(12) Patent Application Publication (10) Pub. No.: US 2008/0280955A1 Mccamish (43) Pub
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US 20080280955A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0280955A1 McCamish (43) Pub. Date: Nov. 13, 2008 (54) METHODS AND COMPOSITIONS FOR Publication Classification SCREENING AND TREATMENT OF (51) Int. Cl. DSORDERS OF BLOOD GLUCOSE A6II 3/4436 (2006.01) REGULATION CI2O I/68 (2006.01) C7H 2L/04 (2006.01) (75) Inventor: Mark A. McCamish, Cupertino, C07K 2/00 (2006.01) CA (US) (52) U.S. Cl. ............. 514/342:435/6:536/24.5:530/300 (57) ABSTRACT Correspondence Address: In one aspect, the invention provides a method of Screening PERLEGEN SCIENCES, INC. and, optionally, treatment of an individual Suffering from an LEGAL DEPARTMENT insulin resistance disorder by Screening an individual in need 2021 STERLIN COURT of treatment for an insulin resistance disorder for one or more MOUNTAIN VIEW, CA 94043 (US) genetic variations indicating a predisposition to a response to an insulin sensitizer; and, optionally, administering or not administering an insulin sensitizer to the individual based on (73) Assignee: Perlegen Sciences, Inc., Mountain the results of the screening. The insulin sensitizer for which View, CA (US) the individual is screened and the insulin sensitizer that is administered or not administered may be the same or differ ent. In another aspect, the invention provides methods com (21) Appl. No.: 11/541,495 prising identifying one or more genetic variations, e.g., one or more single nucleotide polymorphisms, that at least partly (22) Filed: Sep. 29, 2006 differentiate between a subset of a plurality of individuals who experience a response when administered an insulin Related U.S. Application Data sensitizer, and a subset of said plurality of individuals who do not experience a response when administered the insulin sen (60) Provisional application No. 60/722,357, filed on Sep. sitizer. The invention also provides nucleic acids, polypep 30, 2005, provisional application No. 60/722,636, tides, antibodies, kits, and business methods associated with filed on Sep. 30, 2005. these screening and association methods. 120 SECONDARY INFORMATION PROCESSING to SYSTEM/DISPLAY 106 GRAPHCS NETWORK PROCESSOR MEMORY ADAPTER ADAPTER 122 INPUT DEVICE HARD DRIVE DATA - GeneticWariation -Phenotype Data (Optional) 1 02 -Response to insulin Sensitizer -/ NDIVIDUAL SUBJECT Patent Application Publication Nov. 13, 2008 Sheet 1 of 2 US 2008/028.0955 A1 ZZ1 }}}\ONOOBS ©NISSADOHdNOLIWWBOHNI Avi?SIC/WHISAS XIHOMLHN HaldwQw" SOIHd\/\15) Haldvdv 3DIABCI1mdNI ^~~. 90|| AHOWAWHOSS-DOud Patent Application Publication Nov. 13, 2008 Sheet 2 of 2 US 2008/0280955A1 Genotype Responders and Non Responder to Drug A (member of Drug-Class X) Identify genetic variation that predicts predisposition to a response to Drug A Genotype Individuals in Clinical Trial for Drug B (member of Drug-Class X) Predict responders and non responders to Drug B based on genotypes of individuals Clinical Trial for Drug B using predictor to stratify or enroll Confirm Responders and Responders to Drug B based on results from Drug A, both members of the same Drug-Class X Modulate Include/Exclude File for labeled use Individuals in Administration of Fuller of Drug B Drug B Studies Fig. 2 US 2008/0280955 A1 Nov. 13, 2008 METHODS AND COMPOSITIONS FOR Genomic Polymorphisms’. U.S. Provisional Patent Applica SCREENING AND TREATMENT OF tion No. 60/648,957, filed Jan. 31, 2005, entitled “Composi DSORDERS OF BLOOD GLUCOSE tions and Methods For Treating, Preventing, and Diagnosing REGULATION Alzheimer's Disease.” U.S. application Ser. No. 10/956.224, filed Sep. 30, 2004, entitled “Methods for genetic analysis.” CROSS-REFERENCES TO RELATED U.S. Provisional Patent Application No. 60/653,672, filed APPLICATIONS Feb. 16, 2005, entitled “Parkinson's Disease-Related Disease Compositions and Methods.” U.S. application Ser. No. 0001. The present application is a nonprovisional of and 10/768,788, filed Jan. 30, 2004, entitled “Apparatus and claims the benefit of U.S. Provisional Application No. Methods for Analyzing and Characterizing Nucleic Acid 60/722.357 and U.S. Provisional Application No. 60/722, Sequences.” U.S. application Ser. No. 10/351,973, filed Jan. 636, both filed Sep. 30, 2005, and both of which are incorpo 27, 2003, entitled “Apparatus and Methods for Determining rated herein by reference in their entireties for all purposes. Individual Genotypes.” U.S. application Ser. No. 10/970,761, filed Nov. 20, 2004, entitled “Improved Analysis Methods BACKGROUND OF THE INVENTION and Apparatus for Individual Genotyping. U.S. application 0002 Recent advances in genetic analysis, e.g., genotyp Ser. No. 10/786,475, filed Feb. 24, 2004, entitled “Analysis ing, indicate that variations in both the natural history of Methods for Individual Genotyping,” and U.S. Provisional various diseases, as well as responses to treatments, including Patent Applications Nos. 60/643,006, 60/635,281 filed Jan. drug treatment, are linked to genetic variations among indi 11, 