Recombinant human albumin

Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, FisceUa M, Yu R, Osborn BE, Cronin PW, Ereimuth WW, McHutchison JG, Subramanian GM (2006) A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 44 671-678... 

Balan V Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfleld RR, Davis GL, Neumann AU, Osborn BE, Ereimuth WW, Subramanian GM (2006) A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy, Antivir Ther 11 35 5... 

Chuang, V.T., Kragh-Hansen, U., and Otagiri, M. 2002. Pharmaceutical strategies utilizing recombinant human serum albumin. Pharmaceutical Research 19(5), 569-577. 

Sakai H, Masada Y, Horinouchi H, et al. Hemoglobin-vesicles suspended in recombinant human serum albumin for resuscitation from hemorrhagic shock in anesthetized rats. Crit Care Med 2004 32 539. 

High temperatures can break native S-S bonds and form new S-S bonds which can lock the protein into a denatured eonfiguration [89]. Low pH, sodium dodecyl sulfate. Tween 80, chaotropie salts, and exogenous proteins have been used to protect proteins from thermal inaetivation [90]. Ethylene glycol at 30-50% was used to protect the antiviral activity of P-interferon preparations [91]. Human serum albumin was used in recombinant human interferon-Psei-n which resulted in increased thermal stability [62]. Water-soluble polysaeeharides sueh as dextrans and amylose [92], as well as point-specific (site-directed) mutagenesis [93] have also been used to increase thermal stability of therapeutie proteins and peptides. 

Clinical trials have demonstrated excellent efficacy with recombinant human factor VIII concentrates available as Recombinate and Kogenate. These recombinant factor VIII products are purified from the cell culture of plasmids, not viral DNA-transfected hamster cells and therefore do not express viral sequences. The addition of human serum albumin for stabilization, constitutes the sole possible source for human viral contamination. More recently recombinant factor IX has been genetically engineered by insertion of the human factor IX gene into a Chinese hamster ovary cell line. It has been proved to be safe and effective in the treatment of patients with hemophilia B. 

Type IV poly(ortho esters) are very similar in structure to type II poly(ortho esters), but they do not need to have excipients in the formulation due to the incorporation of no acidic moieties in the polymer backbone (Ng et al. 1997). Rods of poly(ortho ester) loaded with recombinant human-growth hormone and bovine serum albumin have been created. The rods are the products of polymer-protein mixture extrusion at a temperature between 50° and 70°C. Particles have also been produced from these rods (Heller et al. 2000). The size of these particles, >106 pm, was much larger than would be expected to be absorbed by the gastrointestinal lining (Florence 1997). If the particle size can be reduced, this type of polymer system may be made to be acceptable for oral administration. 

Celletti et al. (2001) have evaluated the impact of recombinant human VEGF (rhVEGF) administration on the progression and destabilization of atherosclerotic plaques. An increase in cross-sectional plaque area and circumferential plaque extension accompanied by increase in thickness was found in rhVEGF-treated apo E-deficient cholesterol-fed mice when compared to control mice, treated with albumin. This effect of rhVEGF is not species specific and has been observed in rabbits and in dogs as well. 

Ang WH, Daldini E, Juillerat-Jeanneret L, Dyson PJ (2007) Strategy to tether organometallic ruthenium-arene anticancer compounds to recombinant human serum albumin. Inorg Chem 46(22) 9048-9050... 

Reactions between cisplatin and serum albumin are thought to be the main route for platinum binding in human blood plasma. Several clinical and experimental observations have suggested that albumin-bound platinum may be anticancer active [47] [48]. Additionally, albumin binding may reduce some of the side-effects of cisplatin treatment, especially its nephrotoxicity [49]. The reaction of cisplatin with intact and chemically modified recombinant human albumin (rHA), and with HSA (human serum al-... 

Ref. 12 describes the preparation of microspheres of lysozyme, insulin, albumin, and recombinant human deoxyribonuclease. Of these proteins, insulin powders demonstrated the highest degree of agglomeration. 

