KR20200074987A - 아데노바이러스 및 이의 용도 - Google Patents
아데노바이러스 및 이의 용도 Download PDFInfo
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- KR20200074987A KR20200074987A KR1020207014975A KR20207014975A KR20200074987A KR 20200074987 A KR20200074987 A KR 20200074987A KR 1020207014975 A KR1020207014975 A KR 1020207014975A KR 20207014975 A KR20207014975 A KR 20207014975A KR 20200074987 A KR20200074987 A KR 20200074987A
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Abstract
Description
도 1은 BLY6.FLuc 및 Ad49.FLuc에 의해 유도되는 세포성 및 체액성 면역 반응을 나타낸다. 도 1A는 실험 구성을 나타낸다. 도 1B는 인터페론 감마(IFN-γ) ELISPOT 분석에 의해 결정한 바와 같은 벡터-암호화된 항원(즉, Fluc, 반딧불이 루시퍼라제)에 대해 Ad26.FLuc, BLY6.FLuc 및 Ad49.FLuc에 의해 유도된 세포성 면역 반응을 나타낸다. y-축은 106개의 비장세포당 스팟 형성 단위(Spot Forming Unit: SFU)의 수를 나타내고, 점선은 배지 자극의 95% 백분위를 나타낸다.
도 2는 BLY6.RSVF-2A-GLuc에 의해 유도되는 세포성 및 체액성 면역 반응을 나타낸다. 도 2a는 실험 구성을 나타낸다. 도 2b는 3가지 상이한 농도(108, 109 및 1010개의 vp)에서 Ad26.RSVF-2A-GLuc로 또는 BLY6.RSVF-2A-GLuc로, 또는 1010개의 vp에서 Ad26.FLuc 또는 BLY6.FLuc로 면역화 후 8주에 수행한 바이러스 중화 분석(virus neutralization assay: VNA) 결과의 그래프를 나타낸다. 도 2c는 IFN-γ ELISPOT 분석에 의해 결정한 바와 같은 면역화 후 Ad26.RSVF-2A-GLuc 및 BLY6.RSVF-2A-GLuc에 의해 유도되는 세포성 면역 반응을 나타낸다. 도 2d는 면역화 후 8주에 면역화된 마우스의 혈청에서 Ad26.RSVF-2A-GLuc 또는 BLY6.RSVF-2A-GLuc에 의해 유도되는 RSVF-특이적 IgG 결합 항체의 그래프를 나타낸다.
도 3은 아데노바이러스 벡터 Ad35, Ad26, Ad49, Ad5, Ad4 및 BLY6으로 면역화된 마우스에서 유도된 상동성 및 이종성 아데노바이러스 중화 역가를 나타낸다.
도 4는 미국(US) 및 유럽 연합(EU)에 살고 있는 18세 내지 55세의 성인으로부터의 200개의 인간 코호트 혈청 샘플에서의 Ad35, Ad26, Ad5 및 BLY6의 혈청유병률을 나타낸다. 각각의 벡터에 대해 이들 혈청에서 측정한 중화 역가를 4개의 범주로 나누고(16 미만(음성), 16 내지 300, 300 내지 1,000, 1000 내지 4000 및 4000 초과), 표시한 바와 같이 차트에 나타내었다.
도 5는 플라스미드 pBLY6.dE1.dE3(서열번호 8)의 개략도를 나타낸다.
도 6은 플라스미드 pBLY6.dE1.dE3.5IXp(서열번호 9)의 개략도를 나타낸다.
도 7은 BLY6 헥손 폴리펩티드(서열번호 2) 및 SAdV-30-1 헥손 폴리펩티드(서열번호 4) 서열의 정렬을 나타낸다.
도 8은 생성 세포주 sPER.C6에서 신규한 벡터 BLY6.Fluc의 생산성을 나타낸다.
Claims (17)
- 서열번호 1의 아미노산 서열 또는 상기 서열번호 1의 아미노산 서열에 대해 전체 길이에 걸쳐 적어도 95% 동일한 아미노산 서열을 갖는 헥손(hexon) 초가변 영역-포함 폴리펩티드를 포함하는 헥손 폴리펩티드 또는 이의 기능성 유도체를 암호화하는, 단리된 핵산 서열.
- 제1항에 있어서, 상기 헥손 폴리펩티드는 상기 서열번호 1의 아미노산 서열을 갖는 헥손 초가변 영역-포함 폴리펩티드를 포함하는, 단리된 핵산 서열.
- 제2항에 있어서, 상기 헥손 폴리펩티드 또는 이의 기능성 유도체는 서열번호 2의 아미노산 서열 또는 상기 서열번호 2의 아미노산 서열에 대해 전체 길이에 걸쳐 적어도 95% 동일한 아미노산 서열을 포함하는, 단리된 핵산 서열.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 섬유 폴리펩티드 또는 이의 기능성 유도체를 암호화하는 핵산 서열을 더 포함하는, 단리된 핵산 서열.
