US5714166A
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US
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Bioactive and/or targeted dendrimer conjugates
Assignee: University of Michigan (System)
•
Filing: 1995-03-07
•
Granted: 1998-02-03
•
Expires: 2015-03-07
Abstract
Abstract Dendritic polymer conjugates which are composed of at least one dendrimer in association with at least one unit of a carried material, where the carrier material can be a biological response modifier, have been prepared. The conjugate can also have a target director present, and when it is present then the carried material may be a bioactive agent. Preferred dendritic polymers are dense star polymers, which have been complexed with biological response modifiers. These conjugates and complexes have particularly advantageous properties due to their unique characteristics.
Inventors
- 👤 Donald A. Tomalia
- 👤 James R. Baker
- 👤 Roberta C. Cheng
- 👤 Anna U. Bielinska
- 👤 Michael J. Fazio
- 👤 David M. Hedstrand
- 👤 Jennifer A. Johnson
- 👤 Donald A. Kaplan, deceased
- 👤 Scott L. Klakamp
- 👤 William J. Kruper, Jr.
- 👤 Jolanta Kukowska-Latallo
- 👤 Bartley D. Maxon
- 👤 Lars T. Piehler
- 👤 Ian A. Tomlinson
- 👤 Larry R. Wilson
- 👤 Rui Yin
- 👤 II Herbert M. Brothers
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:04
CPC Classifications
A; A01; A01N; A01N25/00; A01N25/08; A01N25/10; A61; A61K; A61K47/00; A61K47/50; A61K47/46; A61K47/51; A61K47/56; A61K47/59; A61K47/595; A61K47/61; A61K47/69; A61K47/6949; A61K49/00; A61K49/06; A61K49/08; A61K49/085; A61K49/10; A61K49/12; A61K49/124; B; B82; B82Y; B82Y5/00; C; C07; C07C; C07C211/00; C07C211/01; C07C211/26; C07C211/29; C07C233/00; C07C233/01; C07C233/02; C07C233/11; C07C237/00; C07C237/02; C07C237/20; C08; C08G; C08G83/00; C08G83/002; C08G83/003; C08L; C08L101/00; C08L101/005; C12; C12N; C12N15/00; C12N15/09; C12N15/87; Y; Y10; Y10S; Y10S424/00; Y10S424/16
Claims Analysis
Total Claims: 158
Claim 1
Independent Claim
41 words
A dense star polymer conjugate which comprises at least one dense star polymer associated with at least one unit of at least one bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent.
Claim 2
Dependent Claim
41 words
A dense star polymer conjugate which comprises at least one dense star polymer associated with at least one unit of at least one bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent.
Claim 3
Dependent Claim
13 words
The conjugate of claim 1 wherein the dense star polymer is a dendrimer.
Claim 4
Dependent Claim
13 words
The conjugate of claim 2 wherein the dendrimer is radially symmetrical in configuration.
Claim 5
Dependent Claim
16 words
The conjugate of claim 2 wherein the dendrimer is generally spherical, ellipsoidal, or rod-shaped in configuration.
Claim 6
Dependent Claim
151 words
The conjugate of claim 1 wherein said dense star polymer comprises at least one solvent soluble, radially symmetrical dense star polymer wherein the dense star polymer has at least one core branch emanating from a core, said branch having at least one terminal group provided that (1) the ratio of terminal groups to the core branches is two or greater, (2) the density of terminal groups per unit volume in the polymer is at least 1.5 times that of an extended conventional star polymer having similar core and monomeric moieties and a comparable molecular weight and number of core branches, each of said branches of the extended conventional star polymer bearing only one terminal group, and (3) molecular volume that is no more than about 80% of the molecular volume of said extended conventional star polymer as determined by dimensional studies using scaled Corey-Pauling molecular models, and has regular dendritic branching.
Claim 7
Dependent Claim
14 words
The conjugate of claim 1 wherein the bioactive agent is a biological response modifier.
Claim 8
Dependent Claim
14 words
The conjugate of claim 6 wherein two or more biological response modifiers are present.
Claim 9
Dependent Claim
21 words
The conjugate of claim 6 wherein said biological response modifier is selected from the group consisting of an interleukin, and interferon.
Claim 10
Dependent Claim
13 words
The conjugate of claim 6 wherein said biological response modifier is genetic material.
Claim 11
Dependent Claim
16 words
The conjugate of claim 9 wherein said dense star polymer comprises predominately amino functional surface groups.
