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1. WO2022139490 - NOVEL MODIFIED REOVIRUS AND USE THEREOF

Publication Number WO/2022/139490
Publication Date 30.06.2022
International Application No. PCT/KR2021/019663
International Filing Date 22.12.2021
IPC
A61K 35/765
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
35Medicinal preparations containing materials or reaction products thereof with undetermined constitution
66Microorganisms or materials therefrom
76Viruses; Subviral particles; Bacteriophages
765Reovirus; Rotavirus
A61P 35/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
CPC
A61K 35/765
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
35Medicinal preparations containing materials or reaction products thereof with undetermined constitution
66Microorganisms or materials therefrom
76Viruses; Subviral particles; Bacteriophages
765Reovirus; Rotavirus
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
Applicants
  • 바이로큐어 주식회사 VIROCURE, INC. [KR]/[KR]
Inventors
  • 유행준 YOO, Haeng Jun
  • 한상경 HAN, Sang Kyoung
  • 이연숙 LEE, Yeon Sook
  • 송기훈 SONG, Ki Hoon
  • 간수크엔크타이반 GANSUKH, Enkhtaivan
Agents
  • 이명진 LEE, Myoung-Jin
Priority Data
10-2020-018082422.12.2020KR
10-2021-018494722.12.2021KR
Publication Language Korean (ko)
Filing Language Korean (KO)
Designated States
Title
(EN) NOVEL MODIFIED REOVIRUS AND USE THEREOF
(FR) NOUVEAU RÉOVIRUS MODIFIÉ ET SON UTILISATION
(KO) 신규한 변형 레오바이러스 및 이의 용도
Abstract
(EN) The present invention relates to a modified reovirus and use thereof, and has been completed by confirming that a novel modified reovirus derived from a wild-type reovirus not only has an excellent anticancer effect on various cancers, including rare cancers, but can also enhance the effect of cancer immunotherapy agents. Particularly, it was confirmed that the modified reovirus according to the present invention significantly reduced the cell viability of all cancer cell lines when used to treat various types of cancer cells, including rare cancers such as melanoma and tongue cancer, and in particular, had an excellent anticancer effect even on taxane-based anticancer drug-resistant cancer cell lines. Furthermore, the modified reovirus according to the present invention exhibited a dose-dependent anticancer effect even in melanoma, bladder cancer and oral cancer mouse models regardless of administration routes, and the anticancer effect was shown to be further increased upon repeated administration or alternate administration with a wild-type reovirus. In particular, it was confirmed that the modified reovirus according to the present invention exhibited a synergistic anticancer effect when used in combination with an immune checkpoint inhibitor. Therefore, the modified reovirus according to the present invention is expected to be effectively used as a new anticancer therapy for treating rare cancers and the like and as a drug used in combination with a cancer immunotherapy agent.
(FR) La présente invention concerne un réovirus modifié et son utilisation, et a été achevée par la confirmation qu'un nouveau réovirus modifié dérivé d'un réovirus de type sauvage a non seulement un excellent effet anticancéreux sur divers cancers, y compris des cancers rares, mais peut également améliorer l'effet d'agents d'immunothérapie anticancéreuse. En particulier, il a été confirmé que le réovirus modifié selon la présente invention réduisait significativement la viabilité cellulaire de toutes les lignées cellulaires cancéreuses lorsqu'il est utilisé pour traiter divers types de cellules cancéreuses, y compris des cancers rares tels que le mélanome et le cancer de la langue, et en particulier, qu'il présentait un excellent effet anticancéreux même sur des lignées cellulaires cancéreuses résistantes aux médicaments anticancéreux à base de taxane. En outre, le réovirus modifié selon la présente invention présentait un effet anticancéreux dépendant de la dose même dans des modèles de souris souffrant de mélanome, de cancer de la vessie et de cancer de la bouche indépendamment des voies d'administration, et il a été démontré que l'effet anticancéreux était en outre accru lors d'une administration répétée ou d'une administration alternée avec un réovirus de type sauvage. En particulier, il a été confirmé que le réovirus modifié selon la présente invention présentait un effet anticancéreux synergique lorsqu'il était utilisé en combinaison avec un inhibiteur de point de contrôle immunitaire. Par conséquent, le réovirus modifié selon la présente invention devrait être utilisé efficacement en tant que nouvelle thérapie anticancéreuse pour le traitement de cancers rares et similaires et en tant que médicament utilisé en combinaison avec un agent d'immunothérapie anticancéreuse.
(KO) 본 발명은 변형 레오바이러스 및 이의 용도에 관한 것으로서, 야생형 레오바이러스로부터 유도한 신규한 변형 레오바이러스가 희귀암을 포함한 다양한 암에 대해 우수한 항암효과를 가질 뿐만 아니라, 면역항암제의 효과를 증강시킬 수 있음을 확인하여 완성된 것이다. 구체적으로, 본 발명에 따른 변형 레오바이러스는 흑색종, 설암 등의 희귀암을 포함한 다양한 종류의 암세포에 처리되었을 때 모든 암세포주의 생존율을 현저히 감소시켰으며, 특히 탁산계 항암제-내성 암세포주에 대해서도 우수한 항암효과를 갖는 것이 확인되었다. 나아가 본 발명에 따른 변형 레오바이러스는 흑색종, 방광암, 및 구강암 마우스 모델에서도 투여경로에 상관 없이 용량-의존적인 항암효과를 발휘하였으며, 반복투여하거나 야생형 레오바이러스와의 교차투여시 항암효과가 더욱 증가하는 것으로 나타났다. 특히, 본 발명에 따른 변형 레오바이러스는 면역관문 억제제와 병용하면 시너지적인 항암효과를 일으키는 것이 확인되었다. 따라서 본 발명에 따른 변형 레오바이러스는 희귀암 등을 치료하기 위한 새로운 항암 요법이자 면역항암제의 병용 약물로 유용히 활용될 것으로 기대된다.
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