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US 2006/0223744 A1Published application
Prostate specific antigens and uses thereof
AssigneeSloan-Kettering Institute for Cancer Research
InventorsSamuel Danishefsky, Vadim Dudkin, Justin Miller, David Scheinberg, Christophe Antczak
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds having formula (I): wherein W1, W2, R1, R3, R4, R2A and R2B are as defined herein. In another aspect, the invention provides an antibody or antibody fragment which binds specifically to a normal or transformed PSA glycan or glycopeptide of the invention.
Claims38
An isolated compound having the structure:
- wherein each occurrence of R1 is independently hydrogen or an oxygen protecting group;
- each occurrence of R2A and R2B is independently hydrogen or a nitrogen protecting group;
- each occurrence of R3 is independently hydrogen, a protecting group or a carbohydrate domain comprising a saccharide moiety having the structure:
- wherein Y is NH or O;
- wherein a, b and c are each independently 0, 1 or 2;
- d is an integer from 1-3;
- with the proviso that the d bracketed structure represents a furanose or pyranose moiety and the sum of b and c is 1 or 2;
- wherein R0 is hydrogen, a linear or branched chain alkyl, acyl, arylalkyl or aryl group;
- wherein each occurrence of R5, R6 and R7 is independently hydrogen, OH, ORi, NRiiRiii, NHCORi, F, CH2OH, CH2ORi, or a substituted or unsubstituted linear or branched chain alkyl, (mono-, di- or tri)hydroxyalkyl, (mono-, di- or tri)acyloxyalkyl, arylalkyl or aryl group;
- wherein each occurrence of Ri, Rii and Riii is independently hydrogen, a protecting group, a sialic acid moiety, CHO, COORiv, or a substituted or unsubstituted linear or branched chain alkyl, acyl, arylalkyl or aryl group, or Rii and Riii, taken together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclic or heteroaryl moiety;
- and wherein each occurrence of Riv is independently H, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group;
- each occurrence of W1 and W2 is independently R1, R3 or a moiety having the structure:
- wherein X is —OR1 or —NR2AR2B;
- and each occurrence of R8 is independently R1 or a sialic acid moiety;
- and wherein the peptide is either identical to or closely related to that the PSA peptide near the N-glycosylation site, said PSA peptide having the structure:
- or truncated, elongated or derivatized version thereof;
- wherein any one or more of the amino acid residues may bear one or more protecting groups;
- with the proviso that the compound is not a naturally occurring PSA glycoprotein.
15 more elements
An antibody or antibody fragment which is specific to any one of the inventive carbohydrate antigens (independently of the others) containing a carbohydrate domain having the structure:
- wherein each occurrence of R1 is independently hydrogen or an oxygen protecting group;
- each occurrence of R2A and R2B is independently hydrogen or a nitrogen protecting group;
- each occurrence of R3 is independently hydrogen, a protecting group or a carbohydrate domain comprising a saccharide moiety having the structure:
- wherein Y is NH or O;
- wherein a, b and c are each independently 0, 1 or 2;
- d is an integer from 1-3;
- with the proviso that the d bracketed structure represents a furanose or pyranose moiety and the sum of b and c is 1 or 2;
- wherein R0 is hydrogen, a linear or branched chain alkyl, acyl, arylalkyl or aryl group;
- wherein each occurrence of R5, R6 and R7 is independently hydrogen, OH, ORi, NRiiRiii, NHCORi, F, CH2OH, CH2ORi, or a substituted or unsubstituted linear or branched chain alkyl, (mono-, di- or tri)hydroxyalkyl, (mono-, di- or tri)acyloxyalkyl, arylalkyl or aryl group;
- wherein each occurrence of Ri, Rii and Riii is independently hydrogen, a protecting group, a sialic acid moiety, CHO, COORiv, or a substituted or unsubstituted linear or branched chain alkyl, acyl, arylalkyl or aryl group, or Rii and Riii, taken together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclic or heteroaryl moiety;
- and wherein each occurrence of Riv is independently H, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group;
- each occurrence of W1 and W2 is independently R1, R3 or a moiety having the structure:
- wherein X is —OR1 or —NR2AR2B;
- and each occurrence of R8 is independently R1 or a sialic acid moiety;
- and wherein said antibody is a purified polyclonal antibody or a monoclonal antibody.
12 more elements
Dependencies are inferred from the claim text.