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Generated: September 19, 2017

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Title:Methods and compositions for targeting adipose cells in mammals
Abstract: Methods and compositions are presented for use in diagnostic, imaging or targeting of therapeutic agents to treat obesity/adiposity-associated disorders, compositions and methods identify and use peptides to selectively target adipose tissue stromal cells in mammals.
Inventor(s): Kolonin; Mikhail G. (Houston, TX), Daquinag; Alexes (Houston, TX), Zhang; Yan (Houston, TX)
Assignee: BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX)
Application Number:14/682,335
Patent Claims:1. A polypeptide comprising the amino acid sequence selected from the group consisting of CSWKYWFGEC (SEQ ID NO:13) and SWKYWFGE (SEQ ID NO:14), wherein the polypeptide binds to cells that express a proteolytic cleavage product of decorin (ADCN).

2. The polypeptide of claim 1, wherein the peptide comprises the amino acid sequence of CSWKYWFGEC (SEQ ID NO:13).

3. The polypeptide of claim 1, wherein said polypeptide is composed entirely of D-amino acids.

4. The polypeptide of claim 1, wherein said polypeptide is coupled to an effector agent selected from the group consisting of: an imaging agent; a cytotoxic agent; a pro-apoptotic agent; a fusion protein; a cytostatic agent; a cytocidal agent; radioisotope; an adipose stromal cell (ASC) cell differentiating agent; mitotic inhibitors; antitumor agent; antibiotic agent; enzymes; chemotherapeutic agent; anti-angiogenic agent or a combination thereof.

5. The polypeptide of claim 4, wherein said polypeptide and effector agent are comprised of D-amino acids.

6. The polypeptide of claim 4 wherein said effector agent is selected from the group consisting of: gramicidin; magainin; mellitin; defensin; cecropin; (KFAKFAK).sub.2 (SEQ ID NO: 37); (KFXAKFXAK).sub.2 (SEQ ID NO: 38); (KHexAKHexAK).sub.2(KLAKLAK).sub.2 (SEQ ID NO: 43); (KLAKKLA).sub.2 (SEQ ID NO: 32); (KAAKKAA).sub.2 (SEQ ID NO: 33); (KLGKKLG).sub.3 (SEQ ID NO: 34); angiotensin; laminin peptides; fibronectin peptides; plasminogen activator inhibitors; tissue metalloproteinase inhibitors; interferons; interleukin 12; platelet factor 4; IP-10; Gro-13; thrombospondin; 2-methoxyoestradiol; proliferin-related protein; carboxiamidotriazole; CM101; Marimastat; pentosan polysulphate; angiopoietin 2; interferon-alpha; herbimycin A; PNU145156E; 16K prolactin fragment; thalidomide; pentoxifylline; genistein; TNP470; endostatin; paclitaxel; accutin; angiostatin; cidofovir; vincristine; AGM-1470; platelet factor 4 or minocycline; 5-fluorouracil; bleomycin; busulfan; camptothecin; carboplatin; chlorambucil; cisplatin (CDDP); cyclophosphamide; dactinomycin; daunorubicin; doxorubicin; estrogen receptor binding agents; etoposide (VP16); farnesyl-protein transferase inhibitors; gemcitabine; ifosfamide; mechlorethamine; melphalan; mitomycin; navelbine; raloxifene; tamoxifen; taxol; temazolomide; transplatinum; vinblastine and methotrexate; alkylating agents; antimetabolites; antitumor antibiotics; corticosteroid hormones; mitotic inhibitors; nitrosoureas; hormone agents; mitotic inhibitors; enzymes; plant alkaloids; docetaxel; teniposide; vinorelbine; PPAR-gamma agonists; thiazolidinediones; rosiglitazone; fluorophores; metal chelate complexes; radioisotopes; fluorescent markers; urease; alkaline phosphatase; liposomes; microcapsules; microparticles; nanoparticles; magnetic beads; microdevices; plicamycin; platinum coordination complexes; anthracenediones; substituted ureas; methyl hydrazine derivatives; amsacrine; L-asparaginase; tretinoin; mitoxantrone; hydroxyurea; procarbazine; IgFc fusion proteins; enzyme fusion proteins; fluorescent proteins; luminescent proteins and combinations thereof.

