Antisense oligonucleotides (ODN) against SMAD7 and uses thereof in medical field

• US 8,648,186 B2
• Filed: 03/15/2013
• Issued: 02/11/2014
• Est. Priority Date: 04/02/2003
• Status: Expired due to Term

• Current Assignee: Nogra Pharma Limited
• Original Assignee: Nogra Pharma Limited
• Inventors: Monteleone, Giovanni
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US13/836,634
• Publication Number:
  US 20130203839A1
• Time in Patent Office: 333 Days
• Field of Search: None
• US Class Current: 536/24.5
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/3125 Methylphosphonates
• CPC Class Codes: C12N 2310/314 Phosphoramidates
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/334 Modified C
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/344 Position-specific modifications, e.g. on every purine, at the 3'-end
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2320/30 Special therapeutic applications

Abstract

The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn'"'"'s disease and ulcerative colitis.

Claims

1. An antisense oligonucleotide against SMAD7 comprising (SEQ ID NO:

4);

2. The antisense oligonucleotide of claim 1 wherein at least one internucleoside linkage is a phosphorothioate linkage.

3. The antisense oligonucleotide of claim 1 wherein the internucleoside linkages are phosphorothioate linkages.

4. The antisense oligonucleotide of claim 1 wherein 2′

-deoxyribonucleotides are replaced by corresponding ribonucleotides.

5. A pharmaceutical composition comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable excipient.

6. A pharmaceutical composition suitable for oral administration, comprising an effective amount of SEQ ID NO:

4 and a pharmaceutically acceptable excipient, wherein when said pharmaceutical composition is administered orally to a patient, it is more effective in treating colitis as compared to administering to a patient the reverse complement of SEQ ID NO;

4.