ERYTHROID CELLS COMPRISING SERINE DEHYDRATASE

• US 20190309262A1
• Filed: 06/04/2019
• Published: 10/10/2019
• Est. Priority Date: 11/18/2013
• Status: Abandoned Application

• Current Assignee: Rubius Therapeutics, Inc.
• Original Assignee: Rubius Therapeutics, Inc.
• Inventors: Kahvejian, Avak, Mata-Fink, Jordi, Round, John, Berry, David Arthur, Afeyan, Noubar B.
• Application Number:
  US16/431,270
• Publication Number:
  US 20190309262A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5068 Cell membranes or bacterial membranes enclosing drugs with additional exogenous lipids A61K9/127; virus envelopes A61K9/5184
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/082 : Hepadnaviridae, e.g. hepatitis B virus
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0641 : Erythrocytes
• CPC Class Codes: C12N 9/88 : Lyases (4.)
• CPC Class Codes: C12Y 204/02004 : Thymidine phosphorylase (2.4.2.4)
• CPC Class Codes: C12Y 304/22 : Cysteine endopeptidases (3.4.22)
• CPC Class Codes: C12Y 403/01024 : Phenylalanine ammonia-lyase (4.3.1.24)
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

Claims

1. An enucleated erythroid cell comprising an exogenous polypeptide comprising serine dehydratase or a functional fragment thereof,

wherein the enucleated erythroid cell is made by a process comprising introducing into an erythroid cell precursor a nucleic acid encoding the exogenous polypeptide.

2. The enucleated erythroid cell of claim 1, which comprises at least 1,000 copies of the exogenous polypeptide.

3. The enucleated erythroid cell of claim 1, which comprises at least 10,000 copies of the exogenous polypeptide.

4. The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide is intracellular.

5. The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide is on the surface of the enucleated erythroid cell.

6. The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide consists essentially of serine dehydratase.

7. The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide consists of serine dehydratase.

8. The enucleated erythroid cell of claim 1, further comprising a second exogenous polypeptide comprising a serine transporter.

9. The enucleated erythroid cell of claim 1, which exhibits an increase in serine dehydratase activity of at least 2-fold relative to that of an enucleated erythroid cell that does not comprise the exogenous polypeptide.

10. The enucleated erythroid cell of claim 1, which is a reticulocyte.

11. The enucleated erythroid cell of claim 1, which is an erythrocyte.

12. The enucleated erythroid cell of claim 1, which lacks A and B antigens.

13. The enucleated erythroid cell of claim 1, which is a human cell.

14. The enucleated erythroid cell of claim 1, which comprises fetal hemoglobin.

15. The enucleated erythroid cell of claim 1, which exhibits substantially the same osmotic membrane fragility as an isolated, unmodified, uncultured enucleated erythroid cell.

16. The enucleated erythroid cell of claim 1, wherein introducing the nucleic acid comprises using a lentiviral vector.

17. The enucleated erythroid cell of claim 1, wherein the process comprises expanding the erythroid cell precursor by at least 20,000-fold in culture.

18. The enucleated erythroid cell of claim 1, wherein the erythroid cell precursor is a CD34+ hematopoietic stem cell.

19. The enucleated erythroid cell of claim 1, wherein the nucleic acid comprises DNA.

20. The enucleated erythroid cell of claim 1, wherein the nucleic acid comprises RNA.

21. A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of claim 1 and a pharmaceutically acceptable carrier.

22. The pharmaceutical composition of claim 21, which is formulated for intravenous administration.

23. The pharmaceutical composition of claim 21, wherein at least about 90% of enucleated erythroid cells in the pharmaceutical composition comprise the exogenous polypeptide.

24. A pharmaceutical composition comprising (i) a plurality of the enucleated erythroid cells of claim 1, wherein at least 70% of cells in the pharmaceutical composition are enucleated, and (ii) a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24, wherein at least 90% of cells in the pharmaceutical composition are enucleated.

28. A method of reducing serine levels in a subject, comprising administering to the subject the pharmaceutical composition of claim 21, thereby reducing serine levels in the subject.

29. A method of treating a solid tumor in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 21, thereby treating said solid tumor in the subject.

26. A nucleated erythroid cell precursor comprising an exogenous polypeptide comprising serine dehydratase or a functional fragment thereof,

wherein the nucleated erythroid cell precursor was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell precursor.

27. The nucleated erythroid cell precursor of claim 26, which has been cultured after the introduction of the exogenous nucleic acid.