Therapeutic dendrimers

Patent metadata

Field	Value
Publication number	US-11717574-B2
Application number	US-202017095043-A
Country	US
Kind code	B2
Filing date	Nov 11, 2020
Priority date	Feb 22, 2017
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

Disclosed are dendrimers of formula (I):and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising the dendrimer of formula (I) and methods of using the same for treating cancer.

First claim

The invention claimed is:

1. A method of treating cancer comprising administering to a subject in need thereof an effective amount of a dendrimer of formula (III):
D -Core- D   (III),

or a pharmaceutically acceptable salt thereof;
wherein,
Core is

AP is an attachment point to another building unit;
W is independently (PM) c or (H) e ;
Z is independently (L-AA) a or (H) e ;
PM is PEG 1800-2400 ;
L-AA is a linker covalently attached to an active agent; wherein L-AA is of the formula:

wherein
wherein
A is —N(CH 3 );
(c+d) is an integer between 50 and 64; and
provided that if (c+d)<64, then any remaining W and Z groups are (H) e , wherein e is 64-(c+d); and d is ≥1.

2. The method of claim 1 , wherein the PEG has an average molecular weight of between about 2000 and about 2200 Da.

3. The method of claim 2 , wherein the PEG has an average molecular weight of about 2150 Da.

4. The method of claim 1 , wherein c is an integer between 25 and about 32.

5. The method of claim 4 , wherein c is an integer between 29 and 32.

6. The method of claim 5 , wherein c is 29 or 30.

7. The method of claim 1 , wherein d is an integer between 25 and 32.

8. The method of claim 7 , wherein d is an integer between 29 and 32.

9. The method of claim 8 , wherein d is 32.

10. The method of claim 1 , wherein (c+d) is equal to an integer between 58 and 64.

11. The method of claim 1 , wherein e is an integer between 0 and 14.

12. The method of claim 11 , wherein e is an integer between 0 and 6.

13. The method of claim 1 , wherein L-AA is

14. The method of claim 1 , wherein BU is

15. The method of claim 1 , wherein Core is

16. The method of claim 1 , wherein the dendrimer has a molecular weight of between about 90 and 120 kDa.

17. The method of claim 16 , wherein the dendrimer has a molecular weight of between about 103 and 107 kDa.

18. The method of claim 1 , wherein the cancer is a hematological or solid malignancy.

19. The method of claim 18 , wherein the hematological malignancy is selected from T-cell leukemias, T-cell lymphomas, acute lymphoblastic lymphoma (ALL), acute myelogenous leukemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), chronic myelogenous leukemia (CML), acute monocytic leukemia, multiple myeloma, mantle cell lymphoma, diffuse large B cell lymphoma (DLBCL), Burkitt's lymphoma, Non-Hodgkin's lymphoma, and follicular lymphoma.

20. The method of claim 18 , wherein the solid malignancy is selected from non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), breast cancer, neuroblastoma, ovarian cancer, prostate cancer, melanoma, pancreatic cancer, uterine, endometrial cancer, and colon cancer.

21. The method of claim 20 , wherein the NSCLC is EGF mutant NSCLC or KRAS mutant NSCLC.

22. The method of claim 20 , wherein the melanoma is BRAF mutant melanoma or KRAS mutant melanoma.

23. The method of claim 20 , wherein the colon cancer is KRAS mutant colon cancer or BRAF mutant colon cancer.

Assignees

• Astrazeneca Ab

Inventors

• Ashford Marianne Bernice
• Grant Iain
• Hennessy Edward John
• Mccoull William
• Giannis Michael
• Kelly Brian
• Owen David
• Secrist John Paul

Classifications

• A61K47/641 Primary

  Branched, dendritic or hypercomb peptides · CPC title

• A61K31/451 Primary

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C08G69/10

  Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)} · CPC title