Humanized anti-complement factor c1q antibodies and uses thereof

Abstract

The present disclosure is directed to humanized anti-C1q antibodies and methods of using them.

1 - 29 . (canceled) 
     
     
         30 . A method of detecting synapses in an individual, the method comprising
 a) administering an anti-C1q antibody to the individual; and   b) detecting the antibody bound to synapses, thereby detecting synapses in the individual,   wherein the antibody comprises:   a heavy chain variable domain, and the heavy chain variable domain comprises an amino acid sequence selected from SEQ ID NOs: 1-4, or an amino acid sequence with at least about 95% homology to the amino acid sequence selected from SEQ ID NOs: 1-4 and wherein the heavy chain variable domain comprises an HVR-H1 having the amino acid sequence of SEQ ID NO: 23, an HVR-H2 having the amino acid sequence of SEQ ID NO: 24, and an HVR-H3 having the amino acid sequence of SEQ ID NO: 25; and   a light chain variable domain, and the light chain variable domain comprises an amino acid sequence selected from SEQ ID NOs: 5-8, or an amino acid sequence with at least about 95% homology to the amino acid sequence selected from SEQ ID NOs: 5-8 and wherein the light chain variable domain comprises an HVR-L1 having the amino acid sequence of SEQ ID NO: 30, an HVR-L2 having the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 having the amino acid sequence of SEQ ID NO: 32.   
     
     
         31 . The method of  claim 30 , wherein the antibody bound to synapses is detected using an imaging technique selected from positron emission tomography (PET), X-ray computed tomography, single-photon emission computed tomography (SPECT), computed tomography (CT), and computed axial tomography (CAT). 
     
     
         32 . The method of  claim 30 , wherein the detection of the antibody bound to synapses provides a quantitative measure of the number of synapses in the individual. 
     
     
         33 . The method of  claim 30 , wherein the individual has a neurodegenerative disease or autoimmune disease. 
     
     
         34 . The method of  claim 30 , wherein the number of synapses in the individual is measured repeatedly over a period of time and a loss of synapses in the individual is detected over time. 
     
     
         35 . The method of  claim 34 , wherein the loss of synapses over time is a measure for the efficacy of a treatment for the neurodegenerative disease or autoimmune disease. 
     
     
         36 . A method of detecting synapses in a biological sample, the method comprising
 a) contacting the biological sample with an anti-C1q antibody; and   b) detecting the antibody bound to synapses, thereby detecting synapses in the biological sample,   wherein the antibody comprises:   a heavy chain variable domain, and the heavy chain variable domain comprises an amino acid sequence selected from SEQ ID NOs: 1-4, or an amino acid sequence with at least about 95% homology to the amino acid sequence selected from SEQ ID NOs: 1-4 and wherein the heavy chain variable domain comprises an HVR-H1 having the amino acid sequence of SEQ ID NO: 23, an HVR-H2 having the amino acid sequence of SEQ ID NO: 24, and an HVR-H3 having the amino acid sequence of SEQ ID NO: 25; and   a light chain variable domain, and the light chain variable domain comprises an amino acid sequence selected from SEQ ID NOs: 5-8, or an amino acid sequence with at least about 95% homology to the amino acid sequence selected from SEQ ID NOs: 5-8 and wherein the light chain variable domain comprises an HVR-L1 having the amino acid sequence of SEQ ID NO: 30, an HVR-L2 having the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 having the amino acid sequence of SEQ ID NO: 32.   
     
     
         37 . The method of  claim 36 , further comprising a step before step a) of obtaining the biological sample from an individual. 
     
     
         38 . The method of  claim 36 , wherein the biological sample comprises a biopsy specimen, a tissue, or a cell. 
     
     
         39 . The method of  claim 36 , wherein the antibody is detected by immunofluorescence microscopy, immunocytochemistry, immunohistochemistry, ELISA, FACS analysis, immunoprecipitation, or micro-positron emission tomography.