IP Library Granted Patent US 9,216,228
Granted Patent B2
US 9,216,228 · App. 12/525,453 · Granted Dec 22, 2015

Receptor and antigen targeted prodrug

Inventor: Felix Kratz (Ehrenkirchen, DE)
Assignee: KTB Tumorforschungsgesellschaft MBM
A61K47/48238A61K47/4813A61K47/48046A61K47/48092A61K47/48107A61K47/48246A61K47/48284A61K47/48338A61K47/48346A61K49/001A61K49/0017A61K49/0056A61K51/065B82Y5/00
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Quick Facts
Patent No.
US 9,216,228
App. No.
12/525,453
Granted
Dec 22, 2015
Kind
B2
Abstract

The present invention relates to a prodrug which comprises at least one pharmaceutically and/or diagnostically active compound bound by a cleavable linker, a receptor and/or antigen targeting moiety and a protein-binding moiety which is capable of binding to a carrier molecule.

Claims (20)

1. A prodrug, comprising

(i) at least one pharmaceutically and/or diagnostically active compound,

(ii) at least one receptor and/or antigen targeting moiety, wherein the receptor and/or antigen targeting moiety is a peptide derivative comprising the sequence (Pyr)-His-Trp-Ser-Tyr-Lys-Leu-Arg-Pro-Gly-NH2 (SEQ ID NO: 1),

(iii) at least one cleavable linker, and

(iv) a protein-binding moiety which binds in situ to serum proteins following administration of the prodrug,

wherein the at least one pharmaceutically and/or diagnostically active compound is bound to the at least one cleavable linker,

wherein the at least one cleavable linker, the protein binding moiety, and the at least one receptor and/or antigen targeting moiety are joined to form a branched structure; and

wherein the protein-binding moiety is selected from the group consisting of a maleinimide group, a halogenacetamide group, a halogenacetate group, a pyridylthio group, a vinylcarbonyl group, an aziridin group, a disulfide group, a substituted or unsubstituted acetylene group, and a hydroxysuccinimide ester group.

2. The prodrug according to claim 1 , wherein the at least one pharmaceutically and/or diagnostically active compound is selected from the group consisting of a cytostatic agent, a cytokine, an immunosuppressant, an antirheumatic, an antiphlogistic, an antibiotic, an analgesic, a virostatic, and an antimycotic agent, a transcription factor inhibitor, a cell cycle modulator, a MDR modulator, a proteasome or protease inhibitor, an apoptosis modulator, an enzyme inhibitor, an angiogenesis inhibitor, a hormone or hormone derivative, a radioactive substance, a light emitting substance, and a light absorbing substance.

3. The prodrug according to claim 1 , wherein the at least one pharmaceutically and/or diagnostically active compound is a cytostatic agent selected from the group consisting of N-nitrosoureas, the anthracyclines doxorubicin, 2-pyrollinoanthracycline, morpholinoanthracycline, diacetatoxyalkylanthracycline, daunorubicin, epirubicin, idarubicin, mitoxantrone and ametantrone, and any derivatives thereof; the alkylating agents chlorambucil, bendamustine, melphalan, and oxazaphosphorines, and any derivatives thereof; the antimetabolites 5-fluorouracil, 2′-deoxy-5-fluorouridine, cytarabine, cladribine, fludarabine, pentostatine, gemcitabine and thioguanine, and any derivatives thereof; the folic acid antagonists methotrexate, raltitrexed, pemetrexed and plevitrexed, the taxanes paclitaxel and docetaxel, and any derivatives thereof; the camptothecins topotecan, irinotecan, 9-aminocamptothecin and camptothecin, and any derivatives thereof; the Vinca alkaloids vinblastine, vincristine, vindesine and vinorelbine, and any derivatives thereof; calicheamicins and any derivatives thereof; maytansinoids and any derivatives thereof; auristatins and any derivatives thereof; epothilones and any derivatives thereof; bleomycin, dactinomycin, plicamycin, mitomycin C and cis-configured platinum(II) complexes.

4. The prodrug according to claim 1 , wherein the cleavable linker can be cleaved hydrolytically and/or enzymatically and/or pH-dependently.

5. The prodrug according claim 1 , wherein the protein-binding moiety binds in situ to cysteine-34 of albumin.

6. The prodrug according to claim 1 , wherein the pharmaceutically and/or diagnostically active compound contains one or more radionuclides, one or more positron emitters, one or more NMR contrast agents, one or more fluorescent compound(s), or one or more near-infrared contrast agents.

7. The prodrug according to claim 1 , wherein

(i) the at least one pharmaceutically and/or diagnostically active compound is selected from the group consisting of doxorubicin, 2-pyrollinodoxorubicin, morpholinodoxorubicin, diacetatoxypentyldoxorubicin, paclitaxel, camptothecin, or a derivative thereof;

(ii) the at least one cleavable linker is selected from the group consisting of an acid-labile linker and a linker cleavable by MMP2 and/or MMP9; and

(iii) the protein-binding moiety is maleinimide or a derivative thereof, and

wherein the doxorubicin, 2-pyrollinodoxorubicin, morpholinodoxorubicin, diacetatoxypentyl-doxorubicin, paclitaxel or camptothecin, or the derivative thereof is bound to the at least one cleavable linker.

8. A pharmaceutical composition, comprising the prodrug according to claim 1 , and optionally a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable adjuvent and/or a diluent.

9. A pharmaceutical composition, comprising the prodrug according to claim 8 , for the treatment of a disease selected from cancer, autoimmune diseases, acute or chronic inflammatory diseases, and diseases caused by viruses and/or microorganisms.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2019
From: KTB TUMORFORSCHUNGSGESELLSCHAFT MBH
To: VERGELL MEDICAL S.A.
Reel/Frame 048503/0308 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2009
From: KRATZ, FELIX
To: KTB TUMORFORSCHUNGSGESELLSCHAFT MBH
Reel/Frame 023100/0889 →
Priority Claims (1)
EP 07003341 · Feb 16, 2007 · regional
Continuity (1)
Related Publication 20100111866A1 · May 6, 2010