Hematopoietin receptor

• US 20040152161A1
• Filed: 11/14/2003
• Published: 08/05/2004
• Est. Priority Date: 10/06/2000
• Status: Abandoned Application

• Current Assignee: Immunex Corporation (Amgen Inc.)
• Original Assignee: Immunex Corporation (Amgen Inc.)
• Inventors: Wiley, Steven R., Cosman, David J., DuBose, Robert F., Mosley, Bruce A.
• Application Number:
  US10/715,667
• Publication Number:
  US 20040152161A1
• Time in Patent Office: Days
• US Class Current: 435/69.1
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

This invention relates to human and murine HPR1 and human and murine HPR2 polypeptides, new members of the hematopoietin receptor polypeptide family; to methods of making such HPR1 and HPR2 polypeptides; to non-human mammals in which the endogenous genomic sequences encoding HPR1 and/or HPR2 polypeptides have been partially or completely inactivated; to methods of using HPR1 or HPR2 polypeptides to identify compounds that alter HPR1 or HPR2 polypeptide activities; and to methods of preparing medicaments for and/or treating conditions associated with hematopoietin receptor function.

Claims

1. An isolated polypeptide having HPR1 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO;

4;

(b) an amino acid sequence selected from the group consisting of;

amino acids 652 though 745 of SEQ ID NO;

4, a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least 20 contiguous amino acids;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least 30 contiguous amino acids;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 that is at least 25% of the length of the sequence of amino acids 652 though 745 of SEQ ID NO;

4;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 that is at least 50% of the length of the sequence of amino acids 652 though 745 of SEQ ID NO;

4; and

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least eight contiguous amino acids and comprising at least one tyrosine residue;

(c) an amino acid sequence comprising at least 8 amino acids and sharing amino acid identity with the amino acid sequences of (b), wherein the percent amino acid identity is selected from the group consisting of;

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%;

(d) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 55 of SEQ ID NO;

1;

amino acids 56 through 77 of SEQ ID NO;

1;

amino acids 5 through 40 of SEQ ID NO;

2;

amino acids 1 through 32 of SEQ ID NO;

4;

amino acids 1 through 241 of SEQ ID NO;

4;

amino acids 1 through 525 of SEQ ID NO;

4;

amino acids 20 through 32 of SEQ ID NO;

4;

amino acids 33 through 134 of SEQ ID NO;

4;

amino acids Xaa1 through Xaa2 of SEQ ID NO;

4, wherein Xaa1 is selected from the group consisting of amino acids 33 through 43 of SEQ ID NO;

4 and Xaa2 is selected from the group consisting of amino acids 228 through 241 of SEQ ID NO;

4;

amino acids 33 through 238 of SEQ ID NO;

4;

amino acids 33 through 241 of SEQ ID NO;

4;

amino acids 33 through 525 of SEQ ID NO;

4;

amino acids 33 through 745 of SEQ ID NO;

4;

amino acids 44 through 94 of SEQ ID NO;

4;

amino acids 139 through 241 of SEQ ID NO;

4;

amino acids 242 through 326 of SEQ ID NO;

4;

amino acids 242 through 514 of SEQ ID NO;

4;

amino acids 337 through 419 of SEQ ID NO;

4;

amino acids 433 through 514 of SEQ ID NO;

4;

amino acids 526 through 556 of SEQ ID NO;

4;

amino acids 533 through 552 of SEQ ID NO;

4;

amino acids 553 through 745 of SEQ ID NO;

4;

amino acids 557 through 745 of SEQ ID NO;

4;

amino acids 563 through 573 of SEQ ID NO;

4;

amino acids 563 through 641 of SEQ ID NO;

4;

amino acids 567 through 581 of SEQ ID NO;

4;

amino acids 588 through 639 of SEQ ID NO;

4;

amino acids 631 through 641 of SEQ ID NO;

4;

SEQ ID NO;

10; and

SEQ ID NO;

11;

(e) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and a fragment of SEQ ID NO;

4 comprising cytokine receptor domain amino acid sequences;

(f) an allelic variant of any of (a)-(e); and

(g) an amino acid sequence of (a)-(f), wherein a polypeptide comprising said amino acid sequence of (a)-(f) binds to an antibody that also binds to a polypeptide comprising an amino acid sequence of any of (b)-(c).

9. A method for identifying compounds that alter HPR1 polypeptide activity comprising

(a) contacting the polypeptide of claim 1 with a test compound;

and

(b) determining whether the test compound alters the effect on intracellular signaling of said polypeptide.

