Receptor-mediated uptake of peptides that bind the human transferrin receptor

• US 6,743,893 B2
• Filed: 11/29/2001
• Issued: 06/01/2004
• Est. Priority Date: 11/30/2000
• Status: Expired due to Fees

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: UAB Research Foundation (University of Alabama System)
• Inventors: Collawn, James F., Moore, Bryan A., Engler, Jeffrey A., Lee, Jae Hwy
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): TURNER, SHARON L
• Application Number:
  US09/995,804
• Publication Number:
  US 20020115824A1
• Time in Patent Office: 915 Days
• Field of Search: 530/300, 530/350, 514/2, 424/1.65, 424/9.1
• US Class Current: 530/300
• CPC Class Codes: A61K 47/6425 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
• CPC Class Codes: A61K 47/644 Transferrin, e.g. a lactoferrin or ovotransferrin
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 15/1037 Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
• CPC Class Codes: C40B 40/02 Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors

Abstract

Peptides have been discovered which are capable of binding to and internalizing with the human transferrin receptor (hTfR). The sequences HAIYPRH (Seq. ID No. 1) and THRPPMWSPVWP (Seq. ID No. 2) are capable of binding to and internalizing with the human transferrin receptor. When these molecules were fused with other molecules, the fusion product was internalized in cells expressing hTfR. The sequences have use for targeting other peptides and proteins into cells expressing hTfR.

Claims

1. A composition of matter comprising a purified peptide containing the sequence THRPPMWSPVWP (Seq. ID No. 2).

2. A composition comprising at least one peptide containing the sequence (Seq. ID No. 2) wherein said peptide is fused to a protein or another peptide.

3. A composition of claim 2 wherein said sequence containing the sequence THRPPMWSPVWP (Seq. ID No. 2) is fused to a chemotherapeutic agent.

4. A composition of claim 2 wherein said sequence containing the sequence THRPPMWSPVWP (Seq. ID No. 2) is fused to an imaging agent.

5. A composition of claim 4 wherein said sequence containing the sequence THRPPMWSPVWP (Seq. ID No. 2) is fused to a fluorescing agent.

6. A composition of claim 2 wherein said sequence containing the sequence THRPPMWSPVWP (Seq. ID No. 2) is fused to an antigen.

7. A method of targeting an active agent to the human transferrin receptor by administration of said agent fused to a sequence containing the sequence THRPPMWSPVWP (Seq. ID No. 2) to a human subject.