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AssigneeBristol-Myers Squibb Company
InventorsKoustubh Ranade, Terrye Delmonte, William Geese
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The invention provides novel polynucleotides and polypeptides associated with the incidence of PPAR-agonist induced edema. The invention also provides polynucleotide fragments corresponding to the genomic and/or coding regions of these polynucleotides which comprise at least one polymorphic locus per fragment. Allele-specific primers and probes which hybridize to these regions, and/or which comprise at least one polymorphic locus are also provided. The polynucleotides, primers, and probes of the present invention are useful in phenotype correlations, medicine, and genetic analysis. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel polynucleotides and polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders, particularly PPAR-agonist induced edema or related indications. The invention further relates to screening methods for identifying agonists of PPAR proteins with decreased risk of inducing periphereal edema in patients.
An isolated nucleic acid molecule comprising a polynuclelotide sequence selected from the group consisting of the polynucleotide sequence provided as SEQ ID NO:1, 2, 3, 4, 5, and 6.
An isolated nucleic acid molecule comprising the polynucleotide sequence provided as SEQ ID NO:7.
A method of identifying a patient who may be at risk of developing dose-dependent peripheral edema upon administration of a PPAR-agonist comprising the step of determining whether said patient has a reference or variable allele at one or more polymorphic loci of the human renin gene.
An isolated nucleic acid molecule comprising a polynucleotide sequence selected from the group consisting of the polynucleotide sequence provided as SEQ ID NO:37, and SEQ ID NO:39, wherein said nucleic acid comprises at least one polymorphic locus, wherein said polymorphic locus is located at nucleotide position 797.
An isolated polypeptide comprising a sequence selected from the group consisting of the polynucleotide sequence provided as SEQ ID NO:38, and SEQ ID NO:40, wherein said polypeptide comprises at least one polymorphic locus, wherein said polymorphic locus is located at amino acid position 198.
A method of identifying a patient who may be at risk of developing dose-dependent peripheral edema upon administration of a PPAR-agonist comprising the step of determining whether said patient has a referenece or variable allele at one or more polymorphic loci of the human endotheline-1 gene or human endotheline-1 polypeptide.
An isolated nucleic acid molecule comprising a polynuclelotide sequence selected from the group consisting of the polynucleotide sequence provided as SEQ ID NO:50, and SEQ ID NO:52, wherein said nucleic acid comprises at least one polymorphic locus, wherein said polymorphic locus is located at nucleotide position 1251.
An isolated polypeptide comprising a sequence selected from the group consisting of the polynucleotide sequence provided as SEQ ID NO:51, and SEQ ID NO:53, wherein said polypeptide comprises at least one polymorphic locus, wherein said polymorphic locus is located at amino acid position 389.
A method of identifying a patient who may be at risk of developing dose-dependent peripheral edema upon administration of a PPAR-agonist comprising the step of determining whether said patient has a reference or variable allele at one or more polymorphic loci of the human β1-adrenergic receptor gene or human β1-adrenergic receptor polypeptide.
A method of identifying a PPAR-agonist compound having a decreased likelihood of inducing dose-dependent peripheral edema in a patient comprising the step of:
A method of identifying a PPAR-agonist compound having a decreased likelihood of inducing dose-dependent peripheral edema in a patient comprising the step of:
A method of identifying a pharmaceutically acceptable amount of a PPAR-agonist for a patient comprising the step of:
A method of identifying a pharmaceutically acceptable amount of a PPAR-agonist for a patient comprising the step of:
Dependencies are inferred from the claim text.