Beta-like glycoprotein hormone polypeptide and heterodimer
AssigneeAmgen Inc.
InventorsChristopher J. R. Paszty, Jin Cao, Dimitry M. Danilenko, Jianhua Gong, David C. Hill
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Abstract
Novel β10 polypeptides and heterodimers thereof, and nucleic acid molecules encoding the same are disclosed. The invention also provides vectors, host cells, selective binding agents, and methods for producing β10 polypeptides and heterodimeric forms thereof, specifically α2/β10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with β10 polypeptides and α2/β10 heterodimers or their respective binding agents.
Claims99
An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
- (a) the nucleotide sequence set forth in SEQ ID No:
- 2;
- (b) a nucleotide sequence encoding the polypeptide set forth in SEQ ID No:
- 1;
- (c) a nucleotide sequence which hybridizes under moderately or highly stringent conditions to the complement of (a) or (b), wherein the encoded polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- and
- (d) a nucleotide sequence complementary to any of (a)-(c).
An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide that is at least about 70, 75, 80, 85, 90, 95, 96, 97, 98, or 99 percent identical to the polypeptide set forth in SEQ ID NO:
- 1, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence set forth in SEQ ID NO:
- 2, wherein the encoded polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (c) a nucleotide sequence of SEQ ID NO:
- 2, (a), or (b) encoding a polypeptide fragment of at least about 25 amino acid residues, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (d) a nucleotide sequence of SEQ ID NO:
- 2 or (a)-(c) comprising a fragment of at least about 16 nucleotides;
- (e) a nucleotide sequence which hybridizes under moderately or highly stringent conditions to the complement of any of (a)-(d), wherein the encoded polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- and
- (f) a nucleotide sequence complementary to any of (a)-(c).
An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide as set forth in SEQ ID NO:
- 1 with at least one conservative amino acid substitution, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (b) a nucleotide sequence encoding a polypeptide as set forth in SEQ ID NO:
- 1 with at least one amino acid insertion, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (c) a nucleotide sequence encoding a polypeptide as set forth in SEQ ID NO:
- 1 with at least one amino acid deletion, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (d) a nucleotide sequence encoding a polypeptide as set forth in SEQ ID NO:
- 1 which has a C- and/or N-terminal truncation, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (e) a nucleotide sequence encoding a polypeptide as set forth in SEQ ID NO:
- 1 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (f) a nucleotide sequence of (a)-(e) comprising a fragment of at least about 16 nucleotides;
- (g) a nucleotide sequence which hybridizes under moderately or highly stringent conditions to the complement of any of (a)-(f), wherein the encoded polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- and
- (h) a nucleotide sequence complementary to any of (a)-(e).
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 3.
An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
- (a) the mature amino acid sequence as set forth in SEQ ID NO:
- 3, comprising a mature amino terminus at residue 1, optionally further comprising an amino-terminal methionine;
- (b) an amino acid sequence for an ortholog of SEQ ID NO:
- 3, wherein the encoded polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (c) an amino acid sequence that is at least about 70, 75, 80, 85, 90, 95, 96, 97, 98, or 99 percent identical to the amino acid sequence of SEQ ID NO:
- 3, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (d) a fragment of the amino acid sequence set forth in SEQ ID NO:
- 3 comprising at least about 25 amino acid residues, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (e) an amino acid sequence for an allelic variant or splice variant of either the amino acid sequence set forth in SEQ ID NO:
- 3 or at least one of (a)-(c) wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer.
An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
- (a) the amino acid sequence set forth in SEQ ID NO:
- 3 with at least one conservative amino acid substitution, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (b) the amino acid sequence set forth in SEQ ID NO:
- 3 with at least one amino acid insertion, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (c) the amino acid sequence set forth in SEQ ID NO:
- 3 with at least one amino acid deletion, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- (d) the amino acid sequence set forth in SEQ ID NO:
- 3 which has a C- and/or N-terminal truncation, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer;
- and
- (e) the amino acid sequence set forth in SEQ ID NO:
- 3, with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the polypeptide, when heterodimerized to human α2 polypeptide, has an activity of the human α2/β10 heterodimer.
An antibody produced by immunizing an animal with a peptide comprising the amino acid sequence of SEQ ID NO:
- 3.
A hybridoma that produces a monoclonal antibody that binds to a peptide comprising the amino acid sequence of SEQ ID NO:
- 3.
A selective binding agent or fragment thereof that specifically binds at least one polypeptide, wherein said polypeptide comprises the amino acid sequence selected from the group consisting of:
- (a) the amino acid sequence set forth in SEQ ID NO:
- 3;
- and
- (b) a fragment of the amino acid sequence set forth in SEQ ID NO:
- 3;
- and
- (c) a naturally occurring variant of (a) or (b).
A selective binding agent or fragment thereof comprising at least one complementarity determining region with specificity for a polypeptide having the amino acid sequence of SEQ ID NO:
- 3.
A selective binding agent produced by immunizing an animal with a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 3.
A heterodimer of human β10 polypeptide and human α2 polypeptide.
A vector comprising nucleic acid molecules encoding human β10 polypeptide and human α2 polypeptide.
An antibody produced by immunizing an animal with a human α2/β10 heterodimer.
A selective binding agent or fragment thereof comprising at least one complementarity determining region with specificity for a human α2/β10 heterodimer.
Dependencies are inferred from the claim text.