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Last Updated: April 26, 2024

Claims for Patent: 9,539,341


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Summary for Patent: 9,539,341
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.

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