Johann Bichler

Novel, human cell line-derived recombinant factor VIII (human-cl rhFVIII; Nuwiq®) in adults with severe haemophilia A: efficacy and safety

Nuwiq® [human cell line‐derived recombinant factor VIII (human‐cl rhFVIII)] is a new generation rFVIII protein, without chemical modification or fusion to any other protein, produced in a human cell line.

Prophylaxis vs. on-demand treatment with Nuwiq(®) (Human-cl rhFVIII) in adults with severe haemophilia A.

Haemophilia A is treated with FVIII, either prophylactically or on demand. Prophylaxis is the gold standard in children and evidence is accumulating in adults.

PK-guided personalized prophylaxis with Nuwiq(®) (human-cl rhFVIII) in adults with severe haemophilia A.

Nuwiq® (human‐cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell‐line.

Efficacy and safety of Nuwiq® (human‐cl rhFVIII) in patients with severe haemophilia A undergoing surgical procedures

Haemophilia A patients are at a high risk of excess bleeding during surgeries. The aim of haemostatic therapy during the perioperative period is to normalize FVIII level perioperatively and postoperatively to maintain normal haemostasis until wound healing is complete.

Individual thrombin generation and spontaneous bleeding rate during personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in previously treated patients with severe haemophilia A

For individuals with haemophilia A, prophylaxis with factor VIII (FVIII) is typically directed towards trough activity >1 IU/dL; however, some patients still experience spontaneous bleeding events (sBEs).

CHO expression of a novel human recombinant IgG1 anti-RhD antibody isolated by phage display: CHO Expression of Human Recombinant Anti-RhD Antibodies

Replacement of the hyperimmune anti‐Rhesus (Rh) D immunoglobulin, currently used to prevent haemolytic disease of the newborn, by fully recombinant human anti‐RhD antibodies would solve the current logistic problems associated with supply and demand. The combination of phage display repertoire cloning with precise selection procedures enables isolation of specific genes that can then be inserted into mammalian expression systems allowing production of large quantities of recombinant human proteins. With the aim of selecting high‐affinity anti‐RhD antibodies, two human Fab libraries were constructed from a hyperimmune donor. Use of a new phage panning procedure involving bromelin‐treated red blood cells enabled the isolation of two high‐affinity Fab‐expressing phage clones, LD‐6‐3 and LD‐6‐33, specific for RhD. These showed a novel reaction pattern by recognizing the D variants DIII, DIVa, DIVb, DVa, DVI types I and II, DVII, Rh33 and DFR. Full‐length immunoglobulin molecules were constructed by cloning the variable regions into expression vectors containing genomic DNA encoding the immunoglobulin constant regions. We describe the first, stable, suspension growth‐adapted Chinese hamster ovary (CHO) cell line producing a high affinity recombinant human IgG1 anti‐RhD antibody adapted to pilot‐scale production. Evaluation of the Fc region of this recombinant antibody by either chemiluminescence or antibody‐dependent cell cytotoxicity (ADCC) assays demonstrated macrophage activation and lysis of red blood cells by human lymphocytes. A consistent source of recombinant human anti‐RhD immunoglobulin produced by CHO cells is expected to meet the stringent safety and regulatory requirements for prophylactic application.