Claim 12
Dependent Claim
23 words
The conjugate of claim 9 wherein said genetic material extends between and serves to connect a plurality of dense star polymer particles together.
Claim 13
Dependent Claim
32 words
The conjugate of claim 9 wherein said dense star polymer has one cross-sectional dimension of at least about 50 Å, wherein said dimension is the narrowest dimension of said dense star polymer.
Claim 14
Dependent Claim
29 words
The conjugate of claim 9 wherein the dense star polymer is a dendrimer and the charge ratio of genetic material to dendrimer is from about 10:1 to about 1:10,000.
Claim 15
Dependent Claim
21 words
The conjugate of claim 13 wherein the charge ratio of genetic material to dendrimer is from about 3:1 to about 1:1,000.
Claim 16
Dependent Claim
21 words
The conjugate of claim 13 wherein the charge ratio of genetic material to dendrimer is from about 1:1 to about 1:100.
Claim 17
Dependent Claim
21 words
The conjugate of claim 13 wherein the charge ratio of genetic material to dendrimer is from about 1:1 to about 1:15.
Claim 18
Dependent Claim
117 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent, said bioactive agent can be the same bioactive agent or a different bioactive agent; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that the bioactive agent is associated with the dense star polymer; with the proviso that the bioactive agent maintains its effectiveness.
Claim 19
Dependent Claim
117 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent, said bioactive agent can be the same bioactive agent or a different bioactive agent; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that the bioactive agent is associated with the dense star polymer; with the proviso that the bioactive agent maintains its effectiveness.
Claim 20
Dependent Claim
160 words
A dense star polymer conjugate of the formula (T).sub.e -(C').sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; T represents a target director; each M represents at least one unit of a carried bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent; y represents an integer of 1 or greater; and * indicates that the carried bioactive agent is associated with the polymer; with the proviso that the carried bioactive agent maintains its effectiveness.
Claim 21
Dependent Claim
160 words
A dense star polymer conjugate of the formula (T).sub.e -(C').sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; T represents a target director; each M represents at least one unit of a carried bioactive agent, selected from the group consisting of a therapeutic agent, a diagnostic agent, and a therapeutic/diagnostic agent; y represents an integer of 1 or greater; and * indicates that the carried bioactive agent is associated with the polymer; with the proviso that the carried bioactive agent maintains its effectiveness.
Claim 22
Dependent Claim
16 words
The conjugate of claim 17 or 18 wherein the dense star polymer, P, is a dendrimer.
Claim 23
Dependent Claim
13 words
The conjugate of claim 19 wherein the dendrimer is polyamidoamine or a polyalkyleneimine.
Claim 24
Dependent Claim
21 words
The conjugate of claim 17 or 18 wherein the target director, T, is a polyclonal or monoclonal antibody or fragment thereof.
Claim 25
Dependent Claim
36 words
The conjugate of claim 17 or 18 wherein M is selected from the group consisting of a drug, pesticide, radionuclide, chelator, chelated metal, toxin, antibody, antibody fragment, antigen, signal generator, signal reflector, signal absorber and fragrance.
Claim 26
Dependent Claim
13 words
The conjugate of claim 22 wherein the signal absorber is a contrast agent.
Claim 27
Dependent Claim
20 words
The conjugate of claim 23 wherein the contrast agent is a chelated metal ion selected from Gd, Mn and Fe.
Claim 28
Dependent Claim
15 words
The conjugate of claim 22 wherein the signal generator is a fluorescing entity or radionuclide.
Claim 29
Dependent Claim
20 words
The conjugate of claim 22 wherein the signal reflector is a metal ion selected from Fe, Rh, Pd and Y.
Claim 30
Dependent Claim
18 words
The conjugate of claim 17 wherein at least one of the carried materials is an electron beam opacifier.
Claim 31
Dependent Claim
14 words
The conjugate of claim 17 or 18 wherein M is an aromatic ultraviolet absorber.
Claim 32
Dependent Claim
14 words
The conjugate of claim 18 wherein said bioactive agent is a biological response modifier.
Claim 33
Dependent Claim
28 words
The conjugate of claim 29 wherein said biological response modifier is selected from the group consisting of an interleukin, interferon, tumor necrosis factor, and granulocyte colony stimulating factor.
Claim 34
Dependent Claim
13 words
The conjugate of claim 30 wherein said biological response modifier is genetic material.
Claim 35
Dependent Claim
25 words
The conjugate of claim 17, 18, 19 or 20 for use as a reagent in positron emission tomography, computer aided tomography, or magnetic resonance imaging.
