US 2014/0271469 A1 · CYSTINE KNOT PEPTIDES THAT BIND ALPHA-V-BETA-6 INTEGRIN

Abstract

Disclosed are peptides comprising a molecular scaffold portion and a loop portion that binds to integrin αvβ6. This integrin is expressed on pancreatic tumors, making the peptides useful as imaging agents, among other uses. The peptides showed single-digit nanomolar dissociation constants similar to antibodies used clinically for imaging and therapy. The peptides rapidly accumulated in αvβ6-positive tumors, which led to excellent tumor-to-normal contrast. The peptides are specific for the targeted integrin αvβ6 receptors expressed on orthotopic pancreatic tumors and various xenografts used. Additionally, pharmacokinetic-stabilization strategies endowed knots with rapid renal clearance, which significantly reduced off-target dosing.

Claims22

Dependent claims

A peptide having specific binding to alpha-V beta 6 integrin, comprising a binding portion between two cysteine residues and a scaffold portion, said peptide being at least 83% identical to a sequence selected from the group consisting of:

(SEQ ID NO:
2)
(a) (R01),
GCILNMRTDLGTLLFRCRRDSDCPGACICRGNGYCG,
(SEQ ID NO:
3)
(b) (R02),
GCRSLARTDLDHLRGRCRRDSDCPGACICRGNGYCG,
(SEQ ID NO:
4)
(c) (E02),
GCRSLARTDLDHLRGRCEEDSDCLAECICEENGFCG,
(SEQ ID NO:
5)
(d) (S02),
GCRSLARTDLDHLRDRCSSDSDCLAECICLENGFCG.
(SEQ ID NO:
63)
(e) (MΔR),
GCILNRRTDLGTLLFRCRRDSDCPGACICRGNGYCG,
(SEQ ID NO:
64)
(f) (MΔG),
GCILNGRTDLGTLLFRCRRDSDCPGACICRGNGYCG,
and
(SEQ ID NO:
65)
(g) (MΔW),
GCILNWRTDLGTLLFRCRRDSDCPGACICRGNGYCG.

26 more elements

Dependencies are inferred from the claim text.

Cystine knot peptides that bind alpha-v-beta-6 integrin

Life of this patent

Cystine knot peptides that bind alpha-v-beta-6 integrin

Life of this patent

Abstract

Claims22