WO2022250070A1 - ウベニメクスと免疫チェックポイント阻害剤の併用 - Google Patents

ウベニメクスと免疫チェックポイント阻害剤の併用 Download PDF

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Publication number
WO2022250070A1
WO2022250070A1 PCT/JP2022/021320 JP2022021320W WO2022250070A1 WO 2022250070 A1 WO2022250070 A1 WO 2022250070A1 JP 2022021320 W JP2022021320 W JP 2022021320W WO 2022250070 A1 WO2022250070 A1 WO 2022250070A1
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WO
WIPO (PCT)
Prior art keywords
ubenimex
antibody
cancer
administration
tumor
Prior art date
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Ceased
Application number
PCT/JP2022/021320
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English (en)
French (fr)
Japanese (ja)
Inventor
直子 飯河
大地 長井
啓子 関根
倫子 相島
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.)
Nippon Kayaku Co Ltd
Original Assignee
Nippon Kayaku Co Ltd
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 Nippon Kayaku Co Ltd filed Critical Nippon Kayaku Co Ltd
Priority to AU2022280511A priority Critical patent/AU2022280511A1/en
Priority to CA3220025A priority patent/CA3220025A1/en
Priority to CN202280037979.2A priority patent/CN117412762A/zh
Priority to KR1020237040875A priority patent/KR20240016267A/ko
Priority to JP2023523496A priority patent/JPWO2022250070A1/ja
Priority to EP22811340.3A priority patent/EP4349362A4/en
Publication of WO2022250070A1 publication Critical patent/WO2022250070A1/ja
Priority to US18/519,225 priority patent/US20240082196A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Definitions

  • Nivolumab (Opdivo (registered trademark)) and pembrolizumab (Keytruda (registered trademark)) as anti-PD-1 antibodies
  • atezolizumab (Tecentriq (registered trademark))
  • durvalumab (Imfinzi (registered trademark)) as anti-PD-L1 antibodies
  • Avelumab (Bavencio®)
  • an anti-CTLA-4 antibody ipilimumab (Yervoy®) are clinically provided.
  • Anti-PD-1 antibodies, anti-PD-L1 antibodies and anti-CTLA-4 antibodies bind to PD-1, PD-L1 or CTLA-4, which are immune checkpoint molecules for regulating tumor immunity. It is a therapeutic agent that blocks the /PD-L1 or CTLA-4 signal transduction pathway and releases the suppressive mechanism against activated T cells to obtain an antitumor effect.
  • the anti-PD-1 antibody, anti-PD-L1 antibody or anti-CTLA-4 antibody is an antibody that binds to PD-1, PD-L1 or CTLA-4 and has a release of tumor immunosuppressive function. It can be applied without particular limitation.
  • combined administration of Ubenimex and ICI has the effect of suppressing the induction of Treg, which is a suppressor factor in antitumor immunity. Suppression of tumor growth via anti-tumor immunity is effective when it functions together with the induction and activation of CTLs that directly attack cancer cells and the release of tumor immunosuppressive mechanisms.
  • the combined administration of Ubenimex and ICI according to the present invention suppresses the induction of Treg as well as the mechanism that induces tumor-infiltrating lymphocytes into cancer cells, and can provide efficient anti-tumor immunotherapy.
  • doses of Ubenimex may be used in pharmaceutically effective amounts.
  • tyrosine kinase inhibitors such as erlotinib, lapatinib, gefitinib, afatinib, osimertinib, axitinib, sunitinib, sorafenib, regorafenib, lenvatinib, alectinib, crizotinib, and pazopanib.
  • Proteasome inhibitors such as bortezomib, carfilzomib and ixazomib. Cyclin dependent kinase inhibitors such as palbociclib.
  • Tumor Cell Mouse melanoma B16-F0 was obtained from ATCC (The American Type Culture Collection). This was cultured in DMEM (Thermo Fisher Scientific Inc.) containing 10% fetal bovine serum (Corning International, Inc.) and 100 ⁇ g/mL kanamycin sulfate in a CO 2 incubator (37° C., 5% carbon dioxide). I used what I did.
  • the murine colon adenocarcinoma cell line MC38 was obtained from GenOway S.A. A.
  • Example 1.3 Immunophenotyping of Tumor-Infiltrating Lymphocytes After confirming the anti-tumor effect, tumor tissue collected by autopsy was analyzed for tumor-infiltrating lymphocytes by flow cytometry. Immunophenotyping was performed using anti-mouse CD45 antibody, anti-mouse CD3 antibody, anti-mouse CD4 antibody, anti-mouse CD8 antibody, anti-mouse/human CD11b antibody, anti-mouse CD25 antibody, anti-mouse/human FOXP3 antibody, anti-mouse CD16/32 antibody.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/JP2022/021320 2021-05-28 2022-05-25 ウベニメクスと免疫チェックポイント阻害剤の併用 Ceased WO2022250070A1 (ja)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2022280511A AU2022280511A1 (en) 2021-05-28 2022-05-25 Combined use of ubenimex and immune checkpoint inhibitor
CA3220025A CA3220025A1 (en) 2021-05-28 2022-05-25 Combined use of ubenimex and immune checkpoint inhibitor
CN202280037979.2A CN117412762A (zh) 2021-05-28 2022-05-25 乌苯美司与免疫检查点抑制剂的并用
KR1020237040875A KR20240016267A (ko) 2021-05-28 2022-05-25 우베니멕스와 면역관문 저해제의 병용
JP2023523496A JPWO2022250070A1 (https=) 2021-05-28 2022-05-25
EP22811340.3A EP4349362A4 (en) 2021-05-28 2022-05-25 COMBINED USE OF UBENIMEX AND IMMUNE CHECKPOINT INHIBITORS
US18/519,225 US20240082196A1 (en) 2021-05-28 2023-11-27 Combined use of ubenimex and immune checkpoint inhibitor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021089984 2021-05-28
JP2021-089984 2021-05-28

