| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 02.04.2002 |
| PATENT TITLE |
Human cardiac/brain tolloid-like protein |
| PATENT ABSTRACT |
HC/BTLP polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hC/BTLP polypeptides and polynucleotides in the design of protocols for the treatment of restenosis, atherosclerosis, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), benign prostatic hypertrophy (BPH), nephritis, fibrosis, glomerulonephritis, gliosis, cirrhosis and anomalies of wound healing, such as keloids among others, and diagnostic assays for such conditions. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | November 1, 1999 |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2. 2. The isolated polypeptide of claim 1 consisting of the amino acid sequence of SEQ ID NO:2. |
| PATENT DESCRIPTION |
FIELD OF INVENTION This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to the astacin protein family, hereinafter referred to as human cardiac/brain tolloid-like protein (hC/BTLP). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. BACKGROUND OF THE INVENTION The hC/BTLP gene appears to possess all of the important protein domains present in the bone morphogenetic protein (BMP)-1/procollagen C-proteinase (PCP) protein. Members of the astacin family of metalloproteinases, such as BMP-1, have previously been linked to cell differentiation and pattern formation during development through a proposed role in the activation of latent growth factors of the TGF-.beta. superfamily. In addition, recent findings indicate that BMP-1 is identical to PCP, which is a metalloproteinase involved in the synthesis of matrix collagen. This observation suggests that a functional link may exist between astacin metalloproteinases, growth factors and cell differentiation and pattern formation during development, as well as fibrotic processes characterized by the accumulation of matrix collagen. Nucleotide and amino acid sequence homologues suggest that hC/BTLP, like BMP-1, possesses PCP activity. PCP activity is one of the essential enzymatic steps required for the extracellular production of insoluble collagen fibrils from soluble procollagen. However, mouse mammalian tolloid-like protein is the most closely related homologues of hC/BTlP. Mouse mammalian tolloid-like protein and BMP-1 are distinct gene products with differential tissue distribution. Based on cross-species comparisons, the regulation and distribution of hC/BTlP would be expected to be distinct from BMP-1. Indeed, mouse mammalian tolloid-like protein exhibits a unique tissue distribution when compared to BMP-1. Thus, the selective inhibition of matrix collagen accumulation is important in highly localized fibrotic disorders, e.g., gliosis associated with neurotrauma and ventricular fibrosis associated with congestive heart failure. This indicates that the astacin protein family has an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further members of the astacin protein family which can play a role in preventing, ameliorating or con g dysfunctions or diseases, including, but not limited to, restenosis, atherosclerosis, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), benign prostatic hypertrophy (BPH), nephritis, fibrosis, glomeruloneplritis, gliosis, cirrhosis and anomalies of wound healing, such as keloids, among others. SUMMARY OF THE INVENTION In one aspect, the invention relates to hC/BTLP polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such hC/BTLP polypeptides and polynucleotides. Such uses include the treatment of restenosis, atherosclerosis, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), benign prostatic hypertrophy (BPH), nephritis, fibrosis, glomenulonephritis, gliosis, cirrhosis and anomalies of wound healing, such as keloids, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with hC/BTLP imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate hC/BTLP activity or levels. |
| PATENT PHOTOCOPY | Available on request |
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