Polyvalent immunotherapeutics

A composition comprising polyvalent venom-specific, modified antibodies obtained from mammals hyperimmunized with the venom, wherein the composition contains at least 17.7% F(ab′)2 fragments of the antibodies and the F(ab′)2 is prepared by a process comprising:

• (a) diluting hyperimmune plasma from the mammals in three volumes of sterile isotonic solution;
• (b) adjusting the pH of the diluted plasma to approximately 3.5 to 4.0 and adding activated pepsin to final concentration of approximately 0.9% to approximately 1.1%;
• (c) digesting proteins contained in the diluted hyperimmune plasma under acidic conditions at approximately 18° C. to approximately 20° C. to hydrolyze albumin, fibrinogen and coagulation factors into smaller peptides, and to separate IgG into F(ab′)2 fragment and fragment crystallizable (Fc) region;
• (d) adding ammonium sulfate to a final concentration of approximately 35% to precipitate components at 2° C. to 8° C.;
• (e) removing the precipitate and recovering a filtrate comprising F(ab′)2 fragments by depth filtration;
• (f) adjusting the pH of the filtrate to 6.8 to 7.0 and storing the filtrate at 2° C. to 8° C.;
• (g) diafiltering the filtrate by continuous tangential flow filtration using a membrane with an approximately 50 kDa cut-off while maintaining a diafiltration sheer below 1000 sec−1;
• (h) adding cryoprotective and tonicity regulating agents and nanofiltering the diafiltered product to provide a liquid formulation;
• and
• (i) lyophilizing the liquid formulation.