Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically highvolume s.c. administration (> 10-15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 and GP40201) that evaluated s.c. crenezumab, an anti-Aβ monoclonal antibody in development for individuals at risk for autosomal-dominant Alzheimer's disease. GP29523 assessed safety, tolerability, and pharmacokinetics (PK) in 68 participants (aged 50-80 years) who received single ascending doses (600-7,200 mg) of crenezumab or placebo (4-40 mL). GP40201 assessed safety, tolerability, and PK in 72 participants (aged 18-80 years) who received different combinations of dose (1,700-6,800 mg), infusion volume (10-40 mL), and flow rate (2-4 mL/minute), with/without recombinant human hyaluronidase (rHuPH20). There were no serious or dose-limiting adverse events in either study. There were no meaningful differences in pain scores among reference placebo (4 mL), test placebo (4-40 mL), or crenezumab (600-7,200 mg) in GP29523, or across treatments with varying infusion volume, flow rate, dose, or rHuPH20 co-administration or concentration in GP40201. Transient erythema was the most common infusion site reaction in both studies. In GP40201 at volumes of ≥ 20 mL, rHuPH20 co-administration appeared to reduce infusion site swelling incidence, but, in some cases, was associated with larger areas of infusion site erythema. Crenezumab exhibited approximately doseproportional PK, and s.c. bioavailability was 66% and independent of dose or rHuPH20 co-administration. High-dose, high-concentration, high-volume s.c. crenezumab formulated with/without rHuPH20 was well-tolerated in healthy participants, with an acceptable safety profile.

Silane adhesion promoters are seeing increasing use in microelectronic packaging applications. For example, they are currently used to adhere the passivating polymer overlayer to oxide. In this paper, we present detailed studies of silane adhesion promoters on the silicon oxide surface. Two common promoters (aminopropyltriethoxysilane and vinyltriethoxysilane) as well as non-functional silanes are investigated. It was found that without a functional end group, long carbon chain silanes can severely degrade adhesion, resulting in interfaces weaker than if no silane is used. Several spin coat solution formulations are used in depositing these films. The resulting surface coverage is examined and quantified using XPS, and the adhesion behavior of various promoter films is tested in sandwich structures using a fracture mechanics approach. Finally, spin-coat solution concentration, surface coverage, and interface fracture energy are compared for the amine functional promoter.

Atomic Force Microscopy (AFM) is used to characterize fracture surfaces in silicon oxide / silane adhesion promoter / BCB polymer systems. Fatigue striations were found on some samples, and these were correlated with the crack growth rate per fatigue cycle. X-ray Photoelectron Spectroscopy (XPS) was used to identify the species present on each surface, and it was found that striations only form when the fracture path is through the polymer.