keyword
https://read.qxmd.com/read/25274508/anti-factor-ixa-x-bispecific-antibody-ace910-prevents-joint-bleeds-in-a-long-term-primate-model-of-acquired-hemophilia-a
#21
JOURNAL ARTICLE
Atsushi Muto, Kazutaka Yoshihashi, Minako Takeda, Takehisa Kitazawa, Tetsuhiro Soeda, Tomoyuki Igawa, Zenjiro Sampei, Taichi Kuramochi, Akihisa Sakamoto, Kenta Haraya, Kenji Adachi, Yoshiki Kawabe, Keiji Nogami, Midori Shima, Kunihiro Hattori
ACE910 is a humanized anti-factor IXa/X bispecific antibody mimicking the function of factor VIII (FVIII). We previously demonstrated in nonhuman primates that a single IV dose of ACE910 exerted hemostatic activity against hemophilic bleeds artificially induced in muscles and subcutis, and that a subcutaneous (SC) dose of ACE910 showed a 3-week half-life and nearly 100% bioavailability, offering support for effective prophylaxis for hemophilia A by user-friendly SC dosing. However, there was no direct evidence that such SC dosing of ACE910 would prevent spontaneous bleeds occurring in daily life...
November 13, 2014: Blood
https://read.qxmd.com/read/24762272/novel-products-for-haemostasis
#22
REVIEW
M Shima, C Hermans, P de Moerloose
The primary major issue in haemophilia treatment remains the development of inhibitors. Recently two novel bypassing products have been developed. First, a humanized bispecific antibody against FIXa and FX, termed hBS23, was produced utilizing these two molecules placed into a spatially appropriate position to mimic FVIIIa, and recently this mimetic activity and the pharmacokinetics of the original antibody were improved by engineering the charge properties of the variable region within the immunoglobulin. Using the new antibody, termed ACE910, a phase 1 study in 64 Japanese and Caucasian healthy adults was performed and data from this trial suggested that the product had medically acceptable safety and tolerability profiles...
May 2014: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://read.qxmd.com/read/24738137/anti-factor-ixa-x-bispecific-antibody-ace910-hemostatic-potency-against-ongoing-bleeds-in-a-hemophilia-a-model-and-the-possibility-of-routine-supplementation
#23
JOURNAL ARTICLE
A Muto, K Yoshihashi, M Takeda, T Kitazawa, T Soeda, T Igawa, Y Sakamoto, K Haraya, Y Kawabe, M Shima, A Yoshioka, K Hattori
BACKGROUND: We previously reported that a humanized anti-factor IXa/X bispecific antibody, hBS23, mimics the function of FVIII even in the presence of FVIII inhibitors, and has preventive hemostatic activity against bleeding in an animal model of acquired hemophilia A. After further molecular engineering of hBS23, we recently identified an improved humanized bispecific antibody, ACE910, for clinical investigation. OBJECTIVES: To elucidate the in vivo hemostatic potency of ACE910 by examining its effect against ongoing bleeds, and to determine its pharmacokinetic parameters for discussion of its potency for prophylactic use...
February 2014: Journal of Thrombosis and Haemostasis: JTH
https://read.qxmd.com/read/24735117/anti-factor%C3%A2-ixa-x-bispecific-antibody-ace910-hemostatic-potency-against-ongoing-bleeds-in-a-hemophilia%C3%A2-a-model-and-the-possibility-of-routine-supplementation
#24
A Muto, K Yoshihashi, M Takeda, T Kitazawa, T Soeda, T Igawa, Y Sakamoto, K Haraya, Y Kawabe, M Shima, A Yoshioka, K Hattori
BACKGROUND: We previously reported that a humanized anti-factor IXa/X bispecific antibody, hBS23, mimics the function of FVIII even in the presence of FVIII inhibitors, and has preventive hemostatic activity against bleeding in an animal model of acquired hemophilia A. After further molecular engineering of hBS23, we recently identified an improved humanized bispecific antibody, ACE910, for clinical investigation. OBJECTIVES: To elucidate the in vivo hemostatic potency of ACE910 by examining its effect against ongoing bleeds, and to determine its pharmacokinetic parameters for discussion of its potency for prophylactic use...
February 2014: Journal of Thrombosis and Haemostasis: JTH
https://read.qxmd.com/read/23468998/identification-and-multidimensional-optimization-of-an-asymmetric-bispecific-igg-antibody-mimicking-the-function-of-factor-viii-cofactor-activity
#25
JOURNAL ARTICLE
Zenjiro Sampei, Tomoyuki Igawa, Tetsuhiro Soeda, Yukiko Okuyama-Nishida, Chifumi Moriyama, Tetsuya Wakabayashi, Eriko Tanaka, Atsushi Muto, Tetsuo Kojima, Takehisa Kitazawa, Kazutaka Yoshihashi, Aya Harada, Miho Funaki, Kenta Haraya, Tatsuhiko Tachibana, Sachiyo Suzuki, Keiko Esaki, Yoshiaki Nabuchi, Kunihiro Hattori
In hemophilia A, routine prophylaxis with exogenous factor VIII (FVIII) requires frequent intravenous injections and can lead to the development of anti-FVIII alloantibodies (FVIII inhibitors). To overcome these drawbacks, we screened asymmetric bispecific IgG antibodies to factor IXa (FIXa) and factor X (FX), mimicking the FVIII cofactor function. Since the therapeutic potential of the lead bispecific antibody was marginal, FVIII-mimetic activity was improved by modifying its binding properties to FIXa and FX, and the pharmacokinetics was improved by engineering the charge properties of the variable region...
2013: PloS One
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