Molecular guide system peptides and uses thereof

Patent metadata

Field	Value
Publication number	US-12441774-B2
Application number	US-202318390354-A
Country	US
Kind code	B2
Filing date	Dec 20, 2023
Priority date	Jul 10, 2017
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.

First claim

What is claimed is:

1. A composition comprising an antibody conjugated to a molecular guidance system (MGS) peptide, directly or via a linker, wherein the MGS peptide is selected from the group consisting of:
YAAWPASGAWT (SEQ ID NO: 6), D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), KQYATPRVFWT (SEQ ID NO: 33), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL -PEG 11 -C-NH 2 (SEQ ID NO: 72), CH 3 CO-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 73), CH 3 CO-D-Leu-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 74), CH 3 CO-FHAVPQSFYT (SEQ ID NO: 80), CH 3 CO-D-Leu-RGDLATLRQL (SEQ ID NO: 81), CH3CO -YAAWPASGAWT (SEQ ID NO: 82), CH 3 CO-KQYATPRVFWT (SEQ ID NO: 84), and CH 3 CO-LQWRRNFGVWARYRL (SEQ ID NO: 85).

2. The composition of claim 1 , wherein the antibody targets an intracellular target, and wherein the MGS peptide is selected from the group consisting of:
YAAWPASGAWT (SEQ ID NO: 6), D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), KQYATPRVFWT (SEQ ID NO: 33), CH 3 CO -YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL -PEG 11 -C-NH 2 (SEQ ID NO: 72), CH 3 CO-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 73), CH 3 CO-D-Leu-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 74), CH 3 CO-FHAVPQSFYT (SEQ ID NO: 80), CH 3 CO-D-Leu-RGDLATLRQL (SEQ ID NO: 81), CH3CO-YAAWPASGAWT (SEQ ID NO: 82) and CH 3 CO-KQYATPRVFWT (SEQ ID NO: 84).

3. The composition of claim 1 , wherein the antibody is a monoclonal antibody.

4. The composition of claim 3 , wherein the monoclonal antibody is an anti-Ras monoclonal antibody.

5. The composition of claim 1 , wherein the antibody is conjugated to the MGS peptide via a linker.

6. The composition of claim 1 , wherein the antibody is conjugated to the MGS peptide as a fusion protein.

7. A method of targeting an intracellular target in a cell in vitro or in a subject, comprising contacting the cell with or administering to the subject a composition according to claim 1 , wherein the antibody targets an intracellular target.

8. The method of claim 7 , wherein the method comprises administering, to the subject having a disease in need thereof, an effective amount of the composition, and wherein the antibody targets the intracellular target involved in the disease process.

9. The method of claim 8 , wherein the subject in need thereof has an infectious disease, cancer, diabetes, a neurological or neurodegenerative disease, a genetically-inherited disease, or has been exposed to a bioterrorism agent.

10. The method of claim 7 , wherein the linker comprises polyethylene glycol (PEG).

11. A molecular guidance system (MGS) peptide selected from the group consisting of:
D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL-PEG 11 -C-NH 2 (SEQ ID NO: 72), and CH 3 CO-LQWRRNFGVWARYRL (SEQ ID NO: 85).

12. The MGS peptide of claim 11 , wherein the MGS peptide is conjugated to an antibody, directly or through a linker.

13. The MGS peptide of claim 12 , wherein the linker comprises polyethylene glycol (PEG).

14. The MGS peptide of claim 11 , wherein the MGS peptide is selected from the group consisting of:
D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), and CH 3 CO-LQWRRNFGVWARYRL-PEG 11 -C-NH 2 (SEQ ID NO: 72).

Assignees

• Stanford Res Inst Int

Inventors

• Brown Kathlynn C
• Collins Nathan
• Li Shunzi “Susan”
• Allred Curtis
• Chung Keen
• Mcguire Michael

Classifications

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• A61K38/00

  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 title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/64 Primary

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• G01N2500/10

  involving cells · CPC title