Conjugates of a polymer, a bisphosphonate and an anti-angiogenesis agent and uses thereof in the treatment and monitoring of bone related diseases

A conjugate comprising a polymeric backbone having attached thereto an anti-angiogenesis agent and a bisphosphonate bone targeting moiety, said polymeric backbone being derived from a polymer selected from the group consisting of dextran, a water soluble polyamino acid, a polyethylenglycol (PEG), a polyglutamic acid (PGA), a polylactic acid (PLA), a polylactic-co-glycolic (PLGA), a poly(D,L-lactide-co-glycolide) (PLA/PLGA), a polyglycerol, a polyamidoamine (PAMAM), and a polyethylenimine (PEI),

• the conjugate being represented by the general formula I:
• [A1]x[A2-L1-B]y[A3-L2-D]w Formula I
• wherein:
• x is an integer having a value such that x/(x+y+w) multiplied by 100 is in the range of from 70 to 99.8;
• y is an integer having a value such that y/(x+y+w) multiplied by 100 is in the range of from 0.1 to 15;
• and
• w is an integer having a value such that w/(x+y+w) multiplied by 100 is in the range of from 0.1 to 15,
• A1, A2, and A3 are each backbone units covalently linked to one another and forming said polymeric backbone, wherein:
• B is said anti-angiogenesis agent;
• D is said bone targeting moiety;
• and
• each of the L1 and L2 is independently a linker or absent;
• such that [A2-L1-B] is a backbone unit having attached thereto said anti-angiogenesis agent;
• and
• [A2-L2-D] is a backbone unit having attached thereto said bone targeting moiety;
• wherein each of the [A1], the [A2-L1-B] and the [A3-L2-D] is either a terminal backbone unit being linked to one of the [A1], the [A2-L1-B] and the [A3-L2-D], or is linked to at least two of the [A1], [A2-L1-B] and the [A3-L2-D], whereby A1, A2 and/or A3 are linked to one another to thereby form said polymeric backbone.