IP Library Granted Patent US 11,730,736
Granted Patent B2
US 11,730,736 · App. 16/181,200 · Granted Aug 22, 2023

Anticancer agents

Inventors: Gene Cutler (San Francisco, CA); William Yew-Wai Ho (San Francisco, CA); Paul David Kassner (San Mateo, CA); Silpa Suthram (San Jose, CA); Brian Russell Wong (Los Altos, CA)
Assignee: RAPT Therapeutics, Inc.
A61K31/4985A61K31/497A61K31/506A61K31/519A61K31/5377A61K45/06
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Quick Facts
Patent No.
US 11,730,736
App. No.
16/181,200
Granted
Aug 22, 2023
Kind
B2
Abstract

Disclosed herein are therapeutic methods of administering compounds that modulate the C—C chemokine receptor type 4 (CCR4) for the treatment of Epstein Bar virus (EBV) positive cancers and malignancies.

Claims (23)

1. A method of treating a malignancy that is positive for Epstein Barr Virus (EBV), the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

L 7 is a bond, unsubstituted alkylene or unsubstituted heteroalkylene;

R 3.2 and R 3.3 are independently halogen;

R 4 is —CX 4.1 3 , —CN, or unsubstituted C 1 -C 4 alkyl;

R 7 is hydrogen, —C(O)R 7D , —C(O)NR 7B R 7C , OR 7A , —NR 7B C(O)R 7D , substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl;

R 7A , R 7B , R 7C , and R 7D are independently hydrogen or substituted or unsubstituted alkyl; and

X 4.1 is —Cl, —Br, —I or —F.

2. The method of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the EBV positive malignancy is Burkitt's lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, NK/T-cell lymphoma, cutaneous T-cell lymphoma, nasopharyngeal carcinoma, gastric cancer, vulvar squamous cell carcinoma, salivary gland cancer, orbit choroidal melanoma, or adenocarcinoma consistent with pancreaticobiliary.

4. The method of claim 3 , further comprising co-administering to a subject in need thereof a chemotherapeutic agent or anticancer agent.

5. The method of claim 4 , wherein the chemotherapeutic agent or anticancer agent is an antiproliferative/antineoplastic drug, an antimetabolite, an antitumor antibiotic, an antimitotic agent, a topoisomerase inhibitor, a cytostatic agent, an estrogen receptor down regulator, an antiandrogen, a LHRH antagonist or LHRH agonist, a progestogen, an aromatase inhibitor, an inhibitor of 5-alpha-reductase, an agent which inhibits cancer cell invasion, an inhibitor of growth factor function, a farnesyl transferase inhibitor, a tyrosine kinase inhibitor, a serine/threonine kinase inhibitor, an inhibitor of the epidermal growth factor family, an inhibitor of the platelet-derived growth factor family, an inhibitor of the hepatocyte growth factor family; an antiangiogenic agent, a vascular damaging agent, an antisense therapy agent, an anti-ras antisense agent, an gene therapy agent, an immunotherapeutic agent, or an antibody.

6. The method of claim 5 , wherein the chemotherapeutic agent or anticancer agent is an anti-proliferative agent, a chemotherapeutic agent, an antimetabolite, an antimicrotubule agent, an alkylating agent, a platinum agent, an anthracycline, an antitumor antibiotic, a topoisomerase inhibitor, a purine antagonist, a pyrimidine antagonist, a cell maturing agent, a DNA repair enzyme inhibitor, an enzyme that prevents cell survival, a histone deacetylase inhibitor, a cytotoxic agent, a hormone, an antibody, an immuno-modulator, a Bcr-Abl kinase inhibitor, a hormone agonist or antagonist, partial agonist or partial antagonist, a kinase inhibitor, surgery, radiotherapy, an endocrine therapy, a biological response modifier, a hyperthermial agent, a cryotherapeutic agent, an immuomodulating agent, an agent to attenuate any adverse effects, a spindle poison, a podophyllotoxin, an antibiotic, or a nitrosourea.

7. The method of claim 6 , wherein the antimetabolite is 5-fluoro uracil, methotrexate, azacitidine, decitabine, fludarabine or cytarabine.

8. The method of claim 6 , wherein the antimicrotubule agent is a vinca alkaloid or a taxane.

9. The method of claim 6 , wherein the alkylating agent is mechlorethamine, chlorambucil, cyclophosphamide, melphalan, carmustine, lomustine, ifosfamide, busulfan, dacarbazine, bischloroethylnitrosurea or hydroxyurea.

10. The method of claim 6 , wherein the platinum agent is cisplatin, carboplatin, oxaliplatin, satraplatin (JM-216) or CI-973.

11. The method of claim 5 , wherein the chemotherapeutic agent or anticancer agent is an antibody.

12. The method of claim 5 , wherein the chemotherapeutic agent or anticancer agent is an immunomodulating agent.

13. Use of the compound of claim 1 to treat a malignancy that is positive for Epstein Barr Virus (EBV), wherein the use comprises administering to a subject in need thereof a therapeutically effective amount of the compound of formula (I).

14. The method of claim 1 , wherein R 4 is —CX 4.1 3 , —CN, or methyl.

15. The method of claim 5 , wherein the chemotherapeutic agent is pembrolizumab.

Assignments (2)
CHANGE OF NAME Recorded Apr 7, 2020
From: FLX BIO, INC.
To: RAPT THERAPEUTICS, INC.
Reel/Frame 052332/0595 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 11, 2018
From: CUTLER, GENE; HO, WILLIAM YEW-WAI; KASSNER, PAUL DAVID; SUTHRAM, SILPA; WONG, BRIAN RUSSELL
To: FLX BIO, INC.
Reel/Frame 047748/0296 →
Continuity (3)
Provisional Application 62723415 · Aug 27, 2018
Provisional Application 62582284 · Nov 6, 2017
Related Publication 20190134031A1 · May 9, 2019
Cited By (1)
US 12,240,837