United States Patent (19) 11 Patent Number: 5,753,631 Paulson Et Al
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US005753631A United States Patent (19) 11 Patent Number: 5,753,631 Paulson et al. 45) Date of Patent: May 19, 1998 54 INTERCELLULAR ADHESION MEDIATORS Tyrrell, David, et al. (1991) "Structural requirements for the carbohydrate ligand of E-selectin", Proc. Natl. Acad. Sci 75 Inventors: James C. Paulson, Sherman Oaks; USA, 88:10372-10376. Mary S. Perez, Carlsbad; Federico C. Derwent Publications Ltd., London, GB:AN 90-135674 & A. Gaeta, La Jolla; Robert M. JP-A-0283 337 (Nichirei KK) Mar. 23, 1990. Abstract. Ratcliffe, Carlsbad, all of Calif. Kannagi, Reiji, et al. (1982) "Possible role of ceramide in defining structure and function of membrane glycolipids”, 73) Assignee: Cytel Corporation, San Diego, Calif. Proc. Natl. Acad. Sci USA, 79:3470-3474. Hakomori, Sen-itiroh, et al. (1984) "Novel Fucolipids Accu (21) Appl. No.: 457,886 mulating in Human Adenocarcinoma', The Journal of Bio (22 Filed: May 31, 1995 logical Chemistry, 259(7):4672-4680. Fukushi, Yasuo, et al. (1984) "Novel Fucolipids Accumu Related U.S. Application Data lating in Human Adenocarcinoma", The Journal of Biologi cal Chemistry, 259(16):10511-10517. 60 Division of Ser. No. 63,181, May 14, 1993, which is a Holmes, Eric H., et al. (1985) Enzymatic Basis for the continuation-in-part of Ser. No. 810,789, Dec. 17, 1991, abandoned, which is a continuation-in-part of Ser. No. Accumulation of Glycolipids with X and Dimeric X Deter 716,735, Jun. 17, 1991, abandoned, which is a continuation minants in Human Lung Cancer Cells (NCI-H69), The in-part of Ser. No. 632,390, Dec. 21, 1990, abandoned, Journal of Biological Chemistry, 260(12:7619-7627. which is a continuation-in-part of Ser. No. 619,319, Nov. 28, Fukuda, Michiko N., et al. (1986) "Structure of a Novel 1990, abandoned, which is a continuation-in-part of Ser. No. Pialylated Fucosyl Lacto-N-nor-hexaosylceramide Isolated 538,853, Jun. 15, 1990, abandoned. from Chronic Myelogenous Leukemia Cells". The Journal (51) Int. Cl. ......................... A61K 31/70; CO7H 15/00 of Biological Chemistry, 261(5):2376-2383. 52 U.S. Cl. ................................... 514/25; 514/8; 514/54; McIntire, Floyd C., et al. (1988) “A polysaccharide fromn 514/61; 514/62; 536/17.2:536/18.2; 536/18.7; Streptococcus sanguis 34 that inhibits Coaggregation of S. 536/53: 536/54; 536/55; 536/55.1536/55.2 sanguis 34 with Actinomyces viscous T14V", Journal of 58 Field of Search .................................... 514/8, 25, 54, Bacteriology, 170(5:2229-2235. 514/61, 62; 536/17.2, 18.2, 18.7, 53, 54, Nilsson, Kurt G.I. (1988) "Enzymatic synthesis of oligosac 55, 55.1, 55.2 charides' Trends in Biotechnology, 6:256-264. Cassels, Frederick J. et al. (1989) “Isolation of a Coaggre (56) References Cited gation-Inhibiting Cell Wall Polysaccharide from Strepto U.S. PATENT DOCUMENTS coccus sanguis H1", Journal of Bacteriology, 171(7):4019-4025. 4,904,596 2/1990 Hakomori .............................. 435/723 Finne, Jukka, et al. (1989) “Novel Polyfucosylated 5,079,353 1/1992 Ratcliffe et al. .......................... 536/53 5296,594 3/1994 Ratcliffe et al. .......................... 536/53 N-Linked Glycopeptides with Blood Group A.H.X and Y 5,324,663 6/1994 Lowe ............... ... 435/320.1 Determinants from Human Small Intestinal Epithelial 5,344,870 9/1994 Ratcliffe et al. ....................... 52.5/54.2 Cells”, The Journal of Biological Chemistry, 5,428,025 6/1995 Brandley et al. ......................... 514/55 264(10):5720-5735. FOREIGN PATENT DOCUMENTS (List continued on next page.) 62-273.99 11/1987 European Pat. Off.. Primary Examiner-Kathleen K. Fonda WO 90/13300 11/1990 WIPO Attorney, Agent, or Firm-Townsend and Townsend and WO 91/06632 5/1991 WIPO. Crew LLP WO 91/07993 6/1991 WIPO : WO 91/19502 12/1991 WIPO. 57 ABSTRACT WO 92/07572 5/1992 WIPO The present invention is directed towards compositions and OTHER PUBLICATIONS methods for reducing or controlling inflammation and for Johnson, Philip H., et al. (1985) "Sialyl compounds as treating inflammatory disease processes and other pathologi acceptor substrates for the human ol-3-and O-3/4-L-fuco cal conditions