Invention Grant
- Patent Title: Modified hexa-acylated neisserial LPS
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Application No.: US16072895Application Date: 2017-01-27
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Publication No.: US11292808B2Publication Date: 2022-04-05
- Inventor: Afshin Zariri , Elder Pupo Escalona , Peter André Van Der Ley
- Applicant: De Staat der Nederlanden, vert. door de minister van VWS, Ministerie van Volksgezondheid, Welzijn en Sport
- Applicant Address: NL The Hague
- Assignee: De Staat der Nederlanden, vert. door de minister van VWS, Ministerie van Volksgezondheid, Welzijn en Sport
- Current Assignee: De Staat der Nederlanden, vert. door de minister van VWS, Ministerie van Volksgezondheid, Welzijn en Sport
- Current Assignee Address: NL The Hague
- Agency: N.V. Nederlandsch Octrooibureau
- Priority: NL2016170 20160128
- International Application: PCT/EP2017/051801 WO 20170127
- International Announcement: WO2017/129761 WO 20170803
- Main IPC: C07H15/06
- IPC: C07H15/06 ; C12N1/20 ; A61K39/095 ; A61P31/04 ; A61K31/7024 ; C12R1/36

Abstract:
The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous lpxL1 gene and to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa- and penta-acylated LPS. By selecting the time and/or temperature at which the bacterium is grown, it is feasible to increase or decrease the amount of hexa-acylated lipid A structure relative to the corresponding penta-acylated structure and thereby modulate the TLR4 agonist activity of the neisserial LPS of the invention, to the exact level of activity required for a particular immunotherapeutic approach.
Public/Granted literature
- US20190031700A1 Modified hexa-acylated neisserial LPS Public/Granted day:2019-01-31
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