Claim 36
Dependent Claim
15 words
The conjugate of claim 17, 18, 19 or 20 for use as a diagnostic agent.
Claim 37
Dependent Claim
33 words
A composition comprising a dendritic polymer complexed with at least one unit of biological response modifier, selected from the group consisting of an interleukin, interferon, tumor necrosis factor, and granulocyte colony stimulating factor.
Claim 38
Dependent Claim
33 words
A composition comprising a dendritic polymer complexed with at least one unit of biological response modifier, selected from the group consisting of an interleukin, interferon, tumor necrosis factor, and granulocyte colony stimulating factor.
Claim 39
Dependent Claim
24 words
A composition comprising a dendritic polymer complexed with at least one unit of biological response modifier, wherein said biological response modifier is genetic material.
Claim 40
Dependent Claim
24 words
A composition comprising a dendritic polymer complexed with at least one unit of biological response modifier, wherein said biological response modifier is genetic material.
Claim 41
Dependent Claim
25 words
The composition of claim 35 wherein said dendritic polymer comprises a dendritic polymer having positive surface functionality over a substantial portion of the polymer surface.
Claim 42
Dependent Claim
20 words
The composition of claim 36 wherein said positive surface functionality is created by amino groups at the dendritic polymer surface.
Claim 43
Dependent Claim
24 words
The composition of claim 36 wherein said dendritic polymer comprises a dendrimer having positive surface functionality over at least 75% of its dendrimer surface.
Claim 44
Dependent Claim
25 words
The composition of claim 36 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 10:1 to about 1:10,000.
Claim 45
Dependent Claim
25 words
The composition of claim 36 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 3:1 to about 1:10,000.
Claim 46
Dependent Claim
25 words
The composition of claim 36 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:1 to about 1:1,000.
Claim 47
Dependent Claim
25 words
The composition of claim 36 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:1 to about 1:15.
Claim 48
Dependent Claim
25 words
The composition of claim 36 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:10 to about 1:10,000.
Claim 49
Dependent Claim
22 words
A composition of claim 36 which comprises a complex of dendritic polymer with genetic material, in solution with either DEAE-dextran or glycerol.
Claim 50
Dependent Claim
25 words
The composition of claim 44 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:1 to about 1:15.
Claim 51
Dependent Claim
25 words
The composition of claim 44 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:5 to about 1:10.
Claim 52
Dependent Claim
23 words
The composition of claim 45 wherein the complex is in solution with DEAE-dextran at a concentration from about 0.125 to about 2 μM.
Claim 53
Dependent Claim
21 words
The composition of claim 47 wherein the concentration of DEAE-dextran in said composition is from about 0.25 to about 1 μM.
Claim 54
Dependent Claim
24 words
The composition of claim 44 wherein said complex is in solution with glycerol at a concentration from about 2.0 to about 10.0% by volume.
Claim 55
Dependent Claim
24 words
The composition of claim 49 wherein said complex is in solution with glycerol at a concentration from about 2.0 to about 5.0% by weight.
Claim 56
Dependent Claim
14 words
The composition of claim 44, 47 or 50 wherein said composition further comprises DMSO.
Claim 57
Dependent Claim
13 words
The composition of claim 44 or 45 wherein said composition further comprises chloroquine.
Claim 58
Dependent Claim
15 words
The composition of claim 36 wherein a target director is associated with said dendritic polymer.
Claim 59
Dependent Claim
25 words
The composition of claim 53 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 10:1 to about 1:10,000.
Claim 60
Dependent Claim
25 words
The composition of claim 53 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 1:1 to about 1:15.
Claim 61
Dependent Claim
25 words
The composition of claim 53 wherein said genetic material and said dendritic polymer are complexed in a charge ratio from about 3:1 to about 1:10.
Claim 62
Dependent Claim
24 words
The composition of claim 53 or 55 which comprises a complex of dendritic polymer with genetic material, in solution with either DEAE-dextran or glycerol.
Claim 63
Dependent Claim
20 words
The composition of claim 53 or 55 wherein the target director is a polyclonal or monoclonal antibody or fragment thereof.
Claim 64
Dependent Claim
20 words
The composition of claim 53 or 55 wherein said target director is galactose trisaccharide, biotin, pyruvic acid, insulin or avidin.
