Hyper comb-branched polymer conjugates

• US 5,919,442 A
• Filed: 08/09/1996
• Issued: 07/06/1999
• Est. Priority Date: 08/11/1995
• Status: Expired due to Term

• Current Assignee: Donald A. Tomalia, AVC Holdings Inc. (Dow, Inc.), Dendritic NanoTechnologies, Inc. (Loveland Products, Inc.)
• Original Assignee: Dendritech Inc., University of Michigan
• Inventors: Yin, Rui, Kukowska-Latallo, Jolanta F., Swanson, Douglas R., Tomalia, Donald A., Baker, James R. Jr., Hedstrand, David M.
• Primary Examiner(s): Levy, Neil S.
• Application Number:
  US08/694,787
• Time in Patent Office: 1,061 Days
• Field of Search: 424/401, 424/405, 424/406, 424/422, 424/486, 424/487, 424/84, 424/85.1, 424/85.8, 424/DIG. 16, 424/78.01, 424/78.02, 424/78.08, 424/1.11, 424/1.33 , 424/1.37, 424/9.1, 424/178.1, 424/184.1, 424/280.1, 424/193, 424/78.17-78.19, 523/105, 523/122, 525/410, 525/417, 525/539, 525/902, 525/279, 525/280, 514/772
• US Class Current: 424/78.18
• CPC Class Codes: A61K 2800/54 Polymers characterized by specific structures/properties
• CPC Class Codes: A61K 2800/57 Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
• CPC Class Codes: A61K 47/56 the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/641 Branched, dendritic or hypercomb peptides
• CPC Class Codes: A61K 47/6885 the conjugate or the polymer being a starburst, a dendrimer, a cascade
• CPC Class Codes: A61K 47/6949 inclusion complexes, e.g. clathrates, cavitates or fullerenes
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 49/0043 Fluorescein, used in vivo
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 8/90 Block copolymers A61K8/89 takes precedence
• CPC Class Codes: A61Q 13/00 Formulations or additives for perfume preparations essential oils or perfumes per se C11B9/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08G 83/005 Hyperbranched macromolecules
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: Y10S 424/16 Dendrimers and dendritic polymers
• CPC Class Codes: Y10S 525/902 : Core-shell

Abstract

A novel class of hyper comb-branched polymers conjugated with carried materials are disclosed.

Claims

1. A hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a carried material;

v is an integer of at least 1; and

b is an integer of at least 1.

2. The conjugate of claim 1 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

3. The conjugate of claim 2 wherein M is an agricultural agent selected from the group consisting of biological response modifiers, scavenging agents, agricultural materials, pheromones, pesticides, herbicides, genetic materials, and combinations thereof.

4. The conjugate of claim 2 wherein M is a bioactive agent selected from the group consisting of pharmaceutical agents, drugs, pharmaceutical intermediaries, radioprotective agents, toxins, antibodies, antibody fragments, hormones, biological response modifiers, scavenging agents, imuno-potentiating agents, genetic materials, antigens, polypeptides, and combinations thereof.

9. The conjugate of claim 1 wherein H has the formula:

##STR18## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR19## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n'"'"' are ≧

2.

10. The conjugate of claim 9 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

11. The conjugate of claim 9 wherein said hyper comb-branched polymer has a hydrophobic exterior formed by grafting hydrophobic polymers selected from the group consisting of polyethylene, polydimethylsiloxane, polybutadiene, polystyrene, polymethylmethacrylate, perfluoropolymer, poly(2-alkyl or phenyl oxazolines), and combinations thereof, at the last grafting step.

12. The conjugate of claim 9 wherein said hyper comb-branched polymer has a hydrophilic exterior formed by grafting hydrophilic polymers selected from the group consisting of poly(2-ethyloxazoline), poly(2-methyloxazoline), polyethylene glycol, polyethylene oxide, polyacrylic acid, polyacrylic amide, polyvinyl pyrrolidone, and combinations thereof.

13. The conjugate of claim 9 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 100,000,000.

14. The conjugate of claim 13 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

15. The conjugate of claim 9 wherein n has a value of from about 2 to about 10,000.

16. The conjugate of claim 9 wherein A is selected from the group consisting of --CH₂ CH₂ --, --CH₂ CH═

CHCH₂ --, --CH₂ C(CH₃)₂ --, --CH₂ CH(CN)--, ##STR20## and combinations thereof, wherein R'"'"' is an alkyl group, aryls, arylalkyl, hydrogen, or carboalkoxy;

R is an alkyl group, aryls, or hydrogen; and

R" is an alkyl group.

