Mrna therapeutic compositions and use to treat diseases and disorders

Patent metadata

Field	Value
Publication number	US-2016184458-A1
Application number	US-201414774263-A
Country	US
Kind code	A1
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	Jun 30, 2016
Grant date	—

Abstract

Disclosed are compositions and methods for producing therapeutic fusion proteins in vivo. The compositions and methods disclosed herein are capable of ameliorating diseases by providing therapeutic protein delivery.

First claim

1 . A composition comprising (a) at least one mRNA molecule, at least a portion of which encodes a therapeutic polypeptide fused to a polypeptide capable of binding to an Fc receptor; and (b) a transfer vehicle.

2 . (canceled)

3 . The composition of claim 1 , wherein the polypeptide capable of binding to an Fc receptor is an immunoglobulin Fc domain.

4 . (canceled)

5 . The composition of claim 1 , wherein the Fc receptor is the neonatal Fc receptor, FcRn.

6 . (canceled)

7 . The composition of claim 1 , wherein the mRNA molecule comprises a 5′ untranslated region.

8 . The composition of claim 7 , wherein the a 5′ untranslated region is from CMV IE1.

9 . The composition of claim 1 , wherein the mRNA molecule comprises a Cap1 structure.

10 . The composition of claim 1 , wherein the mRNA comprises a m7GpppG cap.

11 . The composition of claim 1 , wherein the mRNA molecule comprises a 3′ untranslated region.

12 . The composition of claim 11 , wherein the 3′ untranslated region is from hGH.

13 - 15 . (canceled)

16 . The composition of claim 1 , wherein the mRNA molecule has been modified to reduce or eliminate CpG motifs, repeat sequences, inverted sequences, cryptic promoter sequences, and to ensure a GC content less than the GC content of the wild type sequence.

17 . The composition of claim 1 , where in the mRNA encodes a protein which is abnormal or deficient in an individual.

18 - 19 . (canceled)

20 . The composition of claim 1 , where in the mRNA encodes an enzyme which is abnormally deficient in an individual with a lysosomal storage disorder.

21 - 23 . (canceled)

24 . The composition of claim 1 , formulated for pulmonary administration.

25 . The composition of claim 1 , wherein the transfer vehicle is polyethyleneimine (PEI).

26 . (canceled)

27 . The composition of claim 1 , wherein the transfer vehicle is a lipid nanoparticle.

28 . (canceled)

29 . The composition of claim 27 , wherein the nanoparticle comprises a cationic lipid nanoparticle selected from: C12-200, XTC, MC3, NC98-5, DLinDMA, HGT5001cis, HGT5001trans, HGT5000, HGT4003, DLinKC2DMA, ALNY100, ICE, DOTAP, DODAP, DOTMA.

30 . (canceled)

31 . The composition of claim 27 , wherein the lipid nanoparticle comprises one or more PEG-modified lipids.

32 . The composition of claim 27 , wherein the lipid nanoparticle comprises a cholesterol.

33 - 39 . (canceled)

40 . A method of inducing expression of a functional polypeptide in a subject, comprising administering the composition of claim 1 .

41 - 43 . (canceled)

44 . A composition comprising (a) at least one mRNA molecule at least a portion of which encodes a therapeutic protein fused to a polypeptide capable of binding to an Fc receptor; and (b) a transfer vehicle comprising a lipid nanoparticle or a lipidoid nanoparticle, wherein the polypeptide is chosen from proteins listed in table S1, table S2, and table S3, mammalian homologs thereof, and homologs from animals of veterinary or industrial interest.

Assignees

• Shire Human Genetic Therapies

Inventors

• Heartlein Michael

Classifications

• A61K48/0075 Primary

  characterised by an aspect of the delivery route, e.g. oral, subcutaneous · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61K48/005

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• C12N15/00

  Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor (mutants or genetically engineered microorganisms, per se C12N1/00, C12N5/00, C12N7/00; new plants per se A01H; plant reproduction by tissue culture techniques A01H4/00; new animals per se A01K67/00; use of medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases, gene therapy A61K48/00) · CPC title