Methods of treating multiple sclerosis using anti-CD20 antibodies
Compositions and methods are provided for treating diseases associated with CD20, including lymphomas, autoimmune diseases, and transplant rejections. Compositions include anti-CD20 antibodies capable of binding to a human CD20 antigen located on the surface of a human CD20-expressing cell, wherein the antibody has increased complement-dependent cell-mediated cytotoxicity (CDC) that is achieved by having at least one optimized CDR engineered within the variable region of the antibody. Compositions also include antigen-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-CD20 antibodies of the invention, or antigen-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier, and methods of use of these anti-CD20 antibodies.
1. A method for treating multiple sclerosis, comprising administering to a subject in need of treatment an effective amount of an immunoglobulin that specifically binds CD20, wherein the immunoglobulin comprises an immunoglobulin heavy chain comprising a variable heavy (VH) domain and an immunoglobulin light chain comprising a variable light (VL) domain, and wherein the VH and VL comprise, respectively, amino acid sequences selected from the group consisting of:
(a) SEQ ID NO: 12 and SEQ ID NO: 10;
(b) SEQ ID NO: 13 and SEQ ID NO: 10;
(c) SEQ ID NO: 14 and SEQ ID NO: 10;
(d) SEQ ID NO: 15 and SEQ ID NO: 10;
(e) SEQ ID NO: 16 and SEQ ID NO: 10;
(f) SEQ ID NO: 17 and SEQ ID NO: 10;
(g) SEQ ID NO: 18 and SEQ ID NO: 10;
(h) SEQ ID NO: 13 and SEQ ID NO: 11; and
(i) SEQ ID NO: 16 and SEQ ID NO: 11.
2. The method of claim 1 , wherein the VH and VL comprise, respectively, the amino acid sequences SEQ ID NO: 16 and SEQ ID NO. 10.
3. The method of claim 1 , wherein the immunoglobulin exhibits increased complement-dependent cytotoxicity (CDC) as compared to rituximab.
4. The method of claim 1 , wherein the immunoglobulin is an IgG1 kappa immunoglobulin.
5. The method of claim 4 , wherein the igGl kappa immunoglobulin comprises a human igGl constant region within the heavy chain of the immunoglobulin and a human kappa constant region within the light chain of said immunoglobulin.
6. The method of claim 1 , wherein the subject is human.