo, wyrób fabryczny, przeciwcialo lub jego fragment do zastosowania w sposobie indukowania apoptozy, izolowany kwas nukleinowy, wektor ekspresji, komórka gospodarza, sposób wytwarzania przeciwciala lub jego fragmentu, plynny preparat i zastosowanie przeciwciala do wytwarzania leku
AU2004205631A1 (en) 2003-01-16 2004-08-05 Genentech, Inc. Synthetic antibody phage libraries
US7871607B2 (en) 2003-03-05 2011-01-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
US20060104968A1 (en) 2003-03-05 2006-05-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
CA2542046A1 (en) 2003-10-08 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Fused protein composition
CA2542125A1 (en) 2003-10-09 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Process for producing antibody composition by using rna inhibiting the function of .alpha.1,6-fucosyltransferase
RS54450B1 (sr) 2003-11-05 2016-06-30 Roche Glycart Ag Molekuli koji se vezuju za antigen sa povećanim afinitetom vezivanja za fc receptor i efektornom funkcijom
DK1725249T3 (en) 2003-11-06 2014-03-17 Seattle Genetics Inc Monomethylvaline compounds capable of conjugating to ligands.
WO2005053742A1 (ja) 2003-12-04 2005-06-16 Kyowa Hakko Kogyo Co., Ltd. 抗体組成物を含有する医薬
MXPA06011199A (es) 2004-03-31 2007-04-16 Genentech Inc Anticuerpos anti-tgf-beta humanizados.
US7785903B2 (en) 2004-04-09 2010-08-31 Genentech, Inc. Variable domain library and uses
EP2067789A1 (en) 2004-04-13 2009-06-10 F. Hoffmann-La Roche Ag Anti-P selectin antibodies
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
ES2579805T3 (es) 2004-09-23 2016-08-16 Genentech, Inc. Anticuerpos y conjugados modificados por ingeniería genética con cisteína
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
KR101498834B1 (ko) 2005-05-09 2015-03-05 오노 야꾸힝 고교 가부시키가이샤 예정 사멸 인자 1(pd-1)에 대한 인간 모노클로날 항체, 및 항-pd-1 항체를 단독 사용하거나 기타 면역 요법제와 병용한 암 치료 방법
HRP20080053A2 (hr) 2005-07-01 2009-08-31 Medarex Ljudska monoklonska protutijela na ligand 1 za programiranu smrt stanice (pd-l1)
US8679490B2 (en) 2005-11-07 2014-03-25 Genentech, Inc. Binding polypeptides with diversified and consensus VH/VL hypervariable sequences
TWI461436B (zh) * 2005-11-25 2014-11-21 Kyowa Hakko Kirin Co Ltd 人類cd134(ox40)之人類單株抗體及其製造及使用方法
WO2007064919A2 (en) 2005-12-02 2007-06-07 Genentech, Inc. Binding polypeptides with restricted diversity sequences
JP2009536527A (ja) 2006-05-09 2009-10-15 ジェネンテック・インコーポレーテッド 最適化されたスキャフォールドを備えた結合ポリペプチド
DK2059533T3 (da) 2006-08-30 2013-02-25 Genentech Inc Multispecifikke antistoffer
US20080226635A1 (en) 2006-12-22 2008-09-18 Hans Koll Antibodies against insulin-like growth factor I receptor and uses thereof
CN100592373C (zh) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 液晶显示面板驱动装置及其驱动方法
US7960515B2 (en) * 2007-12-14 2011-06-14 Bristol-Myers Squibb Company Binding molecules to the human OX40 receptor
AU2009204501B2 (en) 2008-01-07 2015-02-12 Amgen Inc. Method for making antibody Fc-heterodimeric molecules using electrostatic steering effects
CN104548091A (zh) 2008-02-11 2015-04-29 治疗科技公司 用于肿瘤治疗的单克隆抗体
US8168757B2 (en) 2008-03-12 2012-05-01 Merck Sharp & Dohme Corp. PD-1 binding proteins
KR101847107B1 (ko) 2008-07-08 2018-04-10 인사이트 홀딩스 코포레이션 인돌아민 2,3-디옥시게나아제의 억제제로서의 1,2,5-옥사디아졸
EP2662383A1 (en) 2008-08-25 2013-11-13 Amplimmune, Inc. PD-I antagonists and methods for treating infectious disease
CA3120172A1 (en) * 2008-12-09 2010-07-08 Genentech, Inc. Anti-pd-l1 antibodies and their use to enhance t-cell function
US20130017199A1 (en) 2009-11-24 2013-01-17 AMPLIMMUNE ,Inc. a corporation Simultaneous inhibition of pd-l1/pd-l2
EP2399604A1 (en) * 2010-06-25 2011-12-28 F. Hoffmann-La Roche AG Novel antibody formulation

Also Published As

Publication number Publication date
PT3126394T (pt) 2019-12-19
WO2015153513A8 (en) 2016-10-13
JP2020072678A (ja) 2020-05-14
BR112016022658A2 (pt) 2017-10-17
PE20211291A1 (es) 2021-07-20
HRP20192285T1 (hr) 2020-03-06
ES2763898T3 (es) 2020-06-01
CN106103486B (zh) 2020-04-21
JP2017514461A (ja) 2017-06-08
MA40682A (fr) 2017-02-08
KR20160145624A (ko) 2016-12-20
EP3632934A1 (en) 2020-04-08
EP3126394B1 (en) 2019-10-30
MX2016012781A (es) 2016-12-14
AU2015241037B2 (en) 2020-10-15
PH12016501894B1 (en) 2021-06-23
TWI680985B (zh) 2020-01-01
SI3126394T1 (sl) 2020-01-31
CN106103486A (zh) 2016-11-09
LT3126394T (lt) 2020-01-27
EP3126394A1 (en) 2017-02-08
TW201620937A (zh) 2016-06-16
AU2015241037A9 (en) 2016-11-03
HUE046767T2 (hu) 2020-03-30
PL3126394T3 (pl) 2020-05-18
UA121112C2 (uk) 2020-04-10
SG11201607969XA (en) 2016-10-28
DK3126394T3 (da) 2020-01-13
JP6637439B2 (ja) 2020-01-29
IL247898A0 (en) 2016-11-30
EA201691974A1 (ru) 2017-04-28
AU2015241037A1 (en) 2016-10-13
WO2015153513A1 (en) 2015-10-08
PH12016501894A1 (en) 2017-01-09
RS59738B1 (sr) 2020-02-28
MA51552A (fr) 2021-03-24
ZA201606630B (en) 2020-12-23
MA40682B1 (fr) 2020-01-31
PE20161571A1 (es) 2017-02-07
CL2016002462A1 (es) 2017-06-23
CR20160500A (es) 2016-12-14

Similar Documents

Publication Publication Date Title
AU2015241037B2 (en) Anti-OX40 antibodies and methods of use
US10730951B2 (en) Anti-OX40 antibodies and methods of use
US20180346586A1 (en) Methods of treating cancer using anti-ox40 antibodies
US20180256711A1 (en) Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists
CA2966507A1 (en) Methods and biomarkers for predicting efficacy and evaluation of an ox40 agonist treatment
HK1232891A1 (en) Anti-ox40 antibodies and methods of use
HK1232891B (en) Anti-ox40 antibodies and methods of use
HK1227043B (zh) 抗ox40抗体和使用方法
HK1227043A1 (en) Anti-ox40 antibodies and methods of use

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20200323

FZDE Discontinued

Effective date: 20220718

FZDE Discontinued

Effective date: 20220718