SG11202002119QA - Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor - Google Patents

Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor

Info

Publication number
SG11202002119QA
SG11202002119QA SG11202002119QA SG11202002119QA SG11202002119QA SG 11202002119Q A SG11202002119Q A SG 11202002119QA SG 11202002119Q A SG11202002119Q A SG 11202002119QA SG 11202002119Q A SG11202002119Q A SG 11202002119QA SG 11202002119Q A SG11202002119Q A SG 11202002119QA
Authority
SG
Singapore
Prior art keywords
ccr2
antagonist
inhibitor
combination therapy
chemokine receptor
Prior art date
Application number
SG11202002119QA
Other languages
English (en)
Inventor
James J Campbell
Zhenhua Miao
Thomas J Schall
Israel Charo
Shijie Li
Christine Marie Janson
Rajinder Singh
Karen Ebsworth
Original Assignee
Chemocentryx 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
Application filed by Chemocentryx Inc filed Critical Chemocentryx Inc
Publication of SG11202002119QA publication Critical patent/SG11202002119QA/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/536Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
SG11202002119QA 2017-09-25 2018-09-24 Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor SG11202002119QA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762562952P 2017-09-25 2017-09-25
PCT/US2018/052408 WO2019060820A1 (en) 2017-09-25 2018-09-24 POLYTHERAPY USING A CHEMOKINE RECEPTOR 2 (CCR2) ANTAGONIST AND A PD-1 / PD-L1 INHIBITOR

Publications (1)

Publication Number Publication Date
SG11202002119QA true SG11202002119QA (en) 2020-04-29

Family

ID=65810578

Family Applications (1)

Application Number Title Priority Date Filing Date
SG11202002119QA SG11202002119QA (en) 2017-09-25 2018-09-24 Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor

Country Status (15)

Country Link
US (2) US11304952B2 (pt)
EP (1) EP3687525A4 (pt)
JP (2) JP7453139B2 (pt)
KR (1) KR20200110300A (pt)
CN (1) CN111712242B (pt)
AR (1) AR112831A1 (pt)
AU (1) AU2018335486A1 (pt)
BR (1) BR112020005284A2 (pt)
CA (1) CA3075638A1 (pt)
IL (1) IL273188B2 (pt)
MA (1) MA50665A (pt)
MX (1) MX2020003192A (pt)
SG (1) SG11202002119QA (pt)
TW (1) TW201922287A (pt)
WO (1) WO2019060820A1 (pt)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190275015A1 (en) * 2017-09-25 2019-09-12 Chemocentryx, Inc. Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor
US20190269664A1 (en) 2018-01-08 2019-09-05 Chemocentryx, Inc. Methods of treating solid tumors with ccr2 antagonists
EP3737367A4 (en) 2018-01-08 2022-11-09 ChemoCentryx, Inc. METHODS OF TREATING SOLID TUMORS USING CCR2 ANTAGONISTS
JP7387616B2 (ja) 2018-02-22 2023-11-28 ケモセントリックス,インコーポレイティド Pd-l1アンタゴニストとしてのインダン-アミン
JP2022539830A (ja) 2019-07-10 2022-09-13 ケモセントリックス,インコーポレイティド Pd-l1阻害剤としてのインダン
EP4045037A4 (en) 2019-10-16 2023-11-15 ChemoCentryx, Inc. HETEROARYL-BIPHENYLAMINES FOR THE TREATMENT OF PD-L1 DISEASES
CN114907267A (zh) * 2021-02-08 2022-08-16 中国科学院上海药物研究所 用于抗肿瘤的药物组合

