Methods for producing enteroendocrine cells that make and secrete insulin

• US 10,544,415 B2
• Filed: 08/19/2016
• Issued: 01/28/2020
• Est. Priority Date: 05/12/2010
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Talchai, Chutima, Accili, Domenico
• Primary Examiner(s): Gangle, Brian
• Assistant Examiner(s): McCollum, Andrea K
• Application Number:
  US15/241,674
• Publication Number:
  US 20170044532A1
• Time in Patent Office: 1,257 Days
• Field of Search: None
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells
• CPC Class Codes: C12N 5/068 Stem cells; Progenitors
• CPC Class Codes: G01N 2333/62 Insulins
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5073 Stem cells

Abstract

Methods are described for producing enteroendocrine cells that make and secrete insulin in a mammal by blocking the expression or biological activity of one or more forkhead box O (Foxo) proteins or biologically active fragments or variants thereof.

Claims

1. A pharmaceutical formulation for treating diabetes, the pharmaceutical formulation comprising a therapeutically effective amount of an isolated inhibitory oligonucleotide selected from the group consisting of an shRNA, siRNA, antisense RNA, antisense DNA, and Chimeric Antisense DNA/RNA, that is sufficiently complementary to mRNA encoding forkhead box 01 (Foxo1) protein to reduce expression of Foxo1, wherein the formulation is formulated for oral administration in an enteric form so as to release the therapeutically effective amount in a duodenum, ileum or colon gut region of a subject.

2. The pharmaceutical formulation of claim 1, wherein the therapeutically effective amount is an amount that produces an effect selected from the group consisting of an increase in glucose tolerance, an increase in serum insulin and the generation of enteroendocrine cells in the gastrointestinal tract that produce and secrete insulin.