ANTI-N3pGlu AMYLOID BETA PEPTIDE ANTIBODIES AND USES THEREOF

Abstract

Antibodies to human N3pGlu Aβ, compositions comprising such N3pGlu Aβ antibodies, and methods of using such N3pGlu Aβ antibodies for the treatment of a disease characterized by deposition of Aβ including clinical or pre-clinical Alzheimer's disease, Down's syndrome, and clinical or pre-clinical cerebral amyloid angiopathy.

We claim: 
     
         1 . An antibody that binds human N3pGlu Aβ, comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises LCDR1 having the amino acid sequence of SEQ ID NO: 4, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 8, and wherein the HCVR comprises HCDR1 having the amino acid sequence of SEQ ID NO: 1, HCDR2 having the amino acid sequence of SEQ ID NO: 2, and HCDR3 having the amino acid sequence of SEQ ID NO: 3. 
     
     
         2 . The antibody of  claim 1 , wherein the LCVR has the amino acid sequence of SEQ ID NO: 10, and the HCVR has the amino acid sequence of SEQ ID NO:9. 
     
     
         3 . The antibody of  claim 1 , comprising a light chain (LC) having the amino acid sequence of SEQ ID NO: 13, and a heavy chain (HC) having the amino acid sequence of SEQ ID NO: 12. 
     
     
         4 . The antibody of  claim 3 , comprising two LCs and two HCs, wherein the amino acid sequence of each LC is SEQ ID NO: 13, and the amino acid sequence of each HC is SEQ ID NO: 12. 
     
     
         5 . A pharmaceutical composition comprising the antibody of  claim 1  and one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         6 . A method of treating a patient having a condition characterized by deposition of Aβ, comprising administering to the patient an effective amount of the antibody of  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein the condition is selected from clinical or pre-clinical AD, Down's syndrome, and clinical or pre-clinical CAA. 
     
     
         8 . The method of  claim 6 , wherein the condition is selected from prodromal AD, mild AD, moderate AD, and severe AD. 
     
     
         9 . A method of treating memory loss or cognitive decline in a patient having a condition characterized by deposition of Aβ, comprising administering to the patient an effective amount of the antibody of  claim 1 . 
     
     
         10 . A method of slowing cognitive or functional decline in a patient having a condition characterized by deposition of Aβ, comprising administering to the patient an effective amount of the antibody of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein the condition is selected from clinical or pre-clinical AD, Down's syndrome, and clinical or pre-clinical CAA. 
     
     
         12 . The method of  claim 10 , wherein the condition is selected from prodromal AD, mild AD, moderate AD, and severe AD. 
     
     
         13 . A method of reducing brain Aβ amyloid plaque load in a patient having a condition characterized by deposition of Aβ, comprising administering to the patient an effective amount of the antibody of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the condition is selected from clinical or pre-clinical AD, Down's syndrome, and clinical or pre-clinical CAA. 
     
     
         15 . The method of  claim 13 , wherein the condition is selected from prodromal AD, mild AD, moderate AD or severe AD. 
     
     
         16 . A DNA molecule comprising a polynucleotide that encodes the antibody heavy chain given by the amino acid sequence of SEQ ID NO:12. 
     
     
         17 . The DNA molecule of  claim 16 , wherein the amino acid sequence of the polynucleotide is SEQ ID NO:15. 
     
     
         18 . A DNA molecule comprising a polynucleotide that encodes the antibody light chain given by the amino acid sequence of SEQ ID NO:13. 
     
     
         19 . The DNA molecule of  claim 18 , wherein the amino acid sequence of the polynucleotide is SEQ ID NO:16. 
     
     
         20 . A DNA molecule comprising a polynucleotide sequence that encodes the antibody heavy chain having the amino acid sequence of SEQ ID NO: 12 and a polynucleotide sequence that encodes the antibody light chain having the amino acid sequence of SEQ ID NO: 13. 
     
     
         21 . The DNA molecule of  claim 20 , wherein the polynucleotide sequence that encodes the antibody heavy chain is SEQ ID NO:15, and the polynucleotide sequence that encodes the antibody light chain is SEQ ID NO:16. 
     
     
         22 . A mammalian cell transformed with the DNA molecule of  claim 16  and the DNA molecule of  claim 18 , wherein the transformed cell is capable of expressing an antibody comprising two heavy chains and two light chains, wherein the amino acid sequence of each heavy chain is given by SEQ ID NO:12 and the amino acid sequence of each light chain is given by SEQ ID NO:13. 
     
     
         23 . A mammalian cell transformed with the DNA molecule of  claim 20 , wherein the transformed cell is capable of expressing an antibody comprising two heavy chains and two light chains, wherein the amino acid sequence of each heavy chain is given by SEQ ID NO:12 and the amino acid sequence of each light chain is given by SEQ ID NO:13. 
     
     
         24 . A process for producing an antibody, wherein the amino sequence of each of the two HCs is SEQ ID NO: 12, and the amino acid sequence of each of the two LCs is SEQ ID NO: 13, and wherein the process comprises: a) cultivating the mammalian cell of  claim 23  under conditions such that the antibody is expressed, and b) recovering the expressed antibody. 
     
     
         25 . An antibody obtainable by the process of  claim 24 .