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4166452A (en) 1976-05-03 1979-09-04 Generales Constantine D J Jr Apparatus for testing human responses to stimuli
US4256108A (en) 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
US4265874A (en) 1980-04-25 1981-05-05 Alza Corporation Method of delivering drug with aid of effervescent activity generated in environment of use
LU86084A1 (fr) 1985-09-20 1987-04-02 Faco Sa Apparei de massage electrique
US5102417A (en) 1985-11-07 1992-04-07 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4800882A (en) 1987-03-13 1989-01-31 Cook Incorporated Endovascular stent and delivery system
US4886062A (en) 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
WO1990013332A1 (en) 1989-05-11 1990-11-15 Cedars-Sinai Medical Center Stent with sustained drug delivery
CA2049973C (en) 1990-02-28 2002-12-24 Rodney G. Wolff Intralumenal drug eluting prosthesis
US5419760A (en) 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5429634A (en) 1993-09-09 1995-07-04 Pdt Systems Biogenic implant for drug delivery and method
US6294192B1 (en) 1999-02-26 2001-09-25 Lipocine, Inc. Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents
AR034257A1 (es) 2000-06-30 2004-02-18 Du Pont Pharm Co Compuesto ureido, composicion farmaceutica que lo comprende y metodo para modular la actividad del receptor de quimiocinas
JP2004506013A (ja) 2000-08-17 2004-02-26 メルク エンド カムパニー インコーポレーテッド シクロペンチル系ケモカイン受容体活性調節剤
IL159256A0 (en) 2001-07-02 2004-06-01 Astrazeneca Ab Piperidine derivatives useful as modulators of chemokine receptor activity
CA2483752C (en) 2002-04-29 2011-03-29 Merck & Co., Inc. Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity
JO2479B1 (en) 2002-04-29 2009-01-20 ميرك شارب اند دوم ليمتد Rates for the activity of the chemokine receptor of tetrahydrobranyl cycloneptil tetrahydrobredo predine
US7166614B2 (en) 2002-04-29 2007-01-23 Merck & Co., Inc. Tetrahydropyranyl cyclopentyl tetrahydroisoquinoline modulators of chemokine receptor activity
US20060030582A1 (en) 2002-04-29 2006-02-09 Demartino Julie Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity
CA2502178A1 (en) 2002-10-30 2004-05-21 Merck & Co., Inc. Heteroarylpiperidine modulators of chemokine receptor activity
WO2004076411A2 (en) 2003-02-24 2004-09-10 Merck & Co., Inc. Aminocyclopentyl fused heterotricylicamide modulators of chemokine receptor activity
CN1787818A (zh) 2003-03-18 2006-06-14 麦克公司 趋化因子受体活性的氨基环丁基酰胺调节剂
CA2521950C (en) 2003-04-15 2009-11-17 Merck & Co., Inc. Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors
CN100384856C (zh) 2003-04-17 2008-04-30 麦克公司 趋化因子受体活性调节剂杂环基环戊基四氢异喹啉和杂环基环戊基四氢吡啶并吡啶
WO2004110376A2 (en) 2003-06-06 2004-12-23 Merck & Co., Inc. Ccr-2 antagonists for treatment of neuropathic pain
CN1870998B (zh) 2003-10-27 2010-10-20 默沙东公司 Ccr-2拮抗剂盐
AR045875A1 (es) 2003-10-27 2005-11-16 Merck & Co Inc Procedimiento para la preparacion del antagonista ccr-2
JP2007519633A (ja) 2004-01-02 2007-07-19 メルク エンド カムパニー インコーポレーテッド アルキルアミノ、アリールアミノおよびスルホンアミドシクロペンチルアミド系のケモカイン受容体活性調節剤
WO2005080371A1 (en) 2004-02-12 2005-09-01 Merck & Co., Inc. Amino heterocyclic modulators of chemokine receptor activity
