Human myosin-like polypeptide expressed predominantly in heart and muscle

• US 20040137589A1
• Filed: 11/26/2003
• Published: 07/15/2004
• Est. Priority Date: 05/26/2000
• Status: Abandoned Application

• Current Assignee: GE Healthcare Limited (General Electric Company)
• Original Assignee: GE Healthcare Limited (General Electric Company)
• Inventors: Ji, Yonggang, Penn, Sharron Gaynor, Rank, David-Russell, Shannon, Mark E., Chen, Wensheng, Hanzel, David Kagen, Gu, Yizhong
• Application Number:
  US10/723,361
• Publication Number:
  US 20040137589A1
• Time in Patent Office: Days
• US Class Current: 435/183
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• 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: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4716 Muscle proteins, e.g. myosin, actin
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/40 containing a tag for immunodetection, or an epitope for immunisation
• CPC Class Codes: C07K 2319/60 containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
• CPC Class Codes: C12N 15/1034 Isolating an individual clone by screening libraries
• CPC Class Codes: C12N 15/66 General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 : Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 25/20 : Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
• CPC Class Codes: G16B 30/00 : ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 : Sequence alignment; Homology search
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Presented are a novel myosin-like protein particularly expressed in human heart and muscle, isolated nucleic acids encoding the myosin-like protein, compounds and compositions derivable directly or indirectly therefrom, and diagnostic and therapeutic methods for using the same.

Claims

1. An isolated nucleic acid comprising:

(i) the nucleotide sequence of SEQ ID NO;

1, (ii) the nucleotide sequence of SEQ ID NO;

2, (iii) a nucleotide sequence that is a degenerate variant of the nucleotide sequence of SEQ ID NO;

2, (iv) a nucleotide sequence that encodes a polypeptide with the amino acid sequence of SEQ ID NO;

3, (v) a nucleotide sequence that encodes a polypeptide with the amino acid sequence of SEQ ID NO;

3 with conservative amino acid substitutions;

(vi) a nucleotide sequence that encodes a polypeptide with the amino acid sequence of SEQ ID NO;

3 with moderately conservative amino acid substitutions, or (vii) a nucleotide sequence that is the complement of the nucleotide sequence of any one of (i)-(vi).

5. An isolated polynucleotide comprising a fragment of at least 17 nucleotides of the isolated nucleic acid of any one of claims 1-4, wherein said isolated nucleic acid is nonidentical in sequence to GenBank accession no. AA993492 and is less than 50 kb in length.

6. The isolated nucleic acid of any one of claims 1-4, wherein said nucleic acid, or the complement of said nucleic acid, encodes a polypeptide having ATPase activity.

7. The isolated nucleic acid of claim 5, wherein said nucleic acid, or the complement of said nucleic acid, encodes a polypeptide having ATPase activity.

8. The isolated nucleic acid of any one of claims 1-4, wherein said nucleic acid, or the complement of said nucleic acid, encodes a polypeptide capable of binding calmodulin.

9. The isolated nucleic acid of claim 5, wherein said nucleic acid, or the complement of said nucleic acid, encodes a polypeptide capable of binding calmodulin.

10. The isolated nucleic acid of any one of claims 1-4, wherein said nucleic acid, or the complement of said nucleic acid, is expressed in skeletal muscle and heart muscle.

11. The isolated nucleic acid of claim 5, wherein said nucleic acid, or the complement of said nucleic acid, is expressed in skeletal muscle and heart muscle.

12. The isolated nucleic acid molecule of any one of claims 1-4, wherein said nucleic acid molecule is operably linked to one or more expression control elements.

13. The isolated nucleic acid molecule of claim 5, wherein said nucleic acid molecule is operably linked to one or more expression control elements.

14. A replicable vector comprising an isolated nucleic acid molecule of any one of claims 1-4.

15. A replicable vector comprising an isolated nucleic acid molecule of claim 5.

16. The isolated nucleic acid molecule of any one of claims 1-4, attached to a substrate.

17. The isolated nucleic acid molecule of claim 5, attached to a substrate.

18. A host cell transformed to contain the nucleic acid molecule of any one of claims 1-4, or the progeny thereof.

19. A host cell transformed to contain the nucleic acid molecule of claim 5, or the progeny thereof.

20. A method for producing a polypeptide, the method comprising:

culturing the host cell of claim 18 under conditions in which the protein encoded by said nucleic acid molecule is expressed.

21. An isolated polypeptide produced by the method of claim 20.

26. A method of modulating the expression of a nucleic acid according to claim 1, the method comprising:

administering an effective amount of an agent which changes the expression of a nucleic acid according to claim 1.

27. A method of modulating at least one activity of a polypeptide according to claim 22, the method comprising:

administering an effective amount of an agent which modulates at least one activity of a polypeptide according to claim 21 or 22.

28. A transgenic non-human animal or transgenic plant modified to contain a nucleic acid molecule of any one of claims 1-4.

29. A transgenic non-human animal or transgenic plant modified to contain a nucleic acid molecule of claim 5.

33. A pharmaceutical composition comprising the nucleic acid of any one of claims 1-4 and a pharmaceutically acceptable excipient.

34. A pharmaceutical composition comprising the nucleic acid of claim 5.

41. A method for treating or preventing a disorder associated with decreased expression or activity of human hGDMLP-1, the method comprising administering to a subject in need of such treatment an effective amount of the pharmaceutical composition of any of claims 33-35 or 37.

43. A diagnostic composition comprising the nucleic acid of any one of claims 1-4, said nucleic acid being detectably labeled.

