Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
1999-08-26
2004-03-23
Gambel, Phillip (Department: 1644)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S130100, C424S141100, C424S143100, C424S144100, C424S154100, C424S173100, C530S387100, C530S388100, C530S388200, C530S388220, C530S388700, C530S388730, C530S388750
Reexamination Certificate
active
06709654
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the manufacture and identification of novel monoclonal antibodies to human B7, i.e., human B7.1 and human B7.2 and primatized forms thereof. More specifically, the present invention relates to the production and identification of macaque antibodies to human B7, i.e., human B7.1 and human B7.2 produced by screening of phage display libraries and monkey heterohybridomas using B lymphocytes obtained from B7 immunized monkeys.
The invention further relates to specific primatized antibodies which bind to human B7, i.e., human B7.1 and B7.2 as well as their corresponding amino acid and nucleic acid sequences.
Also, the present invention relates to pharmaceutical compositions containing monkey monoclonal or primatized antibodies specific to human B7.1 and/or human B7.2 and their use as immunosuppressants by modulating the B7:CD28 pathway, e.g., for the treatment of autoimmune disorders, and the prevention of organ rejection.
BACKGROUND OF THE INVENTION
The clinical interface between immunology, hematology, and oncology has long been appreciated. Many conditions treated by the hematologist or oncologist have either an autoimmune or immunodeficient component to their pathophysiology that has led to the widespread adoption of immunosuppressive medications by hematologists, whereas oncologists have sought immunologic adjuvants that might enhance endogenous immunity to tumors. To date, these interventions have generally consisted of nonspecific modes of immunosuppression and immune stimulation. In addition to the limited efficacy of these interventions, toxicities secondary to their nonspecificity have also limited their overall success. Therefore, alternative strategies have been sought.
Elucidation of the functional role of a rapidly increasing number of cell surface molecules has contributed greatly to the integration of immunology with clinical hematology and oncology. Nearly 200 cell surface antigens have been identified on cells of the immune and hematopoietic systems (Schlossman S F. Boumsell L. Gilks J M, Harlan T. Kishimoto, C. Morimoto C, Ritz J. Shaw S, Silverstein R L, Springer T A, Tedder T F, Todd R F:CD antigens (1993),
Blood
83:879, 1994). These antigens represent both lineage-restricted and more widely distributed molecules involved in a variety of processes, including cellular recognition, adhesion, induction and maintenance of proliferation, cytokine secretion, effector function, and even cell death. Recognition of the functional attributes of these molecules has fostered novel attempts to manipulate the immune response. Although molecules involved in cellular adhesion and antigen-specific recognition have previously been evaluated as targets of therapeutic immunologic intervention, recent attention has focused on a subgroup of cell surface molecules termed co-stimulatory molecules (Bretscher P: “The two-signal model of lymphocyte activation twenty-one years later.”
Immunol. Today
13:73, (1992); Jenkins M K, Johnson J G: “Molecules involved in T-cell co-stimulation.”
Curr Opin Immunol
5:351, 1993; Geppert T, Davis L. Gur H. Wacholtz M. Lipsky P: “Accessory cell signals involved in T-cell activation.”
Immunol Rev
117:5, (1990); Weaver C T, Unanue E R: “The co-stimulatory function of antigen-presenting cells.”
Immunol Today
11:49, (1990); Stennam R M, Young J W: “Signals arising from antigen-presenting cells.”
Curr Opin Immunol
3:361, (1991)). Co-stimulatory molecules do not initiate but rather enable the generation and amplification of antigen-specific T-cell responses and effector function (Bretscher P: “The two-signal model of lymphocyte activation twenty-one years later.”
Immunol. Today
13:73, (1992); Jenkins M K, Johnson J G: “Molecules involved in T-cell co-stimulation.”
Curr Opin Immunol
5:351, (1993); Geppert T, Davis L. Gur H. Wacholtz M. Lipsky P: “Accessory cell signals involved in T-cell activation.”
Immunol Rev
117:5, (1990); Weaver C T, Unanue E R: “The co-stimulatory function of antigen-presenting cells.”
Immunol Today
11:49, (1990); Stennam R M, Young J W: “Signals arising from antigen-presenting cells.”
Curr Opin Immunol
3:361, (1991); June C H, Bluestone J A, Linsley P S, Thompson C D: “Role of the CD28 receptor in T-cell activation.”
