Secreted proteins and uses thereof

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

Reexamination Certificate

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C530S350000, C536S023500, C435S320100, C435S325000, C435S363000, C435S361000, C435S252300, C435S006120

Reexamination Certificate

active

06406884

ABSTRACT:

BACKGROUND OF THE INVENTION
Many secreted proteins, for example, cytokines and cytokine receptors, play a vital role in the regulation of cell growth, cell differentiation, and a variety of specific cellular responses. A number of medically useful proteins, including erythropoietin, granulocyte-macrophage colony stimulating factor, human growth hormone, and various interleukins, are secreted proteins. Thus, an important goal in the design and development of new therapies is the identification and characterization of secreted and transmembrane proteins and the genes which encode them.
Many secreted proteins are receptors which bind a ligand and transduce an intracellular signal, leading to a variety of cellular responses. The identification and characterization of such a receptor enables one to identify both the ligands which bind to the receptor and the intracellular molecules and signal transduction pathways associated with the receptor, permitting one to identify or design modulators of receptor activity, e.g., receptor agonists or antagonists and modulators of signal transduction.
SUMMARY OF THE INVENTION
The present invention is based, at least in part, on the discovery of cDNA molecules which encode the TANGO 253, 257 and 281 proteins and the INTERCEPT 258 protein, all of which are either wholly secreted or transmembrane proteins.
The TANGO 253 proteins are C1q domain-containing polypeptides that exhibit homologue to a human adipocyte complement-related protein precursor.
The TANGO 257 proteins are homologous to the human extracellular molecule olfactomedin, a molecule important in the maintenance, growth and differentiation of chemosensory cilia of olfactory neurons.
The INTERCEPT 258 proteins are Ig domain-containing polypeptides that exhibit homology to an antigen (A33) expressed in colonic and small bowel epithelium, a protein that may represent a cancer cell marker.
The TANGO 281 proteins represent proteins downregulated in megakaryocytes that fail to express the gata-1 transcription factor (a factor critical for blood cell formation) and can, therefore, represent direct or indirect gata-1 targets.
The TANGO 253, TANGO 257, INTERCEPT 258 and TANGO 281 proteins, fragments, derivatives, and variants thereof are collectively referred to herein as “polypeptides of the invention” or “proteins of the invention.” Nucleic acid molecules encoding the polypeptides or proteins of the invention are collectively referred to as “nucleic acids of the invention.”
The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes. Accordingly, in one aspect, this invention provides isolated nucleic acid molecules encoding a polypeptide of the invention or a biologically active portion thereof The present invention also provides nucleic acid molecules which are suitable for use as primers or hybridization probes for the detection of nucleic acids encoding a polypeptide of the invention.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, the nucleotide sequence of the cDNA insert of an EpT253 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:8, SEQ ID NO:9, the nucleotide sequence of the cDNA insert of an EpTm253 clone deposited with ATCC as Accession Number 207215, or a complement thereof.
The invention features nucleic acid molecules which are at least 95% or 98% identical to the nucleotide sequence of SEQ ID NO:15, the nucleotide sequence of the cDNA insert of an EpT257 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 95% or 98% identical to the nucleotide sequence of SEQ ID NO:21, the nucleotide sequence of the cDNA insert of an EpTm257 clone deposited with ATCC as Accession Number 207217, or a complement thereof.
The invention features nucleic acid molecules which are at least 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:26, SEQ ID NO:27, the nucleotide sequence of the cDNA insert of an EpT258 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:37, SEQ ID NO:38, the nucleotide sequence of the cDNA insert of an EpTm258 clone deposited with ATCC as Accession Number 207221, or a complement thereof.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 35 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:46, the nucleotide sequence of the cDNA insert of an EpT281 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:56, the nucleotide sequence of the cDNA insert of an EpmT281 clone deposited with ATCC as patent deposit Number PTA-224, or a complement thereof.
The invention features nucleic acid molecules of at least 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 1000, 1100, 1200 or 1300 nucleotides of the nucleotide sequence of SEQ ID NO:1, the nucleotide sequence of an EpT253 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700 or 720 nucleotides of the nucleotide sequence of SEQ ID NO:2, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 540, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200 or 1250 nucleotides of the nucleotide sequence of SEQ ID NO:8 the nucleotide sequence of an EpTm253 cDNa of ATCC Accession Number 207215, or a complement thereof.
The invention features nucleic acid molecules of at least 310, 350, 400, 450, 500, 550, 600, 650 or 700 nucleotides of the nucleotide sequence of SEQ ID NO:9, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 1800 nucleotides of the nucleotide sequence of SEQ ID NO:15 or its complement.
The invention features nucleic acid molecules which include a fragment of at least 1150 or 1200 nucleotides of the nucleotide sequence of SEQ ID NO:16, or its complement.
The invention features nucleic acid molecules which include a fragment of at least 1100, 1200, 1300, 1400, 1500, 1600 or 1700 nucleotides of the nucleotide sequence of SEQ ID NO:21 the nucleotide sequence of an EpTm257 cDNA of ATCC Accession Number 207217, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 1150 or 1200 nucleotides of the nucleotide sequence of SEQ ID NO:22, or its complement.
The invention features nucleic acid molecules which include a fragment of at least 420, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:26 the nucleotide sequence of an EpT258 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:27, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 675, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:37 the nucleotide sequence of an EpTm258 cDNA of ATCC Accession Number 207221, or a c

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