Treatment of renal cell carcinoma
Inventors
Haraldsson, Borje • Nilsson, Ulf • Buvall, Lisa • Nystrom, Jenny
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9005580-B2
Publication Date
2015-04-14
Expiration Date
Abstract
Methods for treating renal cancer by administration of certain 3,3′,4,4′-tetrahydroxy-2,2′-bipyridine-N,N′-dioxide compounds, especially 3,3′,4,4′-tetrahydroxy-2,2′-bipyridine-N,N′-dioxide (Orellanine), conjugated to an alpha-emitting radionuclide (e.g. Astatine-211) to increase the efficacy of the formulation and/or a large molecule (e.g. a oligomer/polymer such as a PEG or a polysaccharide such as a dextran or a Ficoll®) to reduce the filtration and consequently the renal exposure. Particular administration protocols and dosing regimens, as well as pharmaceutical compositions suitable for use in the treatment methods can be used.
Core Innovation
The invention relates to treating renal cell carcinoma by administering a conjugate that includes a compound according to Formula I and a second component. The conjugate includes either a macromolecule covalently bound to the Formula I compound or at least one cytotoxic agent, and optionally both, for use against renal cell carcinoma in patients in need thereof.
The macromolecule is of sufficient molecular weight and molecular diameter to substantially or completely prevent passage of the conjugate through the glomerular filter of the kidneys and entering primary urine. The cytotoxic component may include a toxin or a radionuclide, and the radionuclides explicitly include Astatine-211, Bismuth-212, Bismuth-213, Actinium-225, Lead-212, and Terbium-149.
The invention also covers the conjugate for use as a medicament in treating renal cell carcinoma, together with pharmaceutical composition concepts containing the Formula I compound and the selected second component. In the described embodiments, the macromolecule component may include polyethylene glycol, dextran, and Ficoll, and pharmaceutical composition variants may include a pharmaceutically acceptable salt of the Formula I compound.
Claims Coverage
The partial content provides two independent claims. Both independent claims share the same core conjugate structure combining a Formula I compound with either a kidney-glomerular-filter-blocking macromolecule, a cytotoxic agent, or both, and they specify the intended therapeutic use against renal cell carcinoma.
Conjugate with glomerular-filter-blocking macromolecule for renal cell carcinoma treatment
A conjugate comprising a compound according to Formula I and at least one macromolecule covalently bound to the Formula I compound, where the macromolecule has sufficient molecular weight and molecular diameter to substantially or completely prevent passage through the glomerular filter of the kidneys and entering primary urine.
Conjugate with cytotoxic agent for renal cell carcinoma treatment
A conjugate comprising a compound according to Formula I and at least one cytotoxic agent, for treatment of renal cell carcinoma.
Defined Formula I substituent selection
A compound according to Formula I where R1, R2, R3 and/or R4 are selected from hydrogen, amino, mercapto, carboxy, phosphate and halo, including fluoro, chloro, and bromo, and C1-C6 alkyl, alkenyl, alkynyl, alkanol, alkenol, alkoxy, and alkenoxy groups with optional further substitution.
Conjugate for use as a medicament against renal cell carcinoma
A conjugate comprising a compound according to Formula I and a compound selected from at least one macromolecule covalently bound to the Formula I compound and/or at least one cytotoxic agent, for use as a medicament in the treatment of renal cell carcinoma.
The main inventive coverage is the use of a Formula I compound conjugate for renal cell carcinoma therapy that either incorporates a high-molecular-weight macromolecule covalently bound to block glomerular filter passage into primary urine and/or incorporates a cytotoxic agent, together with specified Formula I substituent constraints and the medicament use context.
Stated Advantages
Reduced renal functional loss, with renal function preservation described via glomerular filtration rate (GFR).
Effective tumor killing, including tumor reduction or eradication.
Documented Applications
Treatment of renal cell carcinoma in a patient, including rat xenograft models and human RCC cases described with renal function preservation (GFR) and tumor reduction or eradication.
Interested in licensing this patent?