Immunol Today
15:321, (1994).
Recently, one specific co-stimulatory pathway termed B7:CD28 has been studied by different research groups because of its significant role in B and T cell activation (June C H, Bluestone J A, Linsley P S, Thompson C D: “Role of the CD28 receptor in T-cell activation.”
Immunol Today
15:321, (1994); June C H, Ledbetter J A: “The role of the CD28 receptor during T-cell responses to antigen.”
Annu Rev Immunol
11:191, (1993); Schwartz R H: “Co-stimulation of T lymphocytes: The role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy.”
Cell
71:1065, (1992)). Since this ligand: receptor pathway was discovered four years ago, a large body of evidence has accumulated suggesting that B7:CD28 interactions represent one of the critical junctures in determining immune reactivity versus anergy (June C H, Bluestone J A, Linsley P S, Thompson C D: “Role of the CD28 receptor in T-cell activation.”
Immunol Today
15:321, (1994); June C H, Ledbetter J A: “The role of the CD28 receptor during T-cell responses to antigen.”
Annu Rev Immunol
11:191, (1993); Schwartz R H: “Co-stimulation of T lymphocytes: The role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy.”
Cell
71:1065, (1992); Cohen J: “Mounting a targeted strike on unwanted immune responses” (news; comment).
Science
257:751, (1992); Cohen J: “New protein steals the show as ‘co-stimulator’ of T cells” (news; comment).
Science
262:844, (1993)).
In particular, the role of the human B7 antigens, i.e., human B7.1 and B7.2, has been reported to play a co-stimulatory role in T-cell activation.
1. B7.1 and B7.2 Co-stimulatory Role in T Cell Activation
The elaboration of a successful immune response depends on a series of specific interactions between a T cell and an antigen presenting cell. Although the essential first step in this process depends upon the binding of antigen to the T cell receptor, in the context of the MHC class II molecule (Lane, P. J. L., F. M. McConnell, G. L. Schieven, E. A. Clark, and J. A. Ledbetter, (1990), “The Role of Class II Molecules in Human B Cell Activation.”
The Journal of Immunology,
144:3684-3692), this interaction alone is not sufficient to induce all the events necessary for a sustained response to a given antigen (Schwartz, R. H. (1990), “A Cell Culture Model for T Lymphocyte Clonal Anergy.”
Science,
248:1349; Jenkins, M. K. (1992). “The Role of Cell Division in the Induction of Clonal Anergy.”
Immunology Today,
13:69; Azuma, M., M. Catabyab, D. Buck, J. H. Phillips, and L. L. Lanier, (1992). “Involvement of CD28 in MHC-unrestricted Cytotoxicity Mediated by a Human Natural Killer Leukemia Cell Line.”
The Journal of Immunology,
149:1556-1561; Azuma, M., M. Catabyab, D. Buck, J. H. Phillips, and L. L. Lanier, (1992). “CD28 Interaction with B7 Costimulates Primary Allogeneic Proliferative Responses and Cytotoxicity Mediated by Small Resting T Lymphocytes.”
J. Exp. Med.,
175:353-360).
The involvement of certain other co-stimulatory molecules is necessary (Norton, S. D., L. Zuckerman, K. B. Urdahl, R. Shefner, J. Miller, and M. K. Jenkins. (1992), “The CD28 Ligand, B7, Enhances IL-2 Production by Providing A Costimulatory Signal to T Cells.” The
Journal of Immunology,
149:1556-1561). “The homodimers CD28 and CTLA-4 expressed on T cells” (June, C. H., J. A. Ledbetter, P. S. Linsley, and C. B. Thompson, (1990), “Role of the CD28 Receptor in T-Cell Activation.”
Immunology Today,
11:211-216; Linsley, P. S., W. Brady, M. Urnes, L. S. Grosmaire, N. K. Damle, and J. A. Ledbetter, (1991), “CTLA-4 is a Second Receptor for the B Cell Activation Antigen B7.
” J. Exp. Med.,
174:561), together with B7.1 (CD80) and B7.2 (CD86) expressed on antigen presenting cells, are major pairs of co-stim
Anderson Darrell R.
Brams Peter
Hanna Nabil
Heard Cheryl
Shestowsky William S.
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