- 제4항에 있어서, 상기 섬유 폴리펩티드는: (1) 서열번호 10의 아미노산 서열을 포함하는 섬유 노브(knob) 폴리펩티드 서열, (2) 서열번호 11의 아미노산 서열을 포함하는 섬유 샤프트(shaft) 폴리펩티드 서열, 및 (3) 서열번호 12의 아미노산 서열을 포함하는 섬유 꼬리 폴리펩티드 서열로 이루어진 군으로부터 선택된 적어도 하나를 포함하며, 바람직하게는 상기 섬유 폴리펩티드 또는 이의 기능성 유도체는 서열번호 3의 아미노산 서열 또는 상기 서열번호 3의 아미노산 서열에 대해 전체 길이에 걸쳐 적어도 95% 동일한 아미노산 서열을 포함하는, 단리된 핵산 서열.
- (1) 서열번호 10의 아미노산 서열을 포함하는 섬유 노브 폴리펩티드 서열; (2) 서열번호 11의 아미노산 서열을 포함하는 섬유 샤프트 폴리펩티드 서열, 및 (3) 서열번호 12의 아미노산 서열을 포함하는 섬유 꼬리 폴리펩티드 서열로 이루어진 군으로부터 선택된 적어도 하나를 포함하는 섬유 폴리펩티드를 암호화하는, 단리된 핵산 서열.
- 제6항에 있어서, 상기 섬유 폴리펩티드는 서열번호 3의 아미노산 서열을 포함하는, 단리된 핵산 서열.
- 제1항 내지 제7항 중 어느 한 항의 핵산을 포함하는 벡터.
- 제8항에 있어서, 아데노바이러스 벡터이며, 이식유전자를 더 포함하는, 벡터.
- 제9항에 있어서, E1 결실 및 E3 결실 중 적어도 하나를 더 포함하는, 아데노바이러스 벡터.
- 제9항 또는 제10항에 있어서, 상기 아데노바이러스 벡터는 하나 이상의 인간 아데노바이러스 핵산 서열을 포함하는 키메라 아데노바이러스 벡터이고, 바람직하게는 상기 인간 아데노바이러스 핵산 서열은 인간 아데노바이러스-4, 인간 아데노바이러스-5, 인간 아데노바이러스-26 또는 인간 아데노바이러스-35 중 적어도 하나로부터 유래된, 아데노바이러스 벡터.
- 제9항 내지 제11항 중 어느 한 항에 있어서, 서열번호 13 및 서열번호 14로 이루어진 군으로부터 선택된 핵산 서열을 포함하는, 아데노바이러스 벡터.
- 제8항 내지 제12항 중 어느 한 항의 벡터를 포함하는 재조합 세포.
- 벡터의 생산 방법으로서,
(a) 상기 벡터의 생산을 위한 조건 하에 제13항의 재조합 세포를 성장시키는 단계; 및
(b) 상기 재조합 세포로부터 상기 벡터를 단리시키는 단계
를 포함하는, 벡터의 생산 방법. - 제9항 내지 제12항 중 어느 한 항의 아데노바이러스 벡터를 포함하는, 면역원성 조성물.
- 면역 반응의 유도가 필요한 대상체에서의 면역 반응 유도 방법으로서, 제15항의 면역원성 조성물을 상기 대상체에게 투여하는 단계를 포함하는, 면역 반응 유도 방법.
- 제9항 내지 제12항 중 어느 한 항에 따른 아데노바이러스 벡터를 약제학적으로 허용 가능한 담체와 조합하는 단계를 포함하는, 백신의 생산 방법.
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| WO2022211373A1 (ko) * | 2021-03-29 | 2022-10-06 | (주)진매트릭스 | 침팬지 아데노바이러스 혈청형 6의 돌기 유전자로 치환된 재조합 키메릭 아데노바이러스 벡터 및 그 응용 |
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2018
- 2018-10-30 CN CN201880071256.8A patent/CN111372943B/zh active Active
- 2018-10-30 US US16/760,518 patent/US11236361B2/en not_active Expired - Fee Related
- 2018-10-30 KR KR1020207014975A patent/KR20200074987A/ko not_active Ceased
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022211373A1 (ko) * | 2021-03-29 | 2022-10-06 | (주)진매트릭스 | 침팬지 아데노바이러스 혈청형 6의 돌기 유전자로 치환된 재조합 키메릭 아데노바이러스 벡터 및 그 응용 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019086456A8 (en) | 2019-07-18 |
| CN111372943A (zh) | 2020-07-03 |
| JP2021500908A (ja) | 2021-01-14 |
| EP3704138A1 (en) | 2020-09-09 |
| MX2020004488A (es) | 2020-08-13 |
| ZA202002184B (en) | 2022-06-29 |
| MA50502A (fr) | 2020-09-09 |
| WO2019086456A1 (en) | 2019-05-09 |
| CA3078771A1 (en) | 2019-05-09 |
| IL274217A (en) | 2020-06-30 |
| AU2018357912A1 (en) | 2020-04-23 |
| JP7366014B2 (ja) | 2023-10-20 |
| US11236361B2 (en) | 2022-02-01 |
| AU2018357912B2 (en) | 2023-11-09 |
| SG11202003290RA (en) | 2020-05-28 |
| US20210198690A1 (en) | 2021-07-01 |
| EA202091004A1 (ru) | 2020-08-10 |
| CN111372943B (zh) | 2023-12-05 |
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