Treatment of chronic nephropathies using soluble complement receptor type I (sCR1)

1. A method for treating dense deposit disease (DDD) and/or glomerulonephritis with isolated C3 deposits (GN-C3) in a mammalian subject comprising administering to a mammalian subject in need of treatment an effective amount of a soluble complement receptor type I (sCR1) polypeptide.

2. The method according to claim 1 , wherein said soluble CR1 polypeptide is selected from the group consisting of:

a fragment of human CR1 comprising at least short consensus repeats 8-11;

a fragment of human CR1 comprising at least short consensus repeats 15-18;

a soluble CR1 polypeptide comprising human CR1 short consensus repeats 8-11 and 15-18;

a fragment of human CR1 comprising long homologous repeat B;

a fragment of human CR1 comprising long homologous repeat C;

a fragment of human CR1 comprising long homologous repeats B and C;

a fragment of human CR1 comprising long homologous repeats B, C and D;

a fragment of human CR1 comprising at least long homologous repeats A and B;

a fragment of human CR1 comprising long homologous repeats A, B and C;

a fragment of human CR1 comprising long homologous repeats A, B, C and D;

a fragment of human CR1 comprising the extracellular domain of CR1;

a fragment of human CR1 comprising the extracellular domain of CR1 and having the N-terminal LHR A deleted (sCR1[desLHR-A]);

a soluble CR1 polypeptide having modified glycosylation to improve serum half-life in vivo;

a soluble CR1 polypeptide having glycosylation modified to exhibit sialyl Lewis X moieties (sCR1-sLe x );

a soluble CR1 construct having two or more CR1 polypeptide moieties linked to a carrier molecule; and

combinations thereof.

3. The method according to claim 2 , wherein said soluble CR1 polypeptide is selected from the group consisting of:

a fragment of human CR1 comprising the extracellular domain of CR1;

a soluble CR1 polypeptide having modified glycosylation to improve serum half-life in vivo;

a soluble CR1 polypeptide having glycosylation modified to exhibit sialyl Lewis X moieties (sCR1-sLe x ); and

combinations thereof.

4. The method accordingly to claim 2 , wherein said soluble CR1 polypeptide exhibits a complement regulatory activity selected from the group consisting of:

(i) the ability to bind C3b;

(ii) the ability to bind C4b;

(iii) the abilities to bind C3b and to bind C4b;

(iv) factor I cofactor activity;

(v) the ability to inhibit classical C3 convertase activity;

(vi) the ability to inhibit alternative C3 convertase activity;

(vii) the ability to inhibit classical C5 convertase activity;

(viii) the ability to inhibit alternative C5 convertase activity;

(ix) the ability to inhibit neutrophil oxidative burst;

(x) the ability to inhibit complement-mediated hemolysis;

(xi) the ability to inhibit C3a production; and

(xii) the ability to inhibit C5a production.

5. The method according to claim 1 , wherein said soluble CR1 polypeptide exhibits the ability to inhibit complement activation via both the classical activation pathway and the alternative activation pathway.

6. The method according to claim 4 , wherein said mammalian subject is a human.

7. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide reduces further C3 deposition in kidney tissue.

8. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide at least partially reverses existing C3 deposition in kidney tissue.

9. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide reduces kidney damage.

10. The method according to claim 9 , wherein the administration of said soluble CR1 polypeptide reduces further kidney damage.

11. The method according to claim 9 wherein the administration of said soluble CR1 polypeptide at least partially reverses existing kidney damage.

12. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide reduces deterioration in renal function.

13. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide improves renal function.

14. The method according to claim 13 , wherein the administration of said soluble CR1 polypeptide improves renal function as indicated by one or more of i) reduced proteinuria, ii) reduced serum creatinine, and/or iii) improved glomerular filtration rate.

15. The method according to claim 6 , wherein the administration of said soluble CR1 polypeptide increases serum levels of C3.

16. The method according to claim 6 , wherein said human subject suffers from dense deposit disease (DDD).

17. The method according to claim 6 , wherein said human subject suffers from primary glomerulonephritis with isolated C3 deposits (GN-C3).

18. The method according to according to claim 1 , wherein said polypeptide is administered by an intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intrathecal, epidural, oral or pulmonary route.

19. A method for treating dense deposit disease (DDD) and/or glomerulonephritis with isolated C3 deposits (GN-C3) in a mammalian subject comprising administering to a mammalian subject in need of treatment an effective amount of a soluble complement receptor type I (sCR1) polypeptide comprising the extracellular domain of mature human CR1 (SEQ ID NO: 1).