IP Library › Granted Patent US 12,594,291
Granted Patent B2
US 12,594,291 · App. 17/288,926 · Granted Apr 7, 2026

Intratumoral alpha-emitter radiation and activation of cytoplasmatic sensors for intracellular pathogen

Inventors: Vered Domankevich (Hod Hasharon, IL); Yona Keisari (Ramat Gan, IL); Itzhak Kelson (Tel Aviv, IL)
Assignee: Alpha Tau Medical Ltd
A61K31/7068A61K31/167A61K31/4406A61K31/454A61K31/497A61K31/675A61K31/708A61K39/12A61K39/39A61K45/06A61K47/34A61N5/1027A61P35/00A61K2039/525A61K2039/53A61K2039/55561A61K2039/585A61N2005/1024A61N2005/1098
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Quick Facts
Patent No.
US 12,594,291
App. No.
17/288,926
Granted
Apr 7, 2026
Kind
B2
Abstract

A method of treating a patient with a tumor, and kits ( 200 ) for such treatment. The method includes administering, to the patient, a substance ( 204 ) which activates cytoplasmatic sensors for intracellular pathogen in the tumor and treating the tumor with intra-tumoral alpha-emitter radiotherapy within two weeks of administering the substance which activates cytoplasmatic sensors for intracellular pathogen in the tumor.

Claims (65)

1 . A method of treating a patient with a tumor, comprising:

administering, to the patient, a substance including a pathogen mimic with a delivery agent suitable for cytoplasmic delivery of the pathogen mimic; and

treating the tumor with intra-tumoral alpha-emitter radiotherapy within two weeks of administering the substance.

2 . The method of claim 1 , wherein administering the pathogen mimic together with a delivery agent comprises administering a single dose of the pathogen mimic in a single session.

3 . The method of claim 1 , wherein administering the pathogen mimic together with a delivery agent comprises administering at least three doses of the pathogen mimic in respective separate sessions.

4 . The method of claim 1 , wherein administering the substance comprises administering the substance with a delivery agent suitable for targeted delivery.

5 . The method of claim 1 , wherein the delivery agent comprises a lipid based delivery agent.

6 . The method of claim 1 , wherein the delivery agent comprises a polymer based delivery agent.

7 . The method of claim 1 , wherein the delivery agent comprises a cationic polymer complex or a cationic lipid.

8 . The method of claim 1 , wherein the delivery agent comprises a liposome or a lipoplex.

9 . The method of claim 1 , wherein the delivery agent comprises polymeric micelles.

10 . The method of claim 1 , wherein the delivery agent comprises a solid nanoparticle.

11 . The method of claim 1 , wherein the delivery agent comprises a metal-based nanoparticle system.

12 . The method of claim 1 , wherein the delivery agent comprises polyethylenimine (PEI).

13 . The method of claim 1 , wherein administering the pathogen mimic comprises administering a bacteria mimic.

14 . The method of claim 1 , wherein administering the pathogen mimic comprises administering a viral mimic.

15 . The method of claim 14 , wherein administering the viral mimic comprises administering double stranded RNA (dsRNA).

16 . The method of claim 15 , wherein administering the dsRNA comprises administering polyIC.

17 . The method of claim 16 , wherein the delivery agent comprises polyethylenimine (PEI).

18 . The method of claim 15 , wherein administering the dsRNA comprises administering 5′ ppp-dsRNA.

19 . The method of claim 15 , wherein administering the dsRNA comprises administering 3p-hpRNA.

20 . The method of claim 15 , wherein administering the dsRNA comprises administering Poly(dA:dT).

21 . The method of claim 15 , wherein administering the dsRNA comprises administering poly-ICLC.

22 . The method of claim 15 , wherein administering the dsRNA comprises administering poly(A:U).

23 . The method of claim 15 , wherein administering the dsRNA comprises administering CpG rich RNA.

24 . The method of claim 1 , wherein administering the pathogen mimic comprises administering a pathogen mimic that is recognized by intracellular receptors as non-self.

25 . The method of claim 1 , further comprising administering an agent which induces production of molecules, which stimulate cytoplasmatic sensors for an intracellular pathogen, within cells of the tumor.

26 . The method of claim 25 , wherein administering the agent comprises administering a DNA methyltransferase (DNMT) inhibitor.

27 . The method of claim 26 , wherein administering the DNA methyltransferase (DNMT) inhibitor comprises administering Decitabine.

28 . The method of claim 26 , wherein administering the DNA methyltransferase (DNMT) inhibitor comprises administering Azacytidine.

