POLYPEPTIDE WITH TUMOUR BINDING ACTIVITY

• US 20200131227A1
• Filed: 02/27/2018
• Published: 04/30/2020
• Est. Priority Date: 02/27/2017
• Status: Abandoned Application

• Current Assignee: Ruprecht-Karls-Universitã¤T Heidelberg
• Original Assignee: Ruprecht-Karls-Universitã¤T Heidelberg
• Inventors: HABERKORN, Uwe, MIER, Walter, SAUTER, Max, ALTMANN, Annette, HEROLD-MENDE, Christel, WARTA, Rolf, ROSCH, Saskia
• Application Number:
  US16/489,261
• Publication Number:
  US 20200131227A1
• Time in Patent Office: Days
• 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: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07K 14/70546 Integrin superfamily
• 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

Abstract

The present invention relates to a polypeptide with tumor binding activity, and its use in the treatment and diagnosis of cancer.

Claims

1. Polypeptide comprising the amino acid sequence of formula (I) or (II)

2. Polypeptide of claim 1 further comprising at least one compound selected from the group consisting of an imaging agent, a therapeutic agent, a linker group or a linker group linked to a therapeutic agent or an imaging agent.

3. Polypeptide of claim 1, wherein the therapeutic agent is present at R1 and/or R2 and is selected from the group consisting of small molecules, biopharmaceuticals, and combinations thereof.

4. Polypeptide of claim 3, wherein the therapeutic agent is a small molecule, and wherein the small molecule is an anti-cancer therapeutic.

5. Polypeptide of claim 3, wherein the therapeutic agent is a biopharmaceutical, and wherein the biopharmaceutical is a protein.

6. Polypeptide of claim 1, wherein the therapeutic agent is present at R1 and/or R2 and further comprises a radioisotope.

7. Polypeptide of claim 1, wherein the imaging agent is present at R1 and/or R2 and is a polydentate chelating agent.

8. Polypeptide of claim 7, wherein the polydentate chelating agent further comprises a radioisotope.

9. Polypeptide of claim 1, wherein the imaging agent is present at R1 and/or R2 and is a molecule comprising a radioisotope selected from the group consisting of 18F, HC, and combinations thereof.

10. Polypeptide of claim 9, wherein the imaging agent is selected from the group consisting of [¹¹C]metomidate, [N-methyl-¹¹C]vorozole, [¹¹C]glucose, and combinations thereof.

11. Polypeptide of claim 1, wherein the imaging agent is present at R1 and/or R2 and is a monodentate complex-forming molecule.

12. Polypeptide of claim 11, wherein the monodentate complex-forming molecule further comprises a radioisotope.

13. Polypeptide of claim 1, wherein the linker group is present at R1 and/or R2 and is selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, arylalkyl, alkoxy, aryloxy, amino, amide, silyl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carbonyl, carboxylic acid, ether, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, and combinations thereof.

14. Polypeptide of claim 1 for use in the treatment of cancer or in the diagnosis and/or evaluation of cancer.

15. Polypeptide of claim 14, wherein the cancer is selected from the group consisting of head and neck squamous cell carcinoma, hypopharynx carcinoma, collangiocarcinoma, breast cancer, brain cancer, pancreatic cancer, ovarian cancer, kidney cancer, bowel cancer, stomach cancer, cervical cancer, thyroid cancer, pancreatic cancer, gastric cancer, lung cancer, colorectal cancer, liver cancer.

16. Polypeptide of claim 1, wherein:

X₁ is an amino acid selected from the group consisting of F, W, T, G, A, I, L, M, V;

X₂ is an amino acid selected from the group consisting of M, A, I, L, V, G;

X₃ is an amino acid selected from the group consisting of Q, D, R and L;

Z₁ is an amino acid selected from the group consisting of F, M, A, V, I, L, Y and W, or not present;

Z₂ is an amino acid selected from the group consisting of T, Q, S, and N, or not present;

Z₃ is any amino acid or not present;

B₁ is an amino acid selected from the group consisting of G, A, H, K and R, and m is 2;

n is 0;

o is 0; and

B₄ is an amino acid selected from the group consisting of Y, W, P, E, and D, and p is

17. Polypeptide of claim 1, wherein:

X₁ is an amino acid selected from the group consisting of F and G;

X₂ is an amino acid selected from the group consisting of M and G;

X₃ is an amino acid selected from the group consisting of Q and R;

Z₁ is an amino acid selected from the group consisting of F, Y and W;

Z₂ is an amino acid selected from the group consisting of T and S;

Z₃ is any amino acid or not present;

B₁ in formula (I) is GH, GK, or GR, and B₁ in formula (II) is HG, KG, or KG;

n is 0;

o is 0; and

B₄ formula (I) is YPD, FPD, WPD, YPE, FPE or WPE and B₄ in formula (II) is DPY, DPF, DPW, EPY, EPF, or EPW.

18. Polypeptide of claim 1, wherein:

X₁ is F;

X₂ is M;

X₃ is Q;

Z_i is F;

Z₂ is T;

Z₃ is any amino acid or not present;

B₁ in formula (I) is GR and in formula (II) is RG, and m is 2;

n is 0;

o is 0;

B₄ is YPD in formula (I) and DPY in formula (II), and p is 3.

19. Polypeptide of claim 4, wherein the small molecule is selected from the group consisting of cyclophosphamide, methotrexate, 5-fluorouracil, mustine, vincristine, procarbazine, prednisolone, doxorubicin, bleomycin, vinblastine, dacarbazine, vincristine, etoposide, cisplatin, epirubicin, capecitabine, folinic acid, oxaliplatin, and combinations thereof.

3-1.