Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Fusion protein or fusion polypeptide
Reexamination Certificate
1995-06-02
2003-04-15
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Fusion protein or fusion polypeptide
C424S133100, C424S134100, C424S178100, C424S182100, C424S193100, C530S350000, C530S387300, C530S391100, C530S391700, C530S395000, C530S402000
Reexamination Certificate
active
06548067
ABSTRACT:
The invention relates to antigenic constructs resulting from the linkage of major histocompatibility complex (MHC) class I antigens with specific carrier molecules.
Tissue-rejection reactions are the strongest-known immune responses mediated by T cells. In individuals of the same species they are caused by allogenic differences in class I and class II MHC antigens. In organ transplants, for example, any allogenic determinants of the MHC antigens present in the donor tissue are recognized as foreign by allospecific T cells of the recipient, a T cell immune response is induced, and the rejection reaction takes place unless an immunosuppressive therapy has been initiated or such a therapy proves insufficient.
It is furthermore known that MHC class I antigens are glycoproteins which are expressed on the surface of all nucleated cells. They are composed of a heavy chain, which is encoded by MHC class I genes, and of a light chain, the &bgr;
2
-microglobulin which is non-covalently associated with the heavy chain. The extracellular part of the heavy chain is folded in three domains, the first two of these domains (alpha
1
and alpha
2
) exhibiting a pronounced polymorphism when the amino acid sequences of hitherto known class I MHC antigens from various individuals are compared. They assist with antigen presentation and carry the allogenic determinants. The third extracellular domain has a more conserved sequence. The association with &bgr;
2
-microglobulin is essential for correct folding of the heavy chain and for the transport of the molecule to the cell surface.
Isolation and characterization of mutated MHC class I antigens in mice showed that merely a few differences in amino acids on the alpha
1
and alpha
2
domains between donor and recipient suffice to induce a rejection reaction (Nathenson et al., Ann. Rev. Immunol., 1986, 4, 471-502). It has also been shown in humans that slight differences between donor and recipient lead to rejection of a transplant (Dausset, J., Rapaport, F. T., Legrand, L., Colombani, J., Marcelli-Barge, A.: Skin allograft survival in 238 human subjects: Role of specific relationships at the four gene sites of the first and the second HL-A loci., Histocompatibility Testing (1970) pages 381-397, Terasaki P. I. (Ed.)). The task which presented itself from that said above was to utilize the specific inducibility and strength of the cellular immune response in the tissue-rejection reaction to damage or destroy selected target cells.
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Bosslet Klaus
Sedlacek Hans Harald
Seeman Gerhard
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Saunders David
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