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

Patent metadata

Field	Value
Publication number	US-11059718-B2
Application number	US-201916524869-A
Country	US
Kind code	B2
Filing date	Jul 29, 2019
Priority date	Jun 22, 2009
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

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.

First claim

What is claimed is:

1. A composition comprising a CendR element and a co-composition, wherein the CendR element and the co-composition are indirectly non-covalently associated with each other, the CendR element and the co-composition are not covalently coupled with each other, and the CendR element and the co-composition are not directly non-covalently associated with each other, wherein the composition does not comprise VEGF, and 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, and wherein X 2 and X 3 can each be, independently, any amino acid.

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

3. The composition of claim 2 , wherein at least one of the accessory molecules comprises an RGD peptide, iRGD, a Lyp-1 peptide, a NGR peptide, iNGR, an RGR peptide, a HER2 binding peptide, or a combination.

4. The composition of claim 2 , 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.

5. The composition claim 4 , wherein one or more of the accessory molecules are homing molecules.

6. The composition of claim 2 , wherein the CendR element selectively homes to a tumor.

7. The composition of claim 6 , wherein the CendR element selectively homes to tumor vasculature.

8. The composition of claim 2 , wherein the CendR element selectively homes to lung tissue.

9. The composition of claim 2 , wherein the CendR element selectively homes to heart tissue.

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

11. The composition of claim 10 , wherein the activatable CendR element is a protease-activatable CendR element.

12. The composition of claim 1 , wherein the CendR element and the co-composition are not bound to each other.

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

14. The composition of claim 1 , wherein the co-composition comprises a detection agent.

15. The composition of claim 1 , wherein the co-composition comprises a carrier, vehicle, or both.

16. The composition of claim 1 , wherein the co-composition comprises a therapeutic protein, a therapeutic compound, a therapeutic composition, a cancer chemotherapeutic agent, a toxin, a cytotoxic agent, an anti-inflammatory agent, an anti-arthritic agent, a growth factor, a cytokine, a chemokine, a compound that modulates one or more signaling pathways, an antibody, a nucleic acid, a nucleic acid analog, a cell, a virus, a phage, a viral particle, a phage particle, a viral capsid, a phage capsid, a virus-like particle, a liposome, a micelle, a bead, a nanoparticle, a microparticle, a chemotherapeutic agent, a contrast agent, an imaging agent, a label, a labeling agent, an anti-angiogenic agent, a pro-angiogenic agent, or a combination.

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

18. The composition of claim 17 , wherein the amino acid sequence is comprised in a protein or peptide.

19. The composition of claim 1 , wherein the CendR element is comprised in a protein or peptide.

20. The composition of claim 6 , wherein the protein or peptide can be internalized into a cell, penetrate tissue, or both when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide.

21. The composition of claim 18 , wherein the protein or peptide can penetrate tissue when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide.

22. The composition of claim 18 , wherein the protein or peptide can be internalized into a cell and penetrate tissue when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide.

23. The composition of claim 17 , wherein the amino acid sequence can be internalized into a cell, penetrate tissue, or both without being associated with the co-composition.

24. The composition of claim 17 , wherein the amino acid sequence can penetrate tissue without being associated with the co-composition.

25. The composition of claim 17 , wherein the amino acid sequence can be internalized into a cell and penetrate tissue without being associated with the co-composition.

26. The composition of claim 17 , wherein the amino acid sequence is the only functional internalization element in the protein or peptide.

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

28. The composition of claim 18 , wherein the CendR element is at the C-terminal end of the protein or peptide.

29. The composition of claim 18 , wherein the internalization, penetration, or both of the co-composition into or through a cell, tissue, or both is enhanced when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide,
wherein the penetration of the co-composition into or through tissue is enhanced when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide,
wherein the internalization and penetration of the co-composition into or through a cell and tissue is enhanced when the amino acid sequence is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide,
wherein the internalization, penetration, or both of the co-composition into or through a cell, tissue, or both is enhanced when the CendR element is present in the protein or peptide but not when the CendR element is not present in the protein or peptide,
wherein the penetration of the co-composition into or through tissue is enhanced when the CendR element is present in the protein or peptide but not when the CendR element is not present in the protein or peptide, or
wherein the internalization and penetration of the co-composition into or through a cell and tissue is enhanced when the CendR element is present in the protein or peptide but not when the amino acid sequence is not present in the protein or peptide.

30. The composition of claim 1 , wherein the CendR element comprises a sequence selected from the group comprising R/K/HXXR/K/H (SEQ ID NO:20), R/KXXR/K (SEQ ID NO:23), and R/K/HXXKG (SEQ ID NO:21).

31. The composition of claim 30 , wherein the CendR element comprises a sequence selected from the group comprising RXXK, RXXH, KXXR, KXXH, HXXR, HXXK, and HXXH.

32. The composition of claim 1 , wherein there is no non-covalent bond involving an atom that is connected via a chain of covalent bonds to the CendR element and an atom that is connected via a chain of covalent bonds to the co-composition.

33. The composition of claim 1 , wherein the co-composition does not comprise a functional internalization element.

34. The composition of claim 1 , wherein the

Assignees

• Sanford Burnham Prebys Medical Discovery Inst
• Sanford Burnham Med Res Inst

Inventors

• Ruoslahti Erkki
• Teesalu Tambet
• Sugahara Kazuki

Classifications

• A61K47/66 Primary

  the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells · CPC title

• B82Y5/00 Primary

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C12Q1/02

  involving viable microorganisms · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title