US5565324A
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US
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Complex combinatorial chemical libraries encoded with tags
Assignee: Cold Spring Harbor Laboratory
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Filing: 1994-04-13
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Granted: 1996-10-15
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Expires: 2014-04-13
Abstract
Abstract Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle. The reaction history of the particles which are positive for the characteristic can be determined by the release of the tags and analysis to define the reaction history of the particle.
Inventors
- 👤 W. Clark Still
- 👤 Michael H. Wigler
- 👤 Michael H. J. Ohlmeyer
- 👤 Lawrence W. Dillard
- 👤 John C. Reader
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 19:42
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/68; C; C07; C07D; C07D243/00; C07D243/06; C07D243/10; C07D243/14; C07D243/16; C07D243/18; C07D243/24; C07H; C07H21/00; C07K; C07K1/00; C07K1/04; C07K1/047; C40; C40B; C40B50/00; C40B50/14; C40B50/16; G01N33/53; G01N33/531; G01N33/532; G01N33/543; G01N33/54353; B; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/0054; B01J2219/00572; C07B; C07B2200/00; C07B2200/11; C40B40/00; C40B70/00
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
250 words
A method for identifying a non-oligomeric compound which is heterocyclic, aromatic, alicyclic, aliphatic, or a combination thereof having a characteristic of interest, from a library of non-oligomeric compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different non-oligomeric compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) testing the library in an assay which identifies a solid support which has bound thereto a compound having the characteristic of interest so as to detect the presence in the library of any solid support having bound thereto a compound having the characteristic of interest; (b) treating the solid support so identified in step (a) so as to cause the tag components of each of the identifiers bound to such solid support to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (c) determining the identity of each tag component so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (d) determining said reaction stages and choices by which said non-oligomeric compound was synthesized, based on the identities of all such tag components so as to thereby identify the non-oligomeric compound having the characteristic of interest.
Claim 2
Independent Claim
250 words
A method for identifying a non-oligomeric compound which is heterocyclic, aromatic, alicyclic, aliphatic, or a combination thereof having a characteristic of interest, from a library of non-oligomeric compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different non-oligomeric compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) testing the library in an assay which identifies a solid support which has bound thereto a compound having the characteristic of interest so as to detect the presence in the library of any solid support having bound thereto a compound having the characteristic of interest; (b) treating the solid support so identified in step (a) so as to cause the tag components of each of the identifiers bound to such solid support to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (c) determining the identity of each tag component so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (d) determining said reaction stages and choices by which said non-oligomeric compound was synthesized, based on the identities of all such tag components so as to thereby identify the non-oligomeric compound having the characteristic of interest.
Claim 3
Independent Claim
293 words
A method for identifying a non-oligomeric compound which is heterocyclic, aromatic, alicyclic, aliphatic, or a combination thereof having a characteristic of interest, from a library of non-oligomeric compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different non-oligomeric compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) treating solid supports in the library so as to release the non-oligomeric compounds from the solid supports while retaining a sample of each such solid support, wherein the release of the compounds from the solid supports is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (b) testing each non-oligomeric compound from step (a) in an assay which identifies whether such compound has the characteristic of interest, so as to detect a compound having the characteristic of interest; (c) for each compound of step (b) treating the corresponding solid support retained in step (a) so as to cause the tag components of each of the identifiers bound thereto to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (d) for each compound of step (b) determining the identity of each tag component of step (c) so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (e) determining said reaction stages and choices by which said non-oligomeric compound was synthesized, based on the identities of all such tag components so as to thereby identify the non-oligomeric compound having the characteristic of interest.
Claim 4
Independent Claim
293 words
A method for identifying a non-oligomeric compound which is heterocyclic, aromatic, alicyclic, aliphatic, or a combination thereof having a characteristic of interest, from a library of non-oligomeric compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different non-oligomeric compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) treating solid supports in the library so as to release the non-oligomeric compounds from the solid supports while retaining a sample of each such solid support, wherein the release of the compounds from the solid supports is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (b) testing each non-oligomeric compound from step (a) in an assay which identifies whether such compound has the characteristic of interest, so as to detect a compound having the characteristic of interest; (c) for each compound of step (b) treating the corresponding solid support retained in step (a) so as to cause the tag components of each of the identifiers bound thereto to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (d) for each compound of step (b) determining the identity of each tag component of step (c) so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (e) determining said reaction stages and choices by which said non-oligomeric compound was synthesized, based on the identities of all such tag components so as to thereby identify the non-oligomeric compound having the characteristic of interest.
