(12) United States Patent (10) Patent No.: US 7482,124 B2 Ranade Et Al
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USOO7482124B2 (12) United States Patent (10) Patent No.: US 7482,124 B2 Ranade et al. (45) Date of Patent: Jan. 27, 2009 (54) METHOD OF IDENTIFYINGA 5,349,053 A 9, 1994 Landolfi PPARGAMMA-AGONIST COMPOUND 5,359,046 A 10/1994 Capon et al. HAVING A DECREASED LIKELIHOOD OF 5,403.484 A 4/1995 Ladner et al. INDUCING DOSE-DEPENDENT 5,413,923 A 5/1995 Kucherlapati et al. PERPHERAL EDEMA 5,427,908 A 6/1995 Dower et al. 5,441,050 A 8, 1995 Thurston et al. 5.447,851 A 9, 1995 Beutler et al. (75) Inventors: Koustubh Ranade, Princeton, NJ (US); 5,474,981 A 12/1995 Leder et al. Terrye Aigeldinger Delmonte, Ewing, 5,478,925 A 12/1995 Wallach et al. NJ (US); William J. Geese, Doylestown, 5,516,637 A 5/1996 Huang et al. PA (US) 5,530,101 A 6/1996 Queen et al. 5,545,806 A 8/1996 Lonberg et al. (73) Assignee: Bristol-Myers Squibb Company, 5,545,807 A 8, 1996 Surani et al. Princeton, NJ (US) 5,565,332 A 10/1996 Hoogenboom et al. 5,569,825 A 10/1996 Lonberg et al. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (Continued) U.S.C. 154(b) by 0 days. FOREIGN PATENT DOCUMENTS (21) Appl. No.: 11/483,290 EP 232262 2, 1987 EP O 367 166 5, 1990 (22) Filed: Jul. 7, 2006 EP O 394 827 10, 1990 EP O 307434 9, 1993 (65) Prior Publication Data EP O 396387 12/1993 EP O 239 400 8, 1994 US 2007/OOO9945A1 Jan. 11, 2007 EP O 401 384 3, 1996 EP O 439 095 5, 1998 Related U.S. Application Data EP 1 OO7712 2, 1999 EP O 592 106 11, 2004 (60) Provisional application No. 60/697.727, filed on Jul. 8, 2005, provisional application No. 60/706,171, filed on Aug. 5, 2005, provisional application No. 60/705,995, (Continued) filed on Aug. 5, 2005. OTHER PUBLICATIONS (51) Int. Cl. Abali, H. et al., “Circulating and Local Bone Marrow Renin CI2O I/68 (2006.01) angiotensin System in Leukemic Hematopoiesis: Preliminary Evi GOIN 33/53 (2006.01) dences”, Hematology, vol. 7, No. 2, pp. 75-82 (2002). (52) U.S. Cl. .......................................... 435/6: 435/7.21 (Continued) (58) Field of Classification Search ....................... None See application file for complete search history. Primary Examiner Robert Landsman (74) Attorney, Agent, or Firm—Stephen C. D'Amico (56) References Cited (57) ABSTRACT U.S. PATENT DOCUMENTS 4,179,337 A 12/1979 Davis et al. The invention provides novel polynucleotides and polypep 4,376, 110 A 3, 1983 David et al. tides associated with the incidence of PPAR-agonist induced 4,444,887 A 4, 1984 Hoffmann edema. The invention also provides polynucleotide fragments 4.474,893 A 10/1984 Reading corresponding to the genomic and/or coding regions of these 4,631,211 A 12/1986 Houghten 4,676.980 A 6/1987 Segal et al. polynucleotides which comprise at least one polymorphic 4,683, 195 A 7, 1987 Mullis et al. locus per fragment. Allele-specific primers and probes which 4,714,681 A 12/1987 Reading hybridize to these regions, and/or which comprise at least one 4,716,111 A 12/1987 Osband et al. polymorphic locus are also provided. The polynucleotides, 4,741,900 A 5, 1988 Alvarez et al. primers, and probes of the present invention are useful in 4,816,397 A 3, 1989 BOSS et al. phenotype correlations, medicine, and genetic analysis. Also 4,816,567 A 3/1989 Cabilly et al. provided are vectors, host cells, antibodies, and recombinant 4,925,648 A 5, 1990 Hansen et al. and synthetic methods for producing said polynucleotides 4.946,778 A 8, 1990 Ladner et al. and/or polypeptides. 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