Novel 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 and 49933 molecules and uses therefor

• US 20040009501A1
• Filed: 02/27/2003
• Published: 01/15/2004
• Est. Priority Date: 03/07/2000
• Status: Abandoned Application

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Curtis, Rory A. J., Meyers, Rachel E., Williamson, Mark J., Rudolph-Owen, Laura A., Logan, Thomas Joseph, Tsai, Fong-Ying, Chun, Miyoung, Glucksmann, Maria Alexandra
• Application Number:
  US10/377,072
• Publication Number:
  US 20040009501A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/395 from Saccharomyces
• CPC Class Codes: C07K 14/43545 from Caenorhabditis
• CPC Class Codes: C07K 14/43581 from Drosophila
• CPC Class Codes: C07K 14/43595 from coelenteratae, e.g. medusae
• CPC Class Codes: C07K 14/463 from amphibians
• CPC Class Codes: C07K 14/465 from birds
• CPC Class Codes: C07K 14/47 from mammals
• 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: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 9/00 Enzymes; Proenzymes; Compositions thereof preparations containing enzymes for cleaning teeth A61K8/66, A61Q11/00; medicinal preparations containing enzymes or proenzymes A61K38/43; enzyme containing detergent compositions C11D; enzymes with nucleic acid structure, e.g. ribozymes, C12N15/113; Processes for preparing, activating, inhibiting, separating or purifying enzymes preparation of malt C12C1/00
• CPC Class Codes: C12N 9/0071 acting on paired donors with incorporation of molecular oxygen (1.14)
• CPC Class Codes: C12N 9/0083 Miscellaneous (1.14.99)
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• CPC Class Codes: C12N 9/18 Carboxylic ester hydrolases (3.1.1)
• CPC Class Codes: C12N 9/20 Triglyceride splitting, e.g. by means of lipase
• CPC Class Codes: C12N 9/88 Lyases (4.)
• CPC Class Codes: C12Y 207/01001 : Hexokinase (2.7.1.1)
• CPC Class Codes: C12Y 301/04003 : Phospholipase C (3.1.4.3)

Abstract

The invention provides isolated nucleic acids molecules, designated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 and 49933 nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 gene has been introduced or disrupted. The invention still further provides isolated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 proteins, fusion proteins, antigenic peptides and anti-25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Claims

1. An isolated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 nucleic acid molecule selected from the group consisting of:

a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______;

b) a nucleic acid molecule comprising a fragment of at least 15 nucleotides of the nucleotide sequence of SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______;

c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______;

d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______;

e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or a complement thereof, under stringent conditions;

f) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______; and

g) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______.

2. The isolated nucleic acid molecule of claim 1, which is the nucleotide sequence SEQ ID NO:

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or 70.

3. A host cell which contains the nucleic acid molecule of claim 1.

7. A method for producing a polypeptide selected from the group consisting of:

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

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______;

b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______;

c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72; and

d) the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or71;

comprising culturing the host cell of claim 3 under conditions in which the nucleic acid molecule is expressed.

8. A method for detecting the presence of a nucleic acid molecule of claim 1 or a polypeptide encoded by the nucleic acid molecule in a sample, comprising:

a) contacting the sample with a compound which selectively hybridizes to the nucleic acid molecule of claim 1 or binds to the polypeptide encoded by the nucleic acid molecule; and

b) determining whether the compound hybridizes to the nucleic acid or binds to the polypeptide in the sample.

9. A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of claim 1 or binds to a polypeptide encoded by the nucleic acid molecule and instructions for use.

13. A method of identifying a nucleic acid molecule associated with a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising:

a) contacting a sample from a subject with a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO;

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or 70 defined in claim 2;

and

b) detecting the presence of a nucleic acid molecule in the sample that hybridizes to the probe, thereby identifying a nucleic acid molecule associated with a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity.

15. A method of identifying a subject having a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising:

a) contacting a sample obtained from the subject comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO;

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or70 defined in claim 2;

and

b) detecting the presence of a nucleic acid molecule in the sample that hybridizes to the probe, thereby identifying a subject having a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity.

