Modified human interferon polypeptides with at least one non-naturally encoded amino acid and their uses

• US 8,097,702 B2
• Filed: 10/19/2007
• Issued: 01/17/2012
• Est. Priority Date: 02/02/2004
• Status: Expired due to Fees

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Cho, Ho Sung, Daniel, Thomas O., Hays, Anna-Maria A., Wilson, Troy E.
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): Seharaseyon, Jegatheesan
• Application Number:
  US11/875,751
• Publication Number:
  US 20080108791A1
• Time in Patent Office: 1,551 Days
• Field of Search: None
• US Class Current: 530/351
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• 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 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/12 : for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07H 21/04 : with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/475 : Growth factors; Growth regulators
• CPC Class Codes: C07K 14/52 : Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/575 : Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/61 : Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C08G 65/33396 : having oxygen in addition to nitrogen
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/6875 : Nucleoproteins

Abstract

Modified interferon polypeptides with at least one non-naturally-encoded amino acid and uses thereof are provided.

Claims

1. A variant of a human beta interferon (hIFNβ

) polypeptide comprising a non-naturally encoded amino acid wherein said non-naturally encoded amino acid is substituted at position 107 and wherein the non-naturally encoded amino acid has the structure;

2. The hIFNβ

variant of claim 1, wherein the non-naturally encoded amino acid is selectively reactive toward the one or more poly (ethylene glycol) moiety or moieties.

3. The hIFNβ

variant of claim 1, wherein the non-naturally encoded amino acid comprises a carbonyl group, an aminooxy group, a hydrazine group, a hydrazide group, a semicarbazide group, an azide group, or an alkyne group.

4. The hIFNβ

variant of claim 1, wherein the hIFNβ

variant comprises one or more post-translational modifications.

5. The hIFNβ

variant of claim 1, wherein the hIFNβ

variant is linked to a multifunctional polymer, bifunctional polymer, or at least one additional hIFNβ

variant.

6. The hIFNβ

variant of claim 1, wherein the hIFNβ

variant further comprises one or more free amide or free sulfhydryl groups.

7. The hIFNβ

variant of claim 6, wherein the free amide or free sulfhydryl groups are present in naturally occurring amino acids.

8. The hIFNβ

variant of claim 1, wherein the serum half-life of the hIFNβ

variant is at least three-fold greater than wild type hIFNβ

.

9. The hIFNβ

variant of claim 8, wherein the hIFNβ

variant comprises a second non-naturally encoded amino acid.

10. The hIFNβ

variant of claim 1, wherein the hIFNβ

variant is linked to a linker, polymer, or biologically active molecule.

11. The hIFNβ

variant of claim 10, wherein the linker or polymer is linked to a second polypeptide.

12. The hIFNβ

variant of claim 11, wherein the second polypeptide is a hIFNβ

variant.