公开(公告)号：US11291682B2

公开(公告)日：2022-04-05

申请号：US16512541

申请日：2019-07-16

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K31/7088 ,  A61K39/12 ,  A61K39/00

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

公开(公告)号：US20180085388A1

公开(公告)日：2018-03-29

申请号：US15725858

申请日：2017-10-05

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Franz Mandl

IPC: A61K31/7088 ,  A61K39/12 ,  A61K39/00

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

公开(公告)号：US12186333B2

公开(公告)日：2025-01-07

申请号：US18333591

申请日：2023-06-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K39/09 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/12

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

公开(公告)号：US12018044B2

公开(公告)日：2024-06-25

申请号：US17157150

申请日：2021-01-25

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Francesco Berlanda Scorza ,  Yingxia Wen ,  Andrew Geall ,  Frederick Porter

IPC: C12Q1/68 ,  B01D15/36 ,  B01D15/38 ,  B01D61/14 ,  C07H1/06 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/10

CPC classification number: C07H21/02 ,  B01D15/36 ,  B01D15/38 ,  B01D15/3847 ,  B01D61/14 ,  C07H1/06 ,  C07H21/00 ,  C07H21/04 ,  C12N15/101 ,  C12N15/1017 ,  B01D2015/3838

Abstract: Methods for purifying RNA from a sample, comprising one or more steps of tangential flow filtration, hydroxyapatite chromatography, core bead flow-through chromatography, or any combinations thereof. These techniques are useful individually, but show very high efficiency when used in combination, or when performed in particular orders. The methods can purify RNA in a highly efficient manner without unduly compromising potency or stability, to provide compositions in which RNA is substantially cleared of contaminants. Moreover, they can be performed without the need for organic solvents.

公开(公告)号：US11883534B2

公开(公告)日：2024-01-30

申请号：US18231692

申请日：2023-08-08

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall

IPC: A61K48/00 ,  A61K9/127 ,  A61K39/12 ,  C12N15/86 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/39

CPC classification number: A61K9/127 ,  A61K9/1272 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  C12N15/86 ,  A61K39/39 ,  A61K2039/53 ,  A61K2039/55555 ,  C12N2710/16134 ,  C12N2760/18534 ,  C12N2770/36134

Abstract: RNA encoding immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially a neutral surface charge at physiological pH and are effective for immunisation.

公开(公告)号：US11857562B2

公开(公告)日：2024-01-02

申请号：US18065111

申请日：2022-12-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K39/00 ,  A61K39/12 ,  A61K31/7088

CPC classification number: A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/55555 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2770/36143

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

公开(公告)号：US11739334B2

公开(公告)日：2023-08-29

申请号：US18065230

申请日：2022-12-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall

IPC: C12N15/117 ,  C12N15/86 ,  A61K39/155 ,  A61K39/39 ,  A61K39/12 ,  A61P31/12 ,  A61P37/04 ,  A61K39/00 ,  A61K48/00

CPC classification number: C12N15/117 ,  A61K39/12 ,  A61K39/155 ,  A61K39/39 ,  A61K48/0041 ,  A61K48/0083 ,  A61P31/12 ,  A61P37/04 ,  C12N15/86 ,  A61K2039/53 ,  A61K2039/552 ,  A61K2039/55555 ,  A61K2039/55566 ,  C12N2760/18534 ,  C12N2770/36143 ,  C12N2820/60

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

公开(公告)号：US11730754B2

公开(公告)日：2023-08-22

申请号：US18065083

申请日：2022-12-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K39/12 ,  A61K39/00 ,  A61K31/7088

CPC classification number: A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/55555 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2770/36143

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

公开(公告)号：US11707482B2

公开(公告)日：2023-07-25

申请号：US18065109

申请日：2022-12-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K39/00 ,  A61K39/12 ,  A61K31/7088

CPC classification number: A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/55555 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2770/36143

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

公开(公告)号：US11690864B2

公开(公告)日：2023-07-04

申请号：US18065106

申请日：2022-12-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Katrin Ramsauer ,  Gillis Otten ,  Christian Walter Mandl

IPC: A61K39/00 ,  A61K39/12 ,  A61K31/7088

CPC classification number: A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/55555 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2770/36143

Abstract: RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.