A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans

(A) Neutrophil counts in splenectomized mice treated with a single injection of Filgrastim (G-CSF) on day 0. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (B) Leukocyte counts in splenectomized mice treated with five daily injections of Filgrastim (G-CSF) on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (C) Neutrophil counts in splenectomized mice treated with a single injection of SD/01 on day 0 compared with mice that received five daily injections of unmodified Filgrastim on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001. (D) Single injection of SD/01 (1000 μg/kg) at day 0 compared to daily injections of 200 μg/kg per day Filgrastim (total dose = 1000 μg Filgrastim/kg). Six hourly neutrophil counts from groups of 10 normal (nonsplenectomized) mice; → = Filgrastim injection

(A) Neutrophil counts in splenectomized mice treated with a single injection of Filgrastim (G-CSF) on day 0. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (B) Leukocyte counts in splenectomized mice treated with five daily injections of Filgrastim (G-CSF) on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (C) Neutrophil counts in splenectomized mice treated with a single injection of SD/01 on day 0 compared with mice that received five daily injections of unmodified Filgrastim on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001. (D) Single injection of SD/01 (1000 μg/kg) at day 0 compared to daily injections of 200 μg/kg per day Filgrastim (total dose = 1000 μg Filgrastim/kg). Six hourly neutrophil counts from groups of 10 normal (nonsplenectomized) mice; → = Filgrastim injection

(A) Neutrophil counts in splenectomized mice treated with a single injection of Filgrastim (G-CSF) on day 0. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (B) Leukocyte counts in splenectomized mice treated with five daily injections of Filgrastim (G-CSF) on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (C) Neutrophil counts in splenectomized mice treated with a single injection of SD/01 on day 0 compared with mice that received five daily injections of unmodified Filgrastim on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001. (D) Single injection of SD/01 (1000 μg/kg) at day 0 compared to daily injections of 200 μg/kg per day Filgrastim (total dose = 1000 μg Filgrastim/kg). Six hourly neutrophil counts from groups of 10 normal (nonsplenectomized) mice; → = Filgrastim injection

(A) Neutrophil counts in splenectomized mice treated with a single injection of Filgrastim (G-CSF) on day 0. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (B) Leukocyte counts in splenectomized mice treated with five daily injections of Filgrastim (G-CSF) on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001. (C) Neutrophil counts in splenectomized mice treated with a single injection of SD/01 on day 0 compared with mice that received five daily injections of unmodified Filgrastim on days 0–4. Each point represents the mean of 5–10 individual mice assessed separately ± SEM. Data are shown from a single representative experiment. The complete experiment was performed three times. No errors are given at day 5 because the blood from five donors was pooled and a single measurement was made. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001. (D) Single injection of SD/01 (1000 μg/kg) at day 0 compared to daily injections of 200 μg/kg per day Filgrastim (total dose = 1000 μg Filgrastim/kg). Six hourly neutrophil counts from groups of 10 normal (nonsplenectomized) mice; → = Filgrastim injection

Platelet numbers fell during treatment of splenectomized mice with human G-CSF preparations. Five individual mice per point (mean ± SEM). The results of a single experiment are shown, the experiment was done twice. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001

GM-CFC mobilization to the blood by repeated injections of Filgrastim (days 0–4) or a single injection of Filgrastim-SD/01 at day 0. Five individual mice per point (mean ± SEM). The results of a single experiment are shown, the experiment was done twice. Where data differ significantly from carrier *p < 0.005 and **p < 0.0001, where data differ significantly from the response in Filgrastim-treated mice ^bp < 0.005 and ^bbp < 0.0001

The survival of mice transplanted with PBPC harvested at day 5 from donors treated with either G-CSF or Filgrastim SD/01. Ten mice were transplanted in each group. The experiment was performed twice

Normal human volunteers were injected with SD/01 at zero time. Analysis of peak ANC and duration of response are given in Table 2

Mobilization of CD34⁺ cells into the blood by a single injection of Filgrstim SD/01 at ascending doses

Mobilization of PBPC (IL-3/SCF responsive GM-CFC) by a single injection of SD/01 to normal volunteers

Dose of SD/01 versus number of GM-CFC in the blood of normal volunteers