Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.
Reexamination Certificate
1999-01-21
2003-05-06
Eyler, Yvonne (Department: 1646)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Glycoprotein, e.g., mucins, proteoglycans, etc.
C530S300000, C530S350000, C435S069100, C435S069700, C514S002600, C424S009340, C536S023100
Reexamination Certificate
active
06559287
ABSTRACT:
BACKGROUND OF THE INVENTION
Heparan sulfate (HS) and chondroitin sulfate (CS) are glycosaminoglycans. Heparan sulfate and chondroitin sulfate modified proteoglycans have been shown to play an important role in regulating the function of a number of glycosaminoglycan (GAG) binding proteins which include growth factors and chemokines. For example, binding of basic fibroblast growth factor (b-FGF) to HS modified proteoglycans has been shown to increase local concentrations of the growth factor and prolong its half life. In addition, it appears that growth factor binding to the proteoglycan changes its conformation and facilitates its interaction with its receptor and also leads to receptor oligomerization enhancing signal transduction.
An example of a proteoglycan of current interest is CD44. CD44 is a widely distributed type I membrane protein which is capable of binding hyaluronan (HA), other extracellular matrix components and osteopontin. The interaction between CD44 and its ligands has been shown to participate in cell migration and activation. The exons encoding the CD44 gene can be variably spliced to give rise to multiple protein isoforms. Expression of these CD44 isoforms can be tissue specific, developmentally regulated and/or regulated by cell activation. Most of these isoforms arise from the variable splicing of exons encoding polypeptide fragments located in the extracellular region of CD44, downstream of the HA binding domain. Changes in the pattern of glycosylation of CD44 resulting from the addition of variably spliced exons, which are modified extensively with O-linked carbohydrates, can effectively modulate the HA binding activity of CD44. Likewise, different CD44 isoforms are modified with different GAG polymers including HS and CS.
SUMMARY OF THE INVENTION
The present invention concerns a method for enhancing the biological activity of a glycosaminoglycan binding protein comprising administering to a subject an effective amount of an artificial proteoglycan which is a recombinant fusion protein having a glycosaminoglycan assembly site comprising the sequence SG to which is bonded chondroitin sulfate or both chondroitin sulfate and heparan sulfate, wherein said recombinant fusion protein comprises:
(a) a first polypeptide which comprises a control sequence and the glycosaminoglycan assembly site wherein the control sequence and the assembly site result in modification of the polypeptide with chondroitin sulfate or both chondroitin sulfate and heparan sulfate, and
(b) a second targeting polypeptide.
In another aspect, the present invention is directed to a method for modifying a protein having a glycosaminoglycan assembly site comprising the sequence SG, said method comprising recombinantly inserting nucleic acid encoding a proteoglycan or fragment thereof containing the control sequence into an expression vector encoding said protein such that said protein is expressed as a fusion protein comprising said proteoglycan or fragment thereof, and when said fusion protein is expressed in a host cell, said fusion protein is modified with chondroitin sulfate or both heparan sulfate and chondroitin sulfate.
Other aspects of the invention are artificial proteoglyans and chimeric nucleic acids encoding artificial proteoglycans.
REFERENCES:
patent: 5164295 (1992-11-01), Kisilevsky et al. et al.
patent: 5180808 (1993-01-01), Ruoslahti
patent: 5486599 (1996-01-01), Saunders et al.
patent: 5541095 (1996-07-01), Hirschberg et al.
patent: 5583103 (1996-12-01), Ruoslahti et al.
patent: 5585467 (1996-12-01), Lee et al.
patent: 5591716 (1997-01-01), Siebert et al.
patent: 5625040 (1997-04-01), Margolis et al.
Fritz et al.,Two N-Acetylglucosaminyltransferases Catalyze the Biosynthesis of Heparin Sulfate, J. Biol Chem. (1994), vol. 269, No. 46, pp. 28809-38814.
Zhang et al.,Accumulation of a Pentasaccharide Terminating in &agr;-N-Acetylgucosamine in an Animal Cell Mutant Defective in Heparan Sulfate Biosynthesis, J. Biol. Chem. (1995) vol. 270, No. 21, pp. 12557-12562.
