Granted Patent B2

US 8,852,585 · App. 12/162,532 · Granted Oct 7, 2014

Abstract

Claims (23)

1. A method for preparing an immunoglobulin preparation comprising immunoglobulin M (IgM) molecules that specifically bind Aβ1-42 peptides from pooled human plasma comprising:

(a) performing a first caprylate precipitation such that a first precipitate and a first supernatant comprising immunoglobulins are formed;

(b) separating the first supernatant from the first precipitate;

(c) performing a second caprylate precipitation such that a second precipitate and a second supernatant comprising immunoglobulins are formed;

(d) separating the second supernatant from the second precipitate;

(e) contacting the second supernatant with a first anion exchange resin;

(f) separating a fraction containing substantially all of the immunoglobulin G and immunoglobulin M from the result of step (e);

(g) contacting the fraction of step (f) with a second anion exchange resin;

(h) eluting IgM from the second anion exchange resin column;

(i) applying the IgM to a gel filtration resin and recovering the IgM;

(j) applying the IgM to an affinity resin comprising immobilized antigens A and B; and

(k) recovering the eluted IgM to obtain a purified, virally inactivated IgM preparation.

2. The method of claim 1 , wherein the immunoglobulin preparation comprises at least about 80% IgM or at least about 90% IgM.

3. The method of claim 1 , wherein the IgM has a titer of specific binding for an Aβ1-42 peptide that is at least 10-times higher than that for an Aβ1-40 peptide.

4. The method of claim 1 , wherein the immunoglobulin preparation comprises less than 5% oligomeric IgM.

5. The method of claim 1 , wherein the IgM is a monomeric or proteolytic fragment of IgM that specifically binds an Aβ1-42 peptide.

6. The method of claim 1 , further comprising:

(a) identifying a patient having an increased risk of developing or showing symptoms of a disease associated with β-amyloid polypeptides; and

(b) administering to the patient an effective amount of the immunoglobulin preparation.

7. The method of claim 6 , wherein the effective amount is about 0.1 μg per kg body weight to about 1000 mg per kg body weight.

8. The method of claim 6 , wherein the effective amount is about 0.5 μg per kg body weight to about 500 mg per kg body weight; about 0.5 μg per kg body weight to about 100 mg per kg body weight; or about 5 μg per kg body weight to about 50 mg per kg body weight.

9. The method of claim 6 , wherein the step of administering comprises administering by a parenteral route.

10. The method of claim 6 , wherein the disease associated with β-amyloid polypeptides in a patient is selected from the group consisting of systemic senile amyloidosis, familial amyloid polynephropathy (Iowa), familial amyloidosis (Finnish), Gerstmann-Straussler-Scheinker syndrome, familial amyloid nephropathy with urticaria and deafness (Muckle-Wells syndrome), isolated atrial amyloid, hemodialysis-associated amyloidosis (HAA), sporadic cerebral amyloid angiopathy, hereditary cerebral amyloid angiopathy, Downs syndrome, Parkinson-dementia of Guam, age-related asymptomatic amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Kuru, Creutzfeldt-Jacob's disease, Parkinson's Disease, Huntington's chorea, and Alzheimer's disease.

Assignments (31)