Lion Bioscience Ag

Precision Instrument Design

Other

Navicyte, Inc.

George M Grass

Patrick J Sinko

Glen D Leesman

Daniel A Norris

John E Wehrli

Stephanie Ann Sweetana

A secondary compound library produced by a method of screening a compound library or portion thereof by absorption is provided. The method includes a step (i) that screens a primary compound library or portion thereof having a plurality of test samples containing isolated compounds or isolated mixtures of compounds per test sample by generating an in vivo absorption profile for each of the test samples from initial dose data and from in vitro bioavailability data comprising permeability and solubility data for each of the test samples, wherein the absorption profile includes at least one of rate of absorption, extent of absorption, and concentration of a test sample. Step (ii) produces a secondary compound library that includes at least one compound from the primary compound library having a desired absorption profile.

Method for screening and producing compound libraries

The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data. The PK tool of the invention may be provided as a computer system, as an article of manufacture in the form of a computer-readable medium, or a computer program product and the like. Subsystems and individual components of the PK tool also can be utilized and adapted in a variety of disparate applications for predicting the fate of an administered compound. The PK tool and methods of the invention can be used to screen and design compound libraries, select and design drugs, as well as predict drug efficacy in mammals from in vitro and/or in vivo data of one or more compounds of interest. The PK tool and methods of the invention also finds use in selecting, designing, and preparing drug compounds, and multi-compound drugs and drug formulations (i.e., drug delivery system) for preparation of medicaments for use in treating mammalian disorders.

Pharmacokinetic-based drug design tool and method

The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver: The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data. The PK tool of the invention may be provided as a computer system, as an article of manufacture in the form of a computer-readable medium, or a computer program product and the like. Subsystems and individual components of the PK tool also can be utilized and adapted in a variety of disparate applications for predicting the fate of an administered compound. The PK tool and methods of the invention can be used to screen and design compound libraries, select and design drugs, as well as predict drug efficacy in mammals from in vitro and/or in vivo data of one or more compounds of interest. The PK tool and methods of the invention also finds use in selecting, designing, and preparing drug compounds, and multi-compound drugs and drug formulations (i.e., drug delivery system) for preparation of medicaments for use in treating mammalian disorders.

A disposable or recyclable device is provided for packaging and transporting ready-to-use viable cell monolayers, particularly confluent cell monolayers. The device includes a liquid impervious housing having a housing base defining an interior filled with fluid medium, a plurality of detachable and spatially separated permeable membrane inserts each having a confluent cell monolayer attached thereon, and a removable lid. The permeable membrane inserts are disposed in an interior of the housing in a spatially addressable array and the housing base is sealed by the lid so as to separate the membrane inserts from an external environment and to exclude excess air from the fluid filled interior. The device optionally includes a disposable or recyclable environmental control system for regulating chemical and/or physical conditions during transport. Cell monolayers of the device are protected from mechanical injury so that assays or other experiments requiring even growth and dense cell populations can be performed upon delivery. The device of the invention also can be utilized for packaging and transporting multiple different types of cell monolayers on a variety of solid and microporous substrata, the cells normalized to any desired stage of cell cycle and/or growth, without the need to recalibrate cell cycle or synchronize growth upon receipt.

Packing device for transporting confluent cell monolayers

The invention provides a compact device and simple method for circulating fluid over the surface of a membrane. The device comprises a housing that in combination with the surface of the membrane defines an enclosed volume through which the fluid is circulated. Some embodiments will include a membrane holding layer, a fluid dispersing layer, or both. The membrane holding layer has an opening through it to expose a predetermined surface area of the membrane to the fluid. The dispersing layer has a set of openings, typically slits, through the dispersing layer to disperse fluid over the surface of the membrane. Some embodiments may include electrodes for sensing or applying electrical potential to the membrane. A particularly preferred embodiment comprises a double sided device including a first housing, dispersing layer and membrane holding layer on one side of a membrane and a second housing dispersing layer and membrane holding layer on the other side of the membrane. A separate fluid may be circulated through each housing over the two sides of the membrane. In some embodiments the membrane will be provided with at least one ridge that defines at least two parallel channels in which different types of cells may be held.

Device and method for circulating fluid over a membrane

The invention provides a compact device of simple construction for holding a membrane in contact with a pair of fluids, one on each side of the membrane. According to the invention, the membrane holder comprises a base and an upper cap, with the membrane held between them. Fluids may be circulated over the surfaces of the membrane. Electrode ports are provided through which electrodes may be placed in proximity to the membrane for measuring or applying electrical potential across the membrane. The membrane holder comprises a base, which includes a lower plate and a center plate secured thereto, and an upper cap, which screws into the base by means of a threaded connection between them. The upper cap may be sealed to provide an enclosed volume for holding one of the fluids or the upper cap may be open to provide an open reservoir for holding the fluid. One or more membrane holders according to the invention may be placed in and held by a specially constructed heater stand. The heater stand includes internal channels for circulating a temperature controlled fluid through the heater stand to transfer heat to or from the base of the membrane holder.

Membrane holder

An apparatus for determining transport characteristics across membranes and tissue sections comprises a plurality of cell blocks, where each cell block includes a pair of half-cells which hold the membrane or tissure section therebetween. A circulation path is provided in each half-cell block for exposing a fluid to one side of the membrane or tissue section. The cell blocks are maintained linearly within a base unit including a front plate and a back plate. The front and back plates are heated to maintain the cell blocks at a desired temperature.

Growing community of inventors

Tahoe City, CA, United States of America

George M Grass