Anti-alpha-4-beta-7 antibodies
The present disclosure provides anti-α4β7 antibodies that bind human α4β7, their methods of making, and their uses to treat patients with HIV infection.
1. An anti-human α4β7 monoclonal antibody which comprises (i) a VH chain region comprising three CDRs; and (ii) a VL chain region comprising three CDRs, wherein:
(SEQ ID NO: 72)
VH CDR #1 is GFNIKNTYMH;
(SEQ ID NO: 73)
VH CDR #2 is RIDPAKGHTEYAPKFLG;
(SEQ ID NO: 74)
VH CDR #3 is VDV;
(SEQ ID NO: 75)
VL CDR #1 is HASQDISDNIG;
(SEQ ID NO: 76)
VL CDR #2 is HGTNLED; and
(SEQ ID NO: 77)
VL CDR #3 is VQYAQFPWT.
2. The anti-human α4β7 monoclonal antibody of claim 1 , which comprises
a VH chain region of:
(SEQ ID NO: 70)
EVQLVQSGAEVKKPGSSVKVSCKASGFNIKNTYMHWVRQAPGQGLEWI
GRIDPAKGHTEYAPKFLGRVTITADESTNTAYMELSSLRSEDTAVYYC
YYVDVWGQGTTVTVSS;
and
a VL chain region of:
(SEQ ID NO: 71)
DIQMTQSPSSLSASVGDRVTITCHASQDISDNIGWLQQKPGKSFKLLIY
HGTNLEDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTF
GGGTKVEIK.
3. The anti-human α4β7 monoclonal antibody of claim 2 , which is an IgG.
4. The anti-human α4β7 monoclonal antibody of claim 3 , comprising a kappa light constant region.
5. The anti-human α4β7 monoclonal antibody of claim 4 , which is an IgG 1 .
6. The anti-human α4β7 monoclonal antibody of claim 5 , comprising a variant CH3 domain having amino acid substitutions D356E and L358M.
7. The anti-human α4β7 monoclonal antibody of claim 1 , which comprises a heavy chain having an amino acid sequence of SEQ ID NO:92 or SEQ ID NO:93, and a light chain having an amino acid sequence of SEQ ID NO:100.
8. The anti-human α4β7 monoclonal antibody of claim 1 , which is an antibody comprising heavy chains each consisting of the amino acid sequence of SEQ ID NO:92, and light chains each consisting of the amino acid sequence of SEQ ID NO:100.
9. The anti-human α4β7 monoclonal