Claim 65
Dependent Claim
36 words
The composition of claim 36, 39, 44, 45, 53 or 55 wherein said dendritic polymer comprises particles whose dimensions are from about 20 Å at their narrowest dimensions to about 1,000 Å at their largest dimensions.
Claim 66
Dependent Claim
14 words
The composition of claim 60 wherein the dendritic polymer is a dense star polymer.
Claim 67
Dependent Claim
13 words
The composition of claim 61 wherein the dense star polymer is a dendrimer.
Claim 68
Dependent Claim
23 words
The composition of claim 61 wherein said dense star polymer comprises dense star dendrimer which is generally spherical, eilipsoidal, or rod-shaped in configuration.
Claim 69
Dependent Claim
34 words
The composition of claim 61 wherein said dendritic polymer comprises aggregates of dendrimers having positive surface functionality and dendrimers having negative surface functionality at a positive:negative charge ratio from about 25:1 to about 100:1.
Claim 70
Dependent Claim
30 words
The composition of claim 61 wherein said dendritic polymer comprises a dense star polymer having amino acids over a substantial portion of its surface, and substantially only on its surface.
Claim 71
Dependent Claim
13 words
The composition of claim 65 wherein said amino acid is lysine or arginine.
Claim 72
Dependent Claim
18 words
The composition of claim 61 wherein the dense star polymer comprises a collection of bridged dense star dendrimers.
Claim 73
Dependent Claim
22 words
The composition of claim 67 wherein said genetic material extends between and serves to connect a plurality of dense star polymer particles.
Claim 74
Dependent Claim
54 words
The composition of claim 61 wherein said dendritic polymer is comprised of a dispersion of different sized dendrimer particles, ranging from particles having a diameter as small as about 20 Å at their smallest dimension to particles having a diameter of about 110 Å, there being other particles of intermediate diameters in said dispersion.
Claim 75
Dependent Claim
46 words
A composition of claim 36, 39, 44, 45, 53, 55 or 57 wherein a genetic material is complexed with a first dendritic polymer which has been placed in a solution containing a second dendritic polymer, said second dendritic polymer being larger than said first dendritic polymer.
Claim 76
Dependent Claim
14 words
The composition of claim 70 wherein said dendritic polymer is a dense star polymer.
Claim 77
Dependent Claim
45 words
The composition of claim 70 or 71 wherein said first dendritic polymer has a diameter at its narrowest dimension from about 22 to about 50 Å, and said second dendritic polymer has at its narrowest dimension a diameter from about 50 to about 1,000 Å.
Claim 78
Dependent Claim
25 words
The composition of claim 70, 71 or 72 wherein one or both of said first and second dendritic polymers are comprised of spherically shaped dendrimers.
Claim 79
Dependent Claim
20 words
The composition of claim 70 wherein both of said first and second dendritic polymers are comprised of spherically shaped dendrimers.
Claim 80
Dependent Claim
21 words
The composition of claim 36, 39, 44, 45, 53 or 55 wherein said dendritic polymer comprises an unsymmetrically branched dendritic polymer.
Claim 81
Dependent Claim
20 words
The composition of claim 75 wherein the monomeric building block of said unsymmetrically branched dendritic polymer is an amino acid.
Claim 82
Dependent Claim
12 words
The composition of claim 76 wherein the said amino acid is lysine.
Claim 83
Dependent Claim
40 words
The composition of claim 36, 39, 44, 45, 53 or 55 wherein said dendritic polymer comprises aggregates of dendrimers having positive surface functionality and dendrimers having negative surface functionality at a positive:negative charge ratio from about 25:1 to about 100:1.
Claim 84
Dependent Claim
36 words
The composition of claim 36, 39, 44, 45, 53 or 55 wherein said dendritic polymer comprises a dense star polymer having amino acids over a substantial portion of its surface, and substantially only on its surface.
Claim 85
Dependent Claim
13 words
The composition of claim 79 wherein said amino acid is lysine or arginine.
Claim 86
Dependent Claim
60 words
The composition of claim 36, 39, 44, 45, 53 or 55 wherein said dendritic polymer is comprised of a dispersion of different sized dendrimer particles, ranging from particles having a diameter as small as about 20 Å at their smallest dimension to particles having a diameter of about 110 Å, there being other particles of intermediate diameters in said dispersion.
Claim 87
Dependent Claim
15 words
The composition of claim 36, 39, 53 or 55 wherein said composition further includes chloroquine.
Claim 88
Dependent Claim
19 words
A formulation which comprises a conjugate of claim 1 having at least one pharmaceutically acceptable diluent or carrier present.