29 . The method of claim 26 , wherein administering the DNA methyltransferase (DNMT) inhibitor comprises administering Guadecitabine.

30 . The method of claim 25 , wherein administering the agent comprises administering a histone deacetylase (HDAC) inhibitor.

31 . The method of claim 30 , wherein administering the histone deacetylase (HDAC) inhibitor comprises administering Entinostat.

32 . The method of claim 30 , wherein administering the histone deacetylase (HDAC) inhibitor comprises administering vorinostat.

33 . The method of claim 25 , further comprising additionally administering to the patient a supportive treatment of cyclophosphamide.

34 . The method of claim 1 , wherein treating the tumor with alpha-emitter radiotherapy comprises inserting a source carrying alpha-emitting radionuclides into the tumor.

35 . The method of claim 34 , wherein the source releases alpha-emitting radionuclides at a rate of less than 25% of the alpha-emitting radionuclides on the source when inserted to the tumor, per day.

36 . The method of claim 34 , wherein the source comprises a Radium source.

37 . The method of claim 1 , wherein treating the tumor with alpha-emitter radiotherapy is performed only after completing the administering of the substance.

38 . The method of claim 1 , wherein administering the substance comprises administering with nanoghosts, which direct the substance to the tumor.

39 . The method of claim 1 , wherein administering the substance comprises administering one or more substances in at least two separate sessions separated from each other by at least 12 hours.

40 . The method of claim 39 , wherein administering the one or more substances comprises administering in at least three separate sessions separated from each other by at least 20 hours.

41 . The method of claim 1 , and further comprising identifying a primary tumor in the patient and wherein administering the substance comprises administering the substance to the identified primary tumor.

42 . The method of claim 1 , wherein treating the tumor with alpha-emitter radiotherapy comprises treating with alpha-emitter radiotherapy less than 80 hours after administering a last dose of the substance.

43 . The method of claim 1 , wherein treating the tumor with alpha-emitter radiotherapy comprises treating with alpha-emitter radiotherapy less than 60 hours after administering a last dose of the substance.

44 . The method of claim 1 , wherein treating the tumor with alpha-emitter radiotherapy comprises treating with alpha-emitter radiotherapy at least 24 hours after administering a last dose of the substance.

45 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment which counters accelerated tissue repair induced by the alpha-emitter radiotherapy.

46 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment which downregulates inflammation.

47 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment which downregulates checkpoint expression.

48 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment of cyclophosphamide.

49 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment of pomalidomide.

50 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment of berzosertib.

51 . The method of claim 1 further comprising additionally administering to the patient a supportive treatment of a checkpoint blockade.

52 . The method of claim 51 , further comprising additionally administering to the patient a supportive treatment of anti PD-1.

53 . The method of claim 51 , further comprising additionally administering to the patient a supportive treatment of anti-PD-L1.

54 . The method of claim 51 , further comprising additionally administering to the patient a supportive treatment of anti-CTLA4.

55 . The method of claim 1 , further comprising additionally administering to the patient a supportive treatment of one or more TLR agonists.

56 . The method of claim 1 , further comprising additionally administering to the patient a supportive treatment of one or more MDSCs inhibitors.

57 . The method of claim 1 , further comprising additionally administering to the patient a supportive treatment of one or more Tregs inhibitors.

58 . The method of claim 1 , further comprising additionally administering to the patient a supportive treatment of one or more DNA repair inhibitors.

59 . The method of claim 1 , further comprising additionally administering to the patient a supportive treatment of one or more Antiangiogenic factors.

60 . The method of claim 1 , further comprising performing surgery to remove the tumor, at least a week after beginning treating the tumor with alpha-emitter radiotherapy.

61 . The method of claim 1 , wherein treating the tumor with intra-tumoral alpha-emitter radiotherapy comprises treating the tumor with intra-tumoral alpha-emitter radiotherapy less than a week after administering the substance which activates cytoplasmatic sensors for intracellular pathogen in the tumor.

62 . The method of claim 1 , wherein administering the substance comprises administering an oncolytic virus.

63 . The method of claim 1 , wherein the pathogen mimic comprises a STING ligand.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2021
From: DOMANKEVICH, VERED; KEISARI, YONA; KELSON, ITZHAK
To: ALPHA TAU MEDICAL LTD.
Reel/Frame 056046/0097 →
Continuity (2)
Provisional Application 62753930 · Nov 1, 2018
Related Publication 20210379096A1 · Dec 9, 2021
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