Modified human interferon-β polypeptides

• US 7,632,492 B2
• Filed: 05/02/2007
• Issued: 12/15/2009
• Est. Priority Date: 05/02/2006
• Status: Active Grant

• Current Assignee: Allozyne, Incorporated (Astrazeneca PLC)
• Original Assignee: Allozyne, Incorporated (Astrazeneca PLC)
• Inventors: Wang, Andrea, Grabstein, Kenneth H., McCraith, Stephen, Datta, Deepshikha, Nairn, Natalie Winblade
• Primary Examiner(s): Landsman; Robert
• Assistant Examiner(s): DANG, IAN D
• Application Number:
  US11/743,608
• Publication Number:
  US 20080125347A1
• Time in Patent Office: 958 Days
• Field of Search: None
• US Class Current: 424/85.6
• 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: C07K 14/565 IFN-beta
• CPC Class Codes: C07K 2319/22 containing a Strep-tag
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/40 containing a tag for immunodetection, or an epitope for immunisation
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C12P 21/02 having a known sequence of two or more amino acids, e.g. glutathione
• 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

The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Claims

1. A modified human interferon-β

polypeptide consisting of the following amino acid alterations;

methionine at position 1 to azidohomoalanine, serine at position 2 to glutamic acid, cysteine at position 17 to serine, methionine at position 36 to isoleucine, isoleucine at position 40 to phenylalanine, isoleucine at position 44 to leucine, methionine at position 62 to isoleucine, and methionine at position 117 to threonine.

2. The polypeptide of claim 1, wherein said polypeptide is conjugated to a polyethylene glycol (PEG) at position 1 of the modified human interferon-β

polypeptide.

3. The polypeptide of claim 2, wherein said PEG is branched or unbranched.

4. The polypeptide of claim 3, wherein said PEG has a molecular weight of from 1,000 Daltons to 100 kDa.

5. The polypeptide of claim 4, wherein said PEG has a molecular weight selected from the group consisting of 2 kDa to 60 kDa;

2 kDa to 30 kDa, 5 kDa to 20 kDa;

10 kDa to 40 kDa;

10 kDa to 20 kDa.

6. The polypeptide of claim 2, wherein said PEG is conjugated to the polypeptide through a triazole linkage, wherein said triazole linkage is formed by a [3+2] cycloaddition reaction.

7. A composition comprising the polypeptide of claim 1, and a pharmaceutically acceptable diluent or excipient.