Carter,Site-Specific Proteolysis of Fusion Proteins, ACS Symposium Ser. Protein Purification: Molec. Mech. Large-Scale Processes(1990), vol. 427, pp. 181-193.
Bennett et al. (1995) J. Cell Biol. 128, 687-698.
Jackson et al. (1995) J. Cell Biol. 128, 673-686.
Noble et al. (1993) J. Clin. Invest. 91, 2368-2377.
Henke et al. (1996) J. Clin. Invest. 97, 2541-2552.
Katoh et al. (1995) J. Exp. Med. 182, 419-429.
Miyake et al. (1990) J. Exp. Med. 172(1), 69-75.
Esko et al. (1996), Curr.Opin. Struct. Biol. 6:663-670.
Faham et al. (1996) Science 271, 1116-1120.
Arch et al. (1992) Science 257,682-685.
Screaton et al. (1992) Proc. Natl. acad. Sci. USA 89, 12160-12164.
Tanaka et al. (1993) Nature 361, 79-82.
Lindahl et al. (1994) Thrombosis Research 75, 1-32.
Weber et al. (1996) Science 271, 509-512.
Brown et al. (1991) J. Cell Biol. 113(1), 207-221.
Spiro et al. (1991) J. Cell Biol. 115, 1463-1473.
Galandrini et al. (1994) J. Immunol. 153, 21-31.
Denning et al. (1990) J. Immunol. 144, 7.
Kanner et al. (1992) J. Immunol. 148, 2023-2029.
Huet et al. (1989) J. Immunol. 143, 798-801.
Shimizu et al. (1989) J. Immunol. 143, 2457-2463.
Peach et al. (1993) J. Cell Biol. 122, 257-264.
Kinsella et al. (1986) J. Cell Biol. 102, 679-687.
Jalkanen et al. (1992) J. Cell Biol. 116(3), 817-825.
Bennett et al. (1995) J. Cell Biol. 131, 1623-1633.
Culty et al. (1990) J. Cell Biol. 111, 2765-2774.
Zhang et al. (1994) J. Biol Chem. 269, 19295-19299.
Uhlin-Hansen et al. (1993) J. Biol. Chem. 268, 17370-17376.
Fritz et al. (1994) J. Biol. Chem. 269, 300-307.
Jackson et al. (1992) J. Biol. Chem. 267, 4732-4739.
Chan et al. (1993) J. Biol. Chem. 268, 24655-24664.
Zhang et al. (1995) J. Biol. Chem. 270, 27127-27135.
Mann et al. (1990) J. Biol. Chem. 265(9), 5317-5323.
Aruffo et al. (1990) Cell 61(7), 1303-1313.
Gunthert et al. (1991) Cell 65, 13-24.
Ruoslahti et al. (1991) Cell 64, 867-869.
Springer et al. (1994) Cell 76, 301-314.
Goldstein et al. (1989) Cell 56, 1063-1072.
Gilat et al. (1996) Immunol. Today 17, 16-20.
Tanaka et al. (1993) Immunol Today 14, 111-115.
Haynes et al. (1989) Immunol. Today 10(12), 423-428.
Midura et al. (1994) Glycobiology 4, 333-342.
Salmivirta et al. (1996) FASEB J. 10, 1270-1279.
Ho et al. (1989) Gene 77, 51-59.
Maresh et al. (1994) Arch. Biochem. Biophys. 311, 95-102.
Jacobsson et al. (1986) Biochem. J. 240, 625-632.
Fransson et al. (1992) Biochem. Biophys. Acta 1137, 287-297.
Hardy (1989) Complex Carbohydrates, pp. 76-78, Academic Press, Bethesda, MD.
Lindahl (1989) Heparin and Heparin Sulphate Proteoglycans-an Overview, pp. 159-189, CRC Press, Boca Raton.
Greenfield et al. (1999) J. Bio Chem. 274:2511-2517.
Wolff et al. (1999) J. Bio. Chem. 274:2518-2524.
Aruffo Alejandro A.
Bennett Kelly L.
Greenfield Brad W.
Wolff Edith A.
Basi Nirmal S.
Bristol-Myers Squibb Co.
Eyler Yvonne
Sher Audrey F.
LandOfFree
Artificial proteoglycans does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Artificial proteoglycans, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Artificial proteoglycans will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3008835