UNIVERSAL FIBRONECTIN TYPE III BINDING-DOMAIN LIBRARIES

• US 20110021746A1
• Filed: 06/21/2010
• Published: 01/27/2011
• Est. Priority Date: 08/10/2007
• Status: Active Grant

• Current Assignee: Protelica Inc.
• Original Assignee: Protelica Inc.
• Inventors: Kirk, Peter B., Crea, Roberto, Hokanson, Craig A., Liston, David R., Cappuccilli, Guido, Shen, Randy
• Granted Patent: US 8,470,966 B2
• Time in Patent Office: Days
• US Class Current: 530/324
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2318/20 Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
• CPC Class Codes: C12N 15/1044 Preparation or screening of libraries displayed on scaffold proteins
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof

Abstract

Fibronectin Type III (FN3) polypeptide libraries are described, along with their use in identifying fibronectin-type binding peptides having hign binding affinities, e.g., greater than 300 nM, for VEGFR2 or Axl proteins.

Claims

1. A VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) binding peptide having a K_d dissociation constant equal to or greater than 300 nM and having a sequence selected from SEQ ID NOS:

223-331.

2. The VEGFR2 binding peptide of claim 1, which has a sequence selected from the group consisting of SEQ ID NOS:

273, 226, 295, 275, 270, 274, 229, 227, 223 and 248.

3. The VEGFR2 binding peptide of claim 2, wherein the dissociation constant K_d is equal to or greater than 50 nM.

4. The VEGFR2 binding peptide of claim 3, wherein the dissociation constant K_d is equal to or greater than 5 nM.

5. The VEGFR2 binding peptide of claim 2, which has the sequence selected from the group consisting of SEQ ID NOS:

273, 226, 295, 275, and 270.

6. The VEGFR2 binding peptide of claim 5, wherein the peptide has the sequence SEQ ID NOS:

273.

7. An Axl transforming receptor tyrosine kinase binding peptide having a K_d dissociation constant equal to or greater than 300 nM and having a sequence selected from SEQ ID NOS:

332-498.

8. The Axl binding peptide of claim 7, which has a sequence selected from the group consisting of SEQ ID NOS:

339, 366, 354, 392, 452, 454, 353, 333, 368, and 369.

9. The Axl binding peptide of claim 8, wherein the dissociation constant K_d is equal to or greater than 50 nM.

10. The Axl binding peptide of claim 9, wherein the dissociation constant K_d is equal to or greater than 5 nM.

11. The Axl binding peptide of claim 8, which has the sequence a sequence selected from the group consisting of SEQ ID NOS:

339, 366, 354, and 392.

12. The Axl binding protein of claim 11, which has the sequence SEQ ID NOS:

339