Claims for Patent: 10,065,993

Summary for Patent: 10,065,993

Title:	Peptides and peptide/active compound conjugates for renal targeting
Abstract:	The present invention relates to a peptide which consists of more than 50% of sequence sections of the formula -(A.sub.n-B.sub.m-C.sub.o)-, and to a conjugate containing the peptide and at least one covalently bonded active compound, and to a process for the preparation of the conjugate. The present invention furthermore relates to the use of the peptide and the conjugate for targeting of the kidney, and to a medicament comprising the peptide or conjugate.
Inventor(s):	Kuebelbeck; Armin (Bensheim, DE), Larbig; Gregor (Gelnhausen, DE), Arnold; Stefan (Muenster, DE), Mier; Walter (Bensheim, DE)
Assignee:	MERCK PATENT GMBH (Darmstadt, DE)
Application Number:	14/890,059
Patent Claims:	1. A peptide comprising 3 to 5 sequence sections selected from the group consisting of -(KKEEE)- (SEQ ID NO: 76), -(RREEE)- (SEQ ID NO: 77), -(KKEE)- (SEQ ID NO: 78), -(KKKEEE)- (SEQ ID NO: 79) and -(KKKEE)-(SEQ ID NO: 80), wherein more than 90% of amino acids in the peptide are the selected sequence sections, wherein E is glutamic acid, K is lysine, and R is arginine. 2. The peptide according to claim 1, which contains 3 to 5 successive sequence sections selected from the group consisting of -(KKEEE)- (SEQ ID NO: 76), -(RREEE)- (SEQ ID NO: 77), -(KKEE)- (SEQ ID NO: 78), -(KKKEEE)- (SEQ ID NO: 79) and -(KKKEE)- (SEQ ID NO: 80). 3. The peptide according to claim 1, which contains sequence sections selected from the group consisting of -(KKEEE)- (SEQ ID NO: 76), --(KKEE)- (SEQ ID NO: 78), -(KKKEEE)- (SEQ ID NO: 79) and -(KKKEE)- (SEQ ID NO: 80), wherein more than 90% of amino acids in the peptide are the selected sequence sections. 4. The peptide according to claim 1, which contains sequence sections -(RREEE)- (SEQ ID NO: 77), wherein more than 90% of amino acids in the peptide are said sequence sections. 5. The peptide according to claim 1, which is selected from the group consisting of (RREEE).sub.3R (SEQ ID NO: 81), (KKEE).sub.5K SEQ ID NO: 82), (KKKEE).sub.3K (SEQ ID NO: 83), (KKKEEE).sub.3K (SEQ ID NO: 84) and (KKEEE).sub.3K (SEQ ID NO: 85). 6. A conjugate containing at least one peptide and at least one active compound which is covalently bonded, optionally via a spacer, wherein the at least one peptide comprises 3 to 5 sequence sections selected from the group consisting of -(KKEEE)- (SEQ ID NO: 76), -(RREEE)- (SEQ ID NO: 77), -(KKEE)- (SEQ ID NO: 78), -(KKKEEE)- (SEQ ID NO: 79) and -(KKKEE)- (SEQ ID NO: 80), wherein more than 50% of amino acids in the peptide are the selected sequence sections, wherein E is glutamic acid, K is lysine, and R is arginine. 7. The conjugate according to claim 6, wherein the active compound is selected from the group consisting of immunosuppressants, cytostatics, immunotherapeutic agents, antiphlogistics, antibiotics, virostatics, anti-hypertensives, ACE inhibitors, sartans, renin inhibitors, protein kinase inhibitors, uricosurics, diuretics and antifibrotics. 8. A conjugate according to claim 6, wherein the at least one active compound is bonded to the N terminal and/or the C terminal of the peptide. 9. A conjugate according to claim 6, wherein the at least one active compound is bonded to an amino acid within the chain. 10. A conjugate according to claim 6, wherein the active compound is bonded via an ester link. 11. A process for preparing the conjugate according to claim 6, comprising conjugating an optionally activated active compound to the peptide. 12. A pharmaceutical composition comprising a peptide according to claim 1 and a pharmaceutically acceptable carrier. 13. A pharmaceutical composition comprising a conjugate according to claim 6 and a pharmaceutically acceptable carrier. 