MXPA06013112A (es) 2004-05-11 2007-02-14 Incyte Corp 3-(4-heteroarilciclohexilamino)ciclopentanocarboxamidas como moduladores de receptores de quimiocinas.
UY29219A1 (es) 2004-11-22 2006-04-28 Incyte Corp Sales de la n-(2- (((3r)-1-(trans-4-hidroxi-4-(6-metoxipiridin-3-il)-cilohexil) pirrolidin-3-il)amino)-2-oxoetil)-3- (trifluorometil) benzamida
US20080194548A1 (en) 2005-01-06 2008-08-14 Forrest Michael J Drug Combination Therapy and Pharmaceutical Compositions for Treating Inflammatory Disorders
US8519135B2 (en) 2006-07-14 2013-08-27 Chemocentryx, Inc. Heteroaryl sulfonamides and CCR2/CCR9
US7671062B2 (en) 2006-07-28 2010-03-02 Bristol-Myers Squibb Company Modulators of chemokine receptor activity, crystalline forms and process
ES2616355T3 (es) 2007-06-18 2017-06-12 Merck Sharp & Dohme B.V. Anticuerpos para el receptor humano de muerte programada PD-1
WO2009009740A1 (en) 2007-07-12 2009-01-15 Chemocentryx, Inc. Fused heteroaryl pyridyl and phenyl benzenesuflonamides as ccr2 modulators for the treament of inflammation
WO2009114335A2 (en) 2008-03-12 2009-09-17 Merck & Co., Inc. Pd-1 binding proteins
KR101814408B1 (ko) 2008-09-26 2018-01-04 다나-파버 캔서 인스티튜트 인크. 인간 항-pd-1, pd-l1, 및 pd-l2 항체 및 그의 용도
AU2009324723B2 (en) 2008-12-10 2015-07-09 Janssen Pharmaceutica Nv 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of CCR2
JP5844159B2 (ja) 2009-02-09 2016-01-13 ユニヴェルシテ デクス−マルセイユUniversite D’Aix−Marseille Pd−1抗体およびpd−l1抗体ならびにその使用
ES2539161T3 (es) 2009-04-16 2015-06-26 Janssen Pharmaceutica Nv Antagonistas 4-azetidinil-1-heteroaril-ciclohexano de CCR2
KR20120006544A (ko) 2009-04-17 2012-01-18 얀센 파마슈티카 엔.브이. Ccr2의 4-아제티디닐-1-페닐-사이클로헥산 길항제
ES2674275T3 (es) 2009-12-17 2018-06-28 Centrexion Therapeutics Corporation Antagonistas del receptor CCR2 y usos de los mismos
EP2534158B1 (en) 2010-02-09 2014-01-08 Bristol-Myers Squibb Company Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity
JP2013526507A (ja) 2010-05-12 2013-06-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規ccr2受容体アンタゴニスト、その製造方法及び薬物としてのその使用
US8642622B2 (en) 2010-06-16 2014-02-04 Bristol-Myers Squibb Company Piperidinyl compound as a modulator of chemokine receptor activity
CN103097375B (zh) 2010-06-17 2015-08-12 詹森药业有限公司 Ccr2的环己基-氮杂环丁烷拮抗剂
PL2684880T3 (pl) 2011-03-10 2018-07-31 Daiichi Sankyo Company, Limited Pochodna dispiropirolidyny
DK2785375T3 (da) 2011-11-28 2020-10-12 Merck Patent Gmbh Anti-pd-l1-antistoffer og anvendelser deraf
US8822460B2 (en) 2012-04-06 2014-09-02 Janssen Pharmaceutica Nv Fused cyclopentyl antagonists of CCR2
SG10201700698WA (en) 2012-05-15 2017-02-27 Bristol Myers Squibb Co Cancer immunotherapy by disrupting pd-1/pd-l1 signaling
EP3556776A1 (en) 2012-05-31 2019-10-23 F. Hoffmann-La Roche AG Methods of treating cancer using pd-1 axis binding antagonists and vegf antagonists
WO2013192596A2 (en) 2012-06-22 2013-12-27 Sorrento Therapeutics Inc. Antigen binding proteins that bind ccr2
US9308236B2 (en) 2013-03-15 2016-04-12 Bristol-Myers Squibb Company Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions
BR112015031073B1 (pt) 2013-06-21 2022-11-29 Zenith Epigenetics Ltd Compostos inibidores bicíclicos de bromodomínio e composição farmacêutica contendo os referidos compostos
