公开(公告)号：US11638693B2

公开(公告)日：2023-05-02

申请号：US17808519

申请日：2022-06-23

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall

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

Abstract: Provided are vaccines for eliciting an immune response. The vaccines for eliciting an immune response comprise RNA encoding an immunogen, which 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：US20220347097A1

公开(公告)日：2022-11-03

申请号：US17848299

申请日：2022-06-23

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall

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

Abstract: Provided are vaccines for eliciting an immune response. The vaccines for eliciting an immune response comprise RNA encoding an immunogen, which 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：US11026964B2

公开(公告)日：2021-06-08

申请号：US15691042

申请日：2017-08-30

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

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

IPC: A61K31/7088 ,  A61K39/12 ,  C12N15/11 ,  A61K39/155 ,  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：US10532067B2

公开(公告)日：2020-01-14

申请号：US15725858

申请日：2017-10-05

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

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

IPC: A61K31/7088 ,  A61K39/12 ,  C12Q1/00 ,  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：US10307374B2

公开(公告)日：2019-06-04

申请号：US15495066

申请日：2017-04-24

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Luis Brito ,  Michelle C. Archer ,  Andrew Geall ,  Derek O'Hagan ,  Manmohan Singh

IPC: A61K9/107 ,  A61K39/12 ,  A61K39/155 ,  A61K31/713 ,  A61K9/00 ,  A61K39/00

Abstract: This invention generally relates to cationic oil-in-water emulsions that can be used to deliver nucleic acid molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The emulsion particles have an average diameter of about 80 nm to about 180 nm, and the emulsion have an N/P ratio of at least 1.1:1.

公开(公告)号：US20180050059A1

公开(公告)日：2018-02-22

申请号：US15691042

申请日：2017-08-30

Applicant: GLAXOSMITHKLINE BIOLOGICALS, SA

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

IPC: A61K31/7088 ,  A61K39/155 ,  C12N15/11 ,  A61K39/12 ,  A61K39/00

CPC classification number: A61K31/7088 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/55505 ,  A61K2039/55555 ,  A61K2039/55566 ,  C12N15/111 ,  C12N2320/32 ,  C12N2760/18534 ,  C12N2770/36143

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：US11857681B2

公开(公告)日：2024-01-02

申请号：US18231693

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 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：US11786467B2

公开(公告)日：2023-10-17

申请号：US17560019

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：US11759475B2

公开(公告)日：2023-09-19

申请号：US18080090

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：US11759422B2

公开(公告)日：2023-09-19

申请号：US16837115

申请日：2020-04-01

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew Geall ,  Ayush Verma

IPC: A61K9/127 ,  A61K9/00 ,  A61K39/39 ,  A61K9/10 ,  A61K39/155 ,  C12N15/88 ,  A61K39/12 ,  A61K39/00

CPC classification number: A61K9/127 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/1271 ,  A61K39/12 ,  A61K39/155 ,  A61K39/39 ,  C12N15/88 ,  A61K2039/53 ,  A61K2039/55505 ,  A61K2039/55555 ,  C12N2710/16134 ,  C12N2760/18534 ,  C12N2770/36143 ,  C12N2770/36171

Abstract: Nucleic acid immunisation is achieved by delivering RNA encapsulated within a PEGylated liposome. The RNA encodes an immunogen of interest. The PEG has an average molecular mass of between 1 kDa and 3 kDa. Thus the invention provides a liposome having a lipid bilayer encapsulating an aqueous core, wherein: (i) the lipid bilayer comprises at least one lipid which includes a polyethylene glycol moiety, such that polyethylene glycol is present on the liposome's exterior, wherein the average molecular mass of the polyethylene glycol is between 1 kDa and 3 kDa; and (ii) the aqueous core includes a RNA which encodes an immunogen. These liposomes are suitable for in vivo delivery of the RNA to a vertebrate cell and so they are useful as components in pharmaceutical compositions for immunising subjects against various diseases.