Merck’s Patent for Peanut Oil Based Vaccine Adjuvant

The present invention is a method for enhancing the immune response of a mammal to a vaccine by administering to such a mammal an effective amount of GM-CSF in conjunction with a vaccine. The present invention further provides for pharmaceutical compositions containing an effective amount of GM-CSF and a vaccine. Kits containing GM-CSF and a vaccine are also disclosed….

To obtain a stronger humoral and/or cellular response, it is common to administer a vaccine in a formulation containing an adjuvant. An adjuvant is a substance that enhances, nonspecifically, the immune response to an antigen, or which causes an individual to respond to an antigen who would otherwise without the adjuvant not respond to the antigen. An adjuvant is usually administered with an antigen, but may also be given before or after antigen administration. Suitable adjuvants for the vaccination of mammals include but are not limited to Adjuvant 65 (containing peanut oil, mannide monooleate and aluminum monostearate); Freund’s complete or incomplete adjuvant; mineral gels such as aluminum hydroxide, aluminum phosphate and alum; surfactants such as hexadecylamine, octadecylamine, lysolecithin, dimethyldioctadecyl-ammonium bromide, N,N-dioctadecyl-N’,N’-bis(2-hydroxymethyl) propanediamine, methoxyhexadecylglycerol and pluronic polyols; polyanions such as pyran, dextran sulfate, poly IC, polyacrylic acid and carbopol; peptides such as muramyl dipeptide, dimethylglycine and tuftsin; and oil emulsions. The antigens could also be administered following incorporation into liposomes or other microcarriers….

According to the present invention, we have surprisingly found that the immune response in a mammal, especially a human, to a vaccine can be effectively enhanced by the administration of an effective amount of GM-CSF in conjunction with the vaccine. The term “in conjunction with” as used herein refers to the administration of GM-CSF concurrently, before or following administration of a vaccine.

As used herein, “GM-CSF” means a protein which (a) has an amino acid sequence that is substantially identical to the sequence of mature (i.e., lacking a signal peptide) human GM-CSF described by Lee et al. Proc. Natl. Acad. Sci. U.S.A. 82: 4360 (1985) and (b) has biological activity that is common to native GM-CSF….

To prepare the sustained release preparation of GM-CSF according to Formulation 2, the aluminum monostearate is mixed into the peanut oil for the gel and heat elevated to form the gel according to known methods.

The dioctyl sodium sulfosuccinate is dissolved into the Water for Injection. The lyophilized GM-CSF is reconstituted with the dioctyl sodium sulfosuccinate solution, the resultant solution is transfered into the peanut oil for emulsion and mixed by vortexing. The resultant emulsion is then mixed into the previously prepared gelled peanut oil and mixed by vortexing….

To prepare the sustained release preparation of GM-CSF according to Formulation 3, the monobasic and dibasic sodium phosphates are dissolved in a portion of the Water for Injection. The lyophilized GM-CSF is then dissolved in this solution and the pH is adjusted to 7.8 with the sodium hydroxide. The copper acetate is then added and the solution is agitated. The solution is brought to final volume using the remaining Water for Injection. Preferably, the sodium hydroxide and copper acetate are added as concentrated aqueous solutions (e.g., for copper acetate, 100 microliters of a 2 mg/ml aqueous solution).

Additional Sustained Release Formulations

Additional sustained release formulations of GM-CSF can be prepared using micoencapsulated or microspheres of GM-CSF prepared using polymers such as polyanhydrides, polyphosphazenes, collagen, alginates, poly(methacrylates), gelatin, poly(hydroxybutyrate), poly(caprolactone), ethylene vinyl acetate or polylactide glycolide….

Well sure why not?   I mean it’s all FDA approved right?  Why not add some FDA approved laundry detergent and EPA approved industrial smokestack scrapings with a side of hexadeathamine to wash it all down?   And for good measure, inject it directly into the brain with a 10 gram “carrier” of Pb.

Their use of “substantially identical” gene sequences to GM-CSF is also comforting.   I mean, it’s mostly junk dna anyway, right?   Or it will be in short order.

Thank goodness for merck that this has nothing to do with the mysterious and sudden epidemic of deadly peanut allergies in children.