Protein-proteophore complexes

1. A composition comprising a hyperbranched polymer attached to a core and to a biologically active moiety, wherein the hyperbranched polymer contains at least two molecular chains, which molecular chains are of sufficient length to be so arranged as to form a cavity to accommodate the biologically active moiety, and wherein the molecular chains contain sterically demanding capping groups; further wherein the composition has the formula (V):

wherein:

(i) B is the core, containing at least one unit selected from the group consisting of >CH—, >C, and respective analogs thereof wherein H is replaced by an organic group, >N—, or >P—;

(ii) each EMC is one of the at least two molecular chains and each comprises oxyethylene groups;

(iii) L is a non-enzymatically cleavable linker and comprises a carbamate group;

(iv) l is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12;

(v) P is the biologically active moiety and is a protein or polypeptide; and

(vi) C is one or more of the capping groups, which comprises linear, branched, or cyclical alkyl groups, and optionally containing S, N, or O heteroatoms.

2. The composition of claim 1 , wherein the hyperbranched polymer is water soluble.

3. The composition according to claim 1 , wherein further groups are present in the polymer chains, the further groups being selected from the groups consisting of S, N, O, (—S—S)—, oxyethylene, oxypropylene, oxybutylene, amide —C(O)NH— or —C(O)NR—, —S-succinimido, amino (—NR—), carboxylic ester (—C(O)O—), sulfonamide (—S(O) 2 —NR—), carbamate (—O—C(O)—NR—), carbonate (—OC(O)—O—), sulfone (—S(O) 2 —), ether (—O—), oxime (—CR═N—O—), hydrazone (—CR═N—NR—), urea (—NR—C(O)—NR—), thiourea (—NR—C(S)—NR—), carbohydrate, glyceryl, phosphate (—O—P(O)(OR)O—), phosphonate (—P(O)(OR)O—), saturated and nonsaturated cyclic groups, and saturated or nonsaturated heterocyclic groups; and wherein R is selected from the group consisting of H, linear, branched, and cyclical alkyl groups, and which may contain therein additional functional groups or hetero atoms.

4. The composition according to claim 1 , wherein the capping groups C contain further groups selected from the groups consisting of S, N, O, (—S—S)—, oxypropylene, oxybutylene, amide (—C(O)NH— or C(O)NR—), —S-succinimido, amino (—NR—), carboxylic ester (—C(O)O—), sulfonamide (—S(O) 2 —NR—), carbamate (—O—C(O)—NR—), carbonate (—O—C(O)—O—), sulfone (—S(O) 2 —), ether (—O—), oxime (—CR═N—O—), hydrazone (—CR═N—NR—), urea (—NR—C(O)—NR—), thiourea (—NR—C(S)—NR—), carbohydrate, glyceryl, phosphate (—O—P(O)(OR)O—), phosphonate (—P(O)(OR)O—), saturated and nonsaturated cyclic groups, and saturated or nonsaturated heterocyclic groups; and wherein R is selected from the group consisting of H, linear, branched, and cyclical alkyl groups, and which may contain therein additional functional groups or hetero atoms.

5. The composition according to claim 1 , wherein the biologically active moiety is a protein or polypeptide selected from the group consisting of ACTH, adenosine deaminase, agalsidase, albumin, alpha-1 antitrypsin (AAT), alpha-1 proteinase inhibitor (API), alteplase, anistreplase, ancrod serine protease, a monoclonal or polyclonal antibody or fragment thereof, antithrombin III, antitrypsins, aprotinin, asparaginases, biphalin, bone-morphogenic proteins, calcitonin, collagenase, DNase, endorphins, enfuvirtide, enkephalins, erythropoietins, factor VIIa, factor VIII, factor VIIIa, factor IX, fibrinolysin, fusion proteins, follicle-stimulating hormones, granulocyte colony stimulating factor (G-CSF), galactosidase, glucagon, glucocerebrosidase, granulocyte macrophage colony stimulating factor (GM-CSF), phospholipase-activating protein (PLAP), gonadotropin chorionic (hCG), hemoglobins, hepatitis B vaccines, hirudin, hyaluronidases, idurnonidase, immune globulins, influenza vaccines, interleukins selected from the group consisting of IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-10, IL-11, and IL-12, IL-1 receptor antagonists (rhIL-1ra), insulins, interferons selected from the group consisting of IFN-α2a, IFN-α2b, IFN-α2c, IFN-β1a, IFN-β1b, IFN-γ1a, and IFN-γ1b, keratinocyte growth factor (KGF), transforming growth factors, lactase, leuprolide, levothyroxine, luteinizing hormone, lyme vaccine, natriuretic peptide, pancrelipase, papain, parathyroid hormone, platelet-derived growth factor (PDGF), pepsin, platelet activating factor acetyihydrolase (PAF-AH), prolactin, protein C, octreotide, secretin, sermorelin, superoxide dismutase (SOD), somatropins (growth hormone), somatostatin, streptokinase, sucrase, tetanus toxin fragment, tilactase, thrombins, thymosin, thyroid stimulating hormone, thyrotropin, tumor necrosis factor (TNF), TNF receptor-IgG Fc, tissue plasminogen activator (tPA), thyroid stimulating factor (TSF), urate oxidase, urokinase, vaccines, and plant protein wherein the plant protein is optionally a lectin or a ricin.

6. The composition of claim 1 , wherein the biologically active moiety is insulin.

7. The composition of claim 1 , wherein the cleavable linker L contains a hydrolysable ester bond and the carbamate.

8. The composition of claim 7 , wherein the hydrolysable ester bond is a phenol ester.

9. A drug containing the composition of claim 1 .

10. The composition of claim 1 , wherein l is 2 or 3 and resulting in a structure of formula (VII) or (VIII):