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Last Updated: March 29, 2024

Claims for Patent: 8,217,012


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Summary for Patent: 8,217,012
Title:Peptides for targeting apoptotic cells and uses thereof
Abstract: A peptide capable of specifically targeting apoptotic cells undergoing apoptosis and a use thereof is described. Peptides having an amino acid sequence represented by any one of SEQ ID NO: 1 to SEQ ID NO: 12 targeted apoptotic cell. Uses for compositions comprising the peptides include detection of apoptotic cells drug delivery and imaging. The peptide of the present invention effectively detects apoptosis which is involved in tissues of neoplastic disease, myocardial infarction, stroke and arteriosclerosis. Accordingly, the peptide of the present invention may be bound to an imaging or treatment reagent to be used in diagnosis of diseases, imaging of drug reactions, and treatment for diseases by selective drug delivery.
Inventor(s): Lee; Byung Heon (Daegu, KR), Kim; In San (Daegu, KR)
Assignee: Kyungpook National University Industry-Academic Cooperation Foundation (Daegu, KR)
Application Number:12/465,007
Patent Claims:1. An isolated polypeptide consisting of SEQ ID NO: 1 or 3 and specifically binding apoptotic cells.

2. A method for detecting apoptotic cells comprising the steps of: (a) mixing the polypeptide of claim 1 with a sample; (b) removing unbound or unspecifically bound polypeptide; and (c) detecting the binding and the location of the polypeptide.

3. The method of claim 2, wherein the polypeptide is labeled with a labeling agent selected from the group consisting of coloring enzyme, radioactive isotope, chromophore, scintillating material, fluorescer, super paramagnetic particles and ultrasuper paramagnetic particles.

4. A method for drug delivery comprising administering the polypeptide of claim 1 and a drug bound thereto to a subject in need thereof at an effective dose.

5. The method of claim 4, wherein the method is specific to the disease selected from the group consisting of neoplastic disease, stroke, myocardial infarction and arteriosclerosis.

6. The method of claim 4, wherein the neoplastic disease is selected from the group consisting of colon cancer, lung cancer, stomach cancer, esophageal cancer, pancreatic cancer, gallbladder cancer, renal cancer, bladder cancer, prostate cancer, testicular cancer, cervical cancer, endometrial cancer, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain cancer, head and neck cancer, malignant melanoma , skin cancer, liver cancer, leukemia, lymphoma, multiple myeloma, chronic myelogenous leukemia, neuroblastoma and aplastic anemia.

7. The method of claim 4, wherein the drug is selected from the group consisting of paclitaxel, doxorubicin, vincristine, daunorubicin, vinblastine, actinomycin-D, docetaxel, etoposide, teniposide, bisantrene, homoharringtonine, Gleevec (STI-571), cisplatin, 5-fluorouracil, Adriamycin, methotrexate, busulfan, chlorambucil, cyclophosphamide, melphalan, nitrogen mustard, nitrosourea, streptokinase, urokinase, alteplase, angiotensin II inhibitor, aldosterone receptor inhibitor, erythropoietin, NMDA (N -methyl-D-aspartate) receptor inhibitor lovastatin, rapamycin, Celebrex, Ticlopin, Marimastat and Trocade.

8. A pharmaceutical composition for treating neoplastic disease comprising i) an isolated polypeptide consisting of SEQ ID NO: 1 or 3 and specifically binding apoptotic cells; and ii) an antitumor agent bound thereto as effective ingredients, wherein the antitumor agent is selected from the group consisting of paclitaxel, doxorubicin, vincristine, daunorubicin, vinblastine, actinomycin-D, docetaxel, etoposide, teniposide, bisantrene, homoharringtonine, Gleevec (STI-571), cisplatin, 5-fluorouracil, adriamycin, methotrexate, busulfan, chlorambucil, cyclophosphamide, melphalan, nitrogen mustard and nitrosourea; wherein the neoplastic disease is selected from the group consisting of colon cancer, lung cancer, stomach cancer, esophageal cancer, pancreatic cancer, gallbladder cancer, renal cancer, bladder cancer, prostate cancer, testicular cancer, cervical cancer, endometrial cancer, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain cancer, head and neck cancer, malignant melanoma, skin cancer, liver cancer, leukemia, lymphoma, multiple myeloma, chronic myelogenous leukemia, neuroblastoma and aplastic anemia.

