Multicomponent assemblies having enhanced binding properties for diagnosis and therapy
First Claim
1. A biocompatible organized mobile multicomponent conjugate (OMMC) comprising:
- (A) a lamellar structure comprising CH3—
(CH2)fCONH(CH2)g—
X, wherein;
(1) X is selected from carboxylate, sulfonate, sulfate, phosphate, and phosphonate; and
(2) each off and g is independently 1-15; and
(B) a first binding compound and a second binding compound, each of which is anchored to the lamellar structure, the first binding compound capable of binding to an exogenous first affinity site, and the second binding compound capable of binding to an exogenous second affinity site, wherein the first and second binding compounds are mobile and self-adjust relative to the lamellar structure to allow for cooperative binding of the first and second binding compounds to said first and second affinity sites, respectively, wherein each binding compound independently comprises;
(1) an anchor region that anchors the binding compound to the lamellar structure, the anchor region being selected from CH3(CH2)a—
W, CH3(CH2)a—
O—
(CH2)b—
W, CH3(CH2)a—
S—
(CH2)b—
W, R1O2CCH2(CHW)CO2R1, CF3(CH2)a—
W, CF3(CF2)a—
W, CF3(CF2)aCH2CH2—
W, CF3(CF2)a—
O—
(CH2)b—
W, and CH3(CH2)a—
S—
S—
(CH2)b—
W, wherein;
(a) each of a and b ranges from 16 to 32, inclusive;
(b) W is selected from —
O—
, —
CO—
, —
CO2—
, —
OCO—
, —
O2CO—
, —
S—
, —
SO—
, —
SO2—
, —
NH—
, —
NHCO—
, —
NHCS—
, —
NHSO2—
, —
PO2H—
, —
OPO2H—
, —
PO2—
, and —
OPO2—
; and
(c) R1 is an alkyl radical containing 16 to 24 carbon atoms; and
(2) a binding region selected from amino acids, peptides, peptidomimics, monosaccharides, disaccharides, oligosaccharides, sialic acid, carminic acid, and anionic compounds of —
(CH2)d—
CO2−
, —
(CH2)d—
SO3−
, —
(CH2)d—
OSO3−
, —
(CH2)d—
PO3═
, —
(CH2)d—
OPO3═
, —
Ar—
SO3−
, DTPA, EDTA, DOTA, and EGTA, wherein d ranges from 1 to 10, inclusive; and
(3) a linker that connects the anchor region to the binding region, the linker being selected from polysorbates, polyglycerols, polypeptides, polynucleotides, polysaccharides, polyvinylpyrrolidones, polyvinylalcohols, polyethyleneglycols, polyglycolate, polylactate, and copolymers of any of the members of this group.
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0 Petitions
Accused Products
Abstract
An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patient who is then diagnosed or treated using the effector molecule.
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Citations
75 Claims
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1. A biocompatible organized mobile multicomponent conjugate (OMMC) comprising:
-
(A) a lamellar structure comprising CH3—
(CH2)fCONH(CH2)g—
X, wherein;(1) X is selected from carboxylate, sulfonate, sulfate, phosphate, and phosphonate; and (2) each off and g is independently 1-15; and (B) a first binding compound and a second binding compound, each of which is anchored to the lamellar structure, the first binding compound capable of binding to an exogenous first affinity site, and the second binding compound capable of binding to an exogenous second affinity site, wherein the first and second binding compounds are mobile and self-adjust relative to the lamellar structure to allow for cooperative binding of the first and second binding compounds to said first and second affinity sites, respectively, wherein each binding compound independently comprises; (1) an anchor region that anchors the binding compound to the lamellar structure, the anchor region being selected from CH3(CH2)a—
W, CH3(CH2)a—
O—
(CH2)b—
W, CH3(CH2)a—
S—
(CH2)b—
W, R1O2CCH2(CHW)CO2R1, CF3(CH2)a—
W, CF3(CF2)a—
W, CF3(CF2)aCH2CH2—
W, CF3(CF2)a—
O—
(CH2)b—
W, and CH3(CH2)a—
S—
S—
(CH2)b—
W, wherein;(a) each of a and b ranges from 16 to 32, inclusive; (b) W is selected from —
O—
, —
CO—
, —
CO2—
, —
OCO—
, —
O2CO—
, —
S—
, —
SO—
, —
SO2—
, —
NH—
, —
NHCO—
, —
NHCS—
, —
NHSO2—
, —
PO2H—
, —
OPO2H—
, —
PO2—
, and —
OPO2—
; and(c) R1 is an alkyl radical containing 16 to 24 carbon atoms; and (2) a binding region selected from amino acids, peptides, peptidomimics, monosaccharides, disaccharides, oligosaccharides, sialic acid, carminic acid, and anionic compounds of —
(CH2)d—
CO2−
, —
(CH2)d—
SO3−
, —
(CH2)d—
OSO3−
, —
(CH2)d—
PO3═
, —
(CH2)d—
OPO3═
, —
Ar—
SO3−
, DTPA, EDTA, DOTA, and EGTA, wherein d ranges from 1 to 10, inclusive; and(3) a linker that connects the anchor region to the binding region, the linker being selected from polysorbates, polyglycerols, polypeptides, polynucleotides, polysaccharides, polyvinylpyrrolidones, polyvinylalcohols, polyethyleneglycols, polyglycolate, polylactate, and copolymers of any of the members of this group. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)
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Specification