Peptide saporin conjugate for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-11738089-B2
Application number	US-201816629803-A
Country	US
Kind code	B2
Filing date	Jul 10, 2018
Priority date	Jul 10, 2017
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

Disclosed herein, are compositions comprising one or more molecular guidance system (MGS) peptides and a cytotoxic agent. Also described herein, are methods of administering the compositions to patients with cancer.

First claim

What is claimed is:

1. A composition comprising one or more molecular guidance system (MGS) peptide(s) covalently attached to a cytotoxic agent, directly or through a linker, wherein the MGS peptide(s) is/are selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84.

2. The composition of claim 1 , wherein the cytotoxic agent is saporin.

3. The composition of claim 1 , wherein the composition comprises two MGS peptides conjugated to one or more cytotoxic agents via one or more chemical linkers, wherein the linkers are covalently linked to one another to form a dimeric structure, and wherein the peptides are not directly linked to each other.

4. The composition of claim 1 , wherein the composition comprises four MGS peptides conjugated to one or more cytotoxic agents via one or more chemical linkers, wherein the linkers are covalently linked to one another and form a tetrameric structure, and wherein the peptides are not directly linked to each other.

5. The composition of claim 1 , wherein the MGS peptide is SEQ ID NO:3 and the cytotoxic agent is saporin.

6. The composition of claim 1 , wherein the linker comprises polyethylene glycol (PEG).

7. The composition of claim 1 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; wherein the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.

8. A pharmaceutical composition comprising the composition of any one of claims 1 , and 7 and a pharmaceutically acceptable carrier.

9. A method of treating a cancer, the method comprising: (a) identifying a patient in need of treatment; (b) administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 8 , wherein the cancer is lung cancer, breast cancer, colorectal cancer, ovarian cancer, or pancreatic cancer.

10. The method of claim 9 , wherein the cancer is a primary, secondary, refractory, or relapsing tumor.

11. The method of claim 9 , further comprising administering to the patient a therapeutically effective amount of radiation therapy, immunotherapy, chemotherapy, or a combination thereof.

12. A method of targeting an intracellular target, the method comprising administering one or more MGS peptide(s) covalently attached to a cytotoxic agent directly or through a linker, wherein the MGS peptide(s) is/are selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84, and wherein the cytotoxic agent targets an intracellular target.

13. The method of claim 12 , wherein the intracellular target is the lysosome.

14. An MGS peptide selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84.

15. The method of claim 12 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.

16. The method of claim 9 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.

17. The composition of claim 3 or 4 , wherein the MGS peptide is selected from SEQ ID NO. 80, 81, 82, and 84.

18. The pharmaceutical composition of claim 8 , wherein the cytotoxic agent is a toxin.

Assignees

• Stanford Res Inst Int

Inventors

• Brown Kathlynn C
• Allred Curtis
• Mcguire Michael

Classifications

• C07K2319/06

  containing a lysosomal/endosomal localisation signal · CPC title

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title

• C07K2319/55

  containing a fusion with a toxin, e.g. diphteria toxin · CPC title

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title