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US18/519,225 Continuation US20240082196A1 (en) 2021-05-28 2023-11-27 Combined use of ubenimex and immune checkpoint inhibitor

Publications (1)

Publication Number Publication Date
WO2022250070A1 true WO2022250070A1 (ja) 2022-12-01

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PCT/JP2022/021320 Ceased WO2022250070A1 (ja) 2021-05-28 2022-05-25 ウベニメクスと免疫チェックポイント阻害剤の併用

Country Status (9)

Country Link
US (1) US20240082196A1 (https=)
EP (1) EP4349362A4 (https=)
JP (1) JPWO2022250070A1 (https=)
KR (1) KR20240016267A (https=)
CN (1) CN117412762A (https=)
AU (1) AU2022280511A1 (https=)
CA (1) CA3220025A1 (https=)
TW (1) TW202313091A (https=)
WO (1) WO2022250070A1 (https=)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012158605A (ja) 2005-05-09 2012-08-23 Ono Pharmaceut Co Ltd ＰｒｏｇｒａｍｍｅｄＤｅａｔｈ１（ＰＤ−１）に対するヒトモノクローナル抗体および抗ＰＤ−１抗体単独または他の免疫療法と併用した癌治療方法
JP2019506438A (ja) 2016-02-24 2019-03-07 チルドレンズ ホスピタル オブ イースタン オンタリオ リサーチ インスティチュート インコーポレイテッド がんの処置のためのｓｍｃ組合せ療法
WO2019175113A1 (en) * 2018-03-12 2019-09-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers
JP2020515600A (ja) 2017-03-31 2020-05-28 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 抗がん併用療法
JP2021506781A (ja) 2017-12-21 2021-02-22 デバイオファーム インターナショナル エス．エー． Ｉａｐアンタゴニスト及び抗ｐｄ−１分子による併用抗癌療法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018112364A1 (en) * 2016-12-16 2018-06-21 Evelo Biosciences, Inc. Combination therapies for treating melanoma
CA3060935A1 (en) * 2017-05-01 2018-11-08 The Children's Medical Center Coporation Methods and compositions relating to anti-pd1 antibody reagents
ES3063234T3 (en) * 2019-12-20 2026-04-15 Formycon Ag Formulations of anti-pd1 antibodies

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012158605A (ja) 2005-05-09 2012-08-23 Ono Pharmaceut Co Ltd ＰｒｏｇｒａｍｍｅｄＤｅａｔｈ１（ＰＤ−１）に対するヒトモノクローナル抗体および抗ＰＤ−１抗体単独または他の免疫療法と併用した癌治療方法
JP2019506438A (ja) 2016-02-24 2019-03-07 チルドレンズ ホスピタル オブ イースタン オンタリオ リサーチ インスティチュート インコーポレイテッド がんの処置のためのｓｍｃ組合せ療法
JP2020515600A (ja) 2017-03-31 2020-05-28 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 抗がん併用療法
JP2021506781A (ja) 2017-12-21 2021-02-22 デバイオファーム インターナショナル エス．エー． Ｉａｐアンタゴニスト及び抗ｐｄ−１分子による併用抗癌療法
WO2019175113A1 (en) * 2018-03-12 2019-09-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Pharmaceutical Interview Form", October 2020, NIPPON KAYAKU CO., LTD., article "Antineoplastic Drugs: Bestatin Capsules 10 mg and Bestatin Capsules 30 mg"
GARANCHER ALEXANDRA; SUZUKI HIROMICHI; HARICHARAN SVASTI; CHAU LIANNE Q.; MASIHI MEHER BEIGI; RUSERT JESSICA M.; NORRIS PAULA S.; : "RETRACTED ARTICLE: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma", NATURE NEUROSCIENCE, vol. 23, no. 7, 18 May 2020 (2020-05-18), New York, pages 842 - 853, XP037641971, ISSN: 1097-6256, DOI: 10.1038/s41593-020-0628-4 *
KEIKO SEKINE: "3782: Investigation of the apoptosis-inducing ability of various aminopeptidase inhibitors including bestatin in tumor cell lines", JAPANESE JOURNAL OF CANCER RESEARCH, vol. 91, no. Suppl., 1 January 2000 (2000-01-01), JP , pages 582, XP009541402, ISSN: 0910-5050 *
See also references of EP4349362A4

Also Published As

Publication number Publication date
KR20240016267A (ko) 2024-02-06
JPWO2022250070A1 (https=) 2022-12-01
TW202313091A (zh) 2023-04-01
US20240082196A1 (en) 2024-03-14
EP4349362A1 (en) 2024-04-10
EP4349362A4 (en) 2025-05-14
CN117412762A (zh) 2024-01-16
AU2022280511A1 (en) 2023-12-14
CA3220025A1 (en) 2022-12-01

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