Chemistry: analytical and immunological testing – Tracers or tags
Reexamination Certificate
1996-10-30
2001-07-24
Snay, Jeffrey (Department: 1743)
Chemistry: analytical and immunological testing
Tracers or tags
C436S086000, C436S524000, C422S091000, C422S119000, C530S334000
Reexamination Certificate
active
06265219
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field
The invention relates to compound synthesis. More particularly, the invention relates to a method and apparatus for tagging the synthesis supports, hence allowing constituents used during various compound syntheses, hence reaction products to be identified, and sorting the constituents used during various compound syntheses.
2. Description of the Prior Art
Combinatorial synthesis of libraries of organic molecules is an important tool for, inter alia, the identification of biologically active compounds. Such libraries may be generated on a solid support, for example by parallel syntheses at an array of spatially separate or spatially addressable constituents, at which compounds are generated as individual products, i.e. single compounds, having structural identities related to their particular location in the reaction array.
Another approach generates compound mixtures, for example by using split and combine synthesis methods. Such approach requires a deconvolution procedure in which the component of interest must be identified from within the compound mixture by repetitive synthesis of smaller and smaller mixtures containing the component of interest. Once the compound is isolated as a single compound, its structure is subsequently determined.
Chemical tagging techniques are used to record the synthetic history of each of the constituents of a synthesis pool to facilitate the subsequent identification of selected members of the library. In practice, introduction, removal, and decoding of chemical tags comprises a large portion of the effort that is required to generate and screen mixture libraries.
It is known to use transponders to tag a particulate derivatised polystyrene resin solid phase contained in polypropylene mesh “tea bags”, and record synthesis steps carried out during a combi-chem synthesis (see R. Armstrong, P. Tempest, J. Cargill,
Microchip Encoded Combinatorial Libraries: Generation of a Spatially Encoded Library from Pool Synthesis,
CHIMIA, June 1996). However, such resin-based tea bags are not suited for automated sorting or handling, and thus, such an approach is therefore not amenable to the synthesis of large libraries.
It would be advantageous to provide an efficient approach to the tagging and automated sorting of synthesis constituents that allowed the manipulation of large numbers of synthesis constituents, and therefore the automated synthesis of large compound libraries.
SUMMARY OF THE INVENTION
The invention provides a method and apparatus that uses a tag, such as a transponder, to identify the constituents used in complex compound syntheses. The invention features a unique rigid solid phase synthesis member (hereinafter referred to as synthesis member) that provides significant advantages over the prior art with regard to the handling of compound libraries and automation of synthesis of libraries containing large numbers of compounds (e.g. up to 10,000 or more compounds) or constituents.
The synthesis member preferably comprises two elements: a crown and a stem. In one method, the crown on a stem (the pin) is attached in an 8×12 Array to a pin holder allowing 96 pins to be handled concurrently but in principle, other numbers of pins may be used. The preferred format allows multiple handling and any number of pins may be used. The crown provides the location at which compounds are synthesized, while the stem is provided to carry information about the synthesis member and/or compound being synthesized.
In a preferred embodiment of the invention, a transponder in the form of a passive integrated circuit is located in the stem of such synthesis member. The combination of a crown for use with compound synthesis and stem requires no locating device such as a pin holder and allows the synthesis of libraries when processing thousands of such synthesis members.
An important aspect of the invention resides in the provision of a solid, typically rigid or resilient synthesis member, as opposed to prior art solid phase synthesis supports comprising particulate resinous materials. A solid synthesis member is readily handled by automated sorting systems and may be adapted for attachment/detachment mechanisms for crown from stem. Thus, the crown may be detachable from the stem and may be detachable from the synthesis member at the end of the synthesis and before compound cleavage from the crown. This arrangement provides a simple and effective approach to separating the transponder from the crown, e.g. for reuse. Further, because each synthesis member is individually tracked and can be logged into a database and/or process flow control system, the approach herein allows the synthesis of several thousand individual compounds in conventional containers, such as round bottom flasks using traditional compound synthesis methods as contrasted with prior art matrix systems, where one vessel for the synthesis of each individual compound has to be used.
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Service, R.F. “Radio Tags Speed Compound Synthesis” Science, vol. 270, p. 577, Oct. 23, 1995.*
Armstrong et al., Microchip Encoded Combinatorial Libraries: Generation of a Spacially Encoded Library from a Pool Synthesis (1995).
Maeji et al., Peptide Research, 8:1 (1995), 33-38, Larger Scale Multipin Peptide Synthesis.
Maeji et al., Reactive Polymers 22 (1994), 203-212, Grafted supports used with the multipin method of peptide synthesis.
Central Animal Records, Letter of Welcome, Central Animal Records Aust. Pty. Ltd., Springvale South 3172, Victoria Australia (1995).
Bray Andrew Malcolm
Giger Rudolf Karl Andreas
Maeji Nobuyoshi Joe
Mattes Henri
Mitokor
Seed Intellectual Property Law Group PLLC
Snay Jeffrey
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