17. The conjugate of claim 9 wherein B is selected from the group consisting of ##STR21## and combinations thereof, wherein R is an alkyl group, aryls, or hydrogen, and R" is an alkyl group.

18. The conjugate of claim 1 wherein said hyper comb-branched polymer has an outer periphery functionalized with ethylene diamine or chloroethylamine.

5. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a grafting density of from about 0.1% to about 90%.

6. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has an interior void volume of from about 10 angstroms to about 500 angstroms.

7. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains wherein said hyper comb-branched polymer comprises alternating regions of (i) a first region having a grafting density of less than about 50%, and (ii) a second region having a grafting density of more than about 50%.

8. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branch polymer has at least one chemical moiety disposed about the periphery of said polymer, said moiety selected from the group consisting of --NH₂, --COOH, --COOMe, --NH₄, --PEOX, --PEG, --PEO, and combinations thereof.

19. A hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b --T.sub.z

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a carried material;

T is a target director;

v is an integer of at least 1;

b is an integer of at least 1; and

z is an integer of at least 1.

20. The conjugate of claim 19 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

21. The conjugate of claim 20 wherein M is a diagnostic agent selected from the group consisting of metal ions, radioactive drugs, radioactive tracers, radio-opaques, radionuclides, signal generators, signal reflectors, signal absorbers, diagnostic opacifier agents, fluorescent moieties, dye moieties, and combinations thereof.

22. The conjugate of claim 20 wherein M is an agricultural agent selected from the group consisting of biological response modifiers, scavenging agents, agricultural materials, pheromones, pesticides, herbicides, genetic materials, and combinations thereof.

23. The conjugate of claim 20 wherein M is a bioactive agent selected from the group consisting of pharmaceutical agents, drugs, pharmaceutical intermediaries, radioprotective agents, toxins, antibodies, antibody fragments, hormones, biological response modifiers, scavenging agents, imuno-potentiating agents, genetic materials, antigens, polypeptides, and combinations thereof.

27. The conjugate of claim 19 wherein H has the formula:

##STR22## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR23## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n¹ are ≧

2.

28. The conjugate of claim 27 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

29. The conjugate of claim 27 wherein said hyper comb-branched polymer has a hydrophobic exterior formed by grafting hydrophobic polymers selected from the group consisting of polyethylene, polydimethylsiloxane, polybutadiene, polystyrene, polymethylmethacrylate, perfluoropolymer, poly(2-alkyl or phenyl oxazolines), and combinations thereof, at the last grafting step, wherein the alkyl group of said poly(2-alkyl oxazoline) has about 4 or more carbon atoms.

30. The conjugate of claim 27 wherein said hyper comb-branched polymer has a hydrophilic exterior formed by grafting hydrophilic polymers selected from the group consisting of poly(2-ethyloxazoline), poly(2-methyloxazoline), polyethylene glycol, polyethylene oxide, polyacrylic acid, polyacrylic amide, polyvinyl pyrrolidone, and combinations thereof.

31. The conjugate of claim 27 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 100,000,000.

32. The conjugate of claim 31 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

33. The conjugate of claim 27 wherein n has a value of from about 2 to about 10,000.

34. The conjugate of claim 27 wherein A is selected from the group consisting of --CH₂ CH₂ --, --CH₂ CH═

CHCH₂ --, --CH₂ C(CH₃)₂ --, --CH₂ CH(CN)--, ##STR24## and combinations thereof, wherein R'"'"' is an alkyl group, aryls, arylalkyl, hydrogen, or carboalkoxy;

R is an alkyl group, aryls, or hydrogen; and

R" is an alkyl group.

35. The conjugate of claim 27 wherein B is selected from the group consisting of ##STR25## and combinations thereof, wherein R is an alkyl group, aryls, or hydrogen, and R" is an alkyl group.

36. The conjugate of claim 19 wherein T is selected from the group consisting of bioactive agents, proteins, antibodies, antibody fragments, saccharides, and oligosaccharides.

24. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material wherein said hyper comb-branched polymer has a maximum diameter of about 100 nm, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.

25. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a hydrophobically-modified region, said region being at least one of an interior region or an exterior region.

26. A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a hydrophilically-modified region, said region being at least one of an interior region or an exterior region.

37. A hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b --M'"'"'.sub.a

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a first carried material;

M'"'"' is a second carried material different than said first carried material;

v is an integer of at least 1;

b is an integer of at least 1; and

a is an integer of at least 1.

