Verily Life Sciences LLC

Stephen Morton

Zhan Wang

Kimberly Kam

Nicole Peck

Graziella Solinas

Zach Scott

James Michael Higbie

Joshua Simon Klein

Mark Audeh

Anthony M Giannetti

The present invention provides methods and systems for producing liposomes by filtration. The methods include passing a heated lipid suspension through a filter assembly comprising two or more filters connected in series, wherein an orifice is disposed between adjacent filters. The methods and systems can produce liposomes having an average diameter that is less than half the diameter of the filter pores. Further, the methods and systems can produce liposomes with <100 nm average diameter, even when the liposomes comprise at least 30% sterol.

Serial filtration to generate small cholesterol-containing liposomes

Provided herein are encapsulated liposomes comprising a lipid bilayer, a first polyethylene glycol (PEG) corona, a targeting molecule and a second PEG corona. The second, encapsulating PEG corona can be reversibly linked to the first PEG corona. Also provided are pharmaceutical compositions comprising the encapsulated liposomes and methods of treating a subject with a disease characterized by production of reactive oxygen species (ROS) with the compositions. Also provided are methods of making the encapsulated liposomes disclosed herein.

ROS-responsive liposomes for specific targeting

Provided herein are liposomal vesicles comprising at least a first lipid bilayer and a second lipid bilayer, and a plurality of crosslinkages between the first lipid bilayer and the second lipid bilayer, wherein the plurality of crosslinkages comprise boronic ester or thioketal bonds. Also provided are pharmaceutical compositions comprising the liposomal vesicles described herein and a pharmaceutically acceptable excipient. Also provided are methods of making and using the liposomal vesicles. Thus, a method of treating a subject with a disease comprising administering to the subject a pharmaceutical composition comprising the liposomal vesicles is described herein. Methods of making multilamellar liposomal vesicles responsive to reactive oxygen species are also provided.

ROS-responsive multilamellar liposomal vesicles for targeting inflammatory macrophages

The present invention provides methods and systems for producing liposomes by filtration. The methods include passing a heated lipid suspension through a filter assembly comprising two or more filters connected in series, wherein an orifice is disposed between adjacent filters. The methods and systems can produce liposomes having an average diameter that is less than half the diameter of the filter pores. Further, the methods and systems can produce liposomes with &#x3c;100 nm average diameter, even when the liposomes comprise at least 30% sterol.

Disclosed herein are methods for producing bi-directionally crosslinked liposomes. The methods include the steps of: providing a lipid composition comprising a plurality of reactive lipids, wherein each of the reactive lipids comprises a reactive hydrophobic group, a reactive hydrophilic group, or a reactive hydrophilic group and a reactive hydrophobic group; forming an un-crosslinked liposome comprising the reactive lipids; and crosslinking at least a portion of the reactive hydrophobic groups or the reactive hydrophilic groups; thereby producing the bi-directionally crosslinked liposomes. Bi-directionally crosslinked liposomes and methods for delivering therapeutic and/or diagnostic agents to subjects using the liposomes are also described.

Bi-directionally crosslinked liposomes and method of making same

Provided herein is a tumor associated macrophage (TAM)-targeting liposome. The liposome has a lipid bilayer, a targeting agent associated with the lipid bilayer, and a repolarizing agent associated with the lipid bilayer. The targeting agent optionally comprises an antibody or fragment thereof that selectively binds a TAM, whereas the repolarizing agent repolarizes the TAM upon binding of the TAM by the targeting agent. Also provided is a pharmaceutical composition comprising the TAM-targeting liposomes and a method of treating a subject with cancer with the compositions or liposomes described herein.

Targeted therapy to repolarize tumor-associated macrophages (TAMs)

Provided herein are tumor associated macrophage (TAM)-targeting liposome having a lipid bilayer; a targeting agent associated with the lipid bilayer, wherein the targeting agent comprises an antibody or fragment thereof that selectively binds a tumor associated macrophage; and a cytotoxic agent associated with the lipid bilayer, wherein the cytotoxic agent depletes tumor associated macrophages at or near the site of a tumor. Also provided are pharmaceutical compositions comprising the TAM-targeting liposomes and methods of treating a subject with cancer with the compositions.

Targeted therapy to deplete tumor-associated macrophages (TAMs)

ROS&#x2014;responsive liposomes for specific targeting

Body-mountable devices are provided to detect the presence or status of an analyte in subsurface vasculature of a body by detecting fluorescent reporters that are bound to instances of the analyte in the subsurface vasculature. Such devices further operate to exert an attractive magnetic force on magnetic nanoparticle-containing probes that are configured to bind to the analyte, thus concentrating the analyte proximate the devices by magnetically exerting attractive forces on such probes that are bound to instances of the analyte. The analyte can be an extracellular vesicle that is characteristic of a cancer, and a body-mountable device as described herein could be used to detect such extracellular vesicles in a portion of subsurface vasculature such that a presence or status of a tumor could be determined based on an amount, presence, or other detected property of the extracellular vesicle.

Growing community of inventors

Mountain View, CA, United States of America

Stephen Morton