mediated by intercellular adhesion. The com syltransferases". Biochem. Soc. Trans, 13(6):1119-1120. positions of the invention include compounds that selec Ching, C.K., et al. (1990) "Purification and Characterization tively bind selectin receptors, the selectin binding activity of a Peanut-Agglutination-Binding Pancreatic-Cancer-Re being mediated by a carbohydrate moiety. The selectin lated Serum Mucus Glycoprotein', Int, J. Cancer, binding moieties of the invention are derivatives of a 45:1022-1027. sialylated, fucosylated N-acetylactosamine unit of the Rosen, Steven D. et al. (1986) "Lymphocyte attachment to Lewis Xantigen. Compounds containing a selectin-binding high endothelial venules during recirculation: A possible moiety in both monovalent and multivalent forms are role for carbohydrates as recognition determinants', included in the invention. The compounds of the invention Molecular and Cellular Biochemistry, 72:153-164. are provided as pharmaceutical compositions which include, Underhill, Charles, et al. (1978) "The Role of Hyaluronic for example, liposomes that carry selectin-binding moieties Acid in Intercellular Adhesion of Cultured Mouse Cells”, of the invention. The invention further includes immuno Experimental Cell Research, 117:155-164. globulins capable of selectively binding an oligosaccharide Picker, Louis J., et al. (1991) "The Neutrophil Selectin ligand that is recognized by a selectin receptor. LECAM-1 Present Carbohydrate Ligands to the Vascular Selectins ELAM-1 and GMP-140". Cell 66:921-933, 9 Claims, 24 Drawing Sheets 5,753,631 Page 2 OTHER PUBLICATIONS Parmentier, Sophie, et al., "Inhibition of Platelet Functions Levery, Steven B., et al. (1988) “H-N.M.R. Analysis of by a Monoclonal Antibody (LYP20) Directed Against a Type-2 Chain Lacto-Gangliosides. Confirmation of Struc Granule Membrane Glycoprotein (GMP-140/PADGEM)”. ture of a Novel Cancer-Associated Fucoganglioside". Car Blood, 77(8):1734-1739 (1991). bohydrate Research, 178:121-144. Hakamori, et al. (1984) J. Biol. Chem, 259(7):4672–4680. Skinner, Michael P. et al., “GMP-140 Binding to Neutro Sakura (1989) Chemical Abstracts, 111:151639b. phils Is Inhibited by Sulfated Glycans”, Journal of Biologi Hansson, Gunnar, C., et al. (1983) "Mouse Monoclonal cal Chemistry, 266(9):5371-5374 (1991). Antibodies against Human Cancer Cell Lines with Specifificities for Blood Group and Related Antigens", The Goelz, Susan E., “ELFT: A Gene That Directs the Expres Journal of Biological Chemistry, 258(7):4091-4097. sion of an ELAM-1 Ligand", Cell, 63:1349-1356 (1990). Hakomori, Sen-itiroh (1985) “Aberrant Glycosylation in Cancer Cell Membranes as Focused on Glycolipids: Over Berg, Ellen L., et al., "A Carbohydrate Domain Common to view and Perspectives". Cancer Research 435:2405-2414. Both Sialyl Le(a) and Sialyl (x) is Recognized by the Yoichi, Sakurai, et al. (1989) “Production and clinical appli Endothelial Cell Leukocyte Adhesion Molecule ELAM-1”, cation of monoclonal antibodies NCC-CO-450,-473 reac Journal of Biological Chemistry, 266(23):14869-14872 tive with high-molecular-weight glycoprotein circulating in (1991). body fluid of gastrointestinal cancer patients”, (Abstract), Immunochemistry, 111:531. Lasky, Laurence A., et al., "The Lectin Cell Adhesion Hautanen, Aarno, et al. (1989) “Effects of Modifications of Molecules (LEC-CAMs): A New Family of Cell Adhesion the RGD Sequence and Its Context on Recognition by the Proteins Involved with Inflammation' Journal Cell Bio Fibronectin Receptor". The Journal of Biological Chemistry, chemistry, 45(2):139-146 (1991). 264(3):1437-1442. Eggens, Ivan, et al. (1989) "Specific Interaction Between Phillips, M. Laurie, et al. "ELAM-1 Mediates Cell Adhe Le” and Le Determinants". The Journal of Biological sion by Recognition of a Carbohydrate Ligand, Sia Chemistry, 264(16):9476-9484. lyl-Le(x)", Science, 250:1130-1132 (1990). Shitara, Kenya, et al. (1991) "Application of anti-Sialyl Le” Monoclonal antibody, KM231, for Immunotherapy of Can Picker, Louis J., et al., ELAM-1 is an adhesion molecule for cer", Anticancer Research, 11:2003-2014. skin-homing T Cells, Nature, 349:796-799 (1991). Zhou, Qun, et al. 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