NTR3, a novel member of the TNF-receptor supergene family
AssigneeAmgen Inc.
InventorHailing Hsu
Life of this patent
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Abstract
The present invention provides a purified polynucleotide encoding a novel receptor, designated NTR3, which belongs to the TNF receptor gene superfamily; to purified NTR3 polypeptide molecules; to antibodies that bind NTR3; to materials comprising such molecules; and to methods of using such molecules.
Claims71
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:
- 1;
- (b) a nucleotide sequence encoding the polypeptide set forth in SEQ ID NO:
- 2;
- (c) a nucleotide sequence which hybridizes under moderately or highly stringent conditions to the complement of (a) or (b), wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- 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 percent identical to the polypeptide set forth in SEQ ID NO:
- 2, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence set forth in SEQ ID NO:
- 1, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (c) a nucleotide sequence of SEQ ID NO:
- 1;
- (a);
- or (b) encoding a polypeptide fragment of at least about 25 amino acid residues, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (d) a nucleotide sequence of SEQ ID NO:
- 1, 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 polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- 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 set forth in SEQ ID NO:
- 2 with at least one conservative amino acid substitution, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (b) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:
- 2 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (c) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:
- 2 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (d) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:
- 2 which has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (e) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:
- 2 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 has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (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 polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- 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:
- 2.
An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
- (a) the mature amino acid sequence set forth in SEQ ID NO:
- 2, 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:
- 2, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (c) an amino acid sequence that is at least about 70 percent identical to the amino acid sequence of SEQ ID NO:
- 2, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (d) a fragment of the amino acid sequence set forth in SEQ ID NO:
- 2 comprising at least about 25 amino acid residues, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (e) an amino acid sequence for an allelic variant or splice variant of either the amino acid sequence set forth in SEQ ID NO:
- 2, or at least one of (a)-(c) wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2.
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:
- 2 with at least one conservative amino acid substitution, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (b) the amino acid sequence set forth in SEQ ID NO:
- 2 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (c) the amino acid sequence set forth in SEQ ID NO:
- 2 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- (d) the amino acid sequence set forth in SEQ ID NO:
- 2 which has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2;
- and
- (e) the amino acid sequence set forth in SEQ ID NO:
- 2, 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 has an activity of the polypeptide set forth in SEQ ID NO:
- 2.
An antibody produced by immunizing an animal with a peptide comprising an amino acid sequence of SEQ ID NO:
- 2.
A hybridoma that produces a monoclonal antibody that binds to a peptide comprising an amino acid sequence of SEQ ID NO:
- 2.
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:
- 2;
- (b) a fragment of the amino acid sequence set forth in at least one of SEQ ID NO:
- 2;
- and
- (c) a naturally occurring variant of (a) or (b).
The variable region fragment of claim 41 which is a Fab or a Fab′ fragment.
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:
- 2.
A selective binding agent produced by immunizing an animal with a polypeptide comprising an amino acid sequence of SEQ ID NO:
- 2.
A device, comprising:
- (a) a membrane suitable for implantation;
- and
- (b) the NTR3 polypeptide encapsulated within said membrane, wherein said membrane is permeable to the polypepetide.
A diagnostic reagent comprising a detectably labeled polynucleotide encoding the amino acid sequence set out in SEQ ID NO:
- 2, or a fragment, variant or homolog thereof including allelic variants and spliced variants thereof.
An antagonist of NTR3 polypeptide activity selected from the group consisting of NTR3 selective binding agents, small molecules, antisense oligonucleotides, and peptides or derivatives thereof having specificity for NTR3 polypeptide.
Dependencies are inferred from the claim text.