38. The conjugate of claim 37 wherein one of M or M'"'"' is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

39. The conjugate of claim 38 wherein one of M or M'"'"' is an agricultural agent selected from the group consisting of biological response modifiers, scavenging agents, agricultural materials, pheromones, pesticides, herbicides, genetic materials, and combinations thereof.

40. The conjugate of claim 38 wherein one of M or M'"'"' is a bioactive agent selected from the group consisting of pharmaceutical agents, drugs, pharmaceutical intermediaries, radioprotective agents, toxins, antibodies, antibody fragments, hormones, biological response modifiers, scavenging agents, imuno-potentiating agents, genetic materials, antigens, polypeptides, and combinations thereof.

41. The conjugate of claim 37 further comprising a target director T.

42. The conjugate of claim 41 wherein T is selected from the group consisting of bioactive agents, proteins, antibodies, antibody fragments, saccharides, and oligosaccarides.

47. The conjugate of claim 37 wherein H has the formula:

##STR28## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR29## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n¹ are ≧

2.

48. The conjugate of claim 47 wherein one of M or M'"'"' is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

49. The conjugate of claim 47 wherein said hyper comb-branched polymer has hydrophobic exterior formed by grafting hydrophobic polymers selected from the group consisting of polyethylene, polydimethylsiloxane, polybutadiene, polystyrene, polymethylmethacrylate, perfluoropolymer, poly(2-alkyl or phenyl oxazolines), and combinations thereof.

50. The conjugate of claim 47 wherein said hyper comb-branched polymer has a hydrophilic exterior formed by grafting hydrophilic polymers selected from the group consisting of poly(2-ethyloxazoline), poly(2-methyloxazoline), polyethylene glycol, polyethylene oxide, polyacrylic acid, polyacrylic amide, polyvinyl pyrrolidone, and combinations thereof.

51. The conjugate of claim 47 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from abut 10,000 to about 100,000,000.

52. The conjugate of claim 51 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

53. The conjugate of claim 47 wherein n has a value of from about 2 to about 10,000.

54. The conjugate of claim 47 wherein A is selected from the group consisting of --CH₂ CH₂ --, --CH₂ CH═

CHCH₂ --, --CH₂ C(CH₃)₂ --, --CH₂ CH(CN)--, ##STR30## and combinations thereof, wherein R'"'"' is an alkyl group, aryls, arylalkyl, hydrogen, or carboalkoxy;

R is an alkyl group, aryls or hydrogen; and

R" is an alkyl group.

55. The conjugate of claim 47 wherein B is selected from the group consisting of ##STR31## and combinations thereof, wherein R is an alkyl group, aryls, or hydrogen, and R" is an alkyl group.

43. A composition comprising a hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a first carried material;

v is an integer of at least 1; and

b is an integer of at least 1.

44. The composition of claim 43 wherein said hyper comb-branched polymer H has the general formula:

##STR26## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR27## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n'"'"' are ≧

2.

45. The composition of claim 44 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

46. The composition of claim 44 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from abut 10,000 to about 100,000,000.

56. The composition of claim 44 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

57. A method of carrying genetic material, said method comprising:

providing a hyper comb-branched polymer having a plurality of positively charged sites, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains; and

conjugating said polymer with genetic material having a plurality of negatively charged sites.

58. The method of claim 57 wherein the ratio of said negatively charged sites to said positively charged sites ranges from about 1:

10 to about 1;

1000.

59. The method claim 57 wherein said hyper comb-branched polymer is modified with a moiety selected from the group consisting of --NH₂, --NH--, poly(ethyloxazoline), chloroethylamine, and combinations thereof.

60. The conjugate product of claim 57.

61. A process for preparing a complex of hyper comb-branched polymer and genetic material comprising:

reacting said hyper comb-branched polymer with said genetic material in a solvent at a temperature which facilitates the complexing of said genetic material with said hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to the zero generation linear oligomeric branch chains.

62. The process of claim 61 which includes attaching a target director to said hyper comb-branched polymer before complexing it with genetic material.

63. The process of claim 62 wherein said target director is selected from the group consisting of bioactive agents, proteins, antibodies, antibody fragments, saccharides, and oligosaccharides.

64. The process of clam 62 wherein said hyper comb-branched polymer has a predominantly cationic surface, said process comprising electrostatically attaching genetic material to said polymer to create said complex.

65. A process for forming a genetic material:

hyper comb-branched polymer complex comprising;

mixing, in water, sufficient genetic material to yield a final concentration from about 1 to about 10 μ

g per mL, with sufficient hyper comb-branched polymer, having positive surface functionality, to yield a genetic material;

polymer charge ratio from about 1;

10 to about 1;

10,000, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

said mixing being done at a pH of about 5 to about 10 and at a temperature from about 20 to about 40°

C.

