Compositions, organisms and methodologies employing a novel human kinase

• US 20040096890A1
• Filed: 10/10/2003
• Published: 05/20/2004
• Est. Priority Date: 10/10/2002
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Liu, Wei, Wu, Leeying
• Application Number:
  US10/684,248
• Publication Number:
  US 20040096890A1
• Time in Patent Office: Days
• US Class Current: 435/6.16
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• CPC Class Codes: C12Q 1/485 involving kinase
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Abstract

This invention provides compositions, organisms and methodologies employing a novel human protein kinase, NRHK1. The novel protein kinase is encoded by a human gene comprising 21 exons. The human gene is localized in or near the 9q34 locus of human chromosome 9. The sequence similarity between the novel human protein and the consensus sequence of NIMA-related kinase indicates that the novel human protein may function as an NIMA-related kinase.

Claims

1. An isolated polynucleotide comprising a nucleic acid sequence which encodes the amino acid sequence depicted in SEQ ID NO:

2.

2. The polynucleotide according to claim 1, wherein the nucleic acid sequence is selected from the group consisting of:

(a) the nucleic acid sequence as shown in SEQ ID NO;

1;

(b) the complement of (a); and

(c) a nucleic acid sequence that differs from (a) or (b) due to the degeneracy of the genetic code.

3. The polynucleotide according to claim 1, wherein the nucleic acid sequence is selected from the group consisting of:

(a) the nucleic acid sequence as shown in SEQ ID NO;

3;

(b) the complement of (a); and

(c) a nucleic acid sequence that differs from (a) or (b) due to the degeneracy of the genetic code.

14. A host cell containing the polynucleotide of claim 1 or a variant thereof.

15. A transgenic non-human animal comprising the polynucleotide of claim 1 or a variant thereof.

4. An isolated polynucleotide comprising a variant of a nucleic acid sequence, wherein said nucleic acid sequence encodes the amino acid sequence depicted in SEQ ID NO:

2, and wherein the variant and said nucleic acid sequence have at least 91% sequence identity.

5. The polynucleotide according to claim 4, wherein the variant and said nucleic acid sequence have at least 95% sequence identity.

6. An isolated polynucleotide that hybridizes under stringent conditions to a polynucleotide consisting of the nucleotide sequence of SEQ ID NO:

1 or the complement thereof, wherein said polynucleotide consists of at least 1000 nuclei acids and does not include the nucleotide sequences of SEQ ID NOS;

4-5 or the complement thereof.

7. An isolated polynucleotide that hybridizes under highly stringent conditions to a polynucleotide consisting of the nucleotide sequence of SEQ ID NO:

1 or the complement thereof, said polynucleotide consists of at least 2000 nuclei acids and encodes a protein kinase.

8. An isolated polypeptide comprising a fragment of SEQ ID NO:

2, wherein said fragment comprising at least 500 consecutive amino acid residues of SEQ ID NO;

2.

9. The polypeptide according to claim 8, wherein the fragment consists of SEQ ID NO:

2.

10. An isolated polypeptide comprising a variant of a fragment of SEQ ID NO:

2, wherein said fragment includes at least 500 consecutive amino acid residues of SEQ ID NO;

2.

11. The polypeptide according to claim 10, wherein the variant and said fragment have at least 95% sequence identity.

12. An antibody capable of binding to the amino acid sequence depicted in SEQ ID NO:

2 with a binding affinity of no less than 10⁵ M<sup>−

1</sup>.

13. An NRHK1 detection kit comprising:

(a) the antibody of claim 12, or

(b) a probe that hybridizes to the nucleotide sequence of SEQ ID NO;

1 or the complement thereof.

16. A non-human animal, wherein at least one allele of a gene in the genome of said animal is functionally disrupted, and wherein said gene encodes a polypeptide that has at least 70% sequence identity to SEQ ID NO:

2.

17. A method for identifying an agent capable of binding to NRHK1 kinase, comprising

contacting a candidate agent with a polypeptide comprising:

(a) an amino acid sequence recited in SEQ ID NO;

2,

(b) a fragment of SEQ ID NO;

2, or

(c) a variant of (a) or (b); and

detecting the binding between said candidate agent and said polypeptide.

18. A method for identifying an agent capable of modulating the level of activity of NRHK1 kinase, comprising:

contacting a candidate agent with an polypeptide comprising;

(a) an amino acid sequence recited in SEQ ID NO;

2, or

(b) a biologically active portion of SEQ ID NO;

2; and

detecting a change in the level of an activity of said polypeptide.

19. A pharmaceutical composition for preventing or treating NRHK1-related diseases, comprising a pharmaceutically acceptable carrier and an agent that modulates an NRHK1 activity or the NRHK1 gene expression.

20. A method for preventing or treating an NRHK1-related disease in a subject, comprising the step of:

introducing into the subject an effective amount of the pharmaceutical composition of claim 19.

21. A polynucleotide capable of inhibiting human NRHK1 gene expression by RNA interference.

22. The polynucleotide according to claim 21, comprising a siRNA sense strand or a siRNA antisense strand selected from Table 4.

23. A method, comprising introducing a polynucleotide of claim 21 into a cell which expresses human NRHK1 gene, thereby inhibiting the expression of said gene in said cell by RNA interference.