公开(公告)号：US11690862B1

公开(公告)日：2023-07-04

申请号：US18065095

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：US11666534B2

公开(公告)日：2023-06-06

申请号：US17560138

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：US11655475B2

公开(公告)日：2023-05-23

申请号：US16656929

申请日：2019-10-18

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：US11638694B2

公开(公告)日：2023-05-02

申请号：US17848299

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：US20220362152A1

公开(公告)日：2022-11-17

申请号：US17808519

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：US20220331248A1

公开(公告)日：2022-10-20

申请号：US17848337

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 methods for eliciting an immune response, the methods comprising administering a vaccine to a subject. 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：US11155572B2

公开(公告)日：2021-10-26

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

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：US20170224616A1

公开(公告)日：2017-08-10

申请号：US15495066

申请日：2017-04-24

Applicant: GLAXOSMITHKLINE BIOLOGICALS SA

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

IPC: A61K9/107 ,  A61K39/12

CPC classification number: A61K9/107 ,  A61K9/0019 ,  A61K31/713 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/53 ,  A61K2039/55566 ,  C12N2760/18534 ,  Y02A50/412 ,  Y02A50/489

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：US20170202960A1

公开(公告)日：2017-07-20

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

CPC classification number: A61K39/39 ,  A61K9/1075 ,  A61K39/12 ,  A61K39/155 ,  A61K39/245 ,  A61K47/02 ,  A61K47/06 ,  A61K47/12 ,  A61K47/22 ,  A61K47/24 ,  A61K47/26 ,  A61K47/34 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/55555 ,  A61K2039/55566 ,  A61K2039/575 ,  C12N7/00 ,  C12N2710/16134 ,  C12N2710/16171 ,  C12N2710/16734 ,  C12N2710/16771 ,  C12N2760/18534 ,  C12N2760/18571 ,  C12N2770/36134 ,  C12N2770/36143 ,  C12N2840/203 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/412

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.