Joint-Homing Peptides and Uses Thereof

• US 20130004415A1
• Filed: 06/29/2012
• Published: 01/03/2013
• Est. Priority Date: 06/29/2011
• Status: Active Grant

• Current Assignee: University of Maryland Baltimore County (University of Maryland)
• Original Assignee: University of Maryland Baltimore County (University of Maryland)
• Inventors: Moudgil, Kamal, Yang, Ying-hua
• Granted Patent: US 8,623,377 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• CPC Class Codes: 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
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The present invention provides peptides that home to a joint of an animal, wherein said peptide comprises an amino acid motif selected from the group consisting of NQR and ADK. Also provided are methods of treating a subject having an arthritic joint, comprising the step of administering to said subject a pharmacologically effective dose of a composition provided herein.

Claims

1. A peptide that homes to a joint of an animal, wherein said peptide comprises an amino acid motif selected from the group consisting of NQR and ADK.

2. The peptide of claim 1, wherein said peptide has the sequence CRNADKFPC (SEQ ID NO. 1).

3. The peptide of claim 1, wherein said peptide has the sequence at least 77% identical to CRNADKFPC (SEQ ID NO. 1).

4. The peptide of claim 1, wherein said peptide has the sequence at least 88% identical to CRNADKFPC (SEQ ID NO. 1).

5. The peptide of claim 1, wherein said peptide has the sequence selected from the group consisting of CLDNQRPKC (SEQ ID NO. 2), a peptide having a sequence at least 77% identical to CLDNQRPKC (SEQ ID NO. 2) and a peptide having a sequence at least 88% identical to CLDNQRPKC (SEQ ID NO. 2).

6. A composition, comprising the peptide of claim 5.

7. The composition of claim 6, further comprising a co-composition, wherein the peptide and the co-composition are not covalently coupled or non-covalently associated with each other.

8. The composition of claim 6, wherein the peptide selectively homes to regenerating tissue, a site of injury, a site of inflammation or a site of arthritis.

9. The composition of claim 7, wherein the peptide and the co-composition are chemically conjugated or bound to each other.

10. The composition of claim 7, wherein the co-composition comprises a therapeutic agent, a therapeutic protein, a therapeutic compound, a therapeutic composition, a chemotherapeutic agent, a cancer chemotherapeutic agent, a toxin, a cytotoxic agent, imatinib, an anti-angiogenic agent, an anti-inflammatory agent, an anti-arthritic agent, a TGF-.beta. inhibitor, decorin, a systemic vasodilator, an anti-coagulant, tissue factor pathway inhibitor (TFPI), site-inactivated factor VIIa, a .beta.-2 agonist, salmeterol, formoterol, N-Acetylcysteine (NAC), Superoxide Dismutase (SOD), a superoxide dismutase mimetic, EUK-8, an endothelin (ET-1) receptor antagonist, a prostacyclin derivative, a phosphodiesterase type 5 inhibitor, Ketoconazole, a small interfering RNA (siRNA), a microRNA (miRNA), a polypeptide, a nucleic acid molecule, a small molecule, a carrier, a vehicle, a virus, a phage, a viral particle, a phage particle, a viral capsid, a phage capsid, a virus-like particle, a liposome, bone remodeling agents, tissue regenerating agents, a micelle, a bead, a nanoparticle, a microparticle, a detectable agent, a contrast agent, an imaging agent, a label, a labeling agent, a fluorophore, fluorescein, rhodamine, FAM, a radionuclide, indium-111, technetium-99, carbon-11, carbon-13, a disease-modifying antirheumatic drug, an analgesic or a combination.

11. The composition of claim 10, wherein said anti-angiogenic agent is selected from the group consisting of thrombospondin, angiostatin5, pigment epithelium-drived factor, angiotensin, laminin peptides, fibronectin peptides, plasminogen activator inhibitors, tissue metalloproteinase inhibitors, interferons, interleukin 12, platelet factor 4, IP-10, Gro-.beta., thrombospondin, 2-methoxyoestradiol, proliferin-related protein, carboxiamidotriazole, CM101, Marimastat, pentosan polysulphate, angiopoietin 2 (Regeneron), interferon-alpha, herbimycin A, PNU145156E, 16K Prolactin fragment, Linomide, thalidomide, pentoxifylline, genistein, TNP-470, endostatin, paclitaxel, Docetaxel, polyamines, a proteasome inhibitor, a kinase inhibitor, a signaling peptide, accutin, cidofovir, vincristine, bleomycin, AGM-1470, platelet factor 4 and minocycline.

12. The composition of claim 10, wherein said anti-inflammatory agent is selected from the group consisting of steroids, cortisone, glucocorticoids, prednisone, prednisolone, hydrocortisone (cortisol), cortisone acetate, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclometasone, and fludrocortisone acetate, non-steroidal anti-inflammatory drug (NSAIDs), ibuprofen, naproxen, meloxicam, etodolac, nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac, diflusinal, indomethicin, ketoprofen, oxaprozin, piroxicam, and nimesulide, salicylates, aspirin (acetylsalicylic acid), diflunisal, salsalate, p-amino phenol derivatives, paracetamol, phenacetin, propionic acid derivatives, ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, loxoprofen, acetic acid derivatives, indomethacin, sulindac, etodolac, ketorolac, diclofenac, nabumetone, enolic acid (oxicam) derivatives, piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam, fenamic acid derivatives (fenamates), mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, selective cox-2 inhibitors (coxibs), celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib, sulphonanilides, nimesulide, and licofelone.

13. The composition of claim 10, wherein said analgesic agent is selected from the group consisting of NSAIDs, COX-2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, acetaminophen, opiates, Dextropropoxyphene, Codeine, Tramadol, Anileridine, Pethidine, Hydrocodone, Morphine, Oxycodone, Methadone, Diacetylmorphine, Hydromorphone, Oxymorphone, Levorphanol, Buprenorphine, Fentanyl, Sufentanyl, Etorphine, Carfentanil, dihydromorphine, dihydrocodeine, Thebaine, Papaverine, diproqualone, Flupirtine, Tricyclic antidepressants, and lidocaine.

14. The composition of claim 10, wherein said disease-modifying antirheumatic drug is selected from the group consisting of mycophenolate mofetil (CellCept), calcineurin inhibitors, cyclosporine, sirolimus, everolimus, oral retinoids, azathioprine, fumeric acid esters, D-penicillamine, cyclophosphamide, immunoadsorption column, Prosorba(r) column, a gold salt, auranofin, sodium aurothiomalate (Myocrisin), hydroxychloroquine, chloroquine, leflunomide, methotrexate (MTX), minocycline, sulfasalazine (SSZ), tumor necrosis factor alpha (TNFa) blockers, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi)), Interleukin 1 (IL-1) blockers, e.g., anakinra (Kineret), monoclonal antibodies against B cells, rituximab (Rituxan)), T cell costimulation blockers, abatacept (Orencia), Interleukin 6 (IL-6) blockers, tocilizumab, RoActemra, and Actemra.

15. The composition of claim 10, wherein said liposome or said nanoparticle is coated on its surface with the peptide of claim 5.

16. A method of treating a subject having an arthritic joint, comprising the step of administering to said subject a pharmacologically effective dose of the composition of claim 6.

17. A method of treating a subject having an arthritic joint, comprising the step of administering to said subject a pharmacologically effective dose of the composition of claim 10.

18. A method of treating a subject having an arthritic joint, comprising the step of administering to said subject a pharmacologically effective dose of the composition of claim 15.