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US20090297475: CYSTEINE DIOXYGENASE POLYMORPHISMS

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Filing Information

Inventor(s) Rosemary Hope Waring · David Boyer Ramsden · Lucy Jane Wilkinson · Hugh Kikuchi ·
Assignee(s) THE UNIVERSITY OF BIRMINGHAM ·
Correspondent RATNERPRESTIA ·
Application Number US11996281
Filing date 07/20/2006
PCT 371 date 09/29/2008
Publication date 12/03/2009
Predicted expiration date 07/20/2026
U.S. Classifications 424/855  · 536/235  · 536/243.1  · 530/389.1  · 435/6  ·
International Classifications A61K3821  · A61P1902  · C07H2104  · C07K1600  · C12Q168  ·
Kind CodeA1
PCT Application Number WO20PCTGB2006002698 - 07/20/2006
Foreign Priority GB0514913.3 - 07/20/2005 ·
29 Claims, 11 Drawings


Abstract

The invention relates to the detection and identification of polymorphisms in cysteine dioxygenase (CDO) for the use of that diagnosis to identify a propensity in a patient towards rheumatoid arthritis and/or to have side effects with a number of drugs, to nucleic acid and isolated proteins encoding the polymorphisms, to assays for CDO activity and for the identification of compounds affecting CDO activity, and additionally to use of interferon-γ optionally in combination with different compounds, to treat rheumatoid arthritis.

Independent Claims | See all claims (29)

  1. 1. A method for diagnosing a cysteine dioxygenase (CDO)-mediated condition, which method comprises: (i) obtaining a sample from an individual; (ii) detecting the presence or absence of a variant CDO, or a nucleic acid encoding a CDO variant and/or a variant of a CDO regulatory region; a (iii) determining the status of the individual by reference to polymorphism in the CDO gene and/or its regulatory region.
  2. 2. A method for diagnosing one or more polymorphisms in the CDO gene, or its regulatory sequence in a human comprising determining the sequence of a nucleic acid molecule encoding at least a portion of the CDO gene and/or a CDO regulatory region and determining the status of the human by reference to polymorphism in the CDO gene and/or its regulatory region.
  3. 9. An allele specific probe or primer capable of detecting a CDO gene or CDO regulatory sequence polymorphism.
  4. 12. An isolated nucleic acid of at least 5 bases long encoding a CDO or CDO-regulatory polymorphism selected from: (i) Exon Position SNP Type Exon 1: +673 A insertion Exon 1: +697 G insertion Exon 1: +1103 C-A substitution Exon 3: +15 A-T substitution Exon 3: +16 T-C substitution Exon 3: +17 A-C substitution Exon 3: +29 T-A substitution Exon 3: +30 G addition Exon 4: +33 A-T substitution Exon 4: +34 G-C substitution Exon 4: +43 A addition Exon 4: +46 C-A substitution and (ii) sequences complementary to such sequences.
  5. 17. A method of determining the effect of a compound on CDO activity comprising: (i) Providing a sample of white blood cells; (ii) Contacting the white blood cells with a CDO substrate and the compound; and (iii) Determining the effect of the compound on the conversion of the substrate to a detectable product by CDO in the white blood cells.
  6. 19. A method of treating rheumatoid arthritis comprising administering a pharmaceutically effective amount of interferon-γ (IFN-γ).
  7. 22-23. (canceled)
  8. 24. A pharmaceutically acceptable composition comprising IFN-γ and at least one of cysteine, methionine, D-penicillamine, N-acetyl cysteine, γ-glutamylcysteine, S-carboxy methyl cysteine, S-methyl cysteine, interleukin-4 or interleukin-10.

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