16. A method for treating a subject having a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, or a subject at risk of developing a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising administering to the subject a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 modulator of the nucleic acid molecule defined in claim 1 or the polypeptide encoded by the nucleic acid molecule or contacting a cell with a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 modulator.

17. The method defined in claim 16 wherein said disorder is a cellular proliferative and/or differentiative disorder, an angiogenic disorder, a brain disorder, a neurological disorder, a blood vessel disorder, a breast disorder, a colon disorder, a kidney disorder, a lung disorder, an ovarian disorder, a prostate disorder, a hematopoeitic disorder, a pancreatic disorder, a skeletal muscle disorder, a skin disorder, a hormonal disorder, an immune e.g., inflammatory, disorder, a cardiovascular disorder, a lipid homeostasis disorder, an endothelial cell disorder, a liver disorder, a disorder of the small intestine, a pain disorder, a viral disease, a metabolic disorder, bone metabolism disorders or platelet disorders.

18. The method of claim 16, wherein the 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 modulator is

a) a small molecule;

b) peptide;

c) phosphopeptide;

d) anti-25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 antibody;

e) a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or a fragment thereof;

f) a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 polypeptide comprising an amino acid sequence which is at least 90 percent identical to the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, wherein the percent identity is calculated using the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4;

or

g) an isolated naturally occurring allelic variant of a polypeptide consisting of the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO;

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or 70 at 6×

SSC at 45°

C., followed by one or more washes in 0.2×

SSC, 0.1% SDS at 65°

C.

19. The method of claim 16, wherein the 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 modulator is

a) an antisense 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 nucleic acid molecule;

b) is a ribozyme;

c) the nucleotide sequence of SEQ ID NO;

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or 70 or a fragment thereof;

d) a nucleic acid molecule encoding a polypeptide comprising an amino acid sequence which is at least 90 percent identical to the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, wherein the percent identity is calculated using the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4;

e) a nucleic acid molecule encoding a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, wherein the nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO;

1, 7, 16, 20, 25, 28, 35, 39, 42, 63, 67 or 70 at 6×

SSC at 45°

C., followed by one or more washes in 0.2×

SSC, 0.1% SDS at 65°

C.;

or

f) a gene therapy vector.

4. An isolated 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 polypeptide selected from the group consisting of:

a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, or a complement thereof;

b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO;

1, 3, 7, 9, 16, 18, 20, 22, 25, 27, 28, 30, 35, 37, 39, 41, 42, 44, 63, 65, 67, 69, 70 or 72, or a complement thereof under stringent conditions;

c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71; and

d) the amino acid sequence of SEQ ID NO;

2, 8, 17, 21, 26, 29, 36, 40, 43, 64, 68 or 71.

5. An antibody which selectively binds to a polypeptide of claim 4.

6. The polypeptide of claim 4, further comprising heterologous amino acid sequences.

10. A method for identifying a compound which binds to a polypeptide or modulates the activity of the polypeptide of claim 4 comprising the steps of:

a) contacting a polypeptide, or a cell expressing a polypeptide of claim 4 with a test compound; and

b) determining whether the polypeptide binds to the test compound or determining the effect of the test compound on the activity of the polypeptide.

11. A method for modulating the activity of a polypeptide of claim 4 comprising contacting the polypeptide or a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.

14. A method of identifying a polypeptide associated with a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising:

a) contacting a sample comprising polypeptides with a 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 polypeptide defined in claim 4;

and

b) detecting the presence of a polypeptide in the sample that binds to the 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 binding partner, thereby identifying the polypeptide associated with a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity.

12. A method for identifying a compound capable of treating a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity, comprising assaying the ability of the compound to modulate 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 nucleic acid expression or 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 polypeptide activity, thereby identifying a compound capable of treating a disorder characterized by aberrant 25869, 25934, 26335, 50365, 21117, 38692, 46508, 16816, 16839, 49937, 49931 or 49933 activity.