Granted Patent B2

US 12,377,161 · App. 18/480,153 · Granted Aug 5, 2025

Inventor: Theresa Hemmerle (Otelfingen, CH)

Assignee: PHILOGEN S.P.A.

A61K47/6813A61P35/00A61K2039/505

Abstract

Claims (58)

1. A method of treating a brain tumor in a patient, comprising administering a TNFα immunoconjugate, the method comprising administering the TNFα immunoconjugate in combination with chemotherapy and radiotherapy to the patient, wherein the TNFα immunoconjugate comprises TNFα linked to an antibody molecule comprising L19 complementarity determining regions (CDRs), wherein the L19 CDRs are:

VH CDR1 

SEQ ID NO: 1

SFSMS 

VH CDR 2 

SEQ ID NO: 2

SISGSSGTTYYADSVKG 

VH CDR 3 

SEQ ID NO: 3

PFPYFDY 

VL CDR 1 

SEQ ID NO: 4

RASQSVSSSFLA 

VL CDR 2 

SEQ ID NO: 5

YASSRAT 

VL CDR 3 

SEQ ID NO: 6

QQTGRIPPT,

wherein the chemotherapy is temozolomide (TMZ), and wherein the brain tumor is a glioma.

2. The method of treatment according to claim 1 , wherein the antibody molecule comprises the L19 VH domain SEQ ID NO: 7 and the L19 VL domain SEQ ID NO: 9.

3. The method of treatment according to claim 1 , wherein the TNFα immunoconjugate comprises TNFα linked to L19 (scFv) as set forth in SEQ ID NO: 10.

4. The method of treatment according to claim 1 , wherein the TNFα immunoconjugate has an amino acid sequence of SEQ ID NO: 13.

5. The method of treatment according to claim 1 , wherein the immunoconjugate is administered by intravenous injection.

6. The according to claim 1 , wherein the immunoconjugate is administered by intratumoural injection or intrathecal injection.

7. The according to claim 1 , wherein the brain tumor is selected from a Grade III/IV glioma, a Grade III/IV glioma at first relapse, an isocitrate dehydrogenase (IDH) wildtype glioma, a Grade IV glioblastoma, a Grade IV glioblastoma at first relapse.

8. The according to claim 1 , wherein temozolomide (TMZ) is administered at 75-200 mg/m2.

9. The method of treatment according to claim 1 , wherein the radiotherapy is administered at 60 Gy/30 fractions.

10. The method of claim 1 , wherein the method comprises subsequent administrations of the TNFα immunoconjugate.

11. A method of treating a glioma in a patient, comprising administering a TNFα immunoconjugate in combination with chemotherapy and radiotherapy to the patient, wherein the TNFα immunoconjugate comprises TNFα linked to an antibody molecule comprising L19 complementarity determining regions (CDRs), wherein the L19 CDRs are:

VH CDR1

SEQ ID NO: 1

SFSMS

VH CDR 2

SEQ ID NO: 2

SISGSSGTTYYADSVKG

VH CDR 3

SEQ ID NO: 3

PFPYFDY

VL CDR 1

SEQ ID NO: 4

RASQSVSSSFLA

VL CDR 2

SEQ ID NO: 5

YASSRAT,

and

VL CDR 3

SEQ ID NO: 6

QQTGRIPPT;

wherein the chemotherapy is temozolomide (TMZ);

wherein the antibody molecule comprises the L19 VH domain SEQ ID NO: 7 and the L19 VL domain SEQ ID NO: 9;

wherein the TNFα immunoconjugate comprises TNFα linked to L19 (scFv) as set forth in SEQ ID NO: 10 and

the TNFα immunoconjugate has an amino acid sequence of SEQ ID NO: 13.

12. The method of claim 11 , wherein the immunoconjugate is administered by a route selected from intravenous injection, intratumoural injection, and intrathecal injection.

13. The method of claim 11 , wherein said glioma is selected from a Grade III/IV glioma, a Grade III/IV glioma at first relapse, an isocitrate dehydrogenase (IDH) wildtype glioma, a newly diagnosed glioblastoma, a newly diagnosed Grade IV glioblastoma, and a Grade IV glioblastoma at first relapse.

14. The method of claim 11 , wherein temozolomide (TMZ) is administered at 75-200 mg/m 2 .

15. The method of treatment according to claim 11 , wherein the radiotherapy is administered at 60 Gy/30 fractions.

16. The method of claim 11 further comprising subsequent administrations of the TNFα immunoconjugate.

Priority Claims (1)

Continuity (2)

References Cited (40)