Patent ID: 8679483

Claim:
A pharmaceutical composition comprising, as the active ingredient, polyclonal human natural antibodies of the IgG isotype that neutralize the activity of human TNFα wherein: (i) said antibodies inhibit at least 50% of the maximal biological activity that is induced by TNFα in vitro, as assessed by the L929 cell assay; (ii) said antibodies originate from the serum of an individual immunized with a stable immunogenic product comprising protein immunogenic heterocomplexes consisting of combinations of (i) molecules of human TNFα and (ii) Keyhole Limpet Hemocyanin (KLH) protein carrier molecules in which less than 40% of the human TNFα molecules (i) are linked with the KLH protein carrier molecules (ii) through a covalent bond, wherein the stable immunogenic product is produced by a method comprising the steps of: (a) incubating in a coupling reaction the TNFα molecules (i) and the KLH molecules (ii) in a molar ratio (i):(ii) of from 5:1 to 50:1 in the presence of glutaraldehyde at a concentration between 0.002M and 0.03 M; (b) removing excess glutaraldehyde after the coupling reaction; (c) treating the product obtained in step (b) in a stabilization reaction with formaldehyde; (d) stopping the stabilization reaction with formaldehyde by the addition of glycine; and (e) recovering the immunogenic product comprising the immunogenic heterocomplexes prepared in step (d); and (iii) said antibodies are selected from the group consisting of: (A) a whole fraction of antibodies purified from the serum of a human individual immunized against said human TNFα; (B) a purified fraction of monospecific polyclonal antibodies neutralizing the activity of the said human TNFα; and (C) Fab or F(ab)′ 2 fragments prepared from the polyclonal antibodies (A) and (B) above.