IP Library › Granted Patent US 12691158
Granted Patent B2
US 12691158 · App. 17/203,469 · Granted Jul 28, 2026

Albumin-proaerolysin prodrugs

Inventors: John T. Isaacs (Phoenix, MD); Samuel R. Denmeade (Ellicott City, MD); W. Nathaniel Brennen (Baltimore, MD)
Assignee: THE JOHNS HOPKINS UNIVERSITY
A61K38/164A61K35/16A61K38/385A61K47/643A61K47/65C07K14/4748C07K14/765C07K19/00C07K2319/21
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Quick Facts
Patent No.
US 12691158
App. No.
17/203,469
Granted
Jul 28, 2026
Kind
B2
Abstract

The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods for treating cancer using albumin-proaerolysin prodrugs. Accordingly, in one aspect, the present invention provides prodrug compositions. In certain embodiments, a prodrug composition comprises a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA; and human serum albumin (HSA) or a fragment thereof fused to the N-terminus of the PSA-activated PA.

Claims (14)

1 . A method of treating prostate cancer or benign prostatic hyperplasia (BPH) in a subject, comprising administering to the subject an effective amount of a prodrug composition comprising;

a. a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA comprising SEQ ID NO: 2; and

b. human serum albumin (HSA), or a fragment thereof, fused to the N-terminus of the PSA-activated PA with a linker sequence comprising at least one PSA cleavable site,

wherein the prodrug composition is administered systemically, and

wherein the prodrug does not bind to GPI-anchored proteins on normal cells thereby lowering non-specific toxicity in subject tissues as compared to administration of the PSA-activated PA alone.

2 . The method of claim 1 , wherein the PSA cleavable linker comprises SEQ ID NO: 5.

3 . The method of claim 1 , wherein the PSA cleavable linker replaces the amino acids at position 427-432 of SEQ ID NO: 2.

4 . The method of claim 1 , wherein the at least one PSA-cleavable site comprises SEQ ID NO: 5.

5 . The method of claim 1 , wherein the HSA or fragment thereof is fused to the N-terminus of the PSA-activated PA with a linker sequence comprising four PSA cleavable sites having SEQ ID NO: 5.

6 . The method of claim 1 , wherein the human serum albumin (HSA), or a fragment thereof, comprises SEQ ID NO: 27, or a fragment of at least 100 amino acids.

7 . The method of claim 6 , wherein the prostate-specific antigen (PSA)-activated pro-aerolysin (PA) comprises SEQ ID NO: 4.

8 . The method of claim 1 , wherein the human serum albumin (HSA), or a fragment thereof, comprises SEQ ID NO: 27, or at least one whole domain thereof.

9 . The method of claim 8 , wherein the prostate-specific antigen (PSA)-activated pro-aerolysin (PA) comprises SEQ ID NO: 4.

10 . The method of claim 1 , wherein the prostate-specific antigen (PSA)-activated pro-aerolysin (PA) comprises SEQ ID NO: 4.