US2016159891A1PendingUtilityA1

Monoclonal antibodies against amyloid beta protein and uses thereof

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Assignee: ABBVIE INCPriority: Nov 30, 2005Filed: Feb 17, 2016Published: Jun 9, 2016
Est. expiryNov 30, 2025(expired)· nominal 20-yr term from priority
Inventors:Heinz HillenStefan BarghornBoris LabkovskyUlrich EbertAndreas StriebingerPatrick Keller
A61P 37/04A61P 25/28G01N 2800/2821C07K 2317/14C07K 2317/24C07K 2317/20G01N 33/6896C07K 2317/92A61K 39/3955C07K 16/46C07K 2317/56C07K 16/18C07K 2317/565A61K 2039/505C07K 2317/21G01N 33/577G01N 33/53G01N 2500/20G01N 2333/4709G01N 33/6893
58
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Claims

Abstract

The subject invention relates to monoclonal antibodies (e.g., 8F5 and 8C5) that may be used, for example, in the prevention, treatment and diagnosis of Alzheimer's Disease or other neurodegenerative disorders.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . An isolated antibody that binds with greater specificity to an amyloid beta (Aβ) protein globulomer than to an amyloid beta protein monomer. 
     
     
         2 . The isolated antibody of  claim 1  wherein said antibody is monoclonal. 
     
     
         3 . The isolated antibody of  claim 2  wherein the ratio of binding specificity to said globulomer and said monomer is at least 1.4. 
     
     
         4 . The isolated antibody of  claim 3  wherein said ratio is 1.4 to 16.9. 
     
     
         5 . The isolated antibody of  claim 4  wherein said amyloid beta protein monomer is selected from the group consisting of Aβ(1-42) monomer and Aβ(1-40) monomer. 
     
     
         6 . The isolated antibody of  claim 5  wherein said monoclonal antibody is produced by a hybridoma having American Type Culture Collection designation number PTA-7238 or PTA-7407. 
     
     
         7 . A hybridoma having American Type Culture Collection designation number PTA-7238. 
     
     
         8 . A monoclonal antibody (8F5) produced by said hybridoma of  claim 7 . 
     
     
         9 . A monoclonal antibody comprising a variable heavy chain encoded by SEQ ID NO:1. 
     
     
         10 . The monoclonal antibody of  claim 9  wherein said antibody is human or humanized. 
     
     
         11 . A monoclonal antibody comprising a variable light chain encoded by SEQ ID NO:2. 
     
     
         12 . The monoclonal antibody of  claim 11  wherein said antibody is human or humanized. 
     
     
         13 . The monoclonal antibody of  claim 11  further comprising a variable light heavy chain encoded by SEQ ID NO:1. 
     
     
         14 . The monoclonal antibody of  claim 13  wherein said antibody is human or humanized. 
     
     
         15 . A monoclonal antibody comprising SEQ ID NO:3. 
     
     
         16 . The monoclonal antibody of  claim 15  wherein said antibody is human or humanized. 
     
     
         17 . A monoclonal antibody comprising SEQ ID NO:4. 
     
     
         18 . The monoclonal antibody of  claim 17  wherein said antibody is human or humanized. 
     
     
         19 . The monoclonal antibody of  claim 17  further comprising SEQ ID NO:3. 
     
     
         20 . The monoclonal antibody of  claim 19  wherein said antibody is human or humanized. 
     
     
         21 . An isolated antibody that binds with greater specificity to an amyloid beta protein globulomer than to an amyloid beta protein fibril. 
     
     
         22 . The isolated antibody of  claim 22  wherein said antibody is monoclonal. 
     
     
         23 . The isolated antibody of  claim 23  wherein said monoclonal antibody is produced by a hybridoma having American Type Culture Collection designation number PTA-7238 or PTA-7407. 
     
     
         24 . A hybridoma having American Type Culture Collection designation number PTA-7407. 
     
     
         25 . A monoclonal antibody (8C5) produced by said hybridoma of  claim 24 . 
     
     
         26 . A monoclonal antibody comprising a variable heavy chain encoded by SEQ ID NO:11. 
     
     
         27 . The monoclonal antibody of  claim 26  wherein said antibody is human or humanized. 
     
     
         28 . A monoclonal antibody comprising a variable light chain encoded by SEQ ID NO:12. 
     
     
         29 . The monoclonal antibody of  claim 28  wherein said antibody is human or humanized. 
     
     
         30 . The monoclonal antibody of  claim 28  further comprising a variable light chain encoded by SEQ ID NO:11. 
     
     
         31 . The monoclonal antibody of  claim 30  wherein said antibody is human or humanized. 
     
     
         32 . A monoclonal antibody comprising SEQ ID NO:19. 
     
     
         33 . The monoclonal antibody of  claim 32  wherein said antibody is human or humanized. 
     
     
         34 . A monoclonal antibody comprising SEQ ID NO:20. 
     
     
         35 . The monoclonal antibody of  claim 34  wherein said antibody is human or humanized. 
     
     
         36 . A monoclonal antibody comprising a variable heavy chain, wherein said variable heavy chain comprises at least one complementarity determining region (CDR) selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. 
     
