公开(公告)号：US11690865B2

公开(公告)日：2023-07-04

申请号：US18080101

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：US11690863B2

公开(公告)日：2023-07-04

申请号：US18065100

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：US11690861B2

公开(公告)日：2023-07-04

申请号：US18065076

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：US10183074B2

公开(公告)日：2019-01-22

申请号：US15467660

申请日：2017-03-23

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

Inventor： Luis Brito ,  Michelle Chan ,  Andrew Geall ,  Derek O'Hagan ,  Manmohan Singh

IPC: A61K9/107 ,  A61K39/00 ,  A61K39/12 ,  A61K47/12 ,  A61K39/39 ,  A61K47/06 ,  A61K47/24 ,  A61K39/155 ,  A61K39/245 ,  A61K47/02 ,  A61K47/22 ,  A61K47/26 ,  A61K47/34 ,  C12N7/00

Abstract: This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

公开(公告)号：US11913001B2

公开(公告)日：2024-02-27

申请号：US17512258

申请日：2021-10-27

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: Provided is RNA encoding an immunogen is delivered to a large mammal at a dose of from 5 μg to 100 μg or at a dose between 0.1 μg per kilogram body mass of the large mammal and 1.5 μg per kilogram body mass of the large mammal. Provided is a method of raising an immune response in a large mammal, comprising administering to the large mammal a dose of from 5 μg to 100 μg or a dose of between 0.1 μg of RNA encoding the immunogen per kilogram body mass of the large mammal and 1.5 μg of RNA encoding the immunogen per kilogram body mass of the large mammal. The delivered RNA can elicit an immune response in the large mammal.

公开(公告)号：US11850305B2

公开(公告)日：2023-12-26

申请号：US18231697

申请日：2023-08-08

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall

IPC: 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 an 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：US11845925B2

公开(公告)日：2023-12-19

申请号：US18065256

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 ,  A61K48/00 ,  A61K39/00

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：US11839686B2

公开(公告)日：2023-12-12

申请号：US17560052

申请日：2021-12-22

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 an 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 neutral surface charge at physiological pH and are effective for immunisation.

公开(公告)号：US11730700B2

公开(公告)日：2023-08-22

申请号：US17560052

申请日：2021-12-22

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 an 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 neutral surface charge at physiological pH and are effective for immunisation.

公开(公告)号：US11596645B2

公开(公告)日：2023-03-07

申请号：US17511762

申请日：2021-10-27

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

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

IPC: A61K39/00 ,  C12N5/00 ,  A61K31/7088 ,  A61K39/12

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.