Novel Heparin-induced CCN-like molecules and uses therefor
AssigneeTrustees of Tufts College
InventorJohn J. Castellot JR.
Life of this patent
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Abstract
Novel HICP polypeptides, proteins, and nucleic acid molecules which play a role in cell proliferation and fibrosis are disclosed. In addition to isolated, full-length HICP proteins, the invention further provides isolated HICP fusion proteins, antigenic peptides and anti-HICP antibodies. The invention also provides HICP nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a HICP gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.
Claims61
An isolated nucleic acid molecule which encodes a HICP protein, comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:
- 1, SEQ ID NO:3 or a complement thereof.
An isolated nucleic acid molecule comprising a nucleotide sequence encoding a protein which comprises an amino acid sequence at least about 60% homologous to the amino acid sequence of SEQ ID NO:2.
An isolated nucleic acid molecule encoding a HICP protein, comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
An isolated nucleic acid molecule comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising nucleotides 1-883 of SEQ ID NO:1.
An isolated nucleic acid molecule at least 500 nucleotides in length which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
An isolated nucleic acid molecule which is at least about 60% homologous to a nucleotide sequence of SEQ ID NO:
- 1, SEQ ID NO:3 or a complement thereof, and encodes a polypeptide which has at least one of the following activities:
- i) it can modulate cell proliferation;
- ii) it can modulate a growth factor signaling pathway;
- iii) it can modulate the activity of CTGF or PDGF;
- or
- iv) it can modulate a heparin-induced response in a heparin-responsive cell.
A nonhuman transgenic animal which contains cells carrying a transgene encoding HICP protein.
A nonhuman homologous recombinant animal which contains cells having an altered HICP gene.
An isolated HICP protein comprising an amino acid sequence at least about 60% homologous to the amino acid sequence of SEQ ID NO:2.
An isolated HICP protein which is encoded by a nucleic acid molecule comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:
- 1, SEQ ID NO:3, or a complement thereof.
An isolated HICP protein which is encoded by a nucleic acid molecule comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
An isolated HICP protein which is sufficiently homolgous to the amino acid sequence of SEQ ID NO:2 and retains HICP biological activity.
An isolated HICP protein comprising an amino acid sequence at least about 60% homolgous to the amino acid sequence of SEQ ID NO:2 and which has at least one of the following biological activities:
- i) it can modulate cell proliferation;
- ii) it can modulate a growth factor signaling pathway;
- iii) it can modulate the activity of CTGF or PDGF;
- iv) it can modulate a heparin-induced response in a heparin-responsive cell;
- v) it can modulate cell motility;
- or
- vi) it can modulate extracellular matrix production.
An isolated protein comprising the amino acid sequence of SEQ ID NO:2.
A fusion protein comprising a HICP polypeptide operatively linked to a non-HICP polypeptide.
An antibody that specifically binds HICP.
A method for modulating a cell-associated activity comprising contacting a cell with an agent which modulates HICP protein activity or HICP nucleic acid expression such that the cell-associated activity is altered relative to the cell-associated activity of the cell in the absence of the agent.
A method for treating a subject having a disorder characterized by aberrant HICP protein activity or nucleic acid expression comprising administering to the subject a HICP modulator such that treatment of the subject occurs.
A method for detecting the presence of HICP activity in a biological sample comprising contacting a biological sample with an agent capable of detecting an indicator of HICP activity such that the presence of HICP activity is detected in the biological sample.
A method for treating a disorder characterized by abberant cell proliferation by administering to a subject having the disorder a HICP agent which alters cell proliferation relative to cell proliferation in the absence of the agent.
A diagnostic assay for identifying a genetic alteration in a cell sample, the presence or absence of the genetic alteration characterized by at least one of (i) aberrant modification or mutation of a gene encoding a HICP protein, and (ii) mis-regulation of said gene or (iii) aberrant post-translational modification of a HICP protein.
A method for isolating a heparin specie which has antiproliferative activity comprising:
- a. contacting a HICP affinity reagent with a composition containing heparin species;
- and
- b. isolating the heparin specie which binds to the HICP affinity reagent to thereby obtain the heparin specie which has antiproliferative activity.
Dependencies are inferred from the claim text.