METHODS AND COMPOSITIONS FOR CELL-PROLIFERATION-RELATED DISORDERS

• US 20150240286A1
• Filed: 10/02/2014
• Published: 08/27/2015
• Est. Priority Date: 10/21/2009
• Status: Abandoned Application

• Current Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Original Assignee: Agios Pharmaceuticals Inc.
• Inventors: Dang, Leonard Luan C, Gross, Stefan, Jang, Hyun Gyung, Jin, Shengfang, Thompson, Craig, Su, Shin-San Michael
• Application Number:
  US14/504,983
• Publication Number:
  US 20150240286A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/015 carbocyclic
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/063 Glutathione
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: C12Q 1/32 involving dehydrogenase
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

Methods of treating and evaluating subjects having neoactive mutants of IDH (e.g., IDH1 or IDH2).

Claims

1-6. -6. (canceled)

7. A method of diagnosing a subject having a cell proliferation-related disorder or suspected of having a cell proliferation-related disorder characterized by:

(a) the presence, distribution, or level of an isocitrate dehydrogenase 2 enzyme having a mutation at residue 140 wherein the arginine residue has been replaced with a glutamine residue (IDH2-R140Q), which has 2HG (2-hydroxyglutarate) neoactivity, wherein 2HG neoactivity is the ability to convert alpha ketoglutarate to 2-hydroxyglutarate;

or

(b) elevated levels of 2HG due to the presence of an IDH2-R140Q mutant enzyme having 2HG neoactivity,

wherein said method comprises analyzing the presence, distribution, or level of 2HG in a tissue, product, or bodily fluid of said subject by a chromatographic method, wherein an increased presence, distribution, or level of 2HG indicates the presence of the cell proliferation-related disorder, thereby diagnosing the subject for the cell proliferation-related disorder.

9. The method of claim 7 wherein said cell proliferation-related disorder is selected from the group consisting of acute lymphoblastic leukemia and acute myelogenous leukemia.

10. The method of claim 7, wherein said bodily fluid is blood, plasma, or urine.

11. The method of claim 7, wherein the chromatographic method is LC-MS.

12. The method of claim 7, wherein the chromatographic method is GC-MS.

8. (canceled)

13-18. -18. (canceled)