9. A pharmaceutical composition for treating stroke comprising i) an isolated polypeptide consisting of SEQ ID NO: 1 or 3 and specifically binding apoptotic cells; and ii) an anti-stroke agent bound thereto as effective ingredients, wherein the anti-stroke agent is selected from the group consisting of streptokinase, urokinase and alteplase.

10. A pharmaceutical composition for treating myocardial infarction comprising i) an isolated polypeptide consisting of SEQ ID NO: 1 or 3 and specifically binding apoptotic cells; and ii) an anti-myocardial infarction agent bound thereto as effective ingredients, wherein the anti-myocardial infarction agent is selected from the group consisting of streptokinase, urokinase, alteplase, angiotensin II inhibitor, aldosterone receptor inhibitor, erythropoietin and N-methyl-D-aspartate receptor inhibitor.

11. A pharmaceutical composition for treating arteriosclerosis comprising i) an isolated polypeptide consisting of SEQ ID NO: 1 or 3 and specifically binding apoptotic cells; and ii) an anti-arteriosclerosis agent bound thereto as effective ingredients, wherein the anti-arteriosclerosis agent is selected from the group consisting of lovastatin, rapamycin, Celebrex, Ticlogin, Marimastat, and Trocade.

12. A method for treating neoplastic disease comprising administering the polypeptide of claim 1 and an antitumor agent bound thereto to a subject in need thereof at an effective dose; wherein the antitumor agent is selected from the group consisting of paclitaxel, doxorubicin, vincristine, daunorubicin, vinblastine, actinomycin-D, docetaxel, etoposide, teniposide, bisantrene, homoharringtonine, Gleevec (STI-571), cisplatin, 5-fluorouracil, adriamycin, methotrexate, busulfan, chlorambucil, cyclophosphamide, melphalan, nitrogen mustard and nitrosourea; and wherein the neoplastic disease is selected from the group consisting of colon cancer, lung cancer, stomach cancer, esophageal cancer, pancreatic cancer, gallbladder cancer, renal cancer, bladder cancer, prostate cancer, testicular cancer, cervical cancer, endometrial cancer, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain cancer, head and neck cancer, malignant melanoma , skin cancer, liver cancer, leukemia, lymphoma, multiple myeloma, chronic myelogenous leukemia, neuroblastoma and aplastic anemia.

13. A method for treating stroke comprising administering the polypeptide of claim 1 and an antistroke agent bound thereto to a subject in need thereof at an effective dose; wherein the anti-stroke agent is selected from the group consisting of streptokinase, urokinase, and alteplase.

14. A method for treating myocardial infarction comprising administering the polypeptide of claim 1 and an anti-myocardial infarction agent bound thereto to a subject in need thereof at an effective dose; wherein the anti-myocardial infarction agent is selected from the group consisting of streptokinase, urokinase, alteplase, angiotensin II inhibitor, aldosterone receptor inhibitor, erythropoietin and N -methyl-D-aspartate receptor inhibitor.

15. A method for treating arteriosclerosis comprising administering the polypeptide of claim 1 and an anti-arteriosclerosis agent bound thereto to a subject in need thereof at an effective dose; wherein the anti-arteriosclerosis agent is selected from the group consisting of lovastatin, rapamycin, Celebrex, Ticlogin, Marimastat and Trocade.

16. A method for imaging a site of disease selected from the group consisting of neoplastic disease, stroke, myocardial infarction and arteriosclerosis comprising administering the polypeptide of claim 1 labeled with a labeling agent, to a subject in need thereof at an effective dose.

17. The method of claim 16, wherein the labeling agent is selected from the group consisting of coloring enzyme, radioactive isotope, chromophore, scintillating material, fluorescer, super paramagnetic particles and ultrasuper paramagnetic particles.

Details for Patent 8,217,012

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Microbix Biosystems Inc. KINLYTIC urokinase For Injection 021846 01/16/1978 ⤷  Try a Trial 2028-05-14
Genentech, Inc. ACTIVASE alteplase For Injection 103172 11/13/1987 ⤷  Try a Trial 2028-05-14
Genentech, Inc. CATHFLO ACTIVASE alteplase For Injection 103172 09/04/2001 ⤷  Try a Trial 2028-05-14
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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