Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin
Reexamination Certificate
2000-04-19
2001-11-20
Mertz, Prema (Department: 1646)
Drug, bio-affecting and body treating compositions
Lymphokine
Interleukin
C514S002600, C514S008100, C514S012200, C514S885000
Reexamination Certificate
active
06319493
ABSTRACT:
FIELD OF THE INVENTION
The invention relates generally to methods and compositions for treating neoplasms, or cancers, in mammals. More particularly, it relates to the use of interleukin-10 (IL-10) compositions for treating various cancers, e.g., IL-2 dependent tumors, including B cell lymphocytic leukemia (B-CLL).
BACKGROUND OF THE INVENTION
Immunologic approaches to cancer therapy are based on the notion that cancer cells have somehow evaded the body's defenses against aberrant or foreign cells and molecules, and that these defenses might be therapeutically stimulated to regain the lost ground, see e.g., pp. 623-648 in Klein (1982)
Immunology,
Wiley-Interscience, New York. The recent observations that various immune effectors can directly or indirectly inhibit tumor growth has led to renewed interest in this approach to cancer therapy, see e.g., Herberman (1985)
Concepts Immunopathol.
1:96-132 (1985) (natural killer cells resist tumor cell growth); Rosenberg, et al. (1988)
Ann. Rev. Immunol.
4:681-709 (clinical use of IL-2-activated killer cells to treat cancer); Ralph, et al. (1988)
J. Exp. Med.
167:712-717 (tumoricidal activity by macrophages stimulated by lymphokines); Tepper, et al. (1989)
Cell
57:503≧512 (IL-4 has anti-tumor activity); M. Cohen, “Lymphokines and Tumor Immunity,” pp. 237-253 in S. Cohen (ed.) (1990)
Lymphokines and the Immune Response,
CRC Press, Boca Raton; and the like.
For example, leukemias are a heterogeneous group of neoplasms arising from the malignant transformation of hematopoietic cells, and can be derived from either lymphoid or myeloid cell types. The transformed cells proliferate primarily in the bone marrow and lymphoid tissue where they interfere with normal hematopoiesis and immunity. They may also emigrate into the blood and infiltrate other tissues often leading to abnormal distributions of different cell types. Examples of leukemias include, acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), hairy cell leukemia, and adult T cell leukemia (ATL).
Leukemias are typically identified as either acute or chronic. Acute forms have a rapid clinical course and without effective treatment can result in death within months. Acute leukemias are typically characterized by excessive proliferation of immature myeloid or lymphoid cells in the bone marrow, as a result of defects in the maturation process. In AML, the cells fail to mature beyond the myeloblast or promyelocyte level. In ALL, the cells fail to mature beyond the lymphoblastoid level.
Chronic leukemias have a more prolonged natural history. CLL is typically characterized by the overproduction and accumulation of mature appearing B lymphocytes. The neoplastic cells usually have B cell associated markers such as monoclonal surface IgM and Fc receptors. Approximately 5 percent of patients with CLL have the T cell form of CLL. The neoplastic cells in these diseases form rosettes with sheep erythrocytes and exhibit other T cell markers.
Hairy cell leukemia is a lymphoid neoplasm characterized by neoplastic cells having cytoplasmic projections. The disease is caused by the expansion of mature B cells which often produce monoclonal immunoglobulins.
Adult T cell leukemia (ATL) is associated with human T cell leukemia virus-I (HTLV-I). It is an aggressive malignancy of mature T cells, and is endemic to parts of Japan, the Caribbean, and Africa.
Lymphomas, in contrast to leukemias, are neoplastic transformations of cells that reside predominantly in lymphoid tissues. Lymphomas are typically divided between Hodgkin's disease and non-Hodgkin's lymphomas. In Hodgkin's disease the majority of the cells are small lymphocytes with a T cell phenotype. More than 90% of all cases of non-Hodgkin's lymphomas are of B cell derivation.
Treatment of the majority of these diseases has not been entirely successful. Prior art approaches have centered primarily on chemotherapy and radiation. To date, however, these treatments generally fail to effect long term remission or cure. Thus, the prior art lacks a safe, reliable treatment of neoplastic cell proliferation, particularly those which are IL-2-dependent. Recently, various models have provided data which support use of IL-10 to treat neoplastic conditions.
