Figure 7. The bispecific anti-TNF-Ang2 Zybodies exhibits superior efficacy in an in vivo model of RA. (A) Mice (n = 8 per group) were treated intraperitoneally twice weekly for seven weeks starting from the third week of age with various doses of ADA-a2H (1, 3 and 10 mg/kg), vehicle control, 3 mg/kg adalimumab or 3 mg/kg control Zybody, TRA-a2H, as indicated. Animals were evaluated for arthritic scores at the indicated times; (B) Mice (n = 8 per group) were treated with 3 mg/kg of ADA-a4H, adalimumab or trastuzumab. Animals were evaluated for arthritic scores at the indicated times; (C) Effect of ADA-a4H on histology scores. After completion of the treatment (week 10) with trastuzumab (n = 5), ADA-a4H (n = 8) and adalimumab (n = 6), the ankle joints were processed and paraffin sections were stained with hematoxylin/eosin. Histopathological scores were evaluated in a blinded fashion; D) Effect of ADA-a3H and adalimumab on arthritic and histological scores. Mice were treated with vehicle control (n = 6), 5 mg/kg ADA-a3H (n = 7) and 5 mg/kg adalimumab (n = 8) as indicated. Histology and arthritic scores were measured after completion of the treatment. Data are presented as mean ± SEM and three independent experiments were performed with Zybodies with the three similar Ang2 peptides shown. *-p < 0.05, **-p < 0.01, ***p < 0.001.