DNA encoding a receptor subunit for oncostatin M

Details DNA encoding a receptor subunit for oncostatin M DNA encoding a receptor subunit for oncostatin M

1999-12-06

2003-02-25

Kemmerer, Elizabeth (Department: 1647)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

C435S252300, C435S320100, C530S350000, C536S023500, C536S023100

Reexamination Certificate

active

06524817

ABSTRACT:

BACKGROUND OF THE INVENTION
Oncostatin M is a secreted single-chain polypeptide cytokine that regulates the growth of certain tumor-derived and normal cell lines. A number of cell types have been found to bind the oncostatin M protein. See, for example, Linsley et al.,
J. Biol. Chem.,
264: 4282 (1989). Oncostatin M has been shown to inhibit proliferation of a number of tumor cell types (Linsley et al. supra). In contrast, however, this protein has been implicated in stimulating proliferation of Kaposi's sarcoma cells (Nair et al.,
Science
255:1430, 1992; Miles et al.,
Science
255:1432, 1992; and Cai et al.,
Am. J. Pathol.
145:74, 1994).
Identifying and isolating oncostatin M-binding proteins, such as cell surface oncostatin M receptors, is desirable for such reasons as enabling study of the biological signal transduced via the receptor. Such receptors in soluble form also could be used to competitively inhibit a biological activity of oncostatin M in various in vitro assays or in vivo procedures. A soluble form of the receptor could be administered to bind oncostatin M in vivo, thus inhibiting the binding of oncostatin M to endogenous cell surface receptors, for example.
A protein known as gp130 has been found to bind oncostatin M, but with relatively low affinity (Gearing et al.,
Science
255:1434, 1992). Heterodimeric receptors comprising a leukemia inhibitory factor (LIF) receptor and gp130 bind oncostatin M with higher affinity than does gp130 alone, but also bind LIF with high affinity (Gearing et al., supra). For certain applications, a receptor that binds oncostatin M with high affinity, but that does not function as a high affinity LIF receptor, would be advantageous. Prior to the present invention, no such receptor had been identified or isolated.
SUMMARY OF THE INVENTION
The present invention provides a novel polypeptide that is designated herein as the oncostatin M receptor &bgr; subunit (OSM-R&bgr;). Also provided is a receptor comprising OSM-R&bgr; linked (preferably covalently) to an oncostatin M-binding protein known as gp130. The gp130 polypeptide may be covalently linked to the OSM-R&bgr; polypeptide by any suitable means, such as via a cross-linking reagent or a polypeptide linker. In one embodiment of the invention, the receptor is a fusion protein produced by recombinant DNA technology. This receptor comprising OSM-R&bgr; and gp130 binds oncostatin M at levels greater than does gp130 alone. Disorders mediated by oncostatin M may be treated by administering a therapeutically effective amount of this inventive receptor to a patient afflicted with such a disorder.


