Genotype-directed local delivery of targeted therapeutics
AssigneesMassachusetts Institute of Technology, The General Hospital Corporation, The Brigham and Women's Hospital, Inc.
InventorsRobert S. Langer, Carlo Giovanni Traverso, Ameya R. Kirtane, Daniel Cahill, Ganesh Shankar
Life of this patent
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Abstract
Provided herein are pharmaceutical compositions for local administration of metabolic inhibitors, methods of locally administering such compositions, and rapid diagnostic methods for identifying mutant allele during the course of a surgical procedure.
Claims45
A pharmaceutical composition comprising
- a population of particles coupled to a nicotinamide adenine dinucleotide (NAD) biosynthesis inhibitor.
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-12. (canceled)
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-25. (canceled)
-33. (canceled)
A diagnostic method, the method comprising
- obtaining a sample from a subject;
- and
- detecting one or more mutations in a target nucleic acid in the sample;
- wherein the detecting is performed by
- isolating a nucleic acid comprising the target nucleic acid from the sample, and
- analyzing the nucleic acid for the presence of one or more allele-specific mutations;
- and
- wherein the detecting is performed in an intraoperative timeframe.
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A method for diagnosis and treatment of a cancer in a subject, comprising
- performing a surgical procedure on the subject;
- obtaining a sample from the subject;
- and
- determining whether the sample contains one or more mutations in a target nucleotide sequence in the sample;
- wherein if the sample is determined to contain the one or more mutations, locally administering an agent with mutation selectivity to the subject during the surgical procedure.
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A nucleic acid comprising the nucleotide sequence provided by any one of SEQ ID NOs:
- 1-26.
A kit, wherein
- (a) the kit is for the rapid detection of IDH1 variants and comprises
- (i) a forward primer comprising a nucleotide sequence provided by SEQ ID NO:
- 2 or 3;
- (ii) a reverse primer comprising a nucleotide sequence provided by SEQ ID NO:
- 18;
- (iii) a probe comprising a nucleotide sequence provided by any one of SEQ ID NOs:
- 9-13, and
- (iv) a peptide nucleic acid (PNA) blocker comprising a nucleotide sequence provided by SEQ ID NO:
- 24;
- or
- (b) the kit is for the rapid detection of TERT promoter variants and comprises
- (i) a forward primer comprising a nucleotide sequence provided by SEQ ID NO:
- 1;
- (ii) a reverse primer comprising a nucleotide sequence provided by SEQ ID NO:
- 17;
- (iii) a probe comprising a nucleotide sequence provided by SEQ ID NO:
- 7 or 8, and
- (iv) a peptide nucleic acid (PNA) blocker comprising a nucleotide sequence provided by SEQ ID NO:
- 22 or 23;
- or
- (c) the kit is for the rapid detection of H3F3A variants and comprises
- (i) a forward primer comprising a nucleotide sequence provided by SEQ ID NO:
- 4;
- (ii) a reverse primer comprising a nucleotide sequence provided by SEQ ID NO:
- 19;
- (iii) a probe comprising a nucleotide sequence provided by SEQ ID NO:
- 14, and
- (iv) a peptide nucleic acid (PNA) blocker comprising a nucleotide sequence provided by SEQ ID NO:
- 25;
- or
- (d) the kit is for the rapid detection of BRAF variants and comprises
- (i) a forward primer comprising a nucleotide sequence provided by SEQ ID NO:
- 5;
- (ii) a reverse primer comprising a nucleotide sequence provided by SEQ ID NO:
- 20;
- (iii) a probe comprising a nucleotide sequence provided by SEQ ID NO:
- 15;
- and
- (iv) a peptide nucleic acid (PNA) blocker comprising a nucleotide sequence provided by SEQ ID NO:
- 26.
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Dependencies are inferred from the claim text.