HER3 binding polypeptides
The present disclosure relates to polypeptides which bind to human epidermal growth factor receptor 3 (HER3) and to use of such polypeptides in imaging and therapy. The disclosure provides an HER3 binding polypeptide comprising a HER3 binding motif, which motif consists of the amino acid sequence EKYX 4 AYX 7 EIW X 11 LPNLTX 17 X 18 QX 20 AAFIGX 26 LX 28 D (SEQ ID NO:110).
1. A HER3 binding polypeptide, comprising a HER3 binding motif (BM), which motif consists of an amino acid sequence selected from SEQ ID NO. 1-35.
2. The HER3 binding polypeptide according to claim 1 , selected from SEQ ID NO:71-105.
3. The HER3 binding polypeptide according to claim 1 , wherein the off-rate (k off ) of the interaction between said HER3 binding polypeptide and human HER3 is at least four-fold reduced, when compared to the off-rate (k off ) of the interaction between a comparative HER3 binding polypeptide comprising the amino acid sequence SEQ ID NO:107 and human HER3, as measured using the same experimental conditions.
4. The HER3 binding polypeptide according to claim 1 , wherein the K D value of the interaction between said HER3 binding polypeptide and human HER3 is at most 1×10 −8 M.
5. The HER3 binding polypeptide according to claim 1 , further comprising a second moiety consisting of a polypeptide having a biological activity.
6. The HER3 binding polypeptide according to claim 5 , wherein said biological activity is selected from a group consisting of a therapeutic activity, a binding activity and an enzymatic activity.
7. The HER3 binding polypeptide according to claim 1 , further comprising a label, wherein said label is selected from the group consisting of fluorescent dyes and metals, chromophoric dyes, chemiluminescent compounds and bioluminescent proteins, enzymes, radionuclides and particles.
8. The HER3 binding polypeptide of claim 7 , further comprising a second moiety comprising a polypeptide having a biological activity.
9. A composition comprising a HER3 binding polypeptide according to claim 1 and at least one excipient or carrier.
10. The composition of claim 9 , wherein the HER3 binding polypeptide further comprises a second moiety comprising a label or a polypeptide having a biological activity.
11. The composition of claim 10 , wherein the second moiety comprises a label.
12. The composition of claim 10 , wherein the second moiety comprises a polypeptide having a biological activity.
13. A polynucleotide encoding an HER3 binding polypeptide according to claim 1 .
14. The polynucleotide of claim 13 , wherein the HER3 binding polypeptide further comprises a second moiety comprising a polypeptide having a biological activity.
15. A method of detecting HER3, comprising contacting a sample suspected to contain HER3 with a HER3 binding polypeptide according to claim 1 , and detecting the binding of the HER3 binding polypeptide to indicate the presence of HER3 in the sample.
16. The method of claim 15 , wherein the HER3 binding polypeptide further comprises a second moiety comprising a label or a polypeptide having a biological activity.
17. The method of claim 16 , wherein the second moiety is the polypeptide having a biological activity.
18. The method of claim 16 , wherein the second moiety is the label.
19. A method of in vivo imaging of the body of a subject having or suspected of having a cancer characterized by over expression of HER3, comprising the steps of:
administering a radiolabeled HER3 binding polypeptide according to claim 7 , wherein the radionuclide is suitable for imaging, into the body of the mammalian subject; and
obtaining one or more images, within 1-72 hours of administration of the radiolabeled polypeptide, of at least a part of the subject's body using a medical imaging instrument, said image(s) indicating the presence of the radionuclide inside the body.
20. The method of claim 19 , wherein the radiolabeled HER3 binding polypeptide further comprises a second moiety comprising a polypeptide having a biological activity.
21. A method of treatment of a HER3-expressing cancer, comprising administering to a subject in need thereof an effective amount of a HER3 binding polypeptide of claim 1 .
22. The method of claim 21 , wherein the HER3 binding polypeptide further comprises a second moiety comprising a label or a polypeptide having a biological activity.
23. The method of claim 22 , wherein the second moiety is the polypeptide having a biological activity.
24. The method of claim 22 , wherein the second moiety is the label.