Use of therapeutic compositions comprising hyaluronan and therapeutic antibodies

Abstract

The present invention relates generally to treatment and prophylactic protocols for cellular disease or disorders, such as diseases and disorders associated with abnormal cellular proliferation. More particularly, the present invention provides uses of compositions comprising therapeutic antibodies and hyaluronan in the treatment or prophylaxis of cellular diseases and disorders.

1 - 32 . (canceled) 
     
     
         33 . A method of treatment for cellular proliferative diseases in a subject, the method comprising administering to a subject in need thereof a therapeutic antibody selected from the group of antibodies consisting of: Bevacizumab, Cetuximab and Rituximab, or an antigen-binding portion thereof and hyaluronan (HA), or salt thereof, wherein the hyaluronan is in the molecular weight range of about 800 kDaltons to 900 kDaltons, and, optionally, one or more, pharmaceutically acceptable carriers, diluents and/or excipients,
 wherein the hyaluronan or synthesized form thereof and the therapeutic antibody, or antigen-binding portion thereof, are not covalently bound,   for a time and under conditions for the symptoms of the cellular proliferative disease to be ameliorated.   
     
     
         34 - 36 . (canceled) 
     
     
         37 . The method of  claim 33  wherein the hyaluronan has a modal molecular weight of about 860 kDaltons. 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 33 , wherein the hyaluronan, or salt thereof, and the antibody, or antigen-binding portion thereof, are present in a composition with a pH range of between pH 2.5 and 10.5. 
     
     
         40 . The method of  claim 33 , wherein the antibody Rituximab or an antigen-binding portion thereof. 
     
     
         41 . The method of  claim 33 , wherein the cellular proliferative disease is any one of cancer, neoplastic disease or any disease involving inflammation of tissue or release of inflammatory agents. 
     
     
         42 . The method  claim 33 , wherein the cellular proliferative disease results in one or more of a tumor, neoplasm, uncontrolled hyper-proliferation or metastasis. 
     
     
         43 . The method  claim 33 , wherein the cellular proliferative disease is present in one or more organs or tissues including the breast, lung, prostate, kidney, skin, neural tissue, ovary, uterus, liver, pancreas, epithelial cells, gastric tissue, intestine, exocrine, endocrine, lymphatic system, hematopoietic system, head tissue and neck tissue. 
     
     
         44 . The method of  claim 33 , wherein the cellular proliferative disease occurs in a mammal. 
     
     
         45 . The method of  claim 33 , wherein the antibody is cetuximab. 
     
     
         46 . The method of  claim 33 , wherein the antibody is bevacizumab. 
     
     
         47 . The method of  claim 33 , for the treatment of colorectal cancer. 
     
     
         48 . The method of  claim 44  wherein the mammal is selected from the group consisting of primate, bovine, canine, equine, feline and porcine animal. 
     
     
         49 . The method of  claim 48  wherein the primate is a human. 
     
     
         50 . The method of  claim 33 , wherein the administering is parenteral. 
     
     
         51 - 52 . (canceled) 
     
     
         53 . The method of  claim 50  wherein the parental administration is by subcutaneous injection, intravenous, intramuscular, intrathecal, intracranial, intrasternal injection or infusion techniques. 
     
     
         54 . The method of  claim 33 , wherein the hyaluronan or an analog or a derivative or synthesized or modified form thereof is administered simultaneously, sequentially, prior to, in combination, during or subsequent to the administration of the antibody, fragment, derivative or portion thereof. 
     
     
         55 - 67 . (canceled) 
     
     
         68 . The method of  claim 33 , wherein the HA is administered in an amount of about 0.01 to about 40 mg/kg of body weight. 
     
     
         69 . The method of  claim 33 , wherein the HA is administered in an amount of about 0.1 to about 27 mg/kg of body weight. 
     
     
         70 . The method of  claim 33 , wherein the HA, or salt thereof, and the antibody, or antigen-binding portion thereof, are present in an aqueous suspension.