IP Library › Granted Patent US 12,290,569
Granted Patent B2
US 12,290,569 · App. 17/373,496 · Granted May 6, 2025

Methods and compositions using peptides and proteins with c-terminal elements

Inventors: Erkki Ruoslahti (La Jolla, CA); Tambet Teesalu (La Jolla, CA); Kazuki Sugahara (La Jolla, CA)
Assignee: Sanford Burnham Prebys Medical Discovery Institute
A61K47/66B82Y5/00
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Quick Facts
Patent No.
US 12,290,569
App. No.
17/373,496
Granted
May 6, 2025
Kind
B2
Abstract

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

Claims (37)

1. A composition comprising a CendR element and a co-composition, wherein the CendR element and the co-composition are not covalently coupled and not directly non-covalently associated with each other,

wherein the CendR element comprises the sequence X 1 X 2 X 3 X 4 , wherein X 1 is selected from the group consisting of R, K or H,

wherein X 4 is selected from the group consisting of R, K, H, or KG,

wherein X 2 and X 3 can each be, independently, any amino acid, and

wherein the CendR element does not comprise RRLR (SEQ ID NO:248), RRRR (SEQ ID NO:249), CRCDKPRR (SEQ ID NO:95), or TKPPR (SEQ ID NO:98).

2. A method of enhancing internalization, penetration, or both of a co-composition into or through a cell, tissue, or both, the method comprising:

exposing the cell, tissue, or both to the composition of claim 1 , thereby enhancing internalization, penetration, or both of the co-composition into or through the cell, tissue, or both.

3. The method of claim 2 , wherein the cell, tissue, or both is in a subject.

4. The method of claim 3 , wherein the cell, tissue, or both are exposed to the CendR element and the co-composition by administering the CendR element and the co-composition to the subject.

5. The method of claim 2 , wherein the CendR element is associated with one or more accessory molecules.

6. The method of claim 5 , wherein one or more of the accessory molecules are independently a homing molecule, a targeting molecule, an affinity ligand, a cell penetrating peptide, an endosomal escape molecule, a subcellular targeting molecule, a nuclear targeting molecule, or a combination thereof.

7. The method of claim 5 , wherein the CendR element selectively homes to a tumor.

8. The method of claim 4 , wherein the CendR element and the co-composition are administered to the subject simultaneously.

9. The method of claim 8 , wherein the CendR element and the co-composition are administered to the subject in a single composition comprising the CendR element and the co-composition,

wherein the CendR element and the co-composition are indirectly non-covalently associated with each other.

10. The method of claim 2 , wherein the co-composition comprises a therapeutic agent.

11. The composition of claim 1 , wherein the CendR element is associated with one or more accessory molecules.

12. The composition of claim 11 , wherein one or more of the accessory molecules are independently a homing molecule, a targeting molecule, an affinity ligand, a cell penetrating peptide, an endosomal escape molecule, a subcellular targeting molecule, a nuclear targeting molecule, or a combination thereof.

13. The composition of claim 11 , wherein the CendR element selectively homes to a tumor.

14. The composition of claim 1 , wherein the CendR element is an activatable CendR element.

15. The composition of claim 14 , wherein the activatable CendR element is a protease-activatable CendR element.

16. The composition of claim 1 , wherein the co-composition comprises a therapeutic agent.

17. The composition of claim 1 , wherein the CendR element is comprised in an amino acid sequence,

wherein the amino acid sequence is comprised in a protein or peptide.

18. The composition of claim 17 , wherein the protein or peptide is circular.

19. A method of enhancing internalization, penetration, or both of a cargo composition into or through a cell, tissue, or both, the method comprising:

exposing the cell, tissue, or both to a composition comprising

(i) a co-composition; and

(ii) a CendR element conjugated to a cargo composition,

wherein the co-composition and the CendR element are not covalently coupled and not directly non-covalently associated with each other,

wherein the cargo composition and the CendR element are covalently coupled or non-covalently associated with each other,

wherein the CendR element comprises the sequence X 1 X 2 X 3 X 4 ,

wherein X 1 is selected from the group consisting of R, K or H,

wherein X 4 is selected from the group consisting of R, K, H, or KG,

wherein X 2 and X 3 can each be, independently, any amino acid,

wherein the CendR element enhances internalization, penetration, or both of the cargo composition into or through the cell, tissue, or both, and

wherein the CendR element does not comprise RRLR (SEQ ID NO:248), RRRR (SEQ ID NO:249), CRCDKPRR (SEQ ID NO:95), or TKPPR (SEQ ID NO:98).

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2021
From: RUOSLAHTI, ERKKI; TEESALU, TAMBET; SUGAHARA, KAZUKI
To: BURNHAM INSTITUTE FOR MEDICAL RESEARCH
Reel/Frame 057651/0745 →
CHANGE OF NAME Recorded Sep 30, 2021
From: BURNHAM INSTITUTE FOR MEDICAL RESEARCH
To: SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE
Reel/Frame 057675/0251 →
Continuity (5)
Continuation 16524869 · Jul 29, 2019
Continuation 12821050 · Jun 22, 2010
Provisional Application 61249140 · Oct 6, 2009
Provisional Application 61219086 · Jun 22, 2009
Related Publication 20220175941A1 · Jun 9, 2022
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