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US4943523A Expired / Lapsed US ⏱️ 0.0 years remaining

Detectable molecules, method of preparation and use

Assignee: Enzo Diagnostics Inc
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Filing: 1987-04-28
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Granted: 1990-07-24
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Expires: 2007-04-28
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Abstract

Abstract A detectable molecule of the formula A3-(-X-R1-E-Detb)m where A3 is A2 or a polymer, where A3 has at least one modifiable reactive group selected from the group consisting of amino, hydroxy, cis OH, halides, aryl, imidazoyl, carbonyl, carboxy, thiol or a residue comprising an activated carbon; -X- is selected from the group consisting of <IMAGE> <IMAGE> <IMAGE> <IMAGE> +TR OCONH <IMAGE> a C1-C10 branched or unbranched alkyl or aralkyl, which may be substituted by -OH; -Y- is a direct bond to -E-, or -Y- is -E-R2- where R is a C1-C10 branched or unbranched alkyl; Za is chlorine, bromine or iodine; E is O, NH or an acyclic divalent sulfur atom; Detb is a chemical moiety capable of being detected, preferably comprising biotin or a metal chelator of the formula: <IMAGE> or the 4-hydroxy or acyloxy derivative thereof, where R3 is C1-C4 alkyl or CH2COOM, M is the same or different and selected from the group consisting of hydrogen, a metal or non-metal cation or is C1-C10 alkyl, aryl or aralkyl; and m is an integer from 1 to the total number of modified reactive groups on A3. The detectable molecules are useful in in vitro or in vivo assays or therapy.

Inventors

  • 👤 Jannis G. Stavrianopoulos

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-01 09:52
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0497; A61K51/08; A61K51/10; A61K51/1093; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/533; G01N33/543; G01N33/551; G01N33/553; Y; Y10; Y10S; Y10S436/00; Y10S436/804

