Selective delivery molecules and methods of use

• US 10,226,539 B2
• Filed: 08/24/2017
• Issued: 03/12/2019
• Est. Priority Date: 01/30/2013
• Status: Active Grant

• Current Assignee: Avelas BioSciences, Inc.
• Original Assignee: Avelas BioSciences, Inc.
• Inventors: Gonzalez, Jesus, Liu, Junjie
• Primary Examiner(s): Jones, D. L.
• Application Number:
  US15/685,942
• Publication Number:
  US 20180000971A1
• Time in Patent Office: 565 Days
• Field of Search: 424 111, 424 165, 424 169, 424 91, 424 92, 424 96, 514 1, 514 11, 514 192, 514 193, 514 194, 514 195, 514 196, 514 215, 530300, 530326, 530327
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/64 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 Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Disclosed herein is a selective delivery molecule comprising: (a) an acidic sequence (portion A) which is effective to inhibit or prevent the uptake into cells or tissue retention, (b) a molecular transport or tissue retention sequence (portion B), and (c) a linker between portion A and portion B, and (d) cargo moieties (portion D_A and D_B).

Claims

1. A selective delivery molecule having the structure of SDM-44:

2. A method of delivering Cy5 and Cy7 to a tissue of interest, comprising administering an effective amount of a selective delivery molecule of claim 1 to the tissue of interest.

3. The method of claim 2, wherein the tissue of interest is cancerous.

4. The method of claim 3, wherein the cancerous tissue is:

breast cancer tissue, colorectal cancer tissue, squamous cell carcinoma tissue, skin cancer tissue, prostate cancer tissue, melanoma tissue, thyroid cancer tissue, ovarian cancer tissue, cancerous lymph node tissue, cervical cancer tissue, lung cancer tissue, pancreatic cancer tissue, head and neck cancer tissue, or esophageal cancer tissue.

5. The method of claim 3, wherein the cancerous tissue is breast cancer tissue.

6. The method of claim 3, wherein the cancerous tissue is colorectal cancer tissue.

7. The tissue sample of claim 3, wherein the cancerous tissue is squamous cell carcinoma tissue.

8. The tissue sample of claim 3, wherein the cancerous tissue is skin cancer tissue.

9. The tissue sample of claim 3, wherein the cancerous tissue is cancerous lymph node tissue.

10. A method of visualizing a tissue of interest in an individual in need thereof, comprising:

(a) administering to the individual a selective delivery molecule of claim 1; and

(b) visualizing at least one of Cy5 or Cy7 of the selective delivery molecule.

11. The method of claim 10, wherein the cancerous tissue is:

breast cancer tissue, colorectal cancer tissue, squamous cell carcinoma tissue, skin cancer tissue, prostate cancer tissue, melanoma tissue, thyroid cancer tissue, ovarian cancer tissue, cancerous lymph node tissue, cervical cancer tissue, lung cancer tissue, pancreatic cancer tissue, head and neck cancer tissue, or esophageal cancer tissue.

12. The method of claim 11, wherein the cancerous tissue is breast cancer tissue.

13. The method of claim 11, wherein the cancerous tissue is colorectal cancer tissue.

14. The tissue sample of claim 11, wherein the cancerous tissue is squamous cell carcinoma tissue.

15. The tissue sample of claim 11, wherein the cancerous tissue is skin cancer tissue.

16. The tissue sample of claim 11, wherein the cancerous tissue is cancerous lymph node tissue.

17. The method of claim 11, further comprising surgically removing the tissue of interest from the individual.

18. The method of claim 17, further comprising preparing a tissue sample from the removed tissue of interest.

19. The method of claim 11, further comprising staging the cancerous tissue.

20. The method of claim 10, further comprising visualizing Cy5 or Cy7 of the selective delivery molecule by an emission ratio imaging method.

21. The method of claim 10, wherein the tissue of interest is visualized intraoperatively.

22. The method of claim 10, wherein the molecule is administered intravenously.

23. A tissue sample comprising a selective delivery molecule of claim 1.

24. The tissue sample of claim 23, wherein the tissue sample is cancerous.

25. The tissue sample of claim 24, wherein the cancerous tissue is:

breast cancer tissue, colorectal cancer tissue, squamous cell carcinoma tissue, skin cancer tissue, prostate cancer tissue, melanoma tissue, thyroid cancer tissue, ovarian cancer tissue, cancerous lymph node tissue, cervical cancer tissue, lung cancer tissue, pancreatic cancer tissue, head and neck cancer tissue, or esophageal cancer tissue.

26. The tissue sample of claim 24, wherein the cancerous tissue is breast cancer tissue.

27. The method of claim 24, wherein the cancerous tissue is colorectal cancer tissue.

28. The tissue sample of claim 24, wherein the cancerous tissue is squamous cell carcinoma tissue.

29. The tissue sample of claim 24, wherein the cancerous tissue is skin cancer tissue.

30. The tissue sample of claim 24, wherein the cancerous tissue is cancerous lymph node tissue.