Key Points• Single subcutaneous dosing of ACE910 has a linear PK profile, a half-life of 4 to 5 weeks, and FVIII-mimetic procoagulant activity in humans.• ACE910 at doses up to 1 mg/kg is well tolerated and has no notable adverse hypercoagulable effect in healthy Japanese and white adults.ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n 5 6 per dose group) or placebo (n 5 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIIIneutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject's withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (antidrug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www

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Fecal extracts from 12 subjects in outbreaks of oyster-associated nonbacterial gastroenteritis were inoculated with BS-C-1 cells for isolation of the causative viruses. Cytopathic agents were isolated from 3 patients. No cross-neutralizing reactions were observed between the isolates and prototypes of human enteroviruses. The isolates were approximately 30 nm in diameter and had a distinct ultrastructure resembling that of astroviruses. Four polypeptide bands with molecular sizes of 42, 28, 27, and 22 kDa were seen on SDS-PAGE analyses. Seroconversion against the isolate was observed in 18 (31.6%) of 57 patients involved in five of seven outbreaks examined by neutralization test. A protein band characteristically reactive with the paired serum samples was detectable at 42 kDa by immunoblot assay. These results suggested that some small round viruses resembling astroviruses might show cytopathic effect in BS-C-1 cells and may be associated with an oyster-related gastroenteritis.

Human norovirus (NoV) strains cause a considerable number of outbreaks of gastroenteritis worldwide. Based on their capsid gene (VP1) sequence, human NoV strains can be grouped into two genogroups (GI and GII) and at least 14 GI and 17 GII genotypes (GI/1-14 and GII/1-17). Human NoV strains cannot be propagated in cell-culture systems, but expression of recombinant VP1 in insect cells results in the formation of virus-like particles (VLPs). In order to understand NoV antigenic relationships better, cross-reactivity among 26 different NoV VLPs was analysed. Phylogenetic analyses grouped these NoV strains into six GI and 12 GII genotypes. An antibody ELISA using polyclonal antisera raised against these VLPs was used to determine cross-reactivity. Antisera reacted strongly with homologous VLPs; however, a number of novel cross-reactivities among different genotypes was observed. For example, GI/11 antiserum showed a broad-range cross-reactivity, detecting two GI and 10 GII genotypes. Likewise, GII/1, GII/10 and GII/12 antisera showed a broad-range cross-reactivity, detecting several other distinct GII genotypes. Alignment of VP1 amino acid sequences suggested that these broad-range cross-reactivities were due to conserved amino acid residues located within the shell and/or P1-1 domains. However, unusual cross-reactivities among different GII/3 antisera were found, with the results indicating that both conserved amino acid residues and VP1 secondary structures influence antigenicity.

A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.