Claims Analysis

Total Claims: 43
Claim 1
Independent Claim 250 words
A detectable molecule of the formula A 3 --(X--R 1 --E--Det b ) m where A 3 is A 2 , an oligo-or polysaccharide, an olgo- or polypeptide or a synthetic polymer, each of said oligo- or polysaccharide, oligo- or polypeptide or synthetic polymer having at least one modifiable reactive group consisting of amino, hydroxy, 1,2-cis diOH, halide aryl, imidazoyl, carbonyl, carboxyl, thiol or a residue comprising an activated carbon; A 2 is a specific binding ligand other than an oligo- or polysaccharide, oligo- or polypeptide or an oligo- or polymucleotide and has a molecular weight of less than about 2,000; --X-- is selected from the group consisting of ##STR52## --N═N--, --NHSO 2 --, --OSO 2 --, --NH--N═N--, ##STR53## -CH 2 --NH, ##STR54## --NH--CH 2 --, ##STR55## --S--CH 2 --; --R 1 -- is selected from the group consisting of ##STR56## and a C 1 -C 10 branched or unbranched alkyl or aralkyl, which may be substituted by --OH; --Y-- is a direct bond to --E--, or --Y-- is --E--R 2 -- where -R 2 -- is a C 1 -C 10 branched or unbranched alkyl; Z a is chlorine, bromine or iodine; --E-- is O, NH or an acyclic divalent sulfur atom; Det b is a chemical moiety capable of being detected, comprising biotin or a substituted or unsubstituted metal chelator or a compound capable of yielding a metal chelator; and m is an integer from 1 to the total number of modified reactive groups on A 3 .
Claim 2
Dependent Claim 250 words
A detectable molecule of the formula A 3 --(X--R 1 --E--Det b ) m where A 3 is A 2 , an oligo-or polysaccharide, an olgo- or polypeptide or a synthetic polymer, each of said oligo- or polysaccharide, oligo- or polypeptide or synthetic polymer having at least one modifiable reactive group consisting of amino, hydroxy, 1,2-cis diOH, halide aryl, imidazoyl, carbonyl, carboxyl, thiol or a residue comprising an activated carbon; A 2 is a specific binding ligand other than an oligo- or polysaccharide, oligo- or polypeptide or an oligo- or polymucleotide and has a molecular weight of less than about 2,000; --X-- is selected from the group consisting of ##STR52## --N═N--, --NHSO 2 --, --OSO 2 --, --NH--N═N--, ##STR53## -CH 2 --NH, ##STR54## --NH--CH 2 --, ##STR55## --S--CH 2 --; --R 1 -- is selected from the group consisting of ##STR56## and a C 1 -C 10 branched or unbranched alkyl or aralkyl, which may be substituted by --OH; --Y-- is a direct bond to --E--, or --Y-- is --E--R 2 -- where -R 2 -- is a C 1 -C 10 branched or unbranched alkyl; Z a is chlorine, bromine or iodine; --E-- is O, NH or an acyclic divalent sulfur atom; Det b is a chemical moiety capable of being detected, comprising biotin or a substituted or unsubstituted metal chelator or a compound capable of yielding a metal chelator; and m is an integer from 1 to the total number of modified reactive groups on A 3 .
Claim 3
Dependent Claim 77 words
A specific binding assay method for determining the presence or absence of an analyte in a sample, which method comprises (a) contacting said sample with a composition comprising the molecule of claim 1 wherein A 3 is a specific binding partner for said analyte, and Det b has the formula ##STR57## wherein M is a radiometal; (b) separating any complex formed between said detectable molecule and said analyte; and (c) observing the amount of detectable complex so-formed.
Claim 4
Dependent Claim 46 words
The assay of claim 2 wherein the analyte is an antigen or antibody therefor and the step of contacting said sample comprises contacting said sample with a composition which comprises the other of said antigen or antibody therefor to which said molecule has been covalently bound.
Claim 5
Dependent Claim 12 words
The assay of claim 3 wherein said radiolabelled molecule is an antibody.
Claim 6
Dependent Claim 12 words
The assay of claim 4 wherein said antibody is a monoclonal antibody.
Claim 7
Dependent Claim 12 words
The assay of claim 3 wherein said radiolabelled molecule is an antigen.
Claim 8
Dependent Claim 29 words
The molecule of claim 1 wherein said modifiable reactive group comprises a residue selected from the group consisting of a histidine and a tyrosine residue present in said polypeptide.
Claim 9
Dependent Claim 11 words
The molecule of claim 7 wherein --R 1 -- is ##STR58##
Claim 10
Dependent Claim 14 words
The molecule of claim 8 wherein R 2 is --CH 2 --CH 2 --.
Claim 11
Dependent Claim 29 words
The molecule of claim 1 wherein the modifiable reactive group comprises an activated carbon residue, X is --N═N-- and R 1 is selected from the group consisting of ##STR59##
Claim 12
Dependent Claim 11 words
The molecule of claim 10 wherein --R 1 -- is ##STR60##
Claim 13
Dependent Claim 11 words