Claim 5
Independent Claim
235 words
A method for identifying a compound having a characteristic of interest, from a library of compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) testing the library in an assay which identifies a solid support which has bound thereto a compound having the characteristic of interest so as to detect the presence in the library of any solid support having bound thereto a compound having the characteristic of interest; (b) treating the solid support so identified in step (a) so as to cause the tag components of each of the identifiers bound to such solid support to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (c) determining the identity of each tag component so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (d) determining said reaction stages and choices by which said compound was synthesized, based on the identities of all such tag components so as to thereby identify the compound having the characteristic of interest.
Claim 6
Independent Claim
235 words
A method for identifying a compound having a characteristic of interest, from a library of compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) testing the library in an assay which identifies a solid support which has bound thereto a compound having the characteristic of interest so as to detect the presence in the library of any solid support having bound thereto a compound having the characteristic of interest; (b) treating the solid support so identified in step (a) so as to cause the tag components of each of the identifiers bound to such solid support to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (c) determining the identity of each tag component so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (d) determining said reaction stages and choices by which said compound was synthesized, based on the identities of all such tag components so as to thereby identify the compound having the characteristic of interest.
Claim 7
Independent Claim
276 words
A method for identifying a compound having a characteristic of interest, from a library of compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) treating solid supports in the library so as to release the compounds from the solid supports while retaining a sample of each such solid support, wherein the release of the compounds from the solid supports is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (b) testing each compound from step (a) in an assay which identifies whether such compound has the characteristic of interest, so as to detect a compound having the characteristic of interest; (c) for each compound of step (b) treating the corresponding solid support retained in step (a) so as to cause the tag components of each of the identifiers bound thereto to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (d) for each compound of step (b) determining the identity of each tag component of step (c) so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (e) determining said reaction stages and choices by which said compound was synthesized, based on the identities of all such tag components so as to thereby identify the compound having the characteristic of interest.
Claim 8
Independent Claim
276 words
A method for identifying a compound having a characteristic of interest, from a library of compounds which comprises a plurality of discrete solid supports, each such support being characterized by having bound thereto a different compound and multiple identifiers which encode the reaction stages and choices associated with the synthesis of the compound bound thereto, each such identifier being separately attached to the solid support and comprising a tag component, said method comprising: (a) treating solid supports in the library so as to release the compounds from the solid supports while retaining a sample of each such solid support, wherein the release of the compounds from the solid supports is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (b) testing each compound from step (a) in an assay which identifies whether such compound has the characteristic of interest, so as to detect a compound having the characteristic of interest; (c) for each compound of step (b) treating the corresponding solid support retained in step (a) so as to cause the tag components of each of the identifiers bound thereto to be released, wherein the release of the tag components from the solid support is effected photolyrically, oxidatively, hydrolyrically, thermolytically, or reductively; (d) for each compound of step (b) determining the identity of each tag component of step (c) so released, wherein determining the identity of each tag component is accomplished by gas chromatography, liquid chromatography, thin layer chromatography, electrophoresis, or mass spectrometry; and (e) determining said reaction stages and choices by which said compound was synthesized, based on the identities of all such tag components so as to thereby identify the compound having the characteristic of interest.
Claim 9
Independent Claim
24 words
A method of claims 1 or 2, wherein the compound bound to each solid support is a diazabicyclic, an azatricyclic or a branched amide.
Claim 10
Dependent Claim
27 words
A method of claim 5, wherein the tag compounds comprise a homologous series of alkylene groups and wherein their identities are determined by electron capture gas chromatography.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-10-15 | 2000-04-15 | 2000-10-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-10-15 | 2004-04-15 | 2004-10-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-10-15 | 2008-04-15 | 2008-10-15 | $7700.00 | Window Closed / Lapsed |