     
         37 . A monoclonal antibody comprising a variable light chain, wherein said variable light chain comprises at least one CDR selected from the group consisting of SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18. 
     
     
         38 . The monoclonal antibody of  claim 37  further comprising a variable heavy chain, wherein said variable heavy chain comprises at least one CDR selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. 
     
     
         39 . A monoclonal antibody comprising a variable heavy chain, wherein said variable heavy chain comprises at least one complementarity determining region (CDR) selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7. 
     
     
         40 . A monoclonal antibody comprising a variable light chain, wherein said variable light chain comprises at least one CDR selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10. 
     
     
         41 . The monoclonal antibody of  claim 40  further comprising a variable heavy chain, wherein said variable heavy chain comprises at least one CDR selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7. 
     
     
         42 . A method of treating or preventing Alzheimer's Disease in a patient in need of said treatment or prevention comprising administering said isolated antibody of  claim 1  or  claim 6  to said patient in an amount sufficient to effect said treatment or prevention. 
     
     
         43 . The method of  claim 42  wherein said isolated antibody is administered via a route selected from the group consisting of intramuscular administration, intravenous administration and subcutaneous administration. 
     
     
         44 . A method of diagnosing Alzheimer's Disease in a patient suspected of having this disease comprising the steps of:
 a. isolating a biological sample from said patient;   b. contacting said biological sample with said isolated antibody of  claim 1  or  claim 6  for a time and under conditions sufficient for formation of antigen/antibody complexes; and   c. detecting presence of said antigen/antibody complexes in said sample, presence of said complexes indicating a diagnosis of Alzheimer's Disease in said patient.   
     
     
         45 . The method of  claim 44  wherein said antigen is a globulomer. 
     
     
         46 . A method of diagnosing Alzheimer's Disease in a patient suspected of having this disease comprising the steps of:
 a. isolating a biological sample from said patient;   b. contacting said biological sample with an antigen for a time and under conditions sufficient for the formation of antibody/antigen complexes;   c. adding a conjugate to the resulting antibody/antigen complexes for a time and under conditions sufficient to allow said conjugate to bind to the bound antibody, wherein said conjugate comprises said isolated antibody of  claim 1  or  claim 6 , attached to a signal generating compound capable of generating a detectable signal; and   d. detecting the presence of an antibody which may be present in said biological sample, by detecting a signal generated by said signal generating compound, said signal indicating a diagnosis of Alzheimer's Disease in said patient.   
     
     
         47 . The method of  claim 46  wherein said antigen is a globulomer. 
     
     
         48 . A method of diagnosing Alzheimer's Disease in a patient suspected of having Alzheimer's Disease comprising the steps of:
 a. isolating a biological sample from said patient;   b. contacting said biological sample with anti-antibody, wherein said anti-antibody is specific for said antibody of  claim 1  or  claim 6 , for a time and under conditions sufficient to allow for formation of anti-antibody/antibody complexes, said complexes containing antibody present in said biological sample;   c. adding a conjugate to resulting anti-antibody/antibody complexes for a time and under conditions sufficient to allow said conjugate to bind to bound antibody, wherein said conjugate comprises an antigen, which binds to a signal generating compound capable of generating a detectable signal; and   d. detecting a signal generated by said signal generating compound, said signal indicating a diagnosis of Alzheimer's Disease in said patient.   
     
     
         49 . A composition comprising said isolated antibody of  claim 1  or  claim 6 . 
     
     
         50 . A method of preventing or treating Alzheimer's Disease in a patient in need of said prevention or treatment comprising the step of administering said composition of  claim 49  to said patient in an amount sufficient to effect said prevention or treatment. 
     
     
         51 . A vaccine comprising said isolated antibody of  claim 1  or  claim 6  and a pharmaceutically acceptable adjuvant. 
     
     
         52 . A method of preventing or treating Alzheimer's Disease in a patient in need of said prevention or treatment comprising the step of administering said vaccine of  claim 51  to said patient in an amount sufficient to effect said prevention or treatment. 
     
     
         53 . A method of identifying compounds suitable for active immunization of a patient predicted to develop Alzheimer's Disease comprising the steps of:
 a) exposing one or more compounds of interest to said isolated antibody of  claim 1  or  claim 6  for a time and under conditions sufficient for said one or more compounds to bind to said isolated antibody of  claim 1  or  claim 6 ; and   b) identifying those compounds which bind to said isolated antibody of  claim 1  or  claim 6 , said identified compounds to be used in active immunization in a patient predicated to develop Alzheimer's Disease.   
     
     
         54 . A kit comprising: a) said isolated antibody of  claim 1  or  claim 6  and b) a conjugate comprising an antibody attached to a signal-generating compound, wherein said antibody of said conjugate is different from said isolated antibody. 
     
     
         55 . A kit comprising: a) an anti-antibody to said isolated antibody of  claim 1  or  claim 6  and b) a conjugate comprising an antigen attached to a signal-generating compound. 
     
     
         56 . The kit of  claim 55  wherein said antigen is a globulomer.

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