Claim 89
Dependent Claim
19 words
A formulation which comprises a conjugate of claim 17 having at least one pharmaceutically acceptable diluent or carrier present.
Claim 90
Dependent Claim
19 words
A formulation which comprises a conjugate of claim 18 having at least one pharmaceutically acceptable diluent or carrier present.
Claim 91
Dependent Claim
19 words
A formulation which comprises a conjugate of claim 34 having at least one pharmaceuticalIy acceptable diluent or carrier present.
Claim 92
Dependent Claim
19 words
A formulation which comprises a conjugate of claim 53 having at least one pharmaceutically acceptable diluent or carrier present.
Claim 93
Dependent Claim
60 words
A process for preparing a conjugate of dendritic polymer and biological response modifier, selected from the group consisting of an interleukin, interferon, tumor necrosis factor, and granulocyte colony stimulating factor, comprising reacting the dendritic polymer with the biological response modifier in a suitable solvent at a temperature which facilitates the association of the biological response modifier and the dendritic polymer.
Claim 94
Dependent Claim
60 words
A process for preparing a conjugate of dendritic polymer and biological response modifier, selected from the group consisting of an interleukin, interferon, tumor necrosis factor, and granulocyte colony stimulating factor, comprising reacting the dendritic polymer with the biological response modifier in a suitable solvent at a temperature which facilitates the association of the biological response modifier and the dendritic polymer.
Claim 95
Dependent Claim
77 words
A process for preparing a conjugate of dendritic polymer and biological response modifier, wherein said biological response modifier comprises genetic material and said dendritic polymer has a predominantly cationic surface character, comprising reacting the dendritic polymer with the biological response modifier in a suitable solvent at a temperature which facilitates the association of the biological response modifier and the dendritic polymer, said process comprising electrostatically attaching said genetic material to said dendritic polymer to create said conjugate.
Claim 96
Dependent Claim
77 words
A process for preparing a conjugate of dendritic polymer and biological response modifier, wherein said biological response modifier comprises genetic material and said dendritic polymer has a predominantly cationic surface character, comprising reacting the dendritic polymer with the biological response modifier in a suitable solvent at a temperature which facilitates the association of the biological response modifier and the dendritic polymer, said process comprising electrostatically attaching said genetic material to said dendritic polymer to create said conjugate.
Claim 97
Dependent Claim
53 words
A process for preparing a complex of dendritic polymer and genetic material comprising: reacting said dendritic polymer with said genetic material in a suitable solvent at a temperature which facilitates the complexing of said genetic material with said dendritic polymer, said process comprising placing said complex in a solution with DEAE-dextran or glycerol.
Claim 98
Dependent Claim
53 words
A process for preparing a complex of dendritic polymer and genetic material comprising: reacting said dendritic polymer with said genetic material in a suitable solvent at a temperature which facilitates the complexing of said genetic material with said dendritic polymer, said process comprising placing said complex in a solution with DEAE-dextran or glycerol.
Claim 99
Dependent Claim
21 words
The process of claim 90 which includes attaching a target director to said dendritic polymer before complexing it with genetic material.
Claim 100
Dependent Claim
29 words
The process of claim 90 wherein said dendritic polymer has a predominantly cationic surface, said process comprising electrostatically attaching genetic material to said dendritic polymer to create said complex.
Claim 101
Dependent Claim
66 words
A process for forming a dendritic polymer-genetic material complex comprising: complexing genetic material with a first dendritic polymer by reacting the polymer with the genetic material in a suitable solvent at a temperature which facilitates association of the genetic material with the polymer; and placing said complex in a solution containing a second dendritic polymer, said second dendritic polymer being larger than said first dendritic polymer.
Claim 102
Dependent Claim
66 words
A process for forming a dendritic polymer-genetic material complex comprising: complexing genetic material with a first dendritic polymer by reacting the polymer with the genetic material in a suitable solvent at a temperature which facilitates association of the genetic material with the polymer; and placing said complex in a solution containing a second dendritic polymer, said second dendritic polymer being larger than said first dendritic polymer.
Claim 103
Dependent Claim
21 words
The process of claim 93 which includes attaching a target director to said dendritic polymer before complexing it with genetic material.
Claim 104
Dependent Claim
26 words
The process of claim 93 wherein said dendritic polymer has a predominately cationic surface, said process comprising electrostatically attaching said genetic material to said dendritic polymer.
