IP Library Granted Patent US 7,118,924
Granted Patent B2
US 7,118,924 · App. 09/798,525 · Granted Oct 10, 2006

Method for producing human antibodies in SCID mice which uses dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents

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Quick Facts
Patent No.
US 7,118,924
App. No.
09/798,525
Granted
Oct 10, 2006
Kind
B2
Abstract

An improved method for producing human antibodies in SCID mice is provided. The improvement includes the use of dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents.

Claims (20)

1. A method for producing human IgG antibodies in a severe combined immunodeficiency (SCID) mouse which has been transplanted with human immune cells, which comprises

injecting human peripheral blood lymphocytes (PBL) into a SCID mouse to produce a SCIDhu PBL mouse that contains human B cells that produces antibodies specific for an antigen with which the SCIDhu PBL mouse is immunized;

immunizing the SCIDhu PBL mouse with antibody-antigen complex; and

immunizing the SCIDhu PBL mouse with human dendritic cells which have been contacted (pulsed) in vitro with the antigen-antibody complex.

2. The method of claim 1 , wherein the dendritic cells comprise autologous peripheral blood dendritic cells.

3. The method of claim 1 , which includes Epstein-Barr virus (EBV) transformation during the immunization step.

4. The method of claim 1 , wherein said SCIDhu PBL mouse is immunized with antigen-antibody complex prior to immunization with dendritic cells which have been contacted (pulsed) with antigen-antibody complex.

5. The method of claim 1 , wherein a first immunization with antigen-antibody complex is followed by a second immunization with human dendritic cells which have been contacted (pulsed) with antigen-antibody complex that is effected about 1 to 15 days after the fist immunization.

6. The method of claim 5 , wherein said second immunization is effected about 7 days after the first immunization.

7. The method of claim 4 , which further includes at least one additional immunization (“boosting”) wherein the SCIDhu PBL mouse is administered antigen or antigen-antibody complex.

8. The method of claim 7 , wherein a boosting step is effected about a week after the first immunization.

9. The method of claim 8 , wherein another boosting step is effected about two weeks after the first immunization.

10. The method of claim 9 , wherein another boosting step is effected about three weeks after the first immunization.

11. The method of claim 1 which results in human IgG antibody titers in the serum of the SCIDhu PBL mouse ranging from about 0.56 to about 2.19 mg/ml.

12. The method of claim 1 , wherein the dendritic cells are generated from peripheral blood mononuclear cell-derived progenitor cells.

13. The method of claim 12 , wherein the dendritic cells are generated by inducing the differentiation of peripheral blood mononuclear cell-derived progenitor cells into dendritic cells in vitro.

14. The method of claim 1 , wherein the antibody of the antigen-antibody complex is a murine IgG antibody that comprises an Fc portion that binds to an Fc receptor of a human dendritic cell.

15. The method of claim 14 , wherein the antibody of the antigen-antibody complex is a murine IgG 2a antibody.

16. The method of claim 1 , wherein the antigen of the antigen-antibody complex is a human tumor-associated antigen.

17. The method of claim 16 , wherein the antigen is p185 (HER/neu) and the antibody is an anti-p185 antibody.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2008
From: COCCIA, MARCO ANTHONY; BRAMS, PETER
To: IDEC PHARMACEUTICALS CORPORATION
Reel/Frame 021886/0060 →
CHANGE OF NAME Recorded Aug 6, 2004
From: IDEC PHARMACEUTICALS CORPORATION
To: BIOGEN IDEC INC.
Reel/Frame 015044/0873 →