Recombinant antibodies against H1N1 influenza
View Patent ↗Antibodies that bind with high affinity to swine H1N1 virus are described. In vivo experiments showed that one such antibody is able to fully protect mice challenged with a lethal dose of swine H1N1 virus. The antibody is also able to cure mice in a therapeutic setting when treated as late as up to 60 hours (2.5 days) after infection with swine H1N1 virus. Also described are recombinant forms of this antibody.
1. A non-naturally occurring chimeric monoclonal antibody, wherein the antibody comprises a heavy chain having a variable and constant region and a light chain having a variable and constant region, wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and wherein the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8, and wherein the antibody specifically binds H1N1.
2. The non-naturally occurring chimeric monoclonal antibody of claim 1 wherein the antibody has Kd for purified H1N1 that is less than 1 ×10 −9 .
3. A composition comprising a non-naturally occurring chimeric monoclonal antibody wherein the antibody comprises a heavy chain having a variable and constant region and a light chain having a variable and constant region, wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and wherein the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8, and wherein the antibody specifically binds H1N1, and a pharmaceutically acceptable carrier.
4. A method for reducing the risk of infection with H1N1 in a human subject, the method comprising
administering a non-naturally occurring chimeric monoclonal antibody comprising a heavy chain having a variable and constant region and a light chain having a variable and constant region, wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and wherein the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8, specifically binds H1N1, to the human subject
thereby reducing the risk of infection of H1N1 in the human subject.
5. A method for treating a patient infected with H1N1 virus, the method comprising
administering a non-naturally occurring chimeric monoclonal antibody comprising a heavy chain having a variable and constant region and a light chain having a variable and constant region, wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and wherein the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8, and wherein the antibody specifically binds H1N1, to the patient infected with the H1N1 virus,
thereby treating the patient.
6. The non-naturally occurring chimeric monoclonal antibody of claim 1 , or the antigen binding fragment thereof, wherein the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 2.
7. The non-naturally occurring chimeric monoclonal antibody of claim 1 , or antigen binding fragment thereof, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 1.
8. The non-naturally occurring chimeric monoclonal antibody of claim 1 , or the antigen binding fragment thereof, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1.
9. A non-naturally occurring chimeric monoclonal antibody, wherein the antibody comprises a heavy chain having a variable and constant region and a light chain having a variable and constant region,
wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and wherein the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8,
wherein the heavy chain constant region comprises SEQ ID NO: 43, and
wherein the antibody specifically binds H1N1.
10. A non-naturally occurring monoclonal antibody specifically binding influenza virus H1N1, having a heavy chain with a constant domain and variable domain, and light chain with a variable domain and constant domain wherein the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8, and
wherein the heavy chain comprises a sequence that is different from any sequences present in naturally derived antibodies for which the light chain variable region comprises CDR1 of SEQ ID NO: 3, CDR2 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 5 and the heavy chain variable region comprises CDR1 of SEQ ID NO: 6, CDR2 of SEQ ID NO: 7 and CDR3 of SEQ ID NO: 8.