Modified IGF1 polypeptides with increased stability and potency

• US 7,355,018 B2
• Filed: 09/30/2004
• Issued: 04/08/2008
• Est. Priority Date: 09/30/2003
• Status: Active Grant

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Glass, David J.
• Primary Examiner(s): Bunner; Bridget E.
• Assistant Examiner(s): DANG, IAN D
• Application Number:
  US10/954,468
• Publication Number:
  US 20050287151A1
• Time in Patent Office: 1,286 Days
• Field of Search: None
• US Class Current: 530/399
• 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 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/65 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70571 for neuromediators, e.g. serotonin receptor, dopamine receptor
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/73 containing coiled-coiled motif (leucine zippers)
• CPC Class Codes: C07K 2319/74 containing a fusion for binding to a cell surface receptor
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins

Abstract

A targeting fusion protein comprising a component that comprises a (i) ligand or derivative or fragment thereof that binds a pre-selected target surface protein, such as a receptor, and (ii) an active agent or therapeutic agent(s), and further optionally (iii) a multimerizing component and/or (iv) a signal sequence. In a preferred embodiment, the targeting fusion polypeptide targets muscle and is useful to treat a muscle-related disease or condition, such as muscle atrophy.

Claims

1. A modified human insulin-like growth factor-1 (IGF-1) fusion polypeptide, comprising:

a deletion of amino acids 1-3 and a deletion of amino acid 37, relative to mature human IGF-1, and a multimerizing component capable of forming a multimer with another said modified IGF-1 fusion polypeptide, wherein the multimerizing component is an Fc domain from IgG1, IgG2, IgG3, or IgG4.

2. The fusion polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:

9.

3. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 1.

4. A composition comprising the fusion polypeptide of claim 1 and a pharmaceutically acceptable carrier.