Flensburg, J. and Belew, M. (2003) Characterization of recombinant human serum albumin using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 

Costantino, H. R., Langer, R., and Klibanov, A. (1995), Aggregation of a lyophilized pharmaceutical protein, recombinant human albumin effect of moisture and stabilization excipients, BioTechnology, 13,493-496. 

Reactions of NO were also studied with the synthetic heme protein discussed earlier, namely the recombinant human serum albumin (rHSA) with eight incorporated TPPFe derivatives bearing a covalently linked axial base, were also investigated. The UV-vis absorption spectrum of the phosphate buffer solution at physiological pH showed absorption band maxima at 425 and 546 nm upon the addition of NO to form the nitrosyl species, which was also formed when the six-coordinate CO-adducts were reacted with NO gas. EPR spectroscopy revealed that the albumin-incorporated iron(II) porphyrin formed six-coordinate nitrosyl complexes. It was observed that the proximal imidazole moiety does not dissociate from the central iron when NO binds to the trans position. The NO-binding affinity P1 /2no was 1.7 X 10 torr at pH 7.3 and 298 K, significantly lower than that of the porphyrin complex itself, and was interpreted as arising from the decreased association rate constant (kon(NO), 8.9 x 10 M s" -1.5 x 10 M s ). Since NO-association is diffusion controlled, incorporation of the synthetic heme into the albumin matrix appears to restrict NO access to the central iron(II). ... 

BSA monomer, ovalbumin (chicken), P-lactoglobulin (bovine milk), serum albumin (human), carbonic anhydrase (bovine), L-glutamic dehydrogenase (bovine liver), a-chymotrypsin (bovine), a-chymotrypsinogen A (bovine), immunoglobulin (bovine milk), pepsin, trypsin (bovine), and heparin were from Sigma. RNase and lysozyme (egg white) were from Calbiochem. The recombinant human basic fibroblast... 

Recombinant human albumin Organic acid excipient molecules with either a carboxyl group or an amino group present at C-1 position completely stabilized rHA against aggregation [27]... 

IR and Raman bands due to vOH from Fe OH and A1 OH units were seen for the minerals cacoxenite and gormanite.334 Dioxygen reacted with recombinant human serum albumin incorporating Fen(TPP) to give v02 at 1158 cm 1 due to coordinated 02.335 The complex (61) forms an 02 adduct with vOO as a Fermi doublet at 877, 893 cm-1.336... 

BSA is considered a semi-defined component that may be contaminated with fatty acids and citrate, and also be a possible source of disease agents [47]. When a completely defined culture medium is required, without reducing the rate of embryo developmenL BSA can be replaced with recombinant human semm albumin (HSA), which has equal developmental potential to BSA and is safe for culturing bovine IVF embryos [52]. 

USA rAHF-PFM antihemophilic Advate Recombinant human coagulation factor VIII produced by a plasma/albumin-free method Hemophilia... 

In addition to ATryn , GTC Biopharmaceuticals has several other products under development in collaboration with Cento-cor, Abbott, Elan, Bristol-Myers Squibbs, Alexion, Progenies Pharmaceuticals, Im-munoGen, and Merrimak Pharmaceuticals. These collaborations and internal programs involve the production of several monoclonal antibodies, recombinant human seram albumin, a malaria vaccine, fusion proteins, and a protein for the treatment of autoimmune conditions. Some of the products that are currently undergoing cHnical trials and will be discussed later [361]. 

A. Baur, R. Reski, G. Gorr, Enhanced recovery of a secreted recombinant human growth factor by stabilising additives and by coexpression of human serum albumin in the moss Physcomitrella patens. Plant Biotechnol. J., in press. 

In January 2004, The Market Health Products Directorate (MHPD) of the Health Products and Food Branch (HPFB) posted some information in regards to this situation. Janssen-Ortho Inc., consulted with Health Canada and revised their prescribing information. They mentioned that Eprex was supplied in two formulations with different stabilizers, one containing polysorbate-80 and the other containing human serum albumin (HSA). It also cautioned that subcutaneous administration of recombinant human proteins may in-... 

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