Engineered nucleic acids encoding a modified erythropoietin and their expression

• US 8,710,200 B2
• Filed: 04/02/2012
• Issued: 04/29/2014
• Est. Priority Date: 03/31/2011
• Status: Active Grant

• Current Assignee: Moderna TX, Inc. (Moderna, Inc.)
• Original Assignee: Moderna Therapeutics, Inc. (Moderna, Inc.)
• Inventors: Schrum, Jason P., Afeyan, Noubar B., Sieczkiewicz, Gregory J., Bancel, Stephane, de Fougerolles, Antonin, Elbashir, Sayda M.
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US13/437,034
• Publication Number:
  US 20120251618A1
• Time in Patent Office: 757 Days
• US Class Current: 536/23.1
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/7115 Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/535 : Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C12N 15/67 : General methods for enhancing the expression
• CPC Class Codes: C12N 15/87 : Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2310/335 : Modified T or U
• CPC Class Codes: C12N 9/644 : Coagulation factor IXa (3.4.21.22)

Abstract

Provided are formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the delivery of biological moieties, and are useful for production of proteins.

Claims

1. An isolated polynucleotide, said polynucleotide comprising SEQ ID NO:

7.

2. The polynucleotide of claim 1, further comprising a 5′

Cap1 structure and a polyA tail of approximately 160 nucleotides in length.

3. A pharmaceutical composition comprising the polynucleotide of claim 2 and a pharmaceutically acceptable excipient.

4. The pharmaceutical composition of claim 3 which is formulated and wherein the formulation is a lipid formulation.

5. A method of producing a polypeptide of interest in a cell, tissue or bodily fluid of a mammalian subject comprising administering to said subject a pharmaceutical composition comprising the isolated polynucleotide of claim 1, wherein upon administration to said subject, the polypeptide of interest is produced in said cell, tissue or bodily fluid.

6. The method of claim 5, wherein the polynucleotide further comprises a 5′

Cap1 structure and a polyA tail of approximately 160 nucleotides in length.

7. The method of claim 6, wherein the pharmaceutical composition is formulated and wherein the formulation is a lipid formulation.

8. The method of claim 5, where the pharmaceutical composition is administered at a total dose of about 0.1 mg/kg to about 40 mg/kg.

9. The method of claim 8, wherein administration occurs on a schedule selected from the group consisting of three time a day, twice a day, once a day, every other day, every third day, weekly, biweekly, every three weeks, every four weekly, and monthly.

10. The method of claim 8, wherein the total dose is administered by multiple administrations.

11. The method of claim 10, wherein the multiple administrations occur on a schedule selected from the group consisting of three times a day, twice a day, once a day, every other day, every third day, weekly, biweekly, every three weeks, every four weekly, and monthly.

12. The method of claim 5, wherein an increase in the level of the polypeptide of interest is observed in tissue or bodily fluid within 8 hours.

13. The method of claim 12, wherein the increased level of the polypeptide of interest is observed in a tissue selected from the group consisting of liver, spleen, kidney, lung, heart, peri-renal adipose tissue, thymus and muscle.

14. The method of claim 5, wherein an increase in the level of the polypeptide of interest is observed in tissue or bodily fluid within 2 hours.