14. A method for targeting a kidney, comprising administering to a subject in need thereof an effective amount of a peptide according to claim 1 or a conjugate containing said peptide and at least one active compound which is covalently bonded, optionally via a spacer. 15. A method for protecting a kidney, comprising administering to a subject in need thereof an effective amount of a peptide according to claim 1. 16. A method for enhancing an image, comprising administering to a subject in need thereof an effective amount of an image-enhancing composition, comprising at least one peptide according to claim 1 or a conjugate containing said peptide and at least one active compound which is covalently bonded, optionally via a spacer. 17. A method for targeting a kidney, comprising administering to a subject in need thereof an effective amount of a conjugate according to claim 6. 18. A method for enhancing an image, comprising administering to a subject in need thereof an effective amount of an image-enhancing composition, comprising at least one conjugate according to claim 6. 19. The peptide according to claim 1, which contains 3 to 5 sequence sections selected from the group consisting of -(KKEEE)- (SEQ ID NO: 76), -(RREEE)- (SEQ ID NO: 77), -(KKKEEE)- (SEQ ID NO: 79) and -(KKKEE)- (SEQ ID NO: 80), wherein more than 90% of amino acids in the peptide are said sequence sections. 20. The conjugate according to claim 6, wherein the active compound is selected from the group consisting of azathioprine, mycophenolate-mofetil, ciclosporin, tacrolimus, sirolimus, fingolimod, triptolide, atrasentan, nintedanib, bleomycin, dactinomycin, mitomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantron, amsacrine, doxofluridine, cisplatin, carboplatin, oxaliplatin, satraplatin, camptothecin, toptecan, irinotecan, etoposide, teniposide, cyclophosphamide, trofosfamide, melphalan, chlorambucil, estramustine, busulfan, chlorambucil, chlormethine, treosulfan, carmustine, lomustine, nimustine, procarbazine, streptozocine, dacarbazine, ifosfamide, temozolomide, thiotepa, vinorelbine, vincristine, vinblastine, vindesine, paclitaxel, docetaxel, methotrexate, pemetrexed, raltitrexed, fluorouracil, capecitabine, cytosinarabinoside, gemcitabine, tioguanine, pentostatin, mercaptopurine, fludarabine, caldribine, hydroxycarbamide, mitotane, azacitidine, cytarabine, nelarabine, bortezomib, anagrelide, imatinib, erlotinib, sunitinib, sorafenib, dasatinib, lapatinib, nilotinib, cetuximab, alemtuzumab, bevacizumab, naproxen, ibuprofen, indometacin, prednisolone, prednisone, hydrocortisone, budesonide, benzylpenicillin, methicillin, amoxicillin, cefuroxim, cefotaxim, cefadroxil, cefixim, clavulanic acid, sulbactam, tazobactam, imipenem, meropenem, aztreonam, tetracycline, chlortetracycline, oxytetracycline, doxycycline, minocycline, tigecycline, erythromycin A, vancomycin, calicheamicin, aciclovir, valaciclovir, ganciclovir, valganciclovir, penciclovir, famciclovir, brivudine, cidofovir, foscarnet, idoxuridine, tromantadine, benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, zofenopril, losartan, balsartan, irbesartan, candesartan, eprosartan, olmesartan, telmisartan, aliskiren, proproanolol, pindolol, sotalol, bopindolol, atenolol, bisorpolol, celiprolol, esmolol, metoprolol, nebivolol, oxprenolol, carvedilol, labetalol, probenecid, benzbromarone, acetazolamide, furosemide, torasemide, bumetanide, piretanide, azosemide, etacrynic acid, etozoline, hydrochlorothiazide, benzthiazide, chlorothiazide, chlorthalidone, indapamide, mefruside, metolazone, clopamide, xipamide, hydroflumethiazide, methyclothiazide, polythiazide, amiloride, triameterene, spironolactone, canrenone, eplerenone, spironolactone, pirfenidone and seliciclib.

Details for Patent 10,065,993

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2033-05-07
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	11/14/2014		2033-05-07
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	10/12/2004		2033-05-07
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2033-05-07