Claim 105
Dependent Claim
76 words
A process for forming a genetic material:dendritic polymer complex comprising: mixing, in water, sufficient genetic material to yield a final concentration from about 1 to about 10 μg per mL, with sufficient dendritic polymer, having positive surface functionality, to yield a genetic material:dendritic polymer charge ratio from about 3:1 to about 1:10,000; said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20° to about 40° C.
Claim 106
Dependent Claim
76 words
A process for forming a genetic material:dendritic polymer complex comprising: mixing, in water, sufficient genetic material to yield a final concentration from about 1 to about 10 μg per mL, with sufficient dendritic polymer, having positive surface functionality, to yield a genetic material:dendritic polymer charge ratio from about 3:1 to about 1:10,000; said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20° to about 40° C.
Claim 107
Dependent Claim
16 words
The process of claim 96 wherein said charge ratio is from about 1:1 to about 1:1,000.
Claim 108
Dependent Claim
29 words
The process of claim 96 which includes adding sufficient DEAE-dextran to said complex after it is formed, to yield a DEAE-dextran concentration from about 0.125 to about 2 μM.
Claim 109
Dependent Claim
16 words
The process of claim 98 wherein said charge ratio is from about 1:1 to about 1:15.
Claim 110
Dependent Claim
16 words
The process of claim 99 wherein said charge ratio is from about 1:5 to about 1:10.
Claim 111
Dependent Claim
22 words
The process of claim 98 wherein sufficient DEAE-dextran is added to yield a DEAE-dextran concentration from about 0.25 to about 1 μM.
Claim 112
Dependent Claim
28 words
The process of claim 98 wherein said dendritic polymer has a diameter from about 50 Å at its narrowest diameter, to a maximum diameter of about 1,000 Å.
Claim 113
Dependent Claim
54 words
The process of claim 96 wherein said dendritic polymer is comprised of a dispersion of different sized dendrimer particles, ranging from particles having a diameter as small as about 20 Å at their smallest dimension to particles having a diameter of about 110 Å, there being other particles of intermediate diameters in said dispersion.
Claim 114
Dependent Claim
45 words
The process of claim 96 wherein said dendritic polymer comprises aggregates of dendrimers having positive surface functionality and dendrimers having negative surface functionality at a positive:negative charge ratio from about 25:1 to about 100:1, said aggregates having diameters of no more than about 1,000 Å.
Claim 115
Dependent Claim
30 words
The process of claim 96 wherein said dendritic polymer comprises a dense star polymer having amino acids over a substantial portion of its surface, and substantially only on its surface.
Claim 116
Dependent Claim
13 words
The process of claim 105 wherein said amino acid is lysine or arginine.
Claim 117
Dependent Claim
53 words
The process of claim 96 wherein said dendritic polymer comprises relatively small dendrimer particles having a diameter of 22 to 50 Å at their smallest dimension; said process further including adding dendritic polymers whose particles have diameters from about 50 to about 110 Å at their smallest dimension, after said complex has formed.
Claim 118
Dependent Claim
16 words
The process of claim 96 wherein said dendritic polymer particles include target director moieties attached thereto.
Claim 119
Dependent Claim
31 words
The process of claim 96 which includes adding sufficient glycerol to said complex after it is formed, to yield a glycerol concentration from about 2 to about 10 percent by weight.
Claim 120
Dependent Claim
19 words
The process of claim 109 wherein said glycerol concentration is from about 2 to about 5 percent by weight.
Claim 121
Dependent Claim
16 words
The process of claim 109 wherein said charge ratio is from about 1:1 to about 1:15.
Claim 122
Dependent Claim
28 words
The process of claim 109 wherein said dendritic polymer has a diameter from about 50 Å at its narrowest diameter, to a maximum diameter of about 1,000 Å.
Claim 123
Dependent Claim
83 words
A process for forming a concentrated genetic material:dendritic polymer complex which can be diluted for use comprising: mixing, in water, sufficient genetic material to yield a concentration from about 1 to about 10 μg per 20 μL, with sufficient dendritic polymer, having positive surface functionality, to yield a genetic material:dendritic polymer charge ratio from about 4:1 to about 1:10,000; said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20° to about 40° C.
Claim 124
Dependent Claim
83 words
A process for forming a concentrated genetic material:dendritic polymer complex which can be diluted for use comprising: mixing, in water, sufficient genetic material to yield a concentration from about 1 to about 10 μg per 20 μL, with sufficient dendritic polymer, having positive surface functionality, to yield a genetic material:dendritic polymer charge ratio from about 4:1 to about 1:10,000; said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20° to about 40° C.
