Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
1998-09-01
2001-06-12
Romeo, David (Department: 1646)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C530S388240
Reexamination Certificate
active
06245896
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates generally to growth factors and specifically to a new member of the transforming growth factor beta (TGF-&bgr;) superfamily, which is denoted, growth differentiation factor-5 (GDF-5).
2. Description of Related Art
The transforming growth factor &bgr; (TGF-&bgr;) superfamily encompasses a group of structurally-related proteins which affect a wide range of differentiation processes during embryonic development. The family includes, Mullerian inhibiting substance (MIS), which is required for normal male sex development (Behringer et al.,
Nature
345:167, 1990), Drosophila decapentaplegic (DPP) gene product, which is required for dorsal-ventral axis formation and morphogenesis of the imaginal disks (Padgett, et al.,
Nature,
325:81-84, 1987), the Xenopus Vg-1 gene product, which localizes to the vegetal pole of eggs ((Weeks, et al.,
Cell,
51 :861-867, 1987), the activins (Mason, et al.,
Biochem, Biophys. Res. Commun,
135:957-964, 1986), which can induce the formation of mesoderm and anterior structures in Xenopus embryos (Thomsen et al.,
Cell
63:485, 1990), and the bone morphogenetic proteins (BMPs, osteogenin, OP-1) which can induce de novo cartilage and bone formation (Sampath, et al.,
J. Biol. Chem.
265:13198, 1990). The TGF-&bgr;s can influence a variety of differentiation processes, including adipogenesis, myogenesis, chondrogenesis, hematopoiesis, and epithelial cell differentiation (for review, see Massague,
Cell
49:437, 1987).
The proteins of the TGF-&bgr; family are initially synthesized as a large precursor protein which subsequently undergoes proteolytic cleavage at a cluster of basic residues approximately 110-140 amino acids from the C-terminus. The C-terminal regions of the proteins are all structurally related and the different family members can be classified into distinct subgroups based on the extent of their homology. Although the homologies within particular subgroups range from 70% to 90% amino acid sequence identity, the homologies between subgroups are significantly lower, generally ranging from only 20% to 50%. In each case, the active species appears to be a disulfide-linked dimer of C-terminal fragments. For most of the family members that have been studied, the homodimeric species has been found to be biologically active, but for other family members, like the inhibins (Ling, et al.,
Nature
321:779, 1986) and the TGF-&bgr;s (Cheifetz, et al.,
Cell,
48:409, 1987), heterodimers have also been detected, and these appear to have different biological properties than the respective homodimers.
Identification of new factors that are tissue-specific in their expression pattern will provide a greater understanding of that tissue's development and function.
SUMMARY OF THE INVENTION
The present invention provides a cell growth and differentiation factor, GDF-5, a polynucleotide sequence which encodes the factor and antibodies which are immunoreactive with the factor. This factor appears to relate to various cell proliferative disorders, especially those involving the uterus, such as endometriosis and uterine tumors, and those involving skeletal tissues.
Thus, in one embodiment, the invention provides a method for detecting a cell proliferative disorder of uterine origin and which is associated with GDF-5. In another embodiment, the invention provides a method of treating a cell proliferative disorder associated with expression of GDF-5, by suppressing or enhancing GDF-5 activity.
REFERENCES:
patent: 4741998 (1988-05-01), Herr et al.
patent: 5061786 (1991-10-01), Burnier et al.
patent: WO 93/16099 (1993-08-01), None
Bowie et al., “Deciphering the message in protein sequences: Tolerance to amino acid substitutions”,Science, vo. 247, 1990, pp. 1306-1310.
Lee, “Identification of a novel member (GDF-1) of the transforming growth factor-beta superfamily”,Molecular Endocrinology, (1990) 4(7) 1034-40.
Daniel et al. Virology, (1994 Aug. 1) 202 (2) 540-549.*
Wang et al. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci U S A, (1990 Mar.) 87 (6) 2220-4.*
Wozney et al. Novel regulators of bone formation: molecualr clones and activities. Science (Dec. 16, 1988) 242:1528-1534.
Huynh Thanh
Lee Se-Jin
Gray Cary Ware & Freidenrich LLP
Haile Lisa A.
Romeo David
The Johns Hopkins University School of Medicine
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