Antibodies to m-csf

Abstract

The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to a M-CSF, preferably human M-CSF, and that function to inhibit a M-CSF. The invention also relates to human anti-M-CSF antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-M-CSF antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-M-CSF antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-M-CSF antibodies. The invention also relates to transgenic animals and transgenic plants comprising nucleic acid molecules of the present invention.

1 - 6 . (canceled) 
     
     
         7 . A monoclonal antibody that specifically binds M-CSF, wherein the antibody is selected from the group consisting of:
 a) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 2 and the light chain amino acid sequence set forth in SEQ ID NO: 4, without the signal sequences;   b) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 6 and the light chain amino acid sequence set forth in SEQ ID NO: 8, without the signal sequences;   c) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 10 and the light chain amino acid sequence set forth in SEQ ID NO: 12, without the signal sequences;   d) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 14 and the light chain amino acid sequence set forth in SEQ ID NO: 16, without the signal sequences;   e) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 18 and the light chain amino acid sequence set forth in SEQ ID NO: 20, without the signal sequences;   f) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 22 and the light chain amino acid sequence set forth in SEQ ID NO: 24, without the signal sequences;   g) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 26 and the light chain amino acid sequence set forth in SEQ ID NO: 28, without the signal sequences;   h) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 38 and the light chain amino acid sequence set forth in SEQ ID NO: 28, without the signal sequences;   i) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 54 and the light chain amino acid sequence set forth in SEQ ID NO: 56, without the signal sequences;   j) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 74 and the light chain amino acid sequence set forth in SEQ ID NO: 56, without the signal sequences;   k) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 78 and the light chain amino acid sequence set forth in SEQ ID NO: 56, without the signal sequences;   l) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 82 and the light chain amino acid sequence set forth in SEQ ID NO: 28, without the signal sequences;   m) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 102 and the light chain amino acid sequence set forth in SEQ ID NO: 28, without the signal sequences;   n) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 30 and the light chain amino acid sequence set forth in SEQ ID NO: 32, without the signal sequences;   o) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 30 and the light chain amino acid sequence set forth in SEQ ID NO: 44, without the signal sequences;   p) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 58 and the light chain amino acid sequence set forth in SEQ ID NO: 60, without the signal sequences;   q) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 62 and the light chain amino acid sequence set forth in SEQ ID NO: 60, without the signal sequences;   r) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 90 and the light chain amino acid sequence set forth in SEQ ID NO: 44, without the signal sequences;   s) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 94 and the light chain amino acid sequence set forth in SEQ ID NO: 60, without the signal sequences;   t) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 98 and the light chain amino acid sequence set forth in SEQ ID NO: 32, without the signal sequences;   u) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 34 and the light chain amino acid sequence set forth in SEQ ID NO: 36, without the signal sequences;   v) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 46 and the light chain amino acid sequence set forth in SEQ ID NO: 48, without the signal sequences;   w) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 50 and the light chain amino acid sequence set forth in SEQ ID NO: 52, without the signal sequences;   x) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 66 and the light chain amino acid sequence set forth in SEQ ID NO: 52, without the signal sequences;   y) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 70 and the light chain amino acid sequence set forth in SEQ ID NO: 52, without the signal sequences; and   z) an antibody comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 86 and the light chain amino acid sequence set forth in SEQ ID NO: 48, without the signal sequences.   
     
     
         8 .- 19 . (canceled) 
     
     
         20 . The monoclonal antibody or antigen-binding portion according to  claim 7 , wherein the C-terminal lysine of the heavy chain of said antibody or antigen-binding portion is not present. 
     
     
         21 . A pharmaceutical composition, comprising the antibody or antigen-binding portion according to  claim 7  or  20  and a pharmaceutically acceptable carrier. 
     
     
         22 . (canceled) 
     
     
         23 . A method for treating a condition selected from the group consisting of arthritis, psoriatic arthritis, ankylosing spondylitis, Reiter's syndrome, rheumatoid arthritis, gout, traumatic arthritis, rubella arthritis and acute synovitis and other arthritic conditions, sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, Alzheimer's disease, stroke, neurotrauma, asthma, adult respiratory distress syndrome, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoidosis, bone resorption disease, osteoporosis, restenosis, cardiac and renal reperfusion injury, thrombosis, glomerularonephritis, diabetes, graft vs. host reaction, allograft rejection, inflammatory bowel disease, Crohn's disease, ulcerative colitis, multiple sclerosis, muscle degeneration, eczema, contact dermatitis, psoriasis, sunburn and conjunctivitis shock in a subject, including a human, comprising the step of administering to said subject in need thereof a therapeutically effective amount of the antibody or antigen-binding portion thereof according to  claim 7  or  20  or the pharmaceutical composition according to  claim 21 , wherein said antibody or portion inhibits M-CSF. 
     
     
         24 .- 25 . (canceled) 
     
     
         26 . A method for treating a solid tumor such as a sarcoma, a carcinoma or a lymphoma in a subject, including a human, comprising the step of administering to said subject the antibody or antigen-binding portion thereof according to  claim 7  or  20  or the pharmaceutical composition according to  claim 21 , wherein said antibody or antigen-binding portion inhibits M-CSF binding to c-fms. 
     
     
         27 . An isolated cell line that produces the antibody or antigen-binding portion thereof according to  claim 7  or  20  or the heavy chain or light chain of said antibody or said antigen-binding portions thereof. 
     
     
         28 . (canceled) 
     
     
         29 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the heavy chain or an antigen-binding portion thereof or the light chain or an antigen-binding portion thereof of an antibody according to  claim 7  or  20 . 
     
     
         30 . A vector comprising the nucleic acid molecule according to  claim 29 , wherein the vector optionally comprises an expression control sequence operably linked to said nucleic acid molecule. 
     
     
         31 . A host cell comprising the vector according to  claim 30  or the nucleic acid molecule according to  claim 29 . 
     
     
         32 . The host cell according to  claim 31  comprising a nucleic acid molecule encoding the heavy chain and a nucleic acid molecule encoding the light chain of an antibody or antigen-binding portion according to  claim 7  or  20 . 
     
     
         33 . A method of making an anti-M-CSF antibody or antigen-binding portion thereof, comprising culturing the host cell according to  claim 32  or the cell line according to  claim 27  under suitable conditions and recovering said antibody or antigen-binding portions. 
     
     
         34 . (canceled)