The molecule of claim 11 wherein --R 1 -- is ##STR61##
Claim 14
Dependent Claim 25 words
The molecule of claim 1 wherein A 3 is a polypeptide selected from the group consisting of a structural protein, an immunoglobulin and an enzyme.
Claim 15
Dependent Claim 12 words
The molecule of claim 13 wherein said immunoglobulin is a monoclonal antibody.
Claim 16
Dependent Claim 94 words
A specific binding assay method for determining the presence or absence of an analyte in a sample, which method comprises (a) contacting said sample with a composition which comprises (i) the detectable molecule of claim 1 wherein A 3 is a specific binding partner for said analyte and (ii) where Det b is a chelator, a detectable metal chelatable thereby or (iii) where Det b is biotin, a detectably labeled specific binging partner therefor; (b) separating any complex formed between the analyte and said complex; and (c) observing the amount of detectable complex so-formed.
Claim 17
Dependent Claim 12 words
The molecule of claim 15 wherein A 3 is A 2 .
Claim 18
Dependent Claim 13 words
The molecule of claim 15 wherein A 3 is an oligo- or polysaccharide.
Claim 19
Dependent Claim 13 words
The molecule of claim 15 wherein A 3 is an oligo- or polypeptide.
Claim 20
Dependent Claim 12 words
The molecule of claim 15 wherein A 3 is a synthetic polymer.
Claim 21
Dependent Claim 10 words
The molecule of claim 15 wherein Det b is biotin.
Claim 22
Dependent Claim 36 words
The molecule of claim 20 wherein the modified reactive group is an amino group, and --X-- is selected from the group consisting of --NH--CO--, --NH--CNH--, --NHSO 2 --, --NH--N═N--, --NH--CO--CH 2 --NH-- and --NH--CO--CH 2 --S--.
Claim 23
Dependent Claim 22 words
The molecule of claim 21 wherein X is selected from the group consisting of --NHCO--, --NH--COCH 2 --NH13 and --NH--CO--CH 2 --S--.
Claim 24
Dependent Claim 30 words
The molecule of claim 22 wherein --X-- is selected from the group consisting of --NH--CO--CH 2 NH-- and --NH--CO--CH 2 --S-- and R 1 is C 1 -C 6 alkyl.
Claim 25
Dependent Claim 14 words
The molecule of claim 23 wherein R 1 is --CH 2 --CH 2 --.
Claim 26
Dependent Claim 14 words
The molecule of claim 111 wherein R 1 is --CH 2 --CH 2 --.
Claim 27
Dependent Claim 16 words
The molecule of claim 21 wherein R 1 is a C 1 -C 10 alkyl group.
Claim 28
Dependent Claim 65 words
The molecule of claim 1 wherein Det b is a metal chelator selected from one having the formula: ##STR62## the 4-hydroxy derivative thereof and the acyloxy derivative thereof, where R 3 is selected from the group consisting of a C 1 -C 4 alkyl and --CH 2 --COOM, and each M is independently selected from the group consisting of a metal and a non-metal cation.
Claim 29
Dependent Claim 23 words
The molecule of claim 27 wherein the activated carbon residue in the modifiable group is capable of covalent coupling to a diazonium compound.
Claim 30
Dependent Claim 10 words
The molecule of claim 28 wherein R 1 is ##STR63##
Claim 31
Dependent Claim 14 words
The molecule of claim 29 wherein R 2 is --CH 2 --CH 2 --.
Claim 32
Dependent Claim 16 words
The molecule of claim 30 wherein R 1 is a C 1 -C 10 alkyl group.
Claim 33
Dependent Claim 11 words
The molecule of claim 27 wherein M is a radioactive metal.
Claim 34
Dependent Claim 11 words
The molecule of claim 27 wherein said metal chelator is ##STR64##
Claim 35
Dependent Claim 11 words
The molecule of claim 27 wherein said metal chelator is ##STR65##
Claim 36
Dependent Claim 14 words
The molecule of claim 1 wherein A 3 is a polypeptide or a polysaccharide.
Claim 37
Dependent Claim 11 words
The molecule of claim 1 wherein said metal chelator is ##STR66##
Claim 38
Dependent Claim 10 words
The molecule of claim 1 wherein Det b is ##STR67##
Claim 39
Dependent Claim 13 words
The molecule of claim 1 wherein E is an acyclic divalent sulfur atom.
Claim 40
Dependent Claim 21 words
The molecule of claim 1 wherein X is ##STR68## and R 1 is C 1 -C 10 branched or unbranched alkyl.
Claim 41
Dependent Claim 23 words
The molecule of claim 1 wherein Det b is selected from the group consisting of biotin and a substituted or unsubstituted metal chelator.
Claim 42
Dependent Claim 14 words
The molecule of claim 1 wherein --X-- is --N═N-- and R 1 is ##STR69##
Claim 43
Dependent Claim 12 words
The molecule of claim 1 wherein A 3 is A 2 .

References Cited (Backward Citations)

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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) 1993-07-23 1994-01-22 1994-07-24 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1997-07-23 1998-01-22 1998-07-24 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2001-07-23 2002-01-22 2002-07-24 $7700.00 Window Closed / Lapsed

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