Systems and methods for rapidly identifying useful chemicals in liquid samples

• US 6,472,218 B1
• Filed: 04/21/1999
• Issued: 10/29/2002
• Est. Priority Date: 05/16/1997
• Status: Expired due to Term

• Current Assignee: Aurora Biotechnologies, Inc. (Azenta, Inc.)
• Original Assignee: Vertex Pharmaceuticals San Diego LLC (Vertex Pharmaceuticals Incorporated)
• Inventors: Beckey, Samuel S., Coassin, Peter J., Stylli, Chari, Shumate, Christopher Bentley
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): WRIGHT, PATRICIA KATHRYN
• Application Number:
  US09/296,435
• Time in Patent Office: 1,287 Days
• Field of Search: 422/63, 422/65, 422/67, 422/68.1, 422/82.05, 422/82.08, 422/100, 422/104, 436/43, 436/47, 436/48, 436/164, 436/180, 435/288.3, 435/288.7, 414/277, 414/278, 414/281, 198/348, 198/465.1, 198/346--34, 198/347.3
• US Class Current: 436/48
• CPC Class Codes: B01J 19/00 Chemical, physical or physico-chemical processes in general; Their relevant apparatus
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00011 Laboratory-scale plants
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00328 Movement by linear translation
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/007 Simulation or vitual synthesis
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for microtitration plates
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/0422 carried on a linear conveyor
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 : Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 : with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Substances having useful pharmacological properties are identified by candidate screeners and screening methods. The substances may be incorporated into medicaments. The substances may have modulating activity with respect to pre-defined molecular targets.

Claims

1. A method of modulating the activity of a selected molecular targets with a selected chemical compound, comprising:

storing a set of chemical compounds in addressable wells in a chemical library;

programming a chemical storage and retrieval module containing said chemical compounds for the selection of a subset of said chemical compounds;

removing said subset of said addressable chemical wells from sad chemical storage module with an automated robotic retriever;

routing said selected subset of addressable chemical wells away from said chemical storage and retrieval module and toward a liquid processing apparatus in a transport pathway;

retrieving said programmed subset of said chemical compounds with said liquid processing apparatus by retrieving liquid samples from less than all of said removed subset of addressable chemical wells;

testing, in said liquid processing apparatus, said selected set of chemical compounds for modulating activity against one or more selected molecular targets;

selecting a chemical compound from among said selected set of chemical compounds that modulates that activity of at least one or more selected molecular targets; and

contacting said selected chemical compound with said selected molecular target such that the activity of said selected molecular target is modulated.

2. The method of claim 1, wherein said chemical compound consists essentially of an entity selected from the group consisting of polypeptides, oligonucleotides, peptoids, peptide nucleic acids, benzodiazapines, nonpeptidal peptidomimetics, oligocarbamates, and peptidyl phosphonates.

3. The method of claim 1, wherein said chemical compound has modulating activity with respect to said molecular target selected from the group consisting of ion channels, N-methyl-D-aspartate receptor, kainite receptors, AMPA receptor, GABA receptors, nicotinic acetylcholine receptors, excitatory amino acid receptors, soluble proteins, membrane proteins, hormone receptors, transcription factors, proteases, kinases, and phosphatases.

4. The method of claim 1, wherein said testing comprises testing at a rate of at least 50,000 chemical compounds in 24 hours.

5. The method of claim 1, wherein said testing comprises testing at a rate of at least 100,000 chemical compounds in 24 hours.

6. The method of claim 1, wherein said testing comprises testing at a rate of at least 300,000 compounds in 24 hours.

7. The method of claim 1, wherein said testing comprises testing at a rate of at least 500,000 chemical compounds in 24 hours.

8. The method of claim 1, wherein said testing comprises testing at a rate of at least 1,000,000 chemical compounds in 24 hours.

9. The method of claim 1, wherein said testing comprises a cell based assay.

10. The method of claim 1, wherein said testing comprises a biochemical assay.

11. The method of claim 1, additionally comprising incorporating a pharmaceutically effective amount of said chemical compound having modulating activity into a biocompatible carrier.

12. The method of claim 1, wherein said molecular target is an enzyme.