A recombinant human enzyme for enhanced interstitial transport of therapeutics

Bookbinder, Louis H.; Hofer, Anthony; Haller, Michael; Zepeda, Monica; Keller, G A; Lim, Jeongah; Edgington, T S; Shepard, H. Michael; Patton, John S.; Frost, Gregory I.

doi:10.1016/j.jconrel.2006.05.027

Cited by 235 publications

(240 citation statements)

References 34 publications

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“…Today, hyaluronidase from bovine, ovine and recombinant-human sources is used clinically to increase the dispersion and absorption of subcutaneously administered drugs. However, animal-derived products are associated with IgE-mediated allergic reactions and are contaminated with proteases, immunoglobulins and factors that increase capillary permeability, all of which limit their use to short-term administration [19].…”

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

“…Hyaluronan is a large, viscous and hydroscopic molecule that impedes movement of fluids from the subcutaneous space to the vasculature. Unlike collagen and elastin and other stable structural components of the ECM, hyaluronan is short lived, with a half-life of 15-20 h [19].…”

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

“…Using genetic recombinant technology, rHuPH20 was engineered using a construct encoding a soluble, neutral-active form of the human PH20 gene resulting in a soluble variant of the human PH20 enzyme that was highly specific (>100,000 United States Pharmacopeia units/mg protein) and 100-times more pure than bovine testes-derived hyaluronidase [19].…”

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

“…The enzymatic activity of rHuPH20 is highly specific for the β1-4 linkage in glycosaminoglycans, and it does not degrade structural protein components in the skin (e.g., collagen or elastin) or increase vascular permeability. rHuPH20 is suitable for long-term use because it is highly purified and not associated with inflammation, increased vascular permeability or frequent allergic reactions [19]. Use of rHuPH20 facilitates the infusion of large volumes of IgG into a single infusion site.…”

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

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Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Wasserman

2017

Immunotherapy

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Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Recombinant human hyaluronidase (rHuPH20) increases SCIG absorption and dispersion. In patients with PIDD, SCIG facilitated with rHuPH20 (IGHy) has been shown to prevent infections, be well-tolerated and reduce infusion frequency and number of infusion sites as compared with conventional SCIG. This article reviews IGHy clinical studies and real-world practice data in patients with PIDD.

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Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

Section: Recombinant Human Hyaluronidasementioning

confidence: 99%

See 2 more Smart Citations

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Wasserman

2017

Immunotherapy

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“…10 A critical consideration in the development of concentrated antibody formulations for subcutaneous administration is the limited volume (1-1.5 mL) available in the subcutaneous space. 11 This necessitates development of stable, highly concentrated antibody formulations. For example, an antibody that requires subcutaneous dosing at 2 mg per kilogram of patient weight will need to be formulated at a concentration of 130-200 mg per mL to accommodate a 100 kg patient.…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

Tomar

Kumar

Singh

et al. 2016

mAbs

152

145

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Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

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Identification and characterization of a bacterial hyaluronidase and its production in recombinant form

et al. 2016

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Hyaluronidases (Hyals) are broadly used in medical applications to facilitate the dispersion and/or absorption of fluids or medications. This study reports the isolation, cloning, and industrial-scale recombinant production, purification and full characterization, including X-ray structure determination at 1.45 A, of an extracellular Hyal from the nonpathogenic bacterium Streptomyces koganeiensis. The recombinant S. koganeiensis Hyal (rHyal_Sk) has a novel bacterial catalytic domain with high enzymatic activity, compared with commercially available Hyals, and is more thermostable and presents higher proteolytic resistance, with activity over a broad pH range. Moreover, rHyal_Sk exhibits remarkable substrate specificity for hyaluronic acid (HA) and poses no risk of animal cross-infection.

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A recombinant human enzyme for enhanced interstitial transport of therapeutics

Cited by 235 publications

References 34 publications

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

Identification and characterization of a bacterial hyaluronidase and its production in recombinant form

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