US2005181987A1PendingUtilityA1
Compositions and methods for treatment of cancer
Est. expiryNov 6, 2018(expired)· nominal 20-yr term from priority
A61K 38/12A61K 38/177A61K 38/10
49
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Claims
Abstract
Compositions containing one or more peptido-mimetics or modified peptido-mimetics of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier are useful for methods of reducing metastasis in a mammal and for inhibiting inflammatory response in a mammal. Particularly useful are embodiments in which the ligand is a Lewis antigen and/or the adhesion molecule is a selectin, e.g., E-selectin. Methods are disclosed for identifying peptido-mimetics of carbohydrate ligands, which may be involved in binding of tumor cells to other cells, such as endothelial cells.
Claims
exact text as granted — not AI-modified1 . A composition comprising a peptido-mimetic of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier.
2 . The composition according to claim 1 , wherein said adhesion molecule is a selectin.
3 . The composition according to claim 1 , wherein said ligand is a Lewis antigen.
4 . The composition according to claim 3 , wherein the Lewis antigen is selected from the group consisting of SA-Le a , SA-LeX, and LeY.
5 . The composition according to claim 2 , wherein said adhesion molecule is E-selectin and said ligand is SA-Le a or SA-LeX.
6 . The composition according to claim 5 , wherein said peptido-mimetic is selected form the group consisting of:
DLWDFVVGKPAG,
SEQ ID NO:63
DLWDWVIGKPAG,
SEQ ID NO:64
DLWDWVVAKPAG,
SEQ ID NO:65
DLWDWVVSKPAG,
SEQ ID NO:66
DLWDWVVEKPAG,
SEQ ID NO:67
DLWDWVVDKPAG,
SEQ ID NO:68
DLWDWVVGEPAG,
SEQ ID NO:69
DLWDWVVGDPAG,
SEQ ID NO:70
DLWDWVVGKEAG,
SEQ ID NO:71
DLWDWVVGKDAG,
SEQ ID NO:72
DLWDWVVGKPDG,
SEQ ID NO:73
DLWDWVVGKPAD,
SEQ ID NO:74
DLWDWVKEKPAG,
SEQ ID NO:75
DLWDWVLAKPAG,
SEQ ID NO:76
DLWDWVVGEDAG,
SEQ ID NO:77
DLWDWVVGKPEK
SEQ ID NO:78
DLWDWVKEEPAG,
SEQ ID NO:79
DLWDWVVGKDEK,
SEQ ID NO:80
DLWDWVVGEDEK,
SEQ ID NO:81
DLWDWVKEEDEK,
SEQ ID NO:82
TKRPDLIVDPIP,
SEQ ID NO:98
DEVRPDLISTEE,
SEQ ID NO:99
NLRPKYIXLDAD,
SEQ ID NO:100 and
TLIAFADLVDVI.
SEQ ID NO:101
7 . The peptide or polypeptide according to claim 6 , which is modified to enhance stability or enhance adhesion molecule binding.
8 . The peptide or polypeptide according to claim 6 , which is a multivalent peptide or polypeptide.
9 . A peptide or polypeptide consisting of from 7 to 15 amino acids, said peptide or polypeptide mimicking a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier, wherein said ligand is a Lewis SA-Le a or SA-LeX antigen.
10 . The peptide or polypeptide according to claim 9 , which is modified to enhance stability or enhance adhesion molecule binding.
11 . The peptide or polypeptide according to claim 9 , which is a multivalent peptide or polypeptide.
12 . The peptide or polypeptide according to claim 9 , which is selected form the group consisting of:
DLWDFVVGKPAG,
SEQ ID NO:63
DLWDWVIGKPAG,
SEQ ID NO:64
DLWDWVVAKPAG,
SEQ ID NO:65
DLWDWVVSKPAG,
SEQ ID NO:66
DLWDWVVEKPAG,
SEQ ID NO:67
DLWDWVVDKPAG,
SEQ ID NO:68
DLWDWVVGEPAG,
SEQ ID NO:69
DLWDWVVGDPAG,
SEQ ID NO:70
DLWDWVVGKEAG,
SEQ ID NO:71
DLWDWVVGKDAG,
SEQ ID NO:72
DLWDWVVGKPDG,
SEQ ID NO:73
DLWDWVVGKPAD,
SEQ ID NO:74
DLWDWVKEKPAG,
SEQ ID NO:75
DLWDWVLAKPAG,
SEQ ID NO:76
DLWDWVVGEDAG,
SEQ ID NO:77
DLWDWVVGKPEK
SEQ ID NO:78
DLWDWVKEEPAG,
SEQ ID NO:79
DLWDWVVGKDEK,
SEQ ID NO:80
DLWDWVVGEDEK,
SEQ ID NO:81
DLWDWVKEEDEK,
SEQ ID NO:82
TKRPDLIVDPIP,
SEQ ID NO:98
DEVRPDLISTEE,
SEQ ID NO:99
NLRPKYIXLDAD,
SEQ ID NO:100 and
TLIAFADLVDVI.
SEQ ID NO:101
13 . A modified peptide or polypeptide mimicking a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier, wherein said ligand is a Lewis antigen and wherein said modification is selected from the group consisting of (i) use of one or more D amino acids, (ii) insertion of a moiety which can provide a net positive charge at the N-terminus of said peptide or polypeptide, (iii) insertion of a spacer of greater than 3 amino acids interposed between the N- and C-termini to cyclize the peptide, (iv) insertion of a free hydroxyl on the C-terminus, (v) insertion of an amide or imide on the C-terminus, and (vi) insertion of a sequence of one or up to about 15 additional amino acids on the C-terminus.
14 . The peptide or polypeptide according to claim 13 which is modified by cyclizing the N- and C-termini.
15 . The peptide or polypeptide according to claim 13 , wherein said modification enhances stability or enhance adhesion molecule binding.
16 . The peptide or polypeptide according to claim 13 , which is a multivalent peptide or polypeptide.Join the waitlist — get patent alerts
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