G-protein coupled receptor molecules and uses thereof
AssigneeAmgen, Inc., A Corporation of the State of Delaware
InventorsSteven G. Elliott, Norma Rogers, Leigh Anne Busse
Life of this patent
Estimating the term…
Abstract
The present invention provides G-Protein Coupled Receptor (GPCR) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing GPCR polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with GPCR polypeptides.
Claims58
An isolated nucleic acid molecule comprising:
- (a) the nucleotide sequence as set forth in any of SEQ ID NO:
- 1, SEQ ID NO:
- 3, or SEQ ID NO:
- 5;
- (b) a nucleotide sequence encoding the polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (c) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of the nucleotide sequence of either (a) or (b);
- or
- (d) a nucleotide sequence complementary to the nucleotide sequence of either (a) or (b).
An isolated nucleic acid molecule comprising:
- (a) a nucleotide sequence encoding a polypeptide that is at least about 70 percent identical to the polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence as set forth in any of SEQ ID NO:
- 1, SEQ ID NO:
- 3, or SEQ ID NO:
- 5 or the nucleotide sequence of (a);
- (c) a region of the nucleotide sequence of any of SEQ ID NO:
- 1, SEQ ID NO:
- 3, or SEQ ID NO:
- 5 or the nucleotide sequence of (a) or (b) encoding a polypeptide fragment of at least about 25 amino acid residues, wherein the polypeptide fragment has an activity of the encoded polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6, or is antigenic;
- (d) a region of the nucleotide sequence of any of SEQ ID NO:
- 1, SEQ ID NO:
- 3, or SEQ ID NO:
- 5 or the nucleotide sequence of any of (a)-(c) comprising a fragment of at least about 16 nucleotides;
- (e) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of the nucleotide sequence of any of (a)-(d);
- or
- (f) a nucleotide sequence complementary to the nucleotide sequence of any of (a)-(d).
An isolated nucleic acid molecule comprising:
- (a) a nucleotide sequence encoding a polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one conservative amino acid substitution, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (b) a nucleotide sequence encoding a polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one amino acid insertion, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (c) a nucleotide sequence encoding a polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one amino acid deletion, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (d) a nucleotide sequence encoding a polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 that has a C- and/or N-terminal truncation, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (e) a nucleotide sequence encoding a polypeptide as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one modification that is an amino acid substitution, an amino acid insertion, an amino acid deletion, C-terminal truncation, or N-terminal truncation, wherein the encoded polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (f) a nucleotide sequence of any of (a)-(e) comprising a fragment of at least about 16 nucleotides;
- (g) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of the nucleotide sequence of any of (a)-(f);
- or
- (h) a nucleotide sequence complementary to the nucleotide sequence of any of (a)-(e).
An isolated polypeptide comprising the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6.
An isolated polypeptide comprising:
- (a) an amino acid sequence for an ortholog of any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (b) an amino acid sequence that is at least about 70 percent identical to the amino acid sequence of any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (c) a fragment of the amino acid sequence set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 comprising at least about 25 amino acid residues, wherein the fragment has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6, or is antigenic;
- or
- (d) an amino acid sequence for an allelic variant or splice variant of the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 or the amino acid sequence of either (a) or (b).
An isolated polypeptide comprising:
- (a) the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one conservative amino acid substitution, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (b) the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (c) the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- (d) the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 that has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6;
- or
- (e) the amino acid sequence as set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6 with at least one modification that is an amino acid substitution, an amino acid insertion, an amino acid deletion, C-terminal truncation, or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6.
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 any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6.
A selective binding agent produced by immunizing an animal with a polypeptide comprising an amino acid sequence of any of SEQ ID NO:
- 2, SEQ ID NO:
- 4, or SEQ ID NO:
- 6.
An isolated polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:
- 2 with at least one conservative amino acid substitution that is a aspartic acid at position 2;
- leucine at position 8;
- glutamic acid at position 12;
- proline at position 13;
- threonine at position 15;
- leucine at position 24;
- valine at position 25;
- leucine at position 27;
- isoleucine or leucine at position 35;
- serine at position 49;
- isoleucine at position 52;
- isoleucine at position 82;
- leucine at position 83;
- alanine at position 87;
- leucine at position 90;
- valine at position 91;
- lysine or methionine at position 94;
- valine at position 111;
- methionine at position 123;
- alanine at position 126;
- N at position 129;
- threonine at position 131;
- alanine at position 134;
- threonine at position 135;
- alanine at position 136;
- valine at position 138;
- threonine at position 141;
- methionine at position, 152;
- serine at position 154;
- arginine at position 159;
- glycine at position 160;
- methionine at position 161;
- leucine or valine at position 162;
- serine at position 163;
- valine at position 179;
- leucine at position 187;
- threonine at position 190;
- valine at position 197;
- asparagine at position 198;
- valine at position 199;
- glutamine at position 205;
- threonine at position 210;
- arginine at position 216;
- arginine at position 217;
- serine at position 227;
- leucine at position 238;
- threonine at position 249;
- threonine or isoleucine at position 258;
- valine at position 262;
- leucine at position 266;
- leucine at position 269;
- leucine at position 285;
- alanine at position 290;
- threonine at position 293;
- arginine at position 295;
- arginine at position 300;
- arginine at position 301;
- arginine at position 304;
- threonine at position 305;
- glutamine at position 306;
- alanine at position 307;
- arginine at position 308;
- serine at position 310;
- glycine at position 319;
- serine at position 320;
- lysine at position 321;
- serine at position 322;
- threonine at position 324;
- aspartic acid at position 325;
- glycine at position 326;
- valine at position 327;
- arginine at position 329;
- serine at position 330;
- arginine at position 332;
- proline at position 334;
- glycine at position 339;
- leucine at position 340;
- glutamine at position 341;
- and valine at position 342;
- wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.