Hgh Innovation Gmbh

  • Who is HGH Innovation GmbH in Munich Germany?
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  • Who is HGH Innovation GmbH in Munich? | HGH Innovation GmbH
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    Who is HGH Innovation GmbH in Munich Germany?

    hgh innovation gmbh Hgh Hgh innovation gmbh is hgh innovation gmbh Private company. As of AugustHgh Innovation has If you'd like to make any changes to this portfolio we'd be happy to help. Of the 0 most recent stories on Hgh Innovation, none are news stories, none are Hgh Innovation blog posts, none are press releases. Screengrabs of how the Hgh Innovation site has evloved.

    July - - Newsletters - News | HGH

    hgh innovation gmbh

    Even so, hGH shares a common problem with most other first-generation protein therapeutics: Because such biologics are relatively small molecules, they are rapidly eliminated by renal filtration 3. So they usually have to be injected daily to accomplish the desired therapeutic effect.

    The same holds true for antibody fragments 4 and for the growing class of alternative protein scaffolds 5. Thus, a technology is needed to prolong their plasma half-lives to meet clinical demands.

    PEGylation technology is an established strategy for extending plasma half-life of small-sized biopharmaceuticals. Through chemical conjugation to polyethylene glycol PEG , the hydrodynamic radius of a protein becomes larger than the pore size of the glomerular filtration barrier in kidneys, so its circulation time in blood is extended to a therapeutically useful range 6. However, chemically activated GMP-grade PEG can be an expensive raw material, and PEGylated proteins have to be recovered from the reaction mixture by additional purification steps that ultimately lower yields and raise manufacturing costs.

    Furthermore, the activity of a PEGylated therapeutic protein can be impaired if amino-acid side chains in the vicinity of its active site become modified through PEG attachment 7. In response to those drawbacks of PEGylation, XL-protein GmbH has developed what we consider to be a competitive technology — called PASylation — that extends the plasma half-life of biopharmaceuticals by applying a natively disordered amino-acid chain as a biological alternative to PEG.

    Through such means, the typically short plasma half-life of small therapeutic proteins can be prolonged by several orders of magnitude Figure 1 , which allows their dosing frequency to be drastically reduced.

    PASylation technology offers significant advantages over other methods for half-life extension, especially an overall reduction of manufacturing cost. Finally, PAS sequences are biodegradable and, unlike PEG, do not accumulate in tissues, which prevents renal vacuolation 7 , 9. PASylated proteins can be conveniently produced by genetically modified Escherichia coli cells. An alternative is periplasmic production in E. Periplasmic production eliminates the need for refolding because proteins can usually form their correct set of disulfide bonds in the oxidizing milieu of the bacterial periplasm.

    However, fermentation yields are typically lower than those from inclusion body processes, most likely due to physical restrictions of the periplasmic space. Using the proprietary E. The company genetically engineered an E. That greatly simplifies bioproduction and processing because biologically active proteins are recovered directly from culture broth without cell disruption. High secretion efficiency and a lack of spatial constraints posed by the bacterial periplasm provides superior yields of high-quality protein products through a cost-efficient manufacturing process.

    Because cell disruption and protein refolding are no longer required, primary recovery and purification schemes are simplified, which significantly improves overall process efficiency We genetically fused a PAS sequence of amino acids to the N-terminus of hGH normally a single polypeptide chain of amino acids.

    PAS-hGH thus can effectively escape renal clearance, and it exhibits a plasma half-life in mice that is roughly fold longer than that of unmodified hGH. Notably, adding L-proline, L-alanine, and L-serine to the culture medium had no titer effect. Furthermore, no significant protein degradation was observed; consequently, protease-deficient strains were not included in our study. Our protein exhibited an expected MW of 73 kDa and was monodisperse Figure 3. We also tested the purified protein using real-time surface plasmon resonance spectroscopy Biacore for its binding activity to the human growth hormone receptor hGHR ectodomain.

    We used the best production parameters temperature, medium, and induction strength identified in the small-scale experiments for fed-batch fermentation while testing different induction time points. It is well known that hGH exposes several aromatic side chains in its native state, giving it a pronounced aggregation tendency It is important that, under those conditions, protein concentration detected by the functional sandwich ELISA perfectly correlated with the SDS-PAGE densitometry data, which indicates that the hormone was biochemically active.

    We also found that the purified PAS-hGH remained monomeric during downstream processing and storage despite high protein concentration and the absence of cyclodextrin data not shown. PASylated proteins are generally well suited to production in E. Nevertheless, at the onset of our study, we had to consider several obstacles with regard to developing a manufacturing process suitable for industrial-scale production.

    First, it might have been challenging for E. Second, we had to demonstrate that the large hydrodynamic volume of the recombinant fusion protein would allow production at high yield.

    In particular, the protein size could have hampered secretory production in E. Notably, sufficient amounts of the three amino acids required for PAS biosynthesis were endogenously produced by the E.

    The yield of secreted PAS-hGH we achieved was over fold greater than that from early laboratory experiments using conventional periplasmic production.

    It is conceivable that such titers could increase further after a fermentation development program. It is well known that hGH is naturally prone to aggregation That allowed for recovery of fully soluble and functional PAS-hGH using standard purification techniques. It is torus shaped with an interior that is extremely hydrophobic. Sugar hydroxyl groups oriented to the outside form a hydrophilic surface exposed to solvent.

    The ability of cyclodextrins to encapsulate small molecules previously inspired their successful use in pharmaceutical formulations of chemical drugs for parenteral administration e. In fact, cyclodextrins have long been regarded as promising formulation excipients for preventing aggregation of therapeutic proteins It is likely that, in addition to playing a beneficial role during PAS-hGH manufacturing, cyclodextrins could also be used as excipients for pharmaceutical hormone formulations.

    Our finding that highly concentrated, purified PASylated hGH remained fully monomeric and active after cyclodextrin depletion suggests a stabilizing effect that deserves further investigation.

    In fact, it may be attributable to the hydrophilic PAS tag. The protein was monodisperse in SEC and MS, an attribute that constitutes a clear advantage over the well-known polydispersity of PEGylated biopharmaceutical products.

    In addition, N-hydroxysuccinimide—activated PEG is poorly specific in its reaction with lysine side chains, so unwanted by-products are usually formed during the coupling reaction By contrast, PASylated fusion proteins are genetically encoded, so the probability of product heterogeneity in terms of the PAS modification is virtually nonexistent. That is especially due to the chemically inert nature of the proline, alanine, and serine residues involved. Even more important, the secreted PAS-hGH retained high receptor affinity, so low doses should be sufficient to elicit a therapeutic effect.

    Proteins can significantly lose their biological activity after PEGylation, requiring companies to test several PEG variants and coupling conditions during process development to ensure protein functionality PASylation technology can improve product quality while extending the plasma half-life of therapeutically relevant proteins based on a PEG-like biophysical mechanism.

    This study provides further evidence that E. In addition, combining both technologies could boost development of other novel therapeutic protein classes such as antibody fragments or alternative binding proteins. Save my name, email, and website in this browser for the next time I comment.

    Richmond, E, and AD Rogol. TOP 30 Biologics Development Trends for Therapeutic Antibody Fragments. Gebauer, M, and A Skerra. Poly ethylene glycol in Drug Delivery: Frokjaer, S, and DE Otzen.

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    Who is HGH Innovation GmbH in Munich? | HGH Innovation GmbH

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