SUMMARY OF THE INVENTION
The invention relates to the use of interleukin-10 (IL-10) to reduce and/or prevent the growth of a tumor. The invention also includes pharmaceutical compositions comprising interleukin-10. Preferably, the interleukin-10 of the invention is selected from the group consisting of the mature polypeptides of the open reading frames defined by the following amino acid sequences:
Met His Ser Ser Ala Leu Leu Cys Cys
(SEQ ID NO: 1)
Leu Val Leu Leu Thr Gly Val Arg Ala
Ser Pro Gly Gln Gly Thr Gln Ser Glu
Asn Ser Cys Thr His Phe Pro Gly Asn
Leu Pro Asn Met Leu Arg Asp Leu Arg
Asp Ala Phe Ser Arg Val Lys Thr Phe
Phe Gln Met Lys Asp Gln Leu Asp Asn
Leu Leu Leu Lys Glu Ser Leu Leu Glu
Asp Phe Lys Gly Tyr Leu Gly Cys Gln
Ala Leu Ser Glu Met Ile Gln Phe Tyr
Leu Glu Glu Val Met Pro Gln Ala Glu
Asn Gln Asp Pro Asp Ile Lys Ala His
Val Asn Ser Leu Gly Glu Asn Leu Lys
Thr Leu Arg Leu Arg Leu Arg Arg Cys
His Arg Phe Leu Pro Cys Glu Asn Lys
Ser Lys Ala Val Glu Gln Val Lys Asn
Ala Phe Asn Lys Leu Gln Glu Lys Gly
Ile Tyr Lys Ala Met Ser Glu Phe Asp
Ile Phe Ile Asn Tyr Ile Glu Ala Tyr
Met Thr Met Lys Ile Arg Asn;
and
Met Glu Arg Arg Leu Val Val Thr Leu
(SEQ ID NO: 2)
Gln Cys Leu Val Leu Leu Tyr Leu Ala
Pro Glu Cys Gly Gly Thr Asp Gln Cys
Asp Asn Phe Pro Gln Met Leu Arg Asp
Leu Arg Asp Ala Phe Ser Arg Val Lys
Thr Phe Phe Gln Thr Lys Asp Glu Val
Asp Asn Leu Leu Leu Lys Glu Ser Leu
Leu Glu Asp Phe Lys Gly Tyr Leu Gly
Cys Gln Ala Leu Ser Glu Met Ile Gln
Phe Tyr Leu Glu Glu Val Met Pro Gln
Ala Glu Asn Gln Asp Pro Glu Ala Lys
Asp His Val Asn Ser Leu Gly Glu Asn
Leu Lys Thr Leu Arg Leu Arg Leu Arg
Arg Cys His Arg Phe Leu Pro Cys Glu
Asn Lys Ser Lys Ala Val Glu Gln Ile
Lys Asn Ala Phe Asn Lys Leu Gln Glu
Lys Gly Ile Tyr Lys Ala Met Ser Glu
Phe Asp Ile Phe Ile Asn Tyr Ile Glu
Ala Tyr Met Thr Ile Lys Ala Arg;
wherein the standard three letter abbreviation is used to indicate L-amino acids, starting from the N-terminus. These two forms of IL-10 are sometimes referred to as human IL-10 (or human cytokine synthesis inhibitory factor) and viral IL-10 (or BCRF1), respectively, e.g., Moore, et al. (1990)
Science
248:1230-1234; Vieira, et al. (1991)
Proc. Nat'l Acad. Sci. USA
88:1172-1176; Fiorentino, et al. (1989)
J. Exp. Med.
170:2081-2095; Hsu, et al. (1990)
Science
250:830-832. More preferably, the mature IL-10 used in the method of the invention is selected from the group consisting of:
Ser Pro Gly Gln Thr Gln Ser Glu
(SEQ ID NO: 3)
Asn Ser Cys Thr His Phe Pro Gly Asn
Leu Pro Asn Met Leu Arg Asp Leu Arg
Asp Ala Phe Ser Arg Val Lys Thr Phe
Phe Gln Met Lys Asp Gln Leu Asp Asn
Leu Leu Leu Lys Glu Ser Leu Leu Glu
Asp Phe Lys Gly Tyr Leu Gly Cys Gln
Ala Leu Ser Glu Met Ile Gln Phe Tyr
Leu Glu Glu Val Met Pro Gln Ala Glu
Asn Gln Asp Pro Asp Ile Lys Ala His
Val Asn Ser Leu Gly Glu Asn Leu Lys
Thr Leu Arg Leu Arg Leu Arg Arg Cys
His Arg Phe Leu Pro Cys Glu Asn Lys
Ser Lys Ala Val Glu Gln Val Lys Asn
Ala Phe Asn Lys Leu Gln Glu Lys Gly
Ile Tyr Lys Ala Met Ser Glu Phe Asp
Ile Phe Ile Asn Tyr Ile Glu Ala Tyr
Met Thr Met Lys Ile Arg Asn;
and
Thr Asp Gln Cys Asp Asn Phe Pro Gln
(SEQ ID NO: 4)
Met Leu Arg Asp Leu Arg Asp Ala Phe
Ser Arg Val Lys Thr Phe Phe Gln Thr
Lys Asp Glu Val Asp Asn Leu Leu Leu
Lys Glu Ser Leu Leu Glu Asp Phe Lys
Gly Tyr Leu Gly Cys Gln Ala Leu Ser
Glu Met Ile Gln Phe Tyr Leu Glu Glu
Val Met Pro Gln Ala Glu Asn Gln Asp
Pro Glu Ala Lys Asp His Val Asn Ser
Leu Gly Glu Asn Leu Lys Thr Leu Arg
Leu Arg Leu Arg Arg Cys His Arg Phe
Leu Pro Cys Glu Asn Lys Ser Lys Ala
Val Glu Gln Ile Lys Asn Ala Phe Asn
Lys Leu Gln Glu Lys Gly Ile Tyr Lys
Ala M
Banchereau Jacques
de Vries Jan E.
De Waal Malefyt Rene
Fluckiger Anne-Catherine
Moore Kevin W.
Foulke Cynthis L.
Mertz Prema
Schering Corporation
Schram David B.
Thampoe Immac J.
LandOfFree
Treatment of neoplastic disease with interleukin-10 does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treatment of neoplastic disease with interleukin-10, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treatment of neoplastic disease with interleukin-10 will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2576970