IP Library › Granted Patent US 12,453,762
Granted Patent B2
US 12,453,762 · App. 17/558,906 · Granted Oct 28, 2025

Complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for treatment of glioblastoma

Inventors: Madiha Derouazi (Grand-Saconnex, CH); Elodie Belnoue (Geneva, CH)
Assignee: Amal Therapeutics SA
A61K39/0011A61K38/10A61K38/17A61K38/177A61K38/18A61K40/19A61K40/24A61K40/42A61K40/4273A61K40/4277A61K47/42A61K47/64A61K47/6425A61K47/6803A61K47/6811A61K47/6865A61P1/00A61P35/00C07K7/06C07K7/08C07K14/47C07K14/475C07K19/00C12N5/10A61K2039/5154A61K2039/6031C07K2319/02C07K2319/03C07K2319/10C07K2319/33C07K2319/40C12N2710/16233Y02A50/30
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Quick Facts
Patent No.
US 12,453,762
App. No.
17/558,906
Granted
Oct 28, 2025
Kind
B2
Abstract

The present invention provides a novel complex for use in the prevention and/or treatment of glioma, in particular glioblastoma, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of glioma, in particular glioblastoma, such as a pharmaceutical compositions and vaccines are provided.

Claims (71)

1 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a complex comprising:

a) a cell penetrating peptide having an amino acid sequence consisting of SEQ ID NO: 6 (CPP/Z13);

b) at least one antigen or antigenic epitope, wherein the at least one antigen or antigenic epitope comprises at least one tumor epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist, having an amino acid sequence consisting of SEQ ID NO: 15,

wherein the components a)-c) are covalently linked.

2 . The method according to claim 1 , wherein the complex is a recombinant polypeptide or a recombinant protein.

3 . The method according to claim 1 , wherein the complex comprises more than one antigen or antigenic epitope.

4 . The method according to claim 1 , wherein the at least one tumor epitope is an epitope of an antigen selected from the group consisting of CMV, EGFRvIII, EphA2, gp100, Her2/neu, IL-13Rα2, survivin, hTert, TRP-2, MAGE-A1, MAGE-A3, YKL-40, brevican, neuroligin 4, and PTPRz1.

5 . The method according to claim 4 , wherein the complex comprises:

a) one or more epitopes of EGFRvIII or a functional variant thereof;

b) one or more epitopes of EphA2 or a functional variant thereof;

c) one or more epitopes of Her2/neu or a functional variant thereof;

d) one or more epitopes of IL-13Rα2 or a functional variant thereof;

e) one or more epitopes of survivin or a functional variant thereof;

f) one or more epitopes of TRP-2 or a functional variant thereof;

g) one or more epitopes of brevican or a functional variant thereof;

h) one or more epitopes of neuroligin 4 or a functional variant thereof; and/or

i) one or more epitopes of PTPRz1 or a functional variant thereof.

6 . The method according to claim 1 , wherein the at least one tumor epitope is an epitope of a glioma-specific neoantigen.

7 . The method according to claim 2 , wherein the components a) to c) of said complex are positioned in N-terminal→C-terminal direction in the order:

(α) component a)-component b)-component c); or

(β) component c)-component a)-component b).

8 . A method for treating glioma or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof, the method comprising administering to the subject a nucleic acid encoding the complex as defined in claim 1 , wherein the complex is a polypeptide or a protein.

9 . A method for treating glioma or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof, the method comprising administering to the subject a vector comprising the nucleic acid as defined in claim 8 .

10 . A method for treating glioma or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof, the method comprising administering to the subject a cell loaded with the complex as defined in claim 1 .

11 . The method according to claim 10 , wherein said cell is an antigen presenting cell.

12 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a vaccine comprising at least one of:

(i) a complex as defined in claim 1 ;

(ii) a nucleic acid encoding the complex as defined in (i);

(iii) a vector comprising the nucleic acid as defined in (ii);

(iv) a host cell comprising the vector as defined in (iii); or

(v) a cell loaded with the complex as defined in (i).

13 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising at least one complex as defined in claim 1 and a pharmaceutically acceptable carrier.

14 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a combination of

(i) a complex as defined in claim 1 ; and

(ii) a chemotherapeutic agent, a targeted drug and/or an immunotherapeutic agent.

15 . The method according to claim 1 , wherein the glioma is gliobastoma.

16 . The method according to claim 7 , wherein the components a) to c) of said complex are positioned in N-terminal→C-terminal direction in the order:

(α) component a)-component b)-component c).

17 . The method according to claim 7 , wherein the components are linked by a further component.

18 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a complex comprising:

a) a cell penetrating peptide, having an amino acid sequence consisting of SEQ ID NO: 6 (CPP/Z13);

b) at least one antigen or antigenic epitope, wherein the at least one antigen or antigenic epitope comprises at least one tumor epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist, having an amino acid sequence consisting of SEQ ID NO: 15,

wherein the components a)-c) are covalently linked, and

wherein the complex is a recombinant polypeptide or a recombinant protein.

19 . The method according to claim 18 , wherein the complex comprises more than one antigen or antigenic epitope.

20 . The method according to claim 18 , wherein the at least one tumor epitope is an epitope of an antigen selected from the group consisting of CMV, EGFRvIII, EphA2, gp100, Her2/neu, IL-13Rα2, survivin, hTert, TRP-2, MAGE-A1, MAGE-A3, YKL-40, brevican, neuroligin 4, and PTPRz1.

21 . The method according to claim 20 , wherein the complex comprises:

a) one or more epitopes of EGFRvIII or a functional variant thereof;

b) one or more epitopes of EphA2 or a functional variant thereof;

c) one or more epitopes of Her2/neu or a functional variant thereof;

d) one or more epitopes of IL-13Rα2 or a functional variant thereof;

e) one or more epitopes of survivin or a functional variant thereof;

f) one or more epitopes of TRP-2 or a functional variant thereof;

g) one or more epitopes of brevican or a functional variant thereof;

h) one or more epitopes of neuroligin 4 or a functional variant thereof; and/or

i) one or more epitopes of PTPRz1 or a functional variant thereof.

22 . The method according to claim 18 , wherein the at least one tumor epitope is an epitope of a glioma-specific neoantigen.

23 . The method according to claim 18 , wherein the components a) to c) of said complex are positioned in N-terminal→C-terminal direction in the order:

(α) component a)-component b)-component c); or

(β) component c)-component a)-component b).

24 . The method according to claim 23 , wherein the components a) to c) of said complex are positioned in N-terminal→C-terminal direction in the order:

(α) component a)-component b)-component c).

25 . The method according to claim 23 , wherein the components are linked by a further component.

26 . A method for treating glioma in a subject in need thereof, the method comprising administering to the subject a complex consisting of:

a) a cell penetrating peptide having an amino acid sequence consisting of SEQ ID NO: 6 (CPP/Z13);

b) at least one antigen or antigenic epitope, wherein the at least one antigen or antigenic epitope comprises at least one tumor epitope;

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist, having an amino acid sequence consisting of SEQ ID NO: 15,

wherein the components a)-c) are covalently linked, and

wherein the complex is a recombinant polypeptide or a recombinant protein.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 26, 2024
From: DEROUAZI, MADIHA; BELNOUE, ELODIE
To: AMAL THERAPEUTICS SA
Reel/Frame 066560/0243 →
Priority Claims (2)
WO PCT/EP2015/000580 · Mar 16, 2015 · international
WO PCT/EP2015/002244 · Nov 9, 2015 · international
Continuity (2)
Continuation 15557651
Related Publication 20220175933A1 · Jun 9, 2022
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