# US 7,745,395 B2 · Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,395 B2 - Document ID: US7745395B2 - Status: Granted - Kind: B2 - Application number: 11/856,543 - Filed: 2007-09-17 - Published: 2008-04-17 - Granted: 2010-06-29 - Earliest claimed: 2001-08-24 - Assignees: University of Victoria Innovatiion and Development Corporation; The Johns Hopkins University - Inventors: Samuel R. Denmeade; John T. Isaacs; J. Thomas Buckley - Web page: https://patentgrep.com/patent/US7745395B2 ## CPC - C07K 14/195: from bacteria - A61K 39/001193: {Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR} - A61K 39/001194: {Prostate specific antigen [PSA]} - A61K 39/001195: {Prostate specific membrane antigen [PSMA]} - A61P 13/08: of the prostate - A61P 35/00: Antineoplastic agents - C07K 14/32: from Bacillus (G) - C07K 14/325: Bacillus thuringiensis crystal peptides, i.e. delta-endotoxins - C07K 14/33: from Clostridium (G) - C12N 9/52: derived from bacteria {or Archaea} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2319/00: Fusion polypeptide - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Disclosed herein are modified proaerolysin (PA) peptide. In some examples, the proteins include a prostate-specific protease cleavage site and can further include a prostate-tissue-specific binding domain which functionally replaces the native PA binding domain. In other examples, the proteins include a furin cleavage site and a prostate tissue-specific binding domain which functionally replaces the native PA binding domain. Methods of using such peptides to treat prostate cancer are also disclosed. ## Claims ### Claim 1 A purified peptide comprising the amino acid sequence shown in SEQ. ID NO:4. ### Claim 2 (depends on 1) The purified peptide of claim 1, wherein the peptide further comprises a polyhistidine tag. ### Claim 3 (depends on 2) The purified peptide of claim 2, wherein the polyhistidine tag comprises six histidines at the C-terminus of SEQ ID NO: 4. ### Claim 4 (depends on 1) A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with the peptide of claim 1. ### Claim 5 (depends on 4) The method of claim 4, wherein contacting prostate cancer cells of the subject with the peptide comprises administering the peptide to the subject. ### Claim 6 (depends on 5) The method of claim 5, wherein the peptide is administered intratumorally and/or intraprostatically. ### Claim 7 (depends on 5) The method of claim 5, wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally. ### Claim 8 (depends on 4) The method of claim 4, wherein the subject has a localized prostate tumor. ### Claim 9 (depends on 4) The method of claim 4, wherein the subject has a metastatic prostate tumor. ### Claim 10 (depends on 4) The method of claim 4, further comprising administering granulocyte macrophage colony stimulating factor [GM-CSF] to the subject. ### Claim 11 (depends on 4) The method of claim 4, further comprising administering irradiated prostate cancer cells to the subject. ### Claim 12 (depends on 4) The method of claim 4, wherein administration results in a reduction in prostate tumor cell volume. ### Claim 13 (depends on 4) The method of claim 4, wherein administration results in a reduction of a metastatic prostate tumor. ### Claim 14 (depends on 9) The method of claim 9, wherein administration results in treatment of the metastatic prostate tumor. ### Claim 15 A method for treating prostate cancer in a subject, comprising contacting prostate cancer cells of the subject with a peptide consisting of the amino acid sequence shown in SEQ ID NO:4. ### Claim 16 A method for treating prostate cancer in a subject, comprising administering a peptide consisting of the amino acid sequence shown in SEQ ID NO:4 to the subject. ### Claim 17 (depends on 16) The method of claim 16, wherein the peptide is administered intratumorally and/or intraprostatically. ### Claim 18 (depends on 16) The method of claim 16, wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally. ### Claim 19 (depends on 15) The method of claim 15, wherein the subject has a localized prostate tumor. ### Claim 20 (depends on 15) The method of claim 15, wherein the subject has a metastatic prostate tumor. ### Claim 21 (depends on 2) A method for treating prostate cancer in a subject, comprising administering the peptide of claim 2, to the subject. ### Claim 22 (depends on 21) The method of claim 21, wherein the peptide is administered intratumorally and/or intraprostatically. ### Claim 23 (depends on 21) The method of claim 21, wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally. ### Claim 24 (depends on 21) The method of claim 21, wherein the subject has a localized prostate tumor. ### Claim 25 (depends on 21) The method of claim 21, wherein the subject has a metastatic prostate tumor. ### Claim 26 (depends on 3) A method for treating prostate cancer in a subject, comprising administering the peptide of claim 3 to the subject. ### Claim 27 (depends on 26) The method of claim 26 wherein the peptide is administered intratumorally and/or intraprostatically. ### Claim 28 (depends on 26) The method of claim 26, wherein the peptide is administered intravenously, intramuscularly, subcutaneously, or orally. ### Claim 29 (depends on 26) The method of claim 26, wherein the subject has a localized prostate tumor. ### Claim 30 (depends on 26) The method of claim 26, wherein the subject has a metastatic prostate tumor.