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

摘要

Conjugates of polymers or copolymers having attached thereto an anti-angiogenesis agent and a bisphosphonate bone targeting agent, and processes of preparing same, are disclosed.;Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of bone related disorders are also disclosed.

主权项

1. A conjugate comprising a polymeric backbone derived from polyglutamic acid (PGA) and comprising a plurality of backbone units covalently linked to one another, wherein a portion of said plurality of backbone units has an anti-angiogenesis agent attached thereto, and another portion of said plurality of backbone units has a bisphosphonate bone targeting moiety attached thereto, 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], the [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.