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US 12,758,571 B2Granted
Treatment of increased lipid levels with sterol regulatory element binding transcription factor 1 (SREBF1) inhibitors
AssigneesRegeneron Pharmaceuticals, Inc., University of Maryland, Baltimore
InventorsAlan Shuldiner, Nehal Gosalia, Cristopher Van Hout, Da-Wei Gong, James A. Perry
Life of this patent
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Abstract
The present disclosure provides methods of treating subjects having increased lipid levels, methods of identifying subjects having an increased risk of developing an increased lipid level, methods of detecting human Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) variant nucleic acid molecules and variant polypeptides, and SREBF1 variant nucleic acid molecules and variant polypeptides.
Claims6
A method of treating a subject having increased total cholesterol and/or increased low density lipoprotein (LDL), the method comprising administering a Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) inhibitor to the subject,
- wherein the SREBF1 inhibitor comprises a small interfering RNA (siRNA) that hybridizes to an SREBF1 mRNA, and
- wherein the subject is either SREBF1 reference or heterozygous for an SREBF1 variant nucleic acid molecule,
- wherein the SREBF1 variant nucleic acid molecule comprises:
- i) a genomic nucleic acid molecule having a nucleotide sequence comprising a thymine at a position corresponding to position 17,922 according to SEQ ID NO:2, or the complement thereof,
- ii) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,185 according to SEQ ID NO:6, or the complement thereof,
- iii) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,260 according to SEQ ID NO:7, or the complement thereof, and/or
- iv) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,056 according to SEQ ID NO:8, or the complement thereof, and
- when the subject is SREBF1 reference, the subject is also administered a therapeutic agent that treats or inhibits an increased lipid level in a standard dosage amount, and
- when the subject is heterozygous for the SREBF1 variant nucleic acid molecule, the subject is also administered a therapeutic agent that treats or inhibits an increased lipid level in a dosage amount that is the same as or lower than the standard dosage amount.
6 more elements
A method of treating a subject with a therapeutic agent that treats or inhibits an increased lipid level, wherein the subject is suffering from an increased lipid level, the method comprising the steps of:
- determining whether the subject has an SREBF1 variant nucleic acid molecule encoding a human SREBF1 polypeptide by:
- obtaining or having obtained a biological sample from the subject;
- and
- performing or having performed a genotyping assay on the biological sample to determine if the subject has a genotype comprising the SREBF1 variant nucleic acid molecule;
- and
- when the subject is SREBF1 reference, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits the increased lipid level in a standard dosage amount, and administering to the subject an SREBF1 inhibitor;
- and
- when the subject is heterozygous for the SREBF1 variant nucleic acid molecule, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits the increased lipid level in an amount that is the same as or lower than a standard dosage amount, and administering to the subject an SREBF1 inhibitor;
- wherein the presence of a genotype having the SREBF1 variant nucleic acid molecule encoding the human SREBF1 polypeptide indicates the subject has a reduced risk of developing the increased lipid level;
- wherein the increased lipid level is increased serum lipid level, increased total cholesterol, or increased LDL;
- and
- wherein the SREBF1 variant nucleic acid molecule is:
- i) a genomic nucleic acid molecule having a nucleotide sequence comprising a thymine at a position corresponding to position 17,922 according to SEQ ID NO:2, or the complement thereof, ii) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,185 according to SEQ ID NO:6, or the complement thereof, iii) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,260 according to SEQ ID NO:7, or the complement thereof, iv) an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 1,056 according to SEQ ID NO:
- 8, or the complement thereof, v) a cDNA molecule produced from an mRNA molecule in the sample, wherein the cDNA molecule has a nucleotide sequence comprising a thymine at a position corresponding to position 1,185 according to SEQ ID NO:12, or the complement thereof, vi) a cDNA molecule produced from an mRNA molecule in the sample, wherein the cDNA molecule has a nucleotide sequence comprising a thymine at a position corresponding to position 1,260 according to SEQ ID NO:13, or the complement thereof, and/or vii) a cDNA molecule produced from an mRNA molecule in the sample, wherein the cDNA molecule has a nucleotide sequence comprising a thymine at a position corresponding to position 1,056 according to SEQ ID NO:
- 14, or the complement thereof.
12 more elements
Dependencies are inferred from the claim text.