Pegylated porcine interferon and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10960080-B2
Application number	US-201716311540-A
Country	US
Kind code	B2
Filing date	Jun 16, 2017
Priority date	Jun 20, 2016
Publication date	Mar 30, 2021
Grant date	Mar 30, 2021

Abstract

Disclosed herein are porcine interferon alpha variants (pIFN-α) comprising a synthetic amino acid at select locations in pIFN-α and a one or two amino acid insertion in the N-terminus after removal of the signal peptide. The pIFN-α variants can further be pegylated. Methods of making and administering these compounds to treat virus infections in pigs and formulations comprising the variants are also provided.

First claim

What is claimed is:

1. A porcine interferon-α (pIFN-α) variant comprising:

(SEQ ID NO: 1)

X a X b CDLPQTHSLAHTRALRLLAQMRRISPFSCLDHRRDFGSPHEAFGGN

QVQKAQAMALVHEMLQQTFQLFSTEGSAAAWNESLLHQFYTGLDQQLRDL

EACVMQEAGL E GTPLLEEDSIRAVRKYFHRLTLYLQEKSYSPCAWEIVRA

EVMRSFSSSRNLQDRLRKKE,

wherein residue E103, E107, L112, Y136, or Q102 (numbering with respect to SEQ ID NO: 4) is substituted with a synthetic amino acid; and
wherein X a X b are variable positions selected from the group consisting of no amino acids, a single proline residue, and a proline-serine dipeptide.

2. The pIFN-α variant of claim 1 , wherein the synthetic amino acid is para-acetyl-phenylalanine (pAF).

3. The pIFN-α variant of claim 1 , wherein the variant is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 19, and SEQ ID NO: 20.

4. The pIFN-α variant of claim 1 , wherein the synthetic amino acid is pegylated.

5. The pIFN-α variant of claim 4 , wherein the pegylated pIFN-α variant is pegylated with about a 5 kDa to 40 kDa PEG.

6. The pIFN-α variant of claim 5 , wherein the PEG is a 30 kDa PEG.

7. The pIFN-α variant of claim 1 in a formulation comprising 20 mM sodium acetate, 100 mM sodium chloride, 5% glycerol at pH 5.0 of about 2.0 to about 6.0 g/L titer of pIFN-α variant.

8. A porcine interferon-α (pIFN-α) variant consisting of:

(SEQ ID NO: 14)

PSCDLPQTHSLAHTRALRLLAQMRRISPFSCLDHRRDFGSPHEAFGGNQV

QKAQAMALVHEMLQQTFQLFSTEGSAAAWNESLLHQFYTGLDQQLRDLEA

CVMQEAGL-pAF-GTPLLEEDSIRAVRKYFHRLTLYLQEKSYSPCAWEIV

RAEVMRSFSSSRNLQDRLRKKE,

wherein a residue corresponding to E107 (numbering with respect to SEQ ID NO: 4) is substituted with para-acetyl-phenylalanine (pAF) and said pAF residue is pegylated with a 30 kDa linear PEG.

9. A method of treating a virus infection in a pig comprising administering subcutaneously to said pig in need thereof a pIFN-α variant; wherein the pIFN-α variant is selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEO ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20.

10. The method of claim 9 , wherein the pIFN-α variant is administered in the range of 25 μg/kg to 150 μg/kg animal weight.

11. The method of claim 10 , comprising a second administration of 25 μg/kg to 150 μg/kg animal weight of said pIFN-α variant.

12. The method of claim 11 , wherein the second administration is 7 to 14 days after first administration.

13. The method of claim 9 , wherein the virus infection is selected from the group consisting of: porcine reproductive and respiratory syndrome virus, foot and mouth disease virus, swine influenza virus, porcine circovirus, porcine epidemic diarrhea virus and transmissible gastroenteritis virus.

14. The method of claim 9 , wherein the pig is a newborn pig or the pig is a pregnant pig.

Assignees

• Elanco Us Inc
• Ambrx Inc

Inventors

• Canning Peter Connor
• Knudsen Nickolas
• Skidmore Lillian

Classifications

• C07K14/56 Primary

  IFN-alpha · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K38/212

  IFN-alpha · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• A61K9/0019

  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 title