Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
1997-10-03
2001-04-03
Chan, Christina Y. (Department: 1644)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S154100, C424S278100, C530S387300, C530S388220, C530S389100
Reexamination Certificate
active
06210669
ABSTRACT:
BACKGROUND OF THE INVENTION
4-1BB is an inducible T cell receptor that belongs to the nerve growth factor receptor superfamily. This novel antigen is expressed on the surface of activated splenic T cells and thymocytes. The extracellular domain of this type I transmembrane protein is homologous to members of the nerve growth factor receptor superfamily. The cytoplasmic domain contains a sequence homologous to the binding site for T-cell-specific tyrosine kinase p56
1ck
.
The in vivo role of 4-1BB remains unclear, although increasing evidence indicates involvement as a signaling molecule in T cell activation. For example, cross-linking of 4-1BB with monoclonal antibody 53A2 on anti-CD3-stimulated T cells results in a 2 to 10-fold enhancement of T cell proliferation (Pollok et al.
J. Immunol
. 151:1255 (1993)). Furthermore, Zhou et al. (
Immunol. Letters
41:177-184 (1994)) have demonstrated that 4-1BB is expressed on activated intestinal intra-epithelial T lymphocytes (IELS), and that activated IELS triggered with anti-4-1BB monoclonal antibody could enhance the level of IEL cytotoxicity against anti-CD4-secreting hybridoma cells. Cross-linking of anti-4-1BB antibody also enhanced proliferation of IELS.
At least two candidate ligands of 4-1BB have been identified. Chalupny et al. (
Proc. Natl. Acad. Sci. U.S.A
. 89:10360-10364 (1992)) used a soluble 4-1BB immunoglobulin fusion protein (4-1BB Rg) to demonstrate that 4-1BB binds to extracellular matrix protein (EMC). Goodwin et al. (
Eur. J. Immunol
. 23:2631 (1993)) reported the isolation of a cDNA for a ligand for murine 4-1BB (4-1-BB-L) that is a member of an emerging family of ligands with C-terminal amino acid homology which includes TNF, lymphotoxin (LT)-alpha and beta, CD40-L, CD27-L, CD30-L, and Fas-L.
The human analog (hu4-1BB) of murine 4-1BB and a human analog (hu4-1-BB-L) of murine 4-1-BB-L have been cloned (Alderson et al.
Eur. J. Immunol
. 24:2219-2227 (1994)). Both monoclonal antibody to hu4-1BB and cells transfected with hu4-1-BB-L induced a strong proliferative response in mitogen co-stimulated primary T cells.
Thus, a need exists for the development of antagonists of 4-1BB. The instant invention addresses this need and more.
SUMMARY OF THE INVENTION
One aspect of the invention is a method for suppressing a primary and secondary humoral response to an antigen in a host comprising administering to the host an effective dose of an anti-4-1BB antibody.
Further aspects of the invention are compositions comprising monoclonal antibodies 1D8, 3B8, or 3E1.
A further aspect of the invention is a composition comprising an anti-4-1BB antibody, wherein the antibody inhibits an antibody response to sheep red blood cells in vivo.
Another aspect of the invention is a method for blocking T cell dependent immune responses in a host comprising administering to the host an effective dose of an anti-4-1BB antibody.
Another aspect of the invention is a method for enhancing lymphocytic killing of tumor cells in a host comprising administering to the host an effective dose of an anti-4-1BB antibody.
Another aspect of the invention is a method for potentiation of development of cytotoxic T cells in a host comprising administering to the host an effective dose of an anti-4-1BB antibody.
Another aspect of the invention is a method for treating a host having a T cell autoimmune disease comprising administering to the host an effective dose of an anti-4-1BB antibody.
REFERENCES:
patent: 5084391 (1992-01-01), Wijdenes et al.
patent: 595659 (1994-05-01), None
patent: 96/29348 (1996-09-01), None
Chalupny et al., “T-Cell Activation Molecule 4-1BB Binds to Extracellular Matrix Proteins,”Proc. Natl. Acad. Sci. 89:10360-10364 (1992).
Hollenbaugh et al., “The Human T Cell Antigen gp39, a Member of the TNF Gene Family, is a Ligand for the CD40 Receptor: Expression of a Soluble Form of gp39 with B Cell Co-Stimulatory Activity,”EMBO J. 11(12) :4313-4321 (1992).
Pollok et al., “Novel T Cell Antigen 4-1BB Associates with the Protein Tyrosine Kinase p56Ick1”J. Immunol. 151:1255 (1993).
Goodwin et al., “Molecular Cloning of a Ligand for the Inducible T Cell Gene 4-1BB: A Member of an Emerging Family of Cytokines with Homology to tumor Necrosis Factor,”Eur. J. Immunol. 23:2631 (1993).
Zhou et al., “Functional Analysis of T-Cell Antigen 4-1BB in Activated Intestinal Intra-epithelial T Lymphocytes,”Immunol. Letters41:177-184 (1994).
Alderson et al., “Molecular and Biological Characterization of Human 4-1BB and its Ligand,”Eur. J. Immunol. 24:2219-2227 (1994).
Aruffo Alejandro A.
Chalupny N. Jan
Chen Lieping
Mittler Robert S.
Shuford Walter W.
Bristol-Myers Squibb Co.
Chan Christina Y.
Townsend and Townsend / and Crew LLP
VanderVegt F. Pierre
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