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.

1 .- 38 . (canceled) 
     
     
         39 . A method of reducing the number of nonclassical CD16+ monocytes in a subject with a CD16+ disorder, comprising administering to the subject a dose of 3 mg/kg to 10 mg/kg of an antibody that binds human colony stimulating factor 1 receptor (CSF1R) every 2 weeks,
 wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to CSF1R and blocks binding of human IL-34 to 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; and   wherein the administration of the antibody reduces the number of nonclassical CD16+ monocytes in the subject by at least 70% for at least two weeks after a first dose of the antibody.   
     
     
         40 . The method of  claim 39 , wherein the dose is about 3 mg/kg. 
     
     
         41 . The method of  claim 39 , wherein the administration of the antibody reduces the number of nonclassical CD16+ monocytes in the subject by at least 90% two weeks after a first dose of the antibody. 
     
     
         42 . The method of  claim 39 , wherein the method further comprises determining the number of nonclassical CD16+ monocytes in a peripheral blood sample from the subject two to six weeks after a first dose of the antibody. 
     
     
         43 . The method of  claim 42 , wherein the method further comprises determining the number of nonclassical CD16+ monocytes in a peripheral blood sample from the subject two to four weeks after a first dose of the antibody. 
     
     
         44 . The method of  claim 43 , wherein the method further comprises determining the number of nonclassical CD16+ monocytes in a peripheral blood sample from the subject two weeks after a first dose of the antibody. 
     
     
         45 . The method of  claim 39 , wherein the antibody is a humanized antibody. 
     
     
         46 . The method of  claim 39 , wherein the antibody is selected from a Fab, an Fv, an scFv, a Fab′, and a (Fab′) 2 . 
     
     
         47 . 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. 
     
     
         48 . The method of  claim 47 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 53 and a light chain comprising the sequence of SEQ ID NO: 60. 
     
     
         49 . A method of reducing the number of nonclassical CD16+ monocytes in a subject with a CD16+ disorder, comprising (a) administering to the subject a first dose of 1 mg/kg to 10 mg/kg of an antibody that binds human colony stimulating factor 1 receptor (CSF1R), wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to CSF1R and blocks binding of human IL-34 to 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; (b) detecting that the number of nonclassical CD16+ monocytes in the subject two to six weeks following administering the first dose of (a) is reduced by at least 70% compared to a number of nonclassical CD16+ monocytes determined prior to administering the first dose; and (c) continuing to administer the antibody to the subject at a dose of 1 mg/kg to 10 mg/kg every two weeks or every three weeks. 
     
     
         50 . The method of  claim 49 , wherein the first dose is between 3 mg/kg and 10 mg/kg. 
     
     
         51 . The method of  claim 49 , wherein the first dose is about 3 mg/kg. 
     
     
         52 . The method of  claim 49 , wherein the first dose of (a) and the dose of (c) are both between 3 mg/kg and 10 mg/kg. 
     
     
         53 . The method of  claim 49 , wherein the first dose of (a) and the dose of (c) are both about 3 mg/kg. 
     
     
         54 . The method of  claim 49 , wherein the first dose of (a) and the dose of (c) are the same. 
     
     
         55 . The method of  claim 50 , wherein the first dose of (a) and the dose of (c) are the same. 
     
     
         56 . The method of  claim 51 , wherein the first dose of (a) and the dose of (c) are the same. 
     
     
         57 . The method of  claim 49 , wherein the method comprises (b) detecting that the number of nonclassical CD16+ monocytes in the subject two to four weeks following administering the first dose of (a) is reduced by at least 70% compared to a number of nonclassical CD16+ monocytes determined prior to administering the first dose. 
     
     
         58 . The method of  claim 49 , wherein the method comprises (b) detecting that the number of nonclassical CD16+ monocytes in the subject two weeks following administering the first dose of (a) is reduced by at least 70% compared to a number of nonclassical CD16+ monocytes determined prior to administering the first dose. 
     
     
         59 . The method of  claim 49 , wherein the method comprises (b) detecting that the number of nonclassical CD16+ monocytes in the subject two to six weeks following administering the first dose of (a) is reduced by at least 90% compared to a number of nonclassical CD16+ monocytes determined prior to administering the first dose. 
     
     
         60 . The method of  claim 59 , wherein the method comprises (b) detecting that the number of nonclassical CD16+ monocytes in the subject two to four weeks following administering the first dose of (a) is reduced by at least 90% compared to a number determined prior to administering the first dose. 
     
     
         61 . The method of  claim 59 , wherein the method comprises (b) detecting that the number of nonclassical CD16+ monocytes in the subject two weeks following administering the first dose of (a) is reduced by at least 90% compared to a number determined prior to administering the first dose. 
     
     
         62 . The method of  claim 49 , wherein the antibody is administered to the subject every two weeks. 
     
     
         63 . The method of  claim 59 , wherein the antibody is administered to the subject every two weeks. 
     
     
         64 . The method of  claim 49 , wherein the antibody is a humanized antibody. 
     
     
         65 . The method of  claim 49 , wherein the antibody is selected from a Fab, an Fv, an scFv, a Fab′, and a (Fab′) 2 . 
     
     
         66 . The method of  claim 49 , 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. 
     
     
         67 . The method of  claim 49 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 53 and a light chain comprising the sequence of SEQ ID NO: 60.