公开(公告)号：US20240216276A1

公开(公告)日：2024-07-04

申请号：US18225749

申请日：2023-07-25

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL ,  Ayush VERMA

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

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 campuses 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.

公开(公告)号：US20230114029A1

公开(公告)日：2023-04-13

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: 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：US20230112475A1

公开(公告)日：2023-04-13

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: 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：US20230111669A1

公开(公告)日：2023-04-13

申请号：US18080164

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

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 μg/kg to 150 μg/kg. The delivered RNA can elicit an immune response in the large mammal.

公开(公告)号：US20230110155A1

公开(公告)日：2023-04-13

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: 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：US20220192997A1

公开(公告)日：2022-06-23

申请号：US17683931

申请日：2022-03-01

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL ,  Christian Walter MANDL ,  Derek Thomas O'HAGAN ,  Manmohan SINGH

IPC: A61K9/50 ,  A61K39/155 ,  A61K39/245 ,  C12N15/86 ,  C12N15/88 ,  A61K39/12 ,  A61K9/127 ,  A61K9/00

Abstract: Nucleic acid immunisation is achieved by delivering a self-replicating RNA encapsulated within a small particle. The RNA encodes an immunogen of interest, and the particle may deliver this RNA by mimicking the delivery function of a natural RNA virus. Thus the invention provides a non-virion particle for in vivo delivery of RNA to a vertebrate cell, wherein the particle comprises a delivery material encapsulating a self-replicating RNA molecule which encodes an immunogen. These particles are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

公开(公告)号：US20200230058A1

公开(公告)日：2020-07-23

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

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.

公开(公告)号：US20230381106A1

公开(公告)日：2023-11-30

申请号：US18231693

申请日：2023-08-08

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL

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

CPC classification number: A61K9/127 ,  A61K9/1272 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/12 ,  C12N15/86 ,  C12N2770/36134 ,  A61K39/39

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：US20230381105A1

公开(公告)日：2023-11-30

申请号：US18231692

申请日：2023-08-08

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL

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

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

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：US20230321132A1

公开(公告)日：2023-10-12

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

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