FILOVIRUS ANTIBODY
The present invention addresses a need for antibodies useful for filovirus infections.
1 . An isolated humanized anti-filovirus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region, and comprising:
(a) a heavy chain CDR1 comprising GFAFNYYDMF (SEQ ID NO:1); a heavy chain CDR2 comprising YIKPGGGNTYYADSV (SEQ ID NO:2); and a heavy chain CDR3 comprising QLYGNSFFDY (SEQ ID NO:3); and
(b) a light chain sequence CDR1 comprising DVTTA (SEQ ID NO:4); a light chain sequence CDR2 comprising WASTR (SEQ ID NO:5); and a light chain sequence CDR3 comprising HYSTPLT (SEQ ID NO:6).
2 . The humanized antibody of claim 1 , wherein the light chain comprises the sequence:
(SEQ ID NO: 7)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW
ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ
GTKVEIK.
3 . The humanized antibody of claim 1 , wherein the light chain comprises the sequence:
(SEQ ID NO: 8)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW
ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGECGGS
or
(SEQ ID NO: 13)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW
ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC.
4 . The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence:
(SEQ ID NO: 9)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY
IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL
YGNSFFDYWGQGTLVTVSS
5 . The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence:
(SEQ ID NO: 10)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY
IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL
YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK,
(SEQ ID NO: 11)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY
IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL
YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG,
or
(SEQ ID NO: 12)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY
IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL
YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.
6 . An antigen-binding fragment of the antibody of claim 1 .
7 . A recombinant nucleic acid encoding the antibody of claim 1 .
8 . A cell, wherein the cell is not in a human subject, transformed with the recombinant nucleic acid of claim 7 .
9 . A composition comprising the antibody of claim 1 or the antigen-binding fragment thereof.
10 . The composition of claim 9 , comprising a pharmaceutically acceptably carrier.
11 . A method of treating a filovirus infection in a subject comprising administering to the subject an amount of the antibody of claim 1 or the antigen-binding fragment thereof effective to treat a filovirus infection in a subject.
12 . The method of claim 11 , wherein the antibody, antigen-binding fragment or composition are administered after the subject has been exposed to the filovirus.
13 . A method of inhibiting a filovirus infection of a subject comprising administering to the subject an amount of claim 1 or the antigen-binding fragment thereof effective to inhibit a filovirus infection in a subject.
14 . The method of claim 13 , wherein the antibody, antigen-binding fragment or composition are administered prior to the subject being exposed to the filovirus.
15 . The method of any of claim 11 , wherein the filovirus is an Ebola virus.
16 . The method of claim 15 , wherein the Ebola virus is the Sudan strain.
17 . The antibody of any of claim 1 or the antigen-binding fragment thereof, wherein the antibody is a neutralizing antibody.