66. The process of claim 65 wherein said charge ratio is from about 1:

10 to about 1;

1,000.

67. The process of claim 65 wherein said charge ratio is from about 1:

100 to about 1;

1000.

68. The process of claim 65 wherein said charge ratio is about 1:

200.

69. The process of claim 65 wherein said hyper comb-branched polymer comprises amino acids over a portion of its surface.

83. The process of claim 69 wherein said amino acid is lysine or arginine.

84. The process of claim 65 wherein said polymer particles include target director moieties attached thereto.

70. A composition comprising a hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b --T.sub.z

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a carried material;

T is a target director;

v is an integer of at least 1;

b is an integer of at least 1; and

z is an integer of at least 1.

71. The composition of claim 70 wherein said hyper comb-branched polymer H has the general formula:

##STR32## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR33## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n¹ are ≧

2.

72. The composition of claim 71 wherein M is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

73. The composition of claim 71 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from abut 10,000 to about 100,000,000.

74. The composition of claim 71 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

75. The conjugate of claim 70 wherein T is selected from the group consisting of bioactive agents, proteins, antibodies, antibody fragments, saccharides, and oligosaccharides.

76. A composition comprising a hyper comb-branched polymer conjugate of the formula:

space="preserve" listing-type="equation">H.sub.v --M.sub.b --M'"'"'.sub.a

wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

M is a first carried material;

M'"'"' is a second carried material different than said first carried material;

v is an integer of at least 1;

b is an integer of at least 1; and

a is an integer of at least 1.

77. The composition of claim 76 wherein said hyper comb-branched polymer H has the general formula:

##STR34## wherein C is a core molecule;

each R is the residual moiety of an initiator selected from a group consisting of free radical initiators, cationic initiators, anionic initiators, coordination polymerization initiators and group transfer initiators;

A and B are polymerizable monomers or comonomers capable of withstanding the conditions required for branching therefrom or grafting thereto, at least during the polymerization of the {(A)--(B)} linear polymer chain and during its grafting to a prior {(A)--(B)} branch or the {(A)--(B)} core branch;

each G is a grafting component, and the designation ##STR35## indicates that G can attach to either an (A) unit or a (B) unit;

n is the degree of polymerization of the indicated generation comb branches;

y is the fraction of B units in the indicated generation branch, and has a value of 0.01 to 1;

the superscripts 0, 1 and i designate the comb-branch generation level, with i beginning at "2" and continuing for the number of reiterative branch set generations in the polymer; and

at least n° and

n¹ are ≧

2.

78. The composition of claim 77 wherein M or M'"'"' is selected from the group consisting of diagnostic agents, agricultural agents, bioactive agents, industrial agents, environmental agents, consumer product agents, and combinations thereof.

79. The composition of claim 77 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from abut 10,000 to about 100,000,000.

80. The composition of claim 76 wherein said hyper comb-branched polymer includes at least one molecule which has a molecular weight of from about 10,000 to about 10,000,000.

81. The composition of claim 76 wherein said conjugate further comprises a target director T.

82. The composition of claim 81 wherein T is selected from the group consisting of bioactive agents, proteins, antibodies, antibody fragments, saccharides, and oligosaccharides.

85. A process for forming a concentrated genetic material:

hyper comb-branched 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 μ

g per 20 μ

L, with sufficient hyper comb-branched polymer, having positive surface functionality, to yield a genetic material;

polymer charge ratio from about 1;

10 to about 1;

10,000, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20 to about 40°

C.

86. The process of claim 85 wherein said charge ratio is from about 1:

10 to about 1;

1,000.

87. The process of claim 85 wherein said charge ratio is from about 1:

100 to about 1;

1000.

88. The process of claim 85 wherein said charge ratio is about 1:

200.

89. A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a hyper comb-branched polymer and genetic material, and making said complex available to cells to be transfected, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.

90. A method for transporting genetic material through a cellular membrane and into a cellular nucleus comprising:

complexing said genetic material with hyper comb-branched polymer, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;

followed by making said complex available to cells to be transfected.

91. A method for protecting genetic material from digestion during transit to and transfection into a cell comprising:

complexing said genetic material with hyper comb-branched polymer prior to exposing said genetic material to digestive enzymes, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.

92. A method for stabilizing and compacting genetic material comprising complexing said genetic material with hyper comb-branched polymer, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.