公开(公告)号：US20230116636A1

公开(公告)日：2023-04-13

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: 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：US20230114607A1

公开(公告)日：2023-04-13

申请号：US18065089

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：US20210290755A1

公开(公告)日：2021-09-23

申请号：US17330826

申请日：2021-05-26

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL ,  Gillis OTTEN ,  Susan BARNETT

IPC: A61K39/155 ,  A61K39/245 ,  A61K39/12 ,  A61P31/20 ,  A61P31/14

Abstract: This invention generally relates to immunogenic compositions that comprise an RNA component and a polypeptide component. Immunogenic compositions that deliver antigenic epitopes in two different forms—a first epitope from a pathogen, in RNA-coded form; and a second epitope from the same pathogen, in polypeptide form—are effective in inducing immune response to the pathogen. The invention also relates to a kit comprising an RNA-based priming composition and a polypeptide-based boosting composition. The kit may be used for sequential administration of the priming and the boosting compositions.

公开(公告)号：US20160024139A1

公开(公告)日：2016-01-28

申请号：US14775760

申请日：2014-03-13

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Francesco BERLANDA SCORZA ,  Yingxia WEN ,  Andrew GEALL ,  Frederick PORTER

IPC: C07H21/02 ,  B01D15/36 ,  B01D15/38 ,  C07H1/06

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

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.

Abstract translation: 用于从样品中纯化RNA的方法，包括一个或多个切向流过滤步骤，羟基磷灰石层析，芯珠流通层析或其任何组合。 这些技术可以单独使用，但是当组合使用时，或者特别是以特定顺序执行时，显示出非常高的效率。 该方法可以高效地纯化RNA，而不会不利地影响效力或稳定性，以提供RNA基本上不含污染物的组合物。 此外，它们可以在不需要有机溶剂的情况下进行。

公开(公告)号：US20240300994A1

公开(公告)日：2024-09-12

申请号：US18664453

申请日：2024-05-15

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Francesco BERLANDA SCORZA ,  Yingxia WEN ,  Andrew GEALL ,  Frederick PORTER

IPC: C07H21/02 ,  B01D15/36 ,  B01D15/38 ,  B01D61/14 ,  C07H1/06 ,  C07H21/00 ,  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：US20240016736A1

公开(公告)日：2024-01-18

申请号：US18114434

申请日：2023-02-27

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL ,  Ayush VERMA

IPC: A61K9/127 ,  A61K9/00 ,  A61P31/14 ,  A61K39/12 ,  C12N15/88 ,  A61K31/713

CPC classification number: A61K9/127 ,  A61K9/1271 ,  A61K9/0019 ,  A61P31/14 ,  A61K39/12 ,  C12N15/88 ,  A61K31/713 ,  C12N2710/16134 ,  A61K2039/57

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 above 3 kDa but less than 11 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 above 3 kDa but less than 11 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：US20230113210A1

公开(公告)日：2023-04-13

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

公开(公告)号：US20230110963A1

公开(公告)日：2023-04-13

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: 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：US20220125726A1

公开(公告)日：2022-04-28

申请号：US17560116

申请日：2021-12-22

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL

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

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：US20220125723A1

公开(公告)日：2022-04-28

申请号：US17560052

申请日：2021-12-22

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

Inventor： Andrew GEALL

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

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.