REFERENCES:
patent: 5073627 (1991-12-01), Curtis et al.
patent: 5106731 (1992-04-01), Salahuddin et al.
patent: 5120535 (1992-06-01), Marquardt et al.
patent: 5262522 (1993-11-01), Gearing et al.
patent: 0 290 948 (1988-11-01), None
patent: 0 411 946 (1991-02-01), None
patent: 0 450 472 (1991-10-01), None
patent: WO 90/12585 (1990-11-01), None
patent: WO 91/09057 (1991-06-01), None
patent: WO 92/10570 (1992-06-01), None
patent: WO 92/21380 (1992-12-01), None
patent: WO 93/10151 (1993-05-01), None
Bork, P. (1996), Go hunting in sequence databases but watch out for the traps. Trends Genetics, 12(10):425-427.*
Bork, P. (1998), Powers and Pitfalls in Sequence Analysis: The 70% Hurdle. Genome Res., 10:398-400, esp. p. 400.*
Doerks, T. (1998), Protein annotation: detective work for function prediction., Trends Genetics. 14(6):248-250.*
Skolnick, J. (2000), From genes to protein structure and function: novel applications of computational approaches in the genomic era., Trends Biotech., 18(1):34-39, esp. p. 36.*
Brenner, S. Errors in genome annotation, (1999) Trends in Genetics, 15(4): 132-133, esp. Fig. 2.*
Zarling et al., “Oncostatin M: A growth regulator produced by differentiated histiocytic lymphoma cells”,Proc. Natl. Acad. Sci. USA83:9739-9743, 1986.
Malik et al., “Molecular Cloning, Sequence Analysis, and Functional Expression of a Novel Growth Regulator, Oncostatin M”,Mol. Cell. Biol.9:2847-2953. 1989.
Linsley et al., “Identification and Characterization of Cellular Receptors for the Growth Regulator, Oncostatin M”,J. Biol. Chem.264:4282-4289, 1989.
Liu et al., “Interleukin-6 Signal Transducer gp 130 Mediates Oncostatin M Signaling”,J. Biol. Chem.267:16763-16766, 1992.
Nair et al., “Identification of a Major Growth Factor for AIDS-Kaposi's Sarcoma Cells as Oncostatin M”,Science255:1430-1432, 1992.
Miles et al., “Oncostatin M as a Potent Mitogen for AIDS-Kaposi's Sarcoma-Derived Cells”,Science255:1432o-1434, 1992.
Gearing et al., “The IL-6 Signal Transduce, gp 130: An Oncostatin M ReReceptor and Affinity Converter for the LIF Receptor”,Science255:1434-1437, 1992.
Gearing and Bruce, “Oncostatin M Binds the High-Affinity Leukemia Inhibitory Factor Receptor”,The New Biologist4:61-65, 1992.
Hibi et al., “Molecular Cloning and Exxpression of an IL-6 Signal Transducer, gp 130”,Cell63:1149-1157, 1990.
Gearing et al., “Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp 130”,EMBO J.10:2839-2848. 1991.
Brown et al., “Regulation of IL-6 Expression by Oncostatin M”,J. Immunol.147:2175-2180, 1991.
De Wit et al., “Interleukin-6 concentrations in the serum of patients with AIDS associated Kaposi's sarcoma during treatment with interferon-alpha”,J. Int. Med.229:539-542, 1991.
Gearing et al., “Reconstitution of high affinity leukemia inhibitory factor (LIF) receptors in haemopoietic cells transfected with the cloned human LIF receptor”, Ciba Foundation Symposium 167:245-255, 1992.
Thoma et al., “Oncostatin M and Leukemia Inhibitory Factor Trigger Overlapping and Different Signals Through Partially Shared Receptor Complexes”,J. Biol. Chem.269:6215-6222.
Thoma et al., “Discrimination Between two Types of Receptors for Oncostatin M: Signal Transduction via MAP Kinase”, Keystone Symposia, Keystone, CO, Jan. 31-Feb. 7, 1993.
Gearing et al., “Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor”,Proc. Natl. Acad. Sci. USA91:1119-1123, 1994.
Byrn et al., “Biological properties of a CD-4 immunoadhesin”,Nature344:667-670, 1990.
Ashkenazi et al., “Protection against endotoxic shock by a tumore necrosis factor receptor immunoadhesin”,Proc. Natl. Acad. Sci USA88:10535-10539, 1991.
Bauman et al., “Reconstitution of the Response to Leukemia Inhibitory Factor, Oncostatin M, and Ciliary Neurotrophic Factor in Hepatoma Cells”,J. Biol. Chem.268:8414-8417, 1993.
Cai et al., “Oncostatin M Is An Autocrine Growth Factor in Kaposi's Sarcoma”,Amer. J. Path.145:74-79, 1994.
Takeshita et al., “Cloning of the &agr; Chain of the Human IL-2 Receptor”,Science257:379-382, 1992.
Park et al., “The LIF/Oncostatin M Receptor System: A Multi-Subunit Cytokine Receptor Family”, Abstract and presentation at workshop on Intra-and Extra-Cellular Signalling in Hematopoiesis, Madrid, May 25-27, 1993.
Liu et al., “Interactions Between Oncostatin M and the IL-6 Signal Transducer, gp 130”,Cytokine6 (3):272-278, May 1994.

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