Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1999-03-22
2001-09-25
Fonda, Kathleen K. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S017200, C536S018700, C514S008100, C514S025000, C514S062000, C424S184100, C424S193100
Reexamination Certificate
active
06294523
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to new human tumor-associated antigens. This invention is more particularly related to extended type 1 chain glycosphingolipids and their uses, e.g., as immunogens and as tumor markers.
BACKGROUND OF THE INVENTION
Despite enormous investments of financial and human resources, cancer remains one of the major causes of death. Current cancer therapies cure only about 50% of the patients who develop a malignant tumor. In most human malignancies, metastasis is the major cause of death.
Metastasis is the formation of a secondary tumor colony at a distant site. In most human malignancies, distant metastases are often too small to be detected at the time the primary tumor is treated. Furthermore, widespread initiation of metastatic colonies usually occurs before clinical symptoms of metastatic disease are evident. The size and age variation in metastases, their dispersed anatomical location, and their heterogeneous composition are all factors that hinder surgical removal and limit the concentration of anticancer drugs that can be delivered to the metastatic colonies. Therefore, detection of malignancies prior to dissemination of the tumor cells from the primary site is needed to enhance the effectiveness of current cancer therapies.
Aberrant glycosylation has been observed to be a common feature for most cancer types. Most of the carbohydrate antigens used for the diagnosis of human cancers carry polylactosamine structures, i.e., they contain Gal&bgr;1→3/4GlcNAc. Polylactosamines are usually classified into two categories according to their polylactosamine unit structure. The polylactosamine having the Gal&bgr;1→3GlcNAc structure is called the type 1 chain, and that having the Gal&bgr;1→4GlcNAc structure is referred to as the type 2 chain. The most common tumor-associated antigens found in major human cancers have the lacto-series type 2 chain structure, which usually has been sialylated and/or fucosylated. Type 1 chain antigens are abundant in normal cells and tissues, and also are cancer-associated. For example, 2→3 sialylated Le
a
antigen (the CA 19-9 antigen defined by the N19-9 antibody) is a cancer-associated type 1 chain antigen. However, cancer diagnostic methods based on the detection of these known antigens have been hampered by high false positive and/or high false negative incidences.
Due to the difficulties in the current approaches to the diagnosis of cancer, there is a need in the art for improved compositions and methods. The present invention fills this need, and further provides other related advantages.
SUMMARY OF THE INVENTION
Briefly stated, the present invention provides isolated compounds and methods of screening for cancers by detecting such compounds. In one aspect, the present invention provides an isolated compound, with or without fucosyl and/or sialyl residues, having the formula:
Gal&bgr;1→3GlcNAc&bgr;1→3Gal&bgr;1→3GlcNAc&bgr;1→(3Gal&bgr;1→3GlcNAc&bgr;1→)
n
3Gal&bgr;1→4Glc&bgr;1→1Cer
wherein n is 0 or an integer of 1 or more, there are at least two fucosyl and/or one or more sialyl residues, Gal represents galactose, Glc represents glucose, GlcNAc represents N-acetylglucosamine, Cer represents a ceramide, and wherein said at least two fucosyl residues are linked to the GlcNAc residues via an &agr;1→4 linkage and/or to the terminal Gal residue via an &agr;1→2 linkage and said one or more sialyl residues are linked to the terminal Gal residue via an &agr;2→3 linkage and/or to one or more of the subterminal GlcNAc residues via an &agr;2→6 linkage.
In a further aspect, the present invention provides the above-described isolated compound having the formula:
wherein Fuc represents fucose and NeuAc represents N-acetylneuraminic acid.
In another aspect the invention provides the first-described compound having the formula:
wherein Fuc represents fucose and NeuAc represents N-acetylneuraminic acid.
In another aspect the invention provides the first described compound having the formula:
wherein Fuc represents fucose and NeuAc represents N-acetylneuraminic acid.
In one embodiment, the present invention provides an isolated compound having the formula:
In another embodiment, the present invention provides an isolated compound having the formula:
In an even further embodiment, the present invention provides an isolated compound having the formula:
Within a related aspect, the present invention provides an isolated compound comprising:
Within another related aspect, the present invention provides an isolated compound comprising:
Within an even further aspect, the present invention provides an isolated ocmpound comprising an epitope having the formula:
In yet other aspects, any of the compounds of the present invention may be used as an immunogen for the production of polyclonal or monoclonal antibodies.
In another aspect of the present invention, methods for screening for cancer are provided. The methods comprise the steps of: (a) isolating a biological sample from a warm-blooded animal; and (b) testing the sample for the presence or amount of a compound according to formulae I, II, III, IV, V, VI.
Within a related aspect, the present invention provides the cell line IMH2, as designated by ATCC No. HB 11026, and the monoclonal antibody produced by the cell line (MAb IMH2).
These and other aspects of the present invention will become evident upon reference to the following detailed description and attached drawings.
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Hakomori Sen-itiroh
Levery Steven B.
Stroud Mark R
Fonda Kathleen K.
Roylance Abrams Berdo & Goodman L.L.P.
The Biomembrane Institute
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