Granted Patent B2

US 12,514,927 · App. 17/773,494 · Granted Jan 6, 2026

Inventors: Darell Bigner (Mebane, NC); Vidyalakshmi Chandramohan (Durham, NC); Ira H. Pastan (Potomac, MD)

Assignees: Duke University; United States of America, as Represented by the Secretary Department of Health and Human Services

A61K47/6829A61K47/6849A61K47/6851A61P35/00C07K16/2863C07K16/2878A61K2039/507C07K2317/622C07K2317/75

Abstract

Claims (20)

1 . A method of treating a solid tumor expressing one or more of EGFRwt and EGFRvIII in an individual, comprising:

administering to the individual a therapeutically effective amount of an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody comprises a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5 and CDR3 of SEQ ID NO: 6; and

concurrently administering a therapeutically effective amount of an anti-CD40 agonist antibody to the individual, wherein the immunotoxin and anti-CD40 agonist antibody are administered intratumorally.

2 . The method of claim 1 , further comprising administering to the individual a therapeutically effective amount of a checkpoint inhibitor comprising one or more of an anti-PD1 antibody or anti-PD-L1 antibody.

3 . The method of claim 2 , wherein the checkpoint inhibitor is administered within 30 days of administering the immunotoxin.

4 . The method of claim 2 , wherein the checkpoint inhibitor is administered within between 7 and 14 days of administering the immunotoxin.

5 . The method of claim 1 , wherein the tumor is a malignant glioma.

6 . The method of claim 1 , wherein the tumor is breast cancer.

7 . The method of claim 1 , wherein the tumor is head and neck squamous cell carcinoma.

8 . The method of claim 1 , wherein the tumor is lung cancer.

9 . The method of claim 1 , wherein the truncated Pseudomonas exotoxin is fused to a KDEL (SEQ ID NO:14) peptide.

10 . The method of claim 1 , further comprising repeated administration of a therapeutically effective amount of an anti-CD40 agonist antibody to the individual.

11 . The method of claim 10 , wherein the repeated administration of the anti-CD40 agonist antibody is administered subcutaneously.

12 . A kit for treating a tumor, comprising:

an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody has a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6; and

an anti-CD40 agonist antibody, wherein the immunotoxin and anti-CD40 agonist antibody are formulated for intratumoral delivery.

13 . The kit of claim 12 , wherein the truncated Pseudomonas exotoxin is fused to a KDEL (SEQ ID NO: 14) peptide.

14 . The kit of claim 12 , further comprising a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

15 . A composition formulated for intratumoral delivery comprising an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody has a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6; and an anti-CD40 agonist antibody.

16 . The composition of claim 15 , further comprising a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

Assignments (2)

Continuity (3)

References Cited (119)