WO2023136518A1 - Protéine de fusion comprenant un domaine extracellulaire cd80 et un fragment d'anticorps anti-lag3 et utilisation associée - Google Patents

Protéine de fusion comprenant un domaine extracellulaire cd80 et un fragment d'anticorps anti-lag3 et utilisation associée Download PDF

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Publication number
WO2023136518A1
WO2023136518A1 PCT/KR2022/021715 KR2022021715W WO2023136518A1 WO 2023136518 A1 WO2023136518 A1 WO 2023136518A1 KR 2022021715 W KR2022021715 W KR 2022021715W WO 2023136518 A1 WO2023136518 A1 WO 2023136518A1
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Prior art keywords
fusion protein
cancer
seq
region
lag3
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PCT/KR2022/021715
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English (en)
Korean (ko)
Inventor
장명호
조영규
오영민
심예인
Original Assignee
㈜ 지아이이노베이션
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Publication of WO2023136518A1 publication Critical patent/WO2023136518A1/fr

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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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • Figure 5a schematically shows the mechanism of action of GI-105 on MHCII.
  • 8B is a graph showing the change in body weight of mice according to the combined administration of GI-105 and an anti-PD-1 antibody in mice transplanted with a colorectal cancer cell line derived from a mouse overexpressing PD-L1.
  • an immune enhancing agent comprising the fusion protein or a dimer thereof is provided.
  • the term "individual” refers to all animals such as rats, mice, livestock, and the like, including humans. Preferably, it may be a mammal including a human.
  • one or more bases may be mutated by substitution, deletion, insertion, or a combination thereof.
  • a synthesis method well known in the art for example, the method described in the literature (Engels and Uhlmann, Angew Chem IntEd Engl., 37:73-127, 1988) can be used. and triester, phosphite, phosphoramidite and H-phosphate methods, PCR and other auto-primer methods, oligonucleotide synthesis methods on solid supports, and the like.
  • the polynucleotide is at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89% of the nucleic acid sequence of SEQ ID NO: 11 , at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% , or a nucleic acid sequence having at least about 100% identity.
  • the polynucleotide may additionally include a signal sequence or a leader sequence.
  • signal sequence refers to a nucleic acid encoding a signal peptide that directs the secretion of a target protein.
  • the signal peptide is cleaved after translation in the host cell.
  • the signal sequence of the present invention is a polynucleotide encoding an amino acid sequence that initiates movement of a protein through an endoplasmic reticulum (ER) membrane.
  • ER endoplasmic reticulum
  • the transformation may be performed by various methods. As long as the fusion protein of the present invention can be produced, it is not particularly limited thereto. Specifically, the transformation method is a CaCl 2 precipitation method, and a CaCl 2 precipitation method using a reducing material called DMSO (dimethyl sulfoxide) Hanahan method, electroporation, calcium phosphate precipitation, protoplast fusion, agitation using silicon carbide fibers, agrobacteria mediated transformation, transformation using PEG, dextran sulfate, lipofectamine and drying / Suppression mediated transformation methods and the like can be used.
  • a target may be delivered into a cell using virus particles as a means of infection.
  • vectors can be introduced into host cells by gene bombardment or the like.
  • Another aspect of the present invention provides a pharmaceutical composition for treating or preventing cancer comprising the above-described fusion protein or dimer thereof and a PD-1 inhibitor as active ingredients.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne un dimère de protéine de fusion comprenant un domaine extracellulaire de CD80 et un scFv d'un anticorps anti-LAG3. Dans le dimère protéique selon la présente invention, CD80 peut se lier à CTLA-4 de lymphocytes T pour réguler l'activité des lymphocytes T. De plus, dans le dimère protéique selon la présente invention, le scFv de l'anticorps anti-LAG3 peut réguler la liaison de LAG3 à CMHII, par liaison à LAG3. En conséquence, il a été confirmé que le dimère de protéine de fusion comprenant CD80 et scFv de l'anticorps anti-LAG3 active de manière efficace des cellules immunitaires. Par conséquent, le dimère de protéine de fusion selon la présente invention peut être utilisé en tant qu'agent anticancéreux, et présente ainsi une grande aptitude à l'application industrielle.
PCT/KR2022/021715 2022-01-13 2022-12-30 Protéine de fusion comprenant un domaine extracellulaire cd80 et un fragment d'anticorps anti-lag3 et utilisation associée WO2023136518A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020220005131A KR102461837B1 (ko) 2022-01-13 2022-01-13 Cd80 세포외도메인 및 항 lag3 항체 단편을 포함하는 융합 단백질 및 이의 용도
KR10-2022-0005131 2022-01-13

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WO2023136518A1 true WO2023136518A1 (fr) 2023-07-20

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WO (1) WO2023136518A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102461837B1 (ko) * 2022-01-13 2022-11-01 ㈜지아이이노베이션 Cd80 세포외도메인 및 항 lag3 항체 단편을 포함하는 융합 단백질 및 이의 용도

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019185040A1 (fr) * 2018-03-30 2019-10-03 Nanjing Legend Biotech Co., Ltd. Anticorps à domaine unique contre lag-3 et leurs utilisations
KR20210065887A (ko) * 2019-11-27 2021-06-04 (주)지아이이노베이션 Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 면역관문 억제제를 포함하는 암 치료용 약학 조성물
KR20210117220A (ko) * 2020-03-18 2021-09-28 (주)지아이이노베이션 Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 항암제를 포함하는 암 치료용 약학 조성물
KR102461837B1 (ko) * 2022-01-13 2022-11-01 ㈜지아이이노베이션 Cd80 세포외도메인 및 항 lag3 항체 단편을 포함하는 융합 단백질 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019185040A1 (fr) * 2018-03-30 2019-10-03 Nanjing Legend Biotech Co., Ltd. Anticorps à domaine unique contre lag-3 et leurs utilisations
KR20210065887A (ko) * 2019-11-27 2021-06-04 (주)지아이이노베이션 Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 면역관문 억제제를 포함하는 암 치료용 약학 조성물
KR20210117220A (ko) * 2020-03-18 2021-09-28 (주)지아이이노베이션 Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 항암제를 포함하는 암 치료용 약학 조성물
KR102461837B1 (ko) * 2022-01-13 2022-11-01 ㈜지아이이노베이션 Cd80 세포외도메인 및 항 lag3 항체 단편을 포함하는 융합 단백질 및 이의 용도

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ALESSANDRO ASCIONE, ARENACCIO CLAUDIA, MALLANO ALESSANDRA, FLEGO MICHELA, GELLINI MARA, ANDREOTTI MAURO, FENWICK CRAIG, PANTALEO G: "Development of a novel human phage display-derived anti-LAG3 scFv antibody targeting CD8+ T lymphocyte exhaustion", BMC BIOTECHNOLOGY, BIOMED CENTRAL, vol. 19, 17 October 2019 (2019-10-17), pages 1 - 15, XP055673119, DOI: 10.1186/s12896-019-0559-x *
CHEN, X. ET AL.: "Construction, expression and functional detection of fusion gene of CD80 extracellular region and anti-human CD33 scFV", XI BAO YU FEN ZI MIAN YI XUE ZA ZHI, vol. 30, no. 2, 2014, pages 179 - 183, XP009547730 *

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