2005, and Dec. 9, 2004, respectively, both entitled “Mark viduals. As an example, disorders of blood glucose regula ers for Metabolic Syndrome Obesity and Insulin Resistance.” tion, including insulin resistance disorders, are a serious and the disclosures all of which are specifically incorporated growing health concern worldwide. These disorders, which herein by reference. The present invention builds upon this include Type I and Type II diabetes, Syndrome X, and obesity previous work. are treatable by a variety of lifestyle changes, as well as by drugs. Of the latter, one of the most effective categories is the SUMMARY OF THE INVENTION peroxisome proliferator-activated receptor (PPAR) modula 0004. The present application discloses methods for tors, especially PPAR-gamma agonists or partial agonists. screening an individual Suffering from a disorder of blood However, an obstacle to the optimal use of drugs to treat glucose regulation, e.g., an insulin resistance disorder, that disorders of blood glucose regulations is the incidence of include screening the individual for a genetic variation indi adverse effects, which are in Some cases serious enough to cating a predisposition to a response to an insulin sensitizer. cause use of the drug to be discontinued. For example, trogli In some embodiments, the individual is also screened for a taZone, which was marketed in the U.S. starting in April, 1997 phenotype indicating a predisposition to a response to an for the treatment of Type II diabetes, was voluntarily with insulin sensitizer. In some embodiments the invention further drawn in March 2000 due to incidents of idiosyncratic liver includes converting the results of said Screening into data that damage. Although these incidents occurred with a frequency is capable of transmission, and, in Some cases, transmitting of only about 1 in 100,000 patients, their severity was such said data to a location different from the location at which the that the drug was withdrawn. More common adverse effects data was created. The methods can also further include Such as edema, weight gain, and adverse effects on lipid administering or not administering an insulin sensitizer to the profiles, while not as severeas idiosyncratic liver damage, can individual based on the results of the screening of the indi nonetheless limit the therapeutic potential of insulin resis vidual; in some cases, administering or not administering the tance modulators. insulin sensitizer is done as part of a drug trial of the insulin 0003 Generally, distinct subgroups of patients respond to sensitizer. The insulin sensitizer for which the individual is a given drug with a given adverse effect. Experience with screened may be the same as or different from the insulin adverse effect profiles for other drugs indicates that the phe sensitizer that is administered or not administered to the indi notype of proclivity for a given adverse effect is a reflection of vidual. If the method includes administering an insulin sen genotype. Great progress has been made in relating genotype sitizer, they may also further include modulating the admin to phenotype in regards to disease etiology and response to istration of the insulin sensitizer based on the results of the treatment. See, e.g., U.S. patent application Ser. No. 11/043, screening of the individual. Modulation of administration can 689, filed Jan. 24, 2005, entitled “Associations Using Geno include, e.g., administering another therapeutic agent in addi types and Phenotypes: U.S. Provisional Application Ser. No. tion to the insulin sensitizer, or adjusting the dosage of the 60/280,530, filed Mar. 30, 2001, entitled “Identifying Human insulin sensitizer, route of administration of the insulin sen SNP Haplotypes, Informative SNPs and Uses Thereof: U.S. sitizer, frequency of administration of the insulin sensitizer, Provisional Application Ser. No. 60/313,264 filed Aug. 17. type of carrier of the insulin sensitizer, duration of treatment 2001, entitled “Identifying Human SNP Haplotypes, Infor with the insulin sensitizer, enantiomeric form of the insulin mative SNPs and Uses Thereof: U.S. Provisional Applica sensitizer, crystal form of the insulin sensitizer, or a combi tion Ser. No. 60/327,006, filed Oct. 5, 2001, entitled “Identi nation thereof, compared to if the screening had not been fying Human SNP Haplotypes, Informative SNPs and Uses performed. If the method includes not administering an insu Thereof: U.S. Provisional Application Ser. No. 60/332.550, lin sensitizer, it may further include administering treatment filed Nov. 26, 2002, entitled “Methods for Genomic Analy for the disorder of blood glucose regulation based on the sis”; U.S. application Ser. No. 10/106,097, filed Mar. 26, results of the screening of the individual. In certain embodi 2002, entitled “Methods for Genomic Analysis”; U.S. Pat. ments, the disorder of blood glucose regulation is diabetes No. 6,897,025, issued May 24, 2005, entitled “Genetic (e.g., Type II diabetes), obesity, or Syndrome X. The genetic Analysis Systems and Methods”; and U.S. application Ser.