Claim 125
Dependent Claim
16 words
The process of claim 113 wherein said charge ratio is from about 1:1 to about 1:1,000.
Claim 126
Dependent Claim
16 words
The process of claim 113 wherein said charge ratio is from about 1:1 to about 1:15.
Claim 127
Dependent Claim
16 words
The process of claim 113 wherein said charge ratio is from about 1:5 to about 1:10.
Claim 128
Dependent Claim
28 words
The process of claim 113 wherein said dendritic polymer has a diameter from about 50 Å at its narrowest diameter, to a maximum diameter of about 1,000 Å.
Claim 129
Dependent Claim
54 words
The process of claim 113 wherein said dendritic polymer is comprised of a dispersion of different sized dendrimer particles, ranging from particles having a diameter as small as about 20 Å at their smallest dimension to particles having a diameter of about 110 Å, there being other particles of intermediate diameters in said dispersion.
Claim 130
Dependent Claim
45 words
The process of claim 113 wherein said dendritic polymer comprises aggregates of dendrimers having positive surface functionality and dendrimers having negative surface functionality at a positive:negative charge ratio from about 25:1 to about 100:1, said aggregates having diameters of no more than about 1,000 Å.
Claim 131
Dependent Claim
30 words
The process of claim 113 wherein said dendritic polymer comprises a dense star polymer having amino acids over a substantial portion of its surface, and substantially only on its surface.
Claim 132
Dependent Claim
13 words
The process of claim 120 wherein said amino acid is lysine or arginine.
Claim 133
Dependent Claim
16 words
The process of claim 113 wherein said dendritic polymer particles include target director moieties attached thereto.
Claim 134
Dependent Claim
55 words
The process of claim 123 wherein said dendritic polymer comprises relatively small dendrimer particles having a diameter of about 22 to about 50 Å at their smallest dimension; said process further including adding dendritic polymers whose particles have diameters from about 50 to about 110 Å at their smallest dimension, after said complex is formed.
Claim 135
Independent Claim
32 words
A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a dendritic polymer and genetic material, and making said complex available to cells to be transfected.
Claim 136
Independent Claim
32 words
A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a dendritic polymer and genetic material, and making said complex available to cells to be transfected.
Claim 137
Independent Claim
34 words
A method for transporting genetic material through a cellular membrane and into a cellular nucleus comprising: complexing said genetic material with dendritic polymer; followed by making said complex available to cells to be transfected.
Claim 138
Independent Claim
34 words
A method for transporting genetic material through a cellular membrane and into a cellular nucleus comprising: complexing said genetic material with dendritic polymer; followed by making said complex available to cells to be transfected.
Claim 139
Independent Claim
34 words
A method for protecting genetic material from digestion during transit to and transfection into a cell comprising: complexing said genetic material with dendritic polymer prior to exposing the said genetic material to digestive enzymes.
Claim 140
Independent Claim
34 words
A method for protecting genetic material from digestion during transit to and transfection into a cell comprising: complexing said genetic material with dendritic polymer prior to exposing the said genetic material to digestive enzymes.
Claim 141
Independent Claim
16 words
A method for stabilizing and compacting genetic material comprising: complexing said genetic material with dendritic polymer.
Claim 142
Independent Claim
16 words
A method for stabilizing and compacting genetic material comprising: complexing said genetic material with dendritic polymer.
Claim 143
Independent Claim
38 words
A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a dendritic polymer and genetic material, in solution with DEAE-dextran or glycerol, and making said complex available to cells to be transfected.
Claim 144
Independent Claim
38 words
A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a dendritic polymer and genetic material, in solution with DEAE-dextran or glycerol, and making said complex available to cells to be transfected.
Claim 145
Dependent Claim
15 words
The method of claim 128 which includes attaching a target director to said dendritic polymer.
Claim 146
Independent Claim
63 words
A method for effecting cell transfection and bioavailability of genetic material comprising: forming a complex of a first dendritic polymer and genetic material, followed by placing said complex in a solution containing a second dendritic polymer, wherein said second dendritic polymer is larger than said first dendritic polymer; and making the resulting complex and second dendritic polymer available to cells to be transfected.
Claim 147
Independent Claim
63 words
A method for effecting cell transfection and bioavailability of genetic material comprising: forming a complex of a first dendritic polymer and genetic material, followed by placing said complex in a solution containing a second dendritic polymer, wherein said second dendritic polymer is larger than said first dendritic polymer; and making the resulting complex and second dendritic polymer available to cells to be transfected.