7. A method of treating cancer in a subject comprising administering an effective amount of a polypeptide according to claim 1 to the subject, wherein said polypeptide is coupled to an effector agent and wherein the subject comprises adipose stromal cells in the tumor tissue.

8. The method of claim 7, wherein the effector agent is a cytotoxic agent.

9. The method of claim 8, wherein the effector agent is a chemotherapeutic agent.

10. The method of claim 7 wherein said effector agent is selected from the group consisting of: gramicidin; magainin; mellitin; defensin; cecropin; (KFAKFAK).sub.2 (SEQ ID NO: 37); (KFXAKFXAK).sub.2 (SEQ ID NO: 38); (KHexAKHexAK).sub.2(KLAKLAK).sub.2 (SEQ ID NO: 43); (KLAKKLA).sub.2 (SEQ ID NO: 32); (KAAKKAA).sub.2 (SEQ ID NO: 33); (KLGKKLG).sub.3 (SEQ ID NO: 34); angiotensin; laminin peptides; fibronectin peptides; plasminogen activator inhibitors; tissue metalloproteinase inhibitors; interferons; interleukin 12; platelet factor 4; IP-10; Gro-13; thrombospondin; 2-methoxyoestradiol; proliferin-related protein; carboxiamidotriazole; CM101; Marimastat; pentosan polysulphate; angiopoietin 2; interferon-alpha; herbimycin A; PNU145156E; 16K prolactin fragment; thalidomide; pentoxifylline; genistein; TNP470; endostatin; paclitaxel; accutin; angiostatin; cidofovir; vincristine; AGM-1470; platelet factor 4 or minocycline; 5-fluorouracil; bleomycin; busulfan; camptothecin; carboplatin; chlorambucil; cisplatin (CDDP); cyclophosphamide; dactinomycin; daunorubicin; doxorubicin; estrogen receptor binding agents; etoposide (VP16); farnesyl-protein transferase inhibitors; gemcitabine; ifosfamide; mechlorethamine; melphalan; mitomycin; navelbine; raloxifene; tamoxifen; taxol; temazolomide; transplatinum; vinblastine and methotrexate; alkylating agents; antimetabolites; antitumor antibiotics; corticosteroid hormones; mitotic inhibitors; nitrosoureas; hormone agents; mitotic inhibitors; enzymes; plant alkaloids; docetaxel; teniposide; vinorelbine; PPAR-gamma agonists; thiazolidinediones; rosiglitazone; fluorophores; metal chelate complexes; radioisotopes; fluorescent markers; urease; alkaline phosphatase; liposomes; microcapsules; microparticles; nanoparticles; magnetic beads; microdevices; plicamycin; platinum coordination complexes; anthracenediones; substituted ureas; methyl hydrazine derivatives; amsacrine; L-asparaginase; tretinoin; mitoxantrone; hydroxyurea; procarbazine; IgFc fusion proteins; enzyme fusion proteins; fluorescent proteins; luminescent proteins and combinations thereof.

11. The method of claim 7, wherein the polypeptide comprises the sequence of SEQ ID NO: 13.

12. The method of claim 7, wherein the polypeptide is comprised of D-amino acids.

13. The method of claim 7, wherein the polypeptide is less than 100 amino acids in length.

14. The method of claim 7, wherein the polypeptide is coupled to the effector agent by a linking moiety.

15. The method of claim 14, wherein the linking moiety comprises aminohexanoic acid; (CH.sub.2).sub.4; (CH.sub.2).sub.5; (CH.sub.2).sub.6; (CH.sub.2).sub.7; or (CH.sub.2).sub.8.

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Inventors Patent Expiration Status Orphan Source
Merck
ELSPAR
asparaginase
VIAL1010630011978-01-10► Subscribe BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX) Kolonin; Mikhail G. (Houston, TX), Daquinag; Alexes (Houston, TX), Zhang; Yan (Houston, TX) ► SubscribeRXsearch
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International Patent Family for Patent: ► Subscribe

Country Document Number Publication Date
Australia2012236199Sep 26, 2013
Canada2830375Oct 04, 2012
China103703140Apr 02, 2014
China103703140Feb 22, 2017
Eurasian Patent Organization201391154Jan 29, 2016
Eurasian Patent Organization201391154Jun 30, 2014
European Patent Office2704736Jul 20, 2016
European Patent Office2704736Mar 12, 2014
Israel228617Dec 31, 2013
Japan2014510758May 01, 2014
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