JP6586087B2 (ja) 2013-08-20 2019-10-02 メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. Pd−1アンタゴニストとジナシクリブとの組合せでの癌治療
SG11201601225RA (en) 2013-09-04 2016-03-30 Bristol Myers Squibb Co Compounds useful as immunomodulators
TWI680138B (zh) 2014-01-23 2019-12-21 美商再生元醫藥公司 抗pd-l1之人類抗體
US9850225B2 (en) 2014-04-14 2017-12-26 Bristol-Myers Squibb Company Compounds useful as immunomodulators
AU2014405919B2 (en) 2014-09-11 2020-02-20 Bristol-Myers Squibb Company Macrocyclic inhibitors of the PD-1/PD-L1 and CD80 (B7-1)/PD-Li protein/protein interactions
US9732119B2 (en) 2014-10-10 2017-08-15 Bristol-Myers Squibb Company Immunomodulators
US9856292B2 (en) 2014-11-14 2018-01-02 Bristol-Myers Squibb Company Immunomodulators
US9861680B2 (en) 2014-12-18 2018-01-09 Bristol-Myers Squibb Company Immunomodulators
US9944678B2 (en) 2014-12-19 2018-04-17 Bristol-Myers Squibb Company Immunomodulators
US20160222060A1 (en) 2015-02-04 2016-08-04 Bristol-Myers Squibb Company Immunomodulators
US9809625B2 (en) 2015-03-18 2017-11-07 Bristol-Myers Squibb Company Immunomodulators
RU2726206C2 (ru) 2015-05-21 2020-07-09 Кемосентрикс, Инк. Модуляторы ccr2
WO2017165125A1 (en) 2016-03-24 2017-09-28 Millennium Pharmaceuticals, Inc. Use of a pd-1 antagonist and an anti-ccr2 antibody in the treatment of cancer
US10251888B2 (en) 2016-06-13 2019-04-09 Chemocentryx, Inc. Method of treating pancreatic cancer
US10195188B2 (en) 2016-06-13 2019-02-05 Chemocentryx, Inc. Method of treating pancreatic cancer
WO2018005374A1 (en) 2016-06-27 2018-01-04 Chemocentryx, Inc. Immunomodulator compounds
CA3058944A1 (en) * 2017-04-19 2018-10-25 Elstar Therapeutics, Inc. Multispecific molecules and uses thereof
US20190275015A1 (en) 2017-09-25 2019-09-12 Chemocentryx, Inc. Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor
EP3737367A4 (en) 2018-01-08 2022-11-09 ChemoCentryx, Inc. METHODS OF TREATING SOLID TUMORS USING CCR2 ANTAGONISTS
US20190269664A1 (en) 2018-01-08 2019-09-05 Chemocentryx, Inc. Methods of treating solid tumors with ccr2 antagonists
EA202091751A1 (ru) 2018-01-22 2020-11-06 Бристол-Маерс Сквибб Компани Композиции и способы лечения рака
US20200297708A1 (en) 2019-03-19 2020-09-24 Chemocentryx, Inc. Combination Therapy Using a Chemokine Receptor 2 (CCR2) Antagonist and a PD-1 and/or PD-L1 Inhibitor

Also Published As

Publication number Publication date
TW201922287A (zh) 2019-06-16
JP2023181168A (ja) 2023-12-21
WO2019060820A1 (en) 2019-03-28
US20190134049A1 (en) 2019-05-09
IL273188B2 (en) 2023-03-01
EP3687525A1 (en) 2020-08-05
US20230023075A1 (en) 2023-01-26
AR112831A1 (es) 2019-12-18
MA50665A (fr) 2020-08-05
CN111712242B (zh) 2023-11-24
RU2020112755A3 (pt) 2022-03-31
CA3075638A1 (en) 2019-03-28
MX2020003192A (es) 2020-07-29
JP2020535144A (ja) 2020-12-03
KR20200110300A (ko) 2020-09-23
IL273188A (en) 2020-04-30
AU2018335486A1 (en) 2020-03-26
RU2020112755A (ru) 2021-10-28
BR112020005284A2 (pt) 2020-09-24
US11304952B2 (en) 2022-04-19
IL273188B (en) 2022-11-01
EP3687525A4 (en) 2021-10-13
CN111712242A (zh) 2020-09-25
JP7453139B2 (ja) 2024-03-19

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