Immunoglobulin fractions
The present invention relates to novel pharmaceutical compositions comprising fractions of human immunoglobulin preparations, novel applications of these compositions and a method for manufacturing the compositions.
1. An isolated fraction of human antibodies from a heterogeneous human donor population, obtained by a method comprising the following steps:
(a) subjecting a human antibody preparation from a heterogeneous donor population to a size fractionation,
(b) recovering a fraction of dimeric antibodies, wherein purity of the dimeric antibody fraction is at least 75% and wherein purity analysis is carried out immediately after size fractionation,
(c) monomerizing the dimeric antibodies having an apparent molecular weight of about 300 kDa to produce remonomerized antibodies, and
(d) optionally admixing the remonomerized antibodies with a pharmaceutically acceptable carrier or excipient.
2. The fraction of claim 1 , wherein the human antibody preparation is a polyclonal human immunoglobulin preparation.
3. The fraction of claim 1 , wherein the fraction of human antibodies is a fraction of dimeric antibodies from an intravenous polyclonal human immunoglobulin preparation (IVIG).
4. The fraction of claim 1 , wherein the fraction of human antibodies has at least a two fold higher reactivity to exoantigens and/or autoantigens than the heterogeneous human donor population.
5. The fraction of claim 1 , wherein step (a) comprises size exclusion separation, gel filtration, ultrafiltration, and/or other gel or membrane separation methods.
6. The fraction of claim 1 , wherein purity of the dimeric antibody fraction recovered in step (b) is at least 80% and wherein the purity analysis is carried out immediately after size fractionation.
7. The fraction of claim 1 , wherein purity of the dimeric antibody fraction recovered in step (b) is at least 85% and wherein the purity analysis is carried out immediately after size fractionation.
8. The fraction of claim 1 , wherein step (c) comprises adjusting to an acidic pH.
9. The fraction of claim 8 , wherein the acidic pH is in a range of about 3 to about 5.
10. The fraction of claim 1 , wherein the fraction has 10% or less dimers after monomerization.
11. The fraction of claim 1 , wherein the remonomerized antibodies do not comprise F(ab′) 2 fragments obtained by proteolytic digestion.
12. The fraction of claim 1 , wherein the fraction of human antibodies has 5% or less dimers after monomerization.
13. A method for manufacturing a pharmaceutical composition comprising a fraction of human antibodies from a heterogeneous human donor population comprising:
(a) subjecting a human antibody preparation from a heterogeneous donor population to a size fractionation;
(b) recovering a fraction of dimeric antibodies, wherein purity of the dimeric antibody fraction is at least 75% and wherein purity analysis is carried out immediately after size fractionation,
(c) monomerizing the dimeric antibodies having an apparent molecular weight of about 300 kDa to produce remonomerized antibodies, and
(d) optionally admixing the remonomerized antibodies with a pharmaceutically acceptable carrier or excipient.
14. The method of claim 13 wherein step (a) comprises size exclusion separation, gel filtration, ultrafiltration, and/or other gel or membrane separation methods.
15. The method of claim 13 , wherein step (c) comprises adjusting to an acidic pH.
16. The method of claim 15 , wherein the acidic pH is in a range of about 3 to about 5.