Methods of Treating Conditions with Antibodies that Bind Colony Stimulating Factor 1 Receptor (CSF1R)

Abstract

Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (CSF1R) are provided. Such methods include, but are not limited to, methods of treating rheumatoid arthritis and associated conditions, methods of treating systemic lupus erythematosus and associated conditions, and methods of treating multiple sclerosis.

1 .- 38 . (canceled) 
     
     
         39 . A method of reducing the number of CD16+ monocytes in a subject with a CD16+ disorder, comprising (a) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject, and (b) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R) such that the number of CD16+ monocytes is reduced by at least 30%; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R, and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20. 
     
     
         40 . The method of  claim 39 , further comprising determining the number of CD16-monocytes in the sample, wherein the antibody is administered such that the number of CD16− monocytes is not reduced or is reduced by less than 20%. 
     
     
         41 . The method of  claim 39 , further comprising (c) determining the number of CD16+ monocytes in a further peripheral blood sample from the subject after administration of the antibody. 
     
     
         42 . The method of  claim 41 , further comprising determining the number of CD16-monocytes in the samples of (a) and (c). 
     
     
         43 . The method of  claim 39 , wherein the method further comprises administering at least one additional therapeutic agent selected from an anti-CD-20 antibody, an anti-CD19 antibody, an anti-GM-CSF antibody, a CTLA-4 antagonist, and an anti-GM-CSF-R antibody. 
     
     
         44 . The method of  claim 39 , comprising administering to the subject the antibody that binds CSF1R such that the number of CD16+ monocytes is reduced by at least 50%. 
     
     
         45 . The method of  claim 39 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46. 
     
     
         46 . The method of  claim 39 , wherein the antibody is a humanized antibody. 
     
     
         47 . The method of  claim 39 , wherein the antibody is a Fab, an Fv, an scFv, a Fab′, or a (Fab′)2. 
     
     
         48 . A method of reducing the number of CD16+ monocytes in a subject with a CD16+ disorder, comprising (a) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R), (b) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject following administration of the antibody, (c) determining whether administration of the antibody reduces the number of CD16+ monocytes in the sample by at least 30% by comparing the number of CD16+ monocytes in the sample of (b) with the number of CD16+ monocytes determined in a peripheral blood sample obtained from the subject prior to administration, and optionally (d) adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20. 
     
     
         49 . The method of  claim 48 , comprising adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced by at least 30%. 
     
     
         50 . The method of  claim 48 , further comprising determining the number of CD16-monocytes in the sample after administration, wherein the antibody is administered such that the number of CD16− monocytes is not reduced or is reduced by less than 20%. 
     
     
         51 . The method of  claim 48 , wherein the method further comprises administering at least one additional therapeutic agent selected from an anti-CD-20 antibody, an anti-CD19 antibody, an anti-GM-CSF antibody, a CTLA-4 antagonist, and an anti-GM-CSF-R antibody. 
     
     
         52 . The method of  claim 48 , comprising determining whether administration of the antibody reduces the number of CD16+ monocytes in the sample by at least 50%, and optionally adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced by at least 50%. 
     
     
         53 . The method of  claim 48 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46. 
     
     
         54 . The method of  claim 48 , wherein the antibody is a humanized antibody. 
     
     
         55 . The method of  claim 48 , wherein the antibody is a Fab, an Fv, an scFv, a Fab′, or a (Fab′)2. 
     
     
         56 . A method of treating neoplasia in a subject, comprising (a) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject, and (b) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R) such that the number of CD16+ monocytes is reduced by at least 30%; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R, and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20. 
     
     
         57 . The method of  claim 56 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46. 
     
     
         58 . The method of  claim 56 , further comprising (c) determining the number of CD16+ monocytes in a further peripheral blood sample from the subject after administration of the antibody.