US 2003/0143667 A1 · Repeat sequences of the CA125 gene and their use for diagnostic and therapeutic interventions

Abstract

The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is assembled by combining five genomic exons, four very short amino terminal sequences and one extraordinarily large exon. This domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. The repeat units encompass an interactive disulfide bridged C-enclosure and the site of OC125 and M11 binding. The repeat sequences demonstrated 70-85% homology to each other. Expression of the repeats was demonstrated in E. coli. The CA125 molecule is anchored at its carboxy terminal through a transmembrane domain and a short cytoplasmic tail. The carboxy terminal also contains a proteolytic cleavage site approximately 50 amino acids upstream from the transmembrane domain, which allows for proteolytic cleavage and release of the CA125 molecule. Any one of the repeat domains has the potential for use as a new gold standard for detecting and monitoring the presence of the CA125 antigen. Further, the repeat domains or other domains, especially the c-terminal to the repeat domain also provide a basis for the development of a vaccine, which would be useful for the treatment of ovarian cancer and other carcinomas where CA125 is elevated.

Claims34

Dependent claims

A CA125 molecule, comprising:

(a) an extracellular amino terminal domain, comprising 5 genomic exons, wherein exons 1 comprises amino acids #1-33 of SEQ ID NO:
299, exon 2 comprises amino acids #34-1593 of SEQ ID NO:
299, exon 3 comprises amino acids #1594-1605 of SEQ ID NO:
299, exon 4 comprises amino acids #1606-1617 of SEQ ID NO:
299, and exon 5 comprises amino acids #1618-1637 of SEQ ID NO:
299;
(b) a multiple repeat domain, wherein each repeat unit comprises 5 genomic exons, wherein exon 1 comprises amino acids #1-42 in any of SEQ ID NOS:
164 through 194;
exon 2 comprises amino acids #43-65 in any of SEQ ID NOS:
195 through 221;
exon 3 comprises amino acids #66-123 in any of SEQ ID NOS:
222 through 249;
exon 4 comprises amino acids #124-135 in any of SEQ ID NOS:
250 through 277;
and exon 5 comprises amino acids #136-156 in any of SEQ ID NOS:
278 through 298;
and
(c) a carboxy terminal domain comprising a transmembrane anchor with a short cytoplasmic domain, and further comprising 9 genomic exons, wherein exon 1 comprises amino acids #1-11 of SEQ ID NO:
300;
exon 2 comprises amino acids #12-33 of SEQ ID NO:
300;
exon 3 comprises amino acids #34-82 of SEQ ID NO:
300;
exon 4 comprises amino acids #83-133 of SEQ ID NO:
300;
exon 5 comprises amino acids #134-156 of SEQ ID NO:
300;
exon 6 comprises amino acids #157-212 of SEQ ID NO:
300;
exon 7 comprises amino acids #213-225 of SEQ ID NO:
300;
exon 8 comprises amino acids #226-253 of SEQ ID NO:
300;
and exon 9 comprises amino acids #254-284 of SEQ ID NO:
300.

32 more elements

Dependencies are inferred from the claim text.

Repeat sequences of the CA125 gene and their use for diagnostic and therapeutic interventions

Life of this patent

Repeat sequences of the CA125 gene and their use for diagnostic and therapeutic interventions

Life of this patent

Abstract

Claims34