Human FGF-21 gene and gene expression products
AssigneeChiron Corporation
InventorsNobuyuki Itoh, W. Michael Kavanaugh
Life of this patent
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Abstract
This invention relates to human fibroblast growth factor (hFGF-21), and to variants thereof and to polynucleotides encoding FGF-21. The invention also relates to diagnostic and therapeutic agents related to the polynucleotides and proteins, including probes and antibodies, and to methods of treating liver disease such as cirrhosis and cancer, methods of treating conditions related to thymic function, and methods of treating conditions of the testis. The invention also relates to mouse fibroblast growth factor (mFGF-21), and to variants thereof and polynucleotides encoding mFGF-21.
Claims59
An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
- (a) a polynucleotide encoding amino acids from about 1 to about 209 of SEQ ID NO:4;
- (b) a polynucleotide encoding amino acids from about 2 to about 209 of SEQ ID NO:4;
- (c) a polynucleotide encoding amino acids from about 1 to about 177 of SEQ ID NO:4;
- (d) a polynucleotide encoding amino acids from about 40 to about 209 of SEQ ID NO:4;
- (e) a polynucleotide encoding amino acids from about 40 to about 177 of SEQ ID NO:4;
- (f) the polynucleotide complement of (a), (b), (c), (d) or (e);
- and
- (g) a polynucleotide at least 90% identical to the polynucleotide of (a), (b), (c), (d) or (e).
An isolated nucleic acid molecule which comprises 20-600 contiguous nucleotides from the coding region of SEQ ID NO:3.
An isolated nucleic acid molecule comprising a polynucleotide encoding a polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of:
- (a) amino acids from about 1 to about 209 of SEQ ID NO:4;
- (b) amino acids from about 2 to about 209 of SEQ ID NO:4;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:4;
- (d) amino acids from about 40 to about 209 of SEQ ID NO:4;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:4.
An isolated polypeptide comprising amino acids at least 95% identical to amino acids selected from the group consisting of:
- (a) amino acids from about 1 to about 209 of SEQ ID NO:4;
- (b) amino acids from about 2 to about 209 of SEQ ID NO:4;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:4;
- (d) amino acids from about 40 to about 209 of SEQ ID NO:4;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:4.
An isolated polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of:
- (a) amino acids from about 1 to about 209 of SEQ ID NO:4;
- (b) amino acids from about 2 to about 209 of SEQ ID NO:4;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:4;
- (d) amino acids from about 40 to about 209 of SEQ ID NO:4;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:4.
An isolated polypeptide comprising amino acids selected from the group consisting of:
- (a) amino acids from about 1 to about 209 of SEQ ID NO:4;
- (b) amino acids from about 2 to about 209 of SEQ ID NO:4;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:4;
- (d) amino acids from about 40 to about 209 of SEQ ID NO:4;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:4.
An epitope-bearing portion of the polypeptide of SEQ ID NO:4.
A method for providing trophic support for cells in a patient in need thereof, the method comprising administering to the patient a composition comprising a polynucleotide encoding the polypeptide of SEQ ID NO:4.
A method for providing trophic support for cells in a patient in need thereof, the method comprising administering to the patient a composition comprising a polypeptide of SEQ ID NO:4.
A method of alleviating a disease condition in the liver of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of slowing degeneration of, restoring function of, and increasing the number of, functional hepatic cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition comprising a polypeptide having the amino acid sequence of SEQ ID NO:4.
A method of alleviating a disease condition in the thymus of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of preventing degeneration of, slowing degeneration of, increasing the number of, functional thymic cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition comprising a polypeptide having the amino acid sequence of SEQ ID NO:4.
A method of alleviating a disease condition in the testis of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of preventing degeneration of, slowing degeneration of, and increasing the number of, functional testicular cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition comprising a polypeptide having the amino acid sequence of SEQ ID NO:4.
An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
- (a) a polynucleotide encoding amino acids from about 1 to about 210 of SEQ ID NO:2;
- (b) a polynucleotide encoding amino acids from about 2 to about 21 of SEQ ID NO:2;
- (c) a polynucleotide encoding amino acids from about 1 to about 177 of SEQ ID NO:2;
- (d) a polynucleotide encoding amino acids from about 40 to about 210 of SEQ ID NO:2;
- (e) a polynucleotide encoding amino acids from about 40 to about 177 of SEQ ID NO:2;
- (f) the polynucleotide complement of (a), (b), (c), (d) or (e);
- and
- (h) a polynucleotide at least 90% identical to the polynucleotide of (a), (b), (c), (d) or (e).
An isolated nucleic acid molecule which comprises 20-600 contiguous nucleotides from the coding region of SEQ ID NO:
- 1.
An isolated nucleic acid molecule comprising a polynucleotide encoding a polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of:
- (a) amino acids from about 1 to about 210 of SEQ ID NO:2;
- (b) amino acids from about 2 to about 210 of SEQ ID NO:2;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:2;
- (d) amino acids from about 40 to about 210 of SEQ ID NO:2;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:4.
An isolated polypeptide comprising amino acids at least 95% identical to amino acids selected from the group consisting of:
- (a) amino acids from about 1 to about 210 of SEQ ID NO:2;
- (b) amino acids from about 2 to about 210 of SEQ ID NO:2;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:2;
- (d) amino acids from about 40 to about 210 of SEQ ID NO:2;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:2.
An isolated polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of:
- (a) amino acids from about 1 to about 210 of SEQ ID NO:2;
- (b) amino acids from about 2 to about 210 of SEQ ID NO:2;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:2;
- (d) amino acids from about 40 to about 210 of SEQ ID NO:2;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:2.
An isolated polypeptide comprising amino acids selected from the group consisting of:
- (a) amino acids from about 1 to about 210 of SEQ ID NO:2;
- (b) amino acids from about 2 to about 210 of SEQ ID NO:2;
- (c) amino acids from about 1 to about 177 of SEQ ID NO:2;
- (d) amino acids from about 40 to about 210 of SEQ ID NO:2;
- and
- (e) amino acids from about 40 to about 177 of SEQ ID NO:2.
An epitope-bearing portion of the polypeptide of SEQ ID NO:2.
Dependencies are inferred from the claim text.