Pegylated liposomes and methods of use
Inventors
FOX, Christopher B. • Lin, Susan S. • Carter, Darrick • Van Hoeven, Neal • Abhyankar, Mayuresh M. • Petri, William A.
Assignees
UVA Licensing and Ventures Group • University of Virginia UVA • Access to Advanced Health Institute
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Publication Number
US-12318484-B2
Publication Date
2025-06-03
Expiration Date
Abstract
Provided herein are PEGylated liposomes, and methods of making and using thereof. The PEGylated liposomes comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less. The PEGylated liposomes are stable and capable of delivery of an agent for the generation of an immune response, for example an agent for vaccine, therapeutic, or diagnostic uses. Compositions and methods related to making the PEGylated liposomes and using the PEGylated liposomes for stimulating an immune response are also provided.
Core Innovation
The invention relates to a composition comprising an antigen and a liposome. The liposome comprises cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, and the PEG in the PEGylated lipid has an average molecular weight of about 2000 Daltons. The liposome formulation is defined by a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid of about 9.8:5.7:0.8 or about 18:5.5:3.
The composition also includes agonists comprising GLA and 3M-052, with at least about twice as much GLA as 3M-052 by weight. The GLA comprises a synthetic GLA of formula (V–IX) or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5, and R6 are C11-C20 alkyl and R2 and R4 are C12-C20 alkyl.
The disclosed PEGylated liposome compositions are characterized as nanoliposomes, with particle size described and measurements including Z-average particle size and polydispersity index using dynamic light scattering. The formulations are described as filter sterilizable using defined filter pore sizes, and stability is discussed using polydispersity index thresholds, size maintenance across multiple temperature ranges, and freeze-thaw tolerance.
Claims Coverage
The document provides one independent claim directed to an antigen-and-PEGylated-liposome composition together with agonists comprising GLA and 3M-052. The claim includes four inventive features centered on the liposome composition, the lipid molar ratio, the agonist mixture with a defined weight relationship, and the synthetic GLA structure.
Antigen combined with PEGylated liposome and defined PEG mass
A composition comprising an antigen and a liposome comprising cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein an average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons.
Specified lipid molar ratio of non-PEGylated neutral lipid, cholesterol, and PEGylated lipid
A composition where a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3.
Agonist mixture of GLA and 3M-052 with defined weight relationship
A composition further comprising agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight.
Synthetic GLA of defined alkyl substituent ranges
The composition wherein the GLA comprises a synthetic GLA of formula (V–IX) or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5, and R6 are C11-C20 alkyl and wherein R2 and R4 are C12-C20 alkyl.
Overall, the independent claim coverage centers on combining an antigen with a cholesterol/non-PEGylated-neutral-lipid/PEGylated-lipid liposome with a defined PEG average molecular weight and one of two specified lipid molar ratios, together with an agonist mixture containing GLA and 3M-052 in which GLA is present at least about twice by weight and the GLA is a synthetic GLA with defined alkyl substituent ranges.
Stated Advantages
Reduced depot effect.
Improved Th1-driving capability.
Improved cytokine and mucosal IgA responses.
Enhanced protection in mouse intestinal amebiasis challenge.
Protection against lethal H5N1 in mice and ferrets with reduced lung viral titers.
Broader and/or balanced antibody responses, including Th1 bias and cross-clade neutralization.
Documented Applications
A vaccine context for amebiasis, including use of GLA-3M-052 liposomes for a LecA amebiasis vaccine and testing in a mouse intestinal amebiasis challenge setting.
Influenza-related vaccination/antigen application, including studies involving PEGylated 3M-052 liposomes providing protection against lethal H5N1 challenge in mice and ferrets, with described reductions in lung viral titers and antibody response characteristics.
An immune response characterization context including mucosal IgA and systemic IgG outcomes following intranasal administration, as described for the disclosed PEGylated liposome compositions.
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