Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1996-12-20
2001-05-08
Schwartzman, Robert A. (Department: 1635)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C536S024300, C435S006120, C435S091100, C435S325000, C435S375000, C514S04400A
Reexamination Certificate
active
06229006
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to antisense oligodeoxynucleotides useful for producing truncated receptor proteins and their uses.
BACKGROUND OF THE INVENTION
An antisense approach is commonly utilized to block the expression of specific genes within cells. See, e.g., R. W. Wagner,
Nature
372, 333-335 (1994); and W. Risau, PCT International Publication Number: WO95/13387 (1995). It is hypothesized that RNase H hydrolyses the RNA strand of a RNA-DNA duplex and is likely to be responsible for the antisense effects of 2′-deoxyoligonucleotides. The translation initiation site of a mRNA is often used as the antisense binding site on the assumption that this region is important and accessible. However, recent studies such as those of Risau, supra, indicate that most regions of the mRNA are in fact accessible to oligonucleotides, except for those with strong secondary structure.
It has been shown that the carboxyl terminus (C-terminus) of the erythropoietin receptor (EPOR) is a negative regulation domain for cell growth. See James Ihle et al.,
Bailliere's Clinical Haemotology
7, 17-48 (1994); and A. D. DeAndrea et al.,
Mol Cell Biol.
11, 1980-1987 (1991). Further, this view is supported by the following evidence:
(i) In EPOR transfectants of Ba/F3 cells, a 40 amino acid truncation at the C-terminus enhances cell proliferation (DeAndrea et al., supra).
(ii) In a naturally occurring human EPOR mutant, a 70 amino acid truncation at the C-terminus caused erythrocytosis. The affected individuals have excellent or superior health without abnormalities (A. D. L Chapelle et al.,
Proc. Natl. Acad. Sci. USA
90, 4495-4499 (1993)).
(iii) Hematopoietic cell phosphatase (HCP), which down regulates the EPO-induced cell proliferation, binds to a region close to the C-terminus of EPOR (Taolin Yi et al.,
Blood
85, 87-95 (1995)).
REFERENCES:
patent: WO 95/13387 (1995-05-01), None
Andrea D. Branch, A good antisense molecule is hard to find, TIBS, 47-48, Feb. 1998.*
Stanley T. Crooke, Basic Principles of Antisense Therapeutics, Springer-Verlag, NY, p. 3, Jul. 1998.*
Jones, S.S.; D'Andrea,A.D.; Haines,L.L.; Wong,G.G.Human erythropoietin receptor: cloning, expression,and biologic characterization.Blood, vol. 76, No. 1, pp. 31-35, 1990.*
R. Wagner, “Gene Inhibition Using Antisense Oligodeoxynucleotides”,Nature, vol. 372, pp. 333-335 (1994).
Ihle et al., “Cytokine Receptors and Signal Transduction”,Baillier's Clinical Haematology, vol. 7, pp. 17-48 (1994).
Andrea et al., “The Cytoplasmic Region of the Erythropoietin Receptor Contain Nonoverlapping Positive and Negative Growth-Regulatory Domains”,Molecular and Cellular Biology, pp. 1980-1987 (1991).
Chapelle et al., “Truncated Erythropoietin Receptor Causes Dominantly Inherited Benign Human Erythrocytosis”,Proc. Natl. Acad. Sci, USA, vol. 90, pp. 4495-4499 (1993).
Yi et al., Hematopoietic Cell Phosphatase Associates With Erythropoietin (Epo) Receptor After Epo-Induced Receptor Tyrosine Phosphorylation: Identification of Potential Binding Sites,Blood, vol. 85, pp. 87-95 (1995).
Jones et al., “Human Erythropoietin Receptor: Cloning, Expression, and Biologic Characterization”,Blood, vol. 76, pp. 31-35 (1990).
E. Uhlmann and A. Peyman, “Antisense Oligonucleotides: A New Therapeutic Principle”,Chemical Reviews, vol. 90, pp. 543-584 (1990).
Kitamura et al., Expression Cloning of the Human IL-3 Receptor cDNA Reveals a Shared •Subunit for the Human IL-3 and GM-CSF Receptors,Cell, vol. 66, pp. 1165-1174 (1991).
Baumeister Kirk
Epps Janet
King William T.
Schwartzman Robert A.
SmithKline Beecham Corporation
LandOfFree
Use of antisense oligodeoxynucleotides to produce truncated... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of antisense oligodeoxynucleotides to produce truncated..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of antisense oligodeoxynucleotides to produce truncated... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2515915