Claim 148
Dependent Claim
21 words
The method of claim 130 wherein at least one of said first and second dendritic polymers has attached a target director.
Claim 149
Dependent Claim
38 words
A dense star polymer conjugate which comprises at least one dense star polymer associated with at least one unit of at least one bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents.
Claim 150
Dependent Claim
38 words
A dense star polymer conjugate which comprises at least one dense star polymer associated with at least one unit of at least one bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents.
Claim 151
Dependent Claim
119 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a bioactive agent, said bioactive agent can be the same bioactive agent or a different bioactive agent, said bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that target director and bioactive agent are associated with the dense star polymer; with the proviso that the bioactive agent maintains its effectiveness.
Claim 152
Dependent Claim
119 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a bioactive agent, said bioactive agent can be the same bioactive agent or a different bioactive agent, said bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that target director and bioactive agent are associated with the dense star polymer; with the proviso that the bioactive agent maintains its effectiveness.
Claim 153
Dependent Claim
164 words
A dense star polymer conjugate of the formula: (T).sub.e -(C').sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; each T represents one or more target directors; each M represents at least one unit of a carried bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents; y represents an integer of 1 or greater; and * indicates that target director and carried bioactive agent are associated with the dense star polymer; with the proviso that the carried bioactive agent maintains its effectiveness.
Claim 154
Dependent Claim
164 words
A dense star polymer conjugate of the formula: (T).sub.e -(C').sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; each T represents one or more target directors; each M represents at least one unit of a carried bioactive agent, selected from the group consisting of therapeutic agents, diagnostic agents, and therapeutic/diagnostic agents; y represents an integer of 1 or greater; and * indicates that target director and carried bioactive agent are associated with the dense star polymer; with the proviso that the carried bioactive agent maintains its effectiveness.
Claim 155
Dependent Claim
122 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a earned material, said carried material can be the same carried material or a different carried material, said carrier material selected from the group consisting of fragrance moieties, scavenging agents, pheromones, pesticides, agricultural materials, and pollutants; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that target director and carried material are associated with the dense star polymer; with the proviso that the carrier material maintains its effectiveness.
Claim 156
Dependent Claim
122 words
A dense star polymer conjugate of the formula: (T).sub.e *(P).sub.x *(M).sub.y (II) wherein: each P represents a dense star polymer; x represents an integer of 1 or greater; each M represents at least one unit of a earned material, said carried material can be the same carried material or a different carried material, said carrier material selected from the group consisting of fragrance moieties, scavenging agents, pheromones, pesticides, agricultural materials, and pollutants; y represents an integer of 1 or greater; each T represents one or more target directors; e represents an integer of 1 or greater; and * indicates that target director and carried material are associated with the dense star polymer; with the proviso that the carrier material maintains its effectiveness.
Claim 157
Dependent Claim
164 words
A dense star polymer conjugate of the formula: (T).sub.e -(C'.sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; each T represents one or more target directors; each M represents at least one unit of a carried material, selected from the group consisting of fragrance moieties, scavenging agents, pheromones, pesticides, agricultural materials, and pollutants; y represents an integer of 1 or greater; and * indicates that target director and carried material are associated with the dense star polymer; with the proviso that the carried material maintains its effectiveness.
Claim 158
Dependent Claim
164 words
A dense star polymer conjugate of the formula: (T).sub.e -(C'.sub.f !.sub.g *(P).sub.x * (C").sub.h -(M).sub.y !.sub.k(III) wherein: each C' represents the same or different connecting group; each C" represents the same or different connecting group; g and k each individually represent an integer of 1 or greater; e represents an integer of 1 or greater; f and h each individually represent an integer of 0 or greater; - indicates a covalent bond in instances where a connecting group is present; each P represents a dense star polymer; x represents an integer of 1 or greater; each T represents one or more target directors; each M represents at least one unit of a carried material, selected from the group consisting of fragrance moieties, scavenging agents, pheromones, pesticides, agricultural materials, and pollutants; y represents an integer of 1 or greater; and * indicates that target director and carried material are associated with the dense star polymer; with the proviso that the carried material maintains its effectiveness.
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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) | 2001-02-02 | 2001-08-04 | 2002-02-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-02-02 | 2005-08-04 | 2006-02-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-02-02 | 2009-08-04 | 2010-02-03 | $7700.00 | Window Closed / Lapsed |