US2016031995A1PendingUtilityA1

Novel antibodies for the treatment of hiv

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Assignee: PF MEDICAMENTPriority: Apr 29, 2009Filed: Jun 22, 2015Published: Feb 4, 2016
Est. expiryApr 29, 2029(~2.8 yrs left)· nominal 20-yr term from priority
Inventors:Christine Klinguer-Hamour
A61P 31/18C07K 2317/24C07K 16/2866A61K 45/06C07K 2317/56A61K 31/439C07K 2317/76C07K 2317/622C07K 16/24A61K 39/3955A61K 2039/505A61K 45/00
44
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Claims

Abstract

The present invention relates to novel isolated antibodies, or the derivatives or antigen binding fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and able to inhibit HIV-1 primary isolate replication in PBMC. More particularly, the present invention relates to the 515H7 and 301aE5 monoclonal antibodies, specific to the CXCR4 protein, as well as their use for the treatment of HIV infection. Pharmaceutical compositions comprising such antibodies and a process for the selection of such antibodies are also covered.

Claims

exact text as granted — not AI-modified
1 - 32 . (canceled) 
     
     
         33 . A method of inhibiting HIV replication, the method comprising administering to a subject in need thereof an antibody, or a CXCR4-binding fragment thereof, wherein said antibody or binding fragment comprises a light chain comprising CDR-L1, CDR-L2 and CDR-L3 comprising respectively the amino acid sequence of SEQ ID Nos. 1, 2 and 3; and a heavy chain comprising CDR-H1, CDR-H2 and CDR-H3 comprising respectively the amino acid sequence of SEQ ID Nos. 4, 5 and 6. 
     
     
         34 . The method of  claim 33 , wherein said antibody or binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID No. 7. 
     
     
         35 . The method of  claim 33 , wherein said antibody or binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No. 8. 
     
     
         36 . The method of  claim 33 , wherein the antibody is chimeric. 
     
     
         37 . The method of  claim 36 , wherein said antibody or binding fragment comprises a light chain of sequence selected in the group consisting of SEQ ID No. 56-58. 
     
     
         38 . The method of  claim 36 , wherein said antibody or binding fragment comprises a heavy chain of sequence SEQ ID No. 59. 
     
     
         39 . The method of  claim 36 , wherein the fragment is chosen from Fv, scFv, Fab, F(ab′) 2 , Fab′, and scFv-Fc fragments. 
     
     
         40 . The method of  claim 33 , wherein the antibody is humanized. 
     
     
         41 . The method of  claim 40 , wherein said antibody or binding fragment comprises a light chain comprising an amino acid sequence selected in the group consisting of SEQ ID Nos. 65, 66, 82, and 83. 
     
     
         42 . The method of  claim 40 , wherein said antibody or binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No. 64. 
     
     
         43 . The method of  claim 40 , wherein said antibody or binding fragment comprises a light chain of sequence selected in the group consisting of SEQ ID Nos. 70, 71, 84, and 85. 
     
     
         44 . The method of  claim 40 , wherein said antibody or binding fragment comprises a heavy chain of sequence selected in the group consisting of SEQ ID Nos.67-69. 
     
     
         45 . The method of  claim 40 , wherein the fragment is chosen from Fv, scFv, Fab, F(ab′) 2 , Fab′, and scFv-Fc fragments. 
     
     
         46 . The method of  claim 33 , further comprising administering a second anti-HIV compound selected among the compounds capable of specifically inhibiting HIV entry and/or replication. 
     
     
         47 . The method of  claim 46 , wherein said at least second anti-HIV compound is chosen from HIV protease inhibitors (PI), nucleoside/nucleotide HIV reverse-transcriptase inhibitors (NRTI/NtRTI), non-nucleoside HIV reverse-transcriptase inhibitors (NNRTI), HIV entry inhibitors, and HIV integrase inhibitors. 
     
     
         48 . The method of  claim 46 , wherein said at least second anti-HIV compound is an anti-CCR5 compound. 
     
     
         49 . The method of  claim 46 , wherein said anti-CCR5 compound is Maraviroc. 
     
     
         50 . A method for HIV disease prevention or treatment, the method comprising administering to a subject in need thereof an antibody, or a CXCR4-binding fragment thereof, wherein said antibody or binding fragment comprises a light chain comprising CDR-L1, CDR-L2 and CDR-L3 comprising respectively the amino acid sequence of SEQ ID Nos. 1, 2 and 3; and a heavy chain comprising CDR-H1, CDR-H2 and CDR-H3 comprising respectively the amino acid sequence of SEQ ID Nos. 4, 5 and 6. 
     
     
         51 . The method of  claim 50 , wherein said antibody or binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID No. 7. 
     
     
         52 . The method of  claim 50 , wherein said antibody or binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No. 8. 
     
     
         53 . The method of  claim 50 , wherein the antibody is chimeric. 
     
     
         54 . The method of  claim 53 , wherein said antibody or binding fragment comprises a light chain of sequence selected in the group consisting of SEQ ID No. 56-58. 
     
     
         55 . The method of  claim 53 , wherein said antibody or binding fragment comprises a heavy chain of sequence SEQ ID NO. 59. 
     
     
         56 . The method of  claim 53 , wherein the fragment is chosen from Fv, scFv, Fab, F(ab′) 2 , Fab′, and scFv-Fc fragments. 
     
     
         57 . The method of  claim 50 , wherein the antibody is humanized. 
     
     
         58 . The method of  claim 57 , wherein said antibody or binding fragment comprises a light chain comprising an amino acid sequence selected in the group consisting of SEQ ID Nos. 65, 66, 82, and 83. 
     
     
         59 . The method of  claim 57 , wherein said antibody or binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No. 64. 
     
     
         60 . The method of  claim 57 , wherein said antibody or binding fragment comprises a light chain of sequence selected in the group consisting of SEQ ID Nos. 70, 71, 84, and 85. 
     
     
         61 . The method of  claim 57 , wherein said antibody or binding fragment comprises a heavy chain of sequence selected in the group consisting of SEQ ID Nos.67-69. 
     
     
         62 . The method of  claim 57 , wherein the fragment is chosen from Fv, scFv, Fab, F(ab′) 2 , Fab′, and scFv-Fc fragments. 
     
     
         63 . The method of  claim 50 , further comprising administering a second anti-HIV compound selected among the compounds capable of specifically inhibiting HIV entry and/or replication. 
     
     
         64 . The method of  claim 63 , wherein said at least second anti-HIV compound is chosen from HIV protease inhibitors (PI), nucleoside/nucleotide HIV reverse-transcriptase inhibitors (NRTI/NtRTI), non-nucleoside HIV reverse-transcriptase inhibitors (NNRTI), HIV entry inhibitors, and HIV integrase inhibitors. 
     
     
         65 . The method of  claim 63 , wherein said at least second anti-HIV compound is an anti-CCR5 compound. 
     
     
         66 . The method of  claim 63 , wherein said anti-CCR5 compound is Maraviroc.

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