Formulation

Manufacture of the Stabilised Complex of the Invention

[0086]Hyperimmune ungulate serum is centrifuged to separate any unwanted components, and the method carried out as a continuous process, avoiding any freezing or thawing step(s) prior to final aliquoting. This avoids any aggregation and loss of the CRH component from the formulation.

[0087]In more detail, a serum composition comprising CRH was stored at 2 to 8 degrees C. (and not frozen) and was diluted at a ratio of 1:2 parts cold PBS, and supersaturated ammonium sulphate was added slowly with constant agitation until a ratio of 47:53 of ammonium sulphate:PBS was reached. This was carried out on a cold tray and the resulting solution was maintained at this temperature for 30 to 60 minutes with constant agitation.

[0088]The serum solution was then centrifuged in a Beckman J6M / E centrifuge at 3500 rpm for 45 minutes at 4 degrees C. The supernatant was removed and discarded. The precipitated solid material was re-suspended in cold 50%

The Stabilised Complex Provides a Persistent, Elevated Concentration of CRH In Vivo

[0092]The stabilised complex of the invention has been compared with prior art formulations as previously disclosed by applicant.

[0093]Applicant has disclosed the same basic manufacture protocols in WO 2003 / 004049, WO 2003 / 064472, WO 2005 / 056053, WO 2005 / 097183, WO 2006 / 021814, and WO 2007 / 077465.

[0094]In this Example, male mice, C57BL / 6, ˜25 gm were divided into three groups: one group was administered the stabilised complex of the invention (“Aimspro”); another group was administered a naïve caprine serum (i.e. from a goat that had not been immunised) but which had been otherwise prepared by exactly the same manufacture (including 35 nanometre filtration step) method of the present invention (“Naïve serum”); and the third group was administered a composition comprising a CRH formulation prepared by Applicant's prior art basic manufacture protocol (“Prior art CRH formulation”).

[0095]Sample

Evidence for the In Vivo Activity of the Stabilised Complex of the Invention

[0102]FIG. 5 shows comparative levels of ACTH in the sera of patients before and after receiving treatment with the stabilised complex of the invention. This is also compared with levels of ACTH in the sera of healthy volunteers. Sera were diluted 1:100 and quantified by an ELISA of sera compared with the product. Data are the mean of three determinations+ / −standard errors. Post treatment n=5; pre treatment n=3; normal human sera n=5. The data show that treatment with the stabilised complex of the invention increases ACTH levels. FIG. 6 shows comparative levels of β endorphin in the serum of patients before and after receiving treatment with the stabilised complex of the invention. This is compared with levels of β endorphin in the sera of healthy volunteers. Sera were diluted 1:100 and quantified by an ELISA of sera compared with the product. Data are the mean of three determinations+ / −standard errors. The