Drug combination treatments using bone-targeting therapeutics for bone and bone-related disease

Abstract

Provided herein is a novel method for creating fixed, non-antagonistic molar ratios of drugs in and around the bone environment for desired periods of time. This method enables treating bone and bone-related disease by administering a pharmaceutical composition comprising a bone-targeted therapeutic agent able to release a drug payload from the bone surface, in addition to a second therapeutic agent. Such methods are useful in the treatment of bone and bone-related diseases, such as cancer-induced bone disease, osteomyelitis and bone infection, bone pain and inflammatory bone disease, metabolic disease, as well as others.

1 .- 23 . (canceled) 
     
     
         24 . A method of treating a subject having cancer induced bone disease or primary bone cancer, the method comprising administering to the subject:
 (i) a pharmaceutical composition comprising a bone-targeted therapeutic agent of either Gemcitabine-Ibandronate conjugate (GEM-IB)   
       
         
           
           
               
               
           
         
       
       or Cytarabine-etidronate conjugate (MBC-11) 
       
         
           
           
               
               
           
         
         in combination with (ii) a second therapeutic agent of either docetaxel or Xofigo. 
       
     
     
         25 . The method of claim  1  wherein the bone-targeted therapeutic agent is MBC-11 and the second therapeutic agent is docetaxel. 
     
     
         26 . The method of claim  1  wherein the bone-targeted therapeutic agent is MBC-11 and the second therapeutic agent is Xofigo. 
     
     
         27 . The method of claim  1  wherein the bone-targeted therapeutic agent is GEM-IB and the second therapeutic agent is docetaxel. 
     
     
         28 . The method of claim  1  wherein the bone-targeted therapeutic agent is GEM-IB and the second therapeutic agent is Xofigo. 
     
     
         29 . The method of claim  1  wherein the bone-targeted therapeutic agent is administered at a dose ranging from 0.02 to 14 mg/kg and the second therapeutic agent is docetaxel administered at a dose ranging from 1.5 micrograms/kg to 15 milligram/kg. 
     
     
         30 . The method of claim  1 , wherein the primary bone cancer is osteosarcoma. 
     
     
         31 . The method of claim  1 , wherein the subject has cancer induced bone disease. 
     
     
         32 . The method of claim  1 , wherein a molar ratio of the bone-targeted therapeutic agent with the second therapeutic agent is derived from cell based or animal-based studies. 
     
     
         33 . The method of claim  1 , wherein the second therapeutic agent is administered up to 48 hours prior to the administration of the bone-targeted therapeutic agent. 
     
     
         34 . The method of claim  1 , wherein the second therapeutic agent is administered up to 48 hours after the bone-targeted therapeutic agent. 
     
     
         35 . The method of claim  1 , wherein the second therapeutic agent is administered during the administration of the bone-targeted therapeutic agent. 
     
     
         36 . The method of claim  1 , wherein the second therapeutic agent is administered at an amount from 1/100th up to its standard dosing while administration of the bone-targeted therapeutic agent is at its standard dosing. 
     
     
         37 . The method of claim  1 , wherein the second therapeutic agent is administered at its standard dosing while administration of the bone-targeted therapeutic agent is in an amount from 1/100th up to standard dosing. 
     
     
         38 . The method of claim  1 , wherein the second therapeutic agent is administered at an amount from 1/100th up to its standard dosing while the bone-targeted therapeutic agent is administered at an amount from 1/100th up to its standard dosing. 
     
     
         39 . The method of claim  1 , wherein the bone-targeted therapeutic agent is administered at or below 5 mg/kg/day via a 2-hour infusion for up to 5 consecutive days. 
     
     
         40 . The method of claim  1 , wherein the subject has a primary bone cancer.