44. A diagnostic composition comprising the nucleic acid of claim 5, said nucleic acid being detectably labeled.

48. The diagnostic composition of claim 43, wherein said composition is further suitable for in vivo administration.

49. The diagnostic composition of claim 44, wherein said composition is further suitable for in vivo administration.

53. A microarray wherein at least one probe of said array is a nucleic acid according to any one of claims 1-4.

54. A microarray wherein at least one probe of said array is a nucleic acid according to claim 5.

55. A method for detecting a target nucleic acid in a sample, said target being a nucleic acid of any one of claims 1-4, the method comprising:

a) hybridizing the sample with a probe comprising at least 30 contiguous nucleotides of a sequence complementary to said target nucleic acid in said sample under hybridization conditions sufficient to permit detectable binding of said probe to said target, and

b) detecting the presence or absence, and optionally the amount, of said binding.

56. A method for detecting a target nucleic acid in a sample, said target being a nucleic acid of claim 5, the method comprising:

a) hybridizing the sample with a probe comprising at least 30 contiguous nucleotides of a sequence complementary to said target nucleic acid in said sample under hybridization conditions sufficient to permit detectable binding of said probe to said target, and

b) detecting the presence or absence, and optionally the amount, of said binding.

2. An isolated nucleic acid comprising a nucleotide sequence that hybridizes under high stringency conditions to a probe, the sequence of which probe (i) consists of SEQ ID NO:

2, (ii) encodes a polypeptide having the sequence of SEQ ID NO;

3, (iii) encodes a polypeptide having the sequence of SEQ ID NO;

3 with conservative amino acid substitutions, or (iv) is the complement of (i)-(iii), wherein said isolated nucleic acid is nonidentical in sequence to GenBank accession no. AA993492 and is less than 50 kb in length.

3. An isolated nucleic acid comprising a nucleotide sequence that hybridizes under moderate stringency conditions to a probe, the sequence of which probe (i) consists of SEQ ID NO:

2, (ii) encodes a polypeptide having the sequence of SEQ ID NO;

3, (iii) encodes a polypeptide having the sequence of SEQ ID NO;

3 with conservative amino acid substitutions;

or (iv) is the complement of (i)-(iii), wherein said isolated nucleic acid is nonidentical in sequence to GenBank accession no. AA993492 and is less than 50 kb in length.

4. An isolated nucleic acid comprising a nucleotide sequence that encodes at least 8 contiguous amino acids of SEQ ID NO:

3, wherein said isolated nucleic acid is nonidentical in sequence to GenBank accession no. AA993492 and is less than 50 kb in length.

22. An isolated polypeptide selected from the group consisting of:

(a) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO;

3;

(b) an isolated polypeptide comprising a fragment of at least 8 amino acids of SEQ ID NO;

3;

(c) an isolated polypeptide according to (a) or (b) in which at least 95% of deviations from the sequence of (a) or (b) are conservative substitutions; and

(d) an isolated polypeptide having at least 65% amino acid sequence identity to the isolated polypeptide of (a) or (b).

23. An isolated antibody or antigen-binding fragment or derivative thereof the binding of which can be competitively inhibited by a polypeptide of claims 22.

24. A method of identifying binding partners for a polypeptide according to claim 22, the method comprising:

contacting said polypeptide to a potential binding partner; and

determining if the potential binding partner binds to said polypeptide.

25. The method of claim 24, wherein said contacting is performed in vivo.

30. A transgenic non-human animal unable to express the endogenous orthologue of the polypeptide of claim 22.

35. A pharmaceutical composition comprising the polypeptide of claim 22 and a pharmaceutically acceptable excipient.

36. A pharmaceutical composition comprising the antibody or antigen-binding fragment or derivative thereof of claim 23 and a pharmaceutically acceptable excipient.

37. A purified agonist of the polypeptide of claim 22.

38. A purified antagonist of the polypeptide of claim 22.

39. A pharmaceutical composition comprising the agonist of claim 37.

40. A pharmaceutical composition comprising the antagonist of claim 38.

42. A method for treating or preventing a disorder associated with increased expression or activity of human hGDMLP-1, the method comprising administering to a subject in need of such treatment an effective amount of the pharmaceutical composition of claim 36 or claim 40.

45. A diagnostic composition comprising the polypeptide of claim 22, said polypeptide being detectably labeled.

46. A diagnostic composition comprising the antibody or antigen-binding fragment or derivative thereof of claim 23.

47. The diagnostic composition of claim 46, wherein said antibody or antigen-binding fragment or derivative thereof is detectably labeled.

50. The diagnostic composition of claim 45, wherein said composition is further suitable for in vivo administration.

51. The diagnostic composition of claim 46, wherein said composition is further suitable for in vivo administration.

52. The diagnostic composition of claim 47, wherein said composition is further suitable for in vivo administraiton.

57. A fusion protein, said fusion protein comprising a polypeptide of claim 22 fused to a heterologous amino acid sequence.

58. The fusion protein of claim 57, wherein said heterologous amino acid sequence is a detectable moiety.

59. The fusion protein of claim 58, wherein said detectable moiety is fluorescent.

60. The fusion protein of claim 57, wherein said heterologous amino acid sequence is an Ig Fc region.

31. A method of diagnosing a disease caused by mutation in human hGDMLP-1, comprising:

detecting said mutation in a sample of nucleic acids that derives from a subject suspected to have said disease.

32. A method of diagnosing or monitoring a disease caused by altered expression of human hGDMLP-1, comprising:

determining the level of expression of human hGDMLP-1 in a sample of nucleic acids or proteins that derives from a subject suspected to have said disease, alterations from a normal level of expression providing diagnostic and/or monitoring information.

61. A method of screening for agents that modulate the expression of human hGDMLP-1, the method comprising:

contacting a cell or tissue sample believed to express human hGDMLP-1 with a chemical or biological agent, and then

comparing the amount of human hGDMLP-1 expression with that of a control.