2. An isolated polypeptide having HPR1 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO;

12;

(b) an amino acid sequence selected from the group consisting of;

amino acids 633 though 726 of SEQ ID NO;

12, a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least 20 contiguous amino acids;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least 30 contiguous amino acids;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 that is at least 25% of the length of the sequence of amino acids 633 though 726 of SEQ ID NO;

12;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 that is at least 50% of the length of the sequence of amino acids 633 though 726 of SEQ ID NO;

12; and

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least eight contiguous amino acids and comprising at least one tyrosine residue;

(c) an amino acid sequence comprising at least 8 amino acids and sharing amino acid identity with the amino acid sequences of (b), wherein the percent amino acid identity is selected from the group consisting of;

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%;

(d) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 28 of SEQ ID NO;

12;

amino acids 1 through 224 of SEQ ID NO;

12;

amino acids 1 through 509 of SEQ ID NO;

12;

amino acids 13 through 28 of SEQ ID NO;

12;

amino acids 29 through 124 of SEQ ID NO;

12;

amino acids Xaa1 through Xaa2 of SEQ ID NO;

12, wherein Xaa1 is selected from the group consisting of amino acids 29 through 39 of SEQ ID NO;

12 and Xaa2 is selected from the group consisting of amino acids 211 through 224 of SEQ ID NO;

12;

amino acids 29 through 128 of SEQ ID NO;

12;

amino acids 29 through 224 of SEQ ID NO;

12;

amino acids 29 through 509 of SEQ ID NO;

12;

amino acids 29 through 726 of SEQ ID NO;

12;

amino acids 129 through 224 of SEQ ID NO;

12;

amino acids 225 through 309 of SEQ ID NO;

12;

amino acids 225 through 499 of SEQ ID NO;

12;

(e) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and a fragment of SEQ ID NO;

12 comprising cytokine receptor domain amino acid sequences;

(f) an allelic variant of any of (a)-(e); and

(g) an amino acid sequence of (a)-(f), wherein a polypeptide comprising said amino acid sequence of (a)-(f) binds to an antibody that also binds to a polypeptide comprising an amino acid sequence of any of (b)-(c).

10. A method for identifying compounds that alter HPR1 polypeptide activity comprising

(a) contacting the polypeptide of claim 2 with a test compound;

and

(b) determining whether the test compound alters the effect on intracellular signaling of said polypeptide.

3. An isolated polypeptide having HPR2 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) SEQ ID NO;

23;

(b) SEQ ID NO;

25;

(c) an amino acid sequence selected from the group consisting of;

an amino acid sequence comprising at least 20 contiguous amino acids of SEQ ID NO;

23 and comprising the contiguous amino acids 318 and 319 of SEQ ID NO;

23; and

amino acids 349 through 356 of SEQ ID NO;

25;

(d) an amino acid sequence comprising at least 8 amino -acids and sharing amino acid identity with the amino acid sequences of (c), wherein the percent amino acid identity is selected from the group consisting of;

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%;

(e) an amino acid sequence comprising both an amino acid sequence of (c) or (d), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 177 of SEQ ID NO;

16;

amino acids 216 through 245 of SEQ ID NO;

16;

SEQ ID NO;

17; and

SEQ ID NO;

18;

(f) an amino acid sequence comprising both an amino acid sequence of (c) or (d), and an amino acid sequences of any of (a)-(b) comprising cytokine receptor domain amino acid sequences;

(g) an allelic variant of any of (a)-(f); and

(h) an amino acid sequence of (a)-(g), wherein a polypeptide comprising said amino acid sequence of (a)-(g) binds to an antibody that also binds to a polypeptide comprising an amino acid sequence of any of (c)-(d).

11. A method for identifying compounds that alter HPR2 polypeptide activity comprising

(a) contacting the polypeptide of claim 3 with a test compound;

and

(b) determining whether the test compound alters the effect on intracellular signaling of said polypeptide.

4. An isolated polypeptide having HPR2 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) SEQ ID NO;

27;

(b) SEQ ID NO;

27 from which amino acids 297 through 316 or amino acids 317 through 336 have been deleted;

(c) an amino acid sequence comprising 20 or more contiguous amino acids of (a) or (b); and

(d) an amino acid sequence comprising 30 or more contiguous amino and sharing at least 90% amino acid identity with the amino acid sequences of (a)-(b).

12. A method for identifying compounds that alter HPR2 polypeptide activity comprising

(a) contacting the polypeptide of claim 4 with a test compound;

and

(b) determining whether the test compound alters the effect on intracellular signaling of said polypeptide.

5. An isolated polypeptide having HPR1 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO;

4;

(b) an amino acid sequence selected from the group consisting of;

amino acids 652 though 745 of SEQ ID NO;

4, a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least 20 contiguous amino acids;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least 30 contiguous amino acids;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 that is at least 25% of the length of the sequence of amino acids 652 though 745 of SEQ ID NO;

4;

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 that is at least 50% of the length of the sequence of amino acids 652 though 745 of SEQ ID NO;

4; and

a fragment of the sequence of amino acids 652 though 745 of SEQ ID NO;

4 comprising at least eight contiguous amino acids and comprising at least one tyrosine residue;

(c) an amino acid sequence comprising at least 8 amino acids and sharing amino acid identity with the amino acid sequences of (b), wherein the percent amino acid identity is selected from the group consisting of;

at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%; and

(d) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 55 of SEQ ID NO;

1;

amino acids 56 through 77 of SEQ ID NO;

1;

amino acids 5 through 40 of SEQ ID NO;

2;

amino acids 1 through 32 of SEQ ID NO;

4;

amino acids 1 through 241 of SEQ ID NO;

4;

amino acids 1 through 525 of SEQ ID NO;

4;

amino acids 20 through 32 of SEQ ID NO;

4;

amino acids 33 through 134 of SEQ ID NO;

4;

amino acids Xaa1 through Xaa2 of SEQ ID NO;

4, wherein Xaa1 is selected from the group consisting of amino acids 33 through 43 of SEQ ID NO;

4 and Xaa2 is selected from the group consisting of amino acids 228 through 241 of SEQ ID NO;

4;

amino acids 33 through 238 of SEQ ID NO;

4;

amino acids 33 through 241 of SEQ ID NO;

4;

amino acids 33 through 525 of SEQ ID NO;

4;

amino acids 33 through 745 of SEQ ID NO;

4;

amino acids 44 through 94 of SEQ ID NO;

4;

amino acids 139 through 241 of SEQ ID NO;

4;

amino acids 242 through 326 of SEQ ID NO;

4;

amino acids 242 through 514 of SEQ ID NO;

4;

amino acids 337 through 419 of SEQ ID NO;

4;

amino acids 433 through 514 of SEQ ID NO;

4;

amino acids 526 through 556 of SEQ ID NO;

4;

amino acids 533 through 552 of SEQ ID NO;

4;

amino acids 553 through 745 of SEQ ID NO;

4;

amino acids 557 through 745 of SEQ ID NO;

4;

amino acids 563 through 573 of SEQ ID NO;

4;

amino acids 563 through 641 of SEQ ID NO;

4;

amino acids 567 through 581 of SEQ ID NO;

4;

amino acids 588 through 639 of SEQ ID NO;

4;

amino acids 631 through 641 of SEQ ID NO;

4;

SEQ ID NO;

10; and

SEQ ID NO;

11.

6. An isolated polypeptide having HPR1 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO;

12;

(b) an amino acid sequence selected from the group consisting of;

amino acids 633 though 726 of SEQ ID NO;

12, a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least 20 contiguous amino acids;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least 30 contiguous amino acids;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 that is at least 25% of the length of the sequence of amino acids 633 though 726 of SEQ ID NO;

12;

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 that is at least 50% of the length of the sequence of amino acids 633 though 726 of SEQ ID NO;

12; and

a fragment of the sequence of amino acids 633 though 726 of SEQ ID NO;

12 comprising at least eight contiguous amino acids and comprising at least one tyrosine residue;

(c) an amino acid sequence comprising at least 8 amino acids and sharing amino acid identity with the amino acid sequences of (b), wherein the percent amino acid identity is selected from the group consisting of;

at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%; and

(d) an amino acid sequence comprising both an amino acid sequence of (b) or (c), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 28 of SEQ ID NO;

12;

amino acids 1 through 224 of SEQ ID NO;

12;

amino acids 1 through 509 of SEQ ID NO;

12;

amino acids 13 through 28 of SEQ ID NO;

12;

amino acids 29 through 124 of SEQ ID NO;

12;

amino acids Xaa1 through Xaa2 of SEQ ID NO;

12, wherein Xaa1 is selected from the group consisting of amino acids 29 through 39 of SEQ ID NO;

12 and Xaa2 is selected from the group consisting of amino acids 211 through 224 of SEQ ID NO;

12;

amino acids 29 through 128 of SEQ ID NO;

12;

amino acids 29 through 224 of SEQ ID NO;

12;

amino acids 29 through 509 of SEQ ID NO;

12;

amino acids 29 through 726 of SEQ ID NO;

12;

amino acids 129 through 224 of SEQ ID NO;

12;

amino acids 225 through 309 of SEQ ID NO;

12;

amino acids 225 through 499 of SEQ ID NO;

12.

7. An isolated polypeptide having HPR2 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) SEQ ID NO;

23;

(b) SEQ ID NO;

25;

(c) an amino acid sequence selected from the group consisting of;

an amino acid sequence comprising at least 20 contiguous amino acids of SEQ ID NO;

23 and comprising the contiguous amino acids 318 and 319 of SEQ ID NO;

23; and

amino acids 349 through 356 of SEQ ID NO;

25;

(d) an amino acid sequence comprising at least 8 amino acids and sharing amino acid identity with the amino acid sequences of (c), wherein the percent amino acid identity is selected from the group consisting of;

at least 80%, at least 85%, at least 90%, at least 95%, at least 97.5%, at least 99%, and at least 99.5%; and

(e) an amino acid sequence comprising both an amino acid sequence of (c) or (d), and an amino acid sequence selected from the group consisting of;

amino acids 1 through 177 of SEQ ID NO;

16;

amino acids 216 through 245 of SEQ ID NO;

16;

SEQ ID NO;

17; and

SEQ ID NO;

18.

8. An isolated polypeptide having HPR2 polypeptide activity comprising an amino acid sequence selected from the group consisting of:

(a) SEQ ID NO;

27;

(b) SEQ ID NO;

27 from which amino acids 297 through 316 or amino acids 317 through 336 have been deleted; and

(c) an amino acid sequence comprising 30 or more contiguous amino acids of (a) or (b).