Claims for Patent: 7,387,993

Summary for Patent: 7,387,993

Title:	Mannan-binding lectin (MBL) treatment of infections in individuals treated with TNF-.alpha.inhibitors
Abstract:	The present invention relates to the use of subunits and oligomers of mannan-binding lectin (MBL) in prophylactic and/or curative treatment of infections in an individual receiving TNF-inhibiting treatment, in particular TNF-.alpha.-inhibiting treatment. The MBL may be administered together with an antimicrobial agent, for example as a kit-of-parts.
Inventor(s):	Fischer; Per (Allerod, DK)
Assignee:	Natimmune A/S (Copenhagen, DK)
Application Number:	10/332,712
Patent Claims:	1. A method of treating or reducing the risk of an infection in an individual at increased risk of infection, due to impaired phagocytic function, as a result of treatment with a TNF-.alpha. inhibitor which inhibitor treatment by itself results in acute suppression of macrophage action leading to reduced recruitment and functionality of macrophages and neutrophils, the method comprising: administering an effective amount of a human mannan-binding lectin (MBL) composition, to an individual who has received or is receiving a medical treatment with a TNF-.alpha. inhibitor, said treatment resulting in impaired phagocytic function, whereby infection is treated or the risk of infection is reduced. 2. The method of claim 1, wherein the MBL composition comprises at least one mannan-binding lectin (MBL) oligomer comprising the at least one mannan-binding lectin (MBL) subunit. 3. The method of claim 2, wherein said oligomer is selected from the group of oligomers consisting of tetramers, pentamers and/or hexamers. 4. The method of claim 1, wherein the infection is an infection caused by a microbial species. 5. The method of claim 4, wherein the microbial species is a fungus. 6. The method of claim 4, wherein the microbial species is a yeast. 7. The method of claim 4, wherein the microbial species is a bacterium. 8. The method of claim 7, wherein the bacterial species is resistant to at least one antibiotic medicament. 9. The method of claim 7, wherein the bacterial species is multiresistant. 10. The method of claim 7, wherein the bacterial species is pathogenic. 11. The method of claim 1 wherein serum MBL levels are determined prior to said administration. 12. The method of claim 11, wherein serum levels of MBL in the individual are determined by quantitative analysis. 13. The method of claim 12, wherein the analysis comprises at least one of enzyme-linked immunosorbent assay (ELISA), time-resolved immunofluorimetric assay (TRIFMA), radioimmunoassay (RIA) or nephelometry. 14. The method of claim 1 in which said TNF-.alpha. inhibitor is capable of reducing MBL levels in said individual. 15. The method of claim 1 wherein said MBL composition comprises a 96 kDa MBL subunit as a separate monomeric molecule rather than as a moiety of an MBL oligomer. 16. The method of claim 1 wherein phagocytic function is determined prior to said administration. 17. The method of claim 1, wherein the individual has, prior to administration, serum levels of MBL below 500 ng/ml. 18. The method of claim 1, wherein the individual has, prior to administration, serum levels of MBL below 400 ng/ml. 19. The method of claim 1, wherein the individual has, prior to administration, serum levels of MBL below 300 ng/ml. 20. The method of claim 1, wherein the individual has, prior to administration, serum levels of MBL below 250 ng/ml. 21. The method of claim 1, wherein the individual has, prior to administration, serum levels of MBL below 200 ng/ml. 22. A method of treating a disease which is a TNF-related pathology, which disease is responsive to treatment with a TNF-.alpha. inhibitor, while mitigating the increased risk of infection attributable, due to impaired phagocytic function, to said treatment with a TNF-.alpha. inhibitor, which inhibitor treatment by itself results in acute suppression of macrophage action, leading to reduced recruitment of macrophages and neutrophils, comprising administering, to an individual, (1) an effective amount of TNF-.alpha. inhibitor in pharmaceutical form, or an effective amount of a substance which elicits production in said individual of an effective amount of a TNF-.alpha. inhibitor, where said inhibitor, if administered alone, would result in impaired phagocytic function, and (2) an effective amount of a human mannanbinding lectin (MBL) composition, to said individual, thereby treating said disease while treating an infection, or mitigating the increased risk of infection, attributable to such treatment in said individual. 23. The method of claim 22, wherein the composition is administered to the individual prior to said TNF-alpha inhibitor treatment. 24. The method of claim 22 wherein the administration of (1) is of a TNF-.alpha. inhibitor in pharmaceutical form. 25. The method according to claim 24, wherein the administration (1) is of a TNF-.alpha. inhibitor which is an antibody directed against TNF-.alpha.. 26. The method according to claim 24, wherein the administration (1) is of a TNF-.alpha. inhibitor which is a fusion protein comprising portions of TNF-.alpha. receptor. 27. The method according to claim 24, wherein the TNF-.alpha. inhibitor is selected from etanercept and infliximab. 28. The method of claim 24, wherein the individual has, prior to administration (2), a serum level of MBL in excess of 10 ng/ml. 29. The method of claim 28, wherein the serum MBL level is the functional serum MBL level. 30. The method of claim 28, wherein the individual has, prior to administration (2), MBL serum levels below 500 ng/ml. 31. The method of claim 30, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 75 ng/ml. 32. The method of claim 30, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 100 ng/ml. 33. The method of claim 30, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 150 np/ml. 34. The method of claim 24, wherein the individual has, prior to administration (2), a serum level of MBL in excess of 50 ng/ml. 35. The method of claim 34, wherein the serum MBL level is the functional serum MBL level. 36. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 75 np/ml. 37. The method of claim 36, wherein the individual has, prior to administration (2), serum levels of MBL below 400 ng/ml. 38. The method of claim 36, wherein the individual has, prior to administration (2), serum levels of MBL below 300 ng/ml. 39. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 100 np/ml. 40. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL in excess of 150 np/ml. 41. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL below 500 ng/ml. 42. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL below 400 ng/ml. 43. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL below 300 ng/ml. 44. The method of claim 24 in which the MBL composition and the TNF-.alpha. inhibitor are administered simultaneously. 45. The method of claim 44 in which the MBL composition and the TNF-.alpha. inhibitor are administered separately. 46. The method of claim 24 in which the MBL composition and the TNF-.alpha. inhibitor are administered sequentially. 47. The method of claim 24 in which said individual, after said TNF-.alpha. inhibitor treatment and prior to treatment with said MBL composition, has MBL levels which are significantly below normal. 48. The method of claim 24, further comprising administration of an effective amount of an antimicrobial medicament, other than an MBL composition, to which said infection is responsive. 49. The method of claim 24 wherein serum or plasma MBL levels are determined prior to said administration (2) and after said administration (1). 50. The method of claim 24 wherein phagocytic function is determined prior to said administration. 51. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL below 250 ng/ml. 52. The method of claim 24, wherein the individual has, prior to administration (2), serum levels of MBL below 200 ng/ml.

Details for Patent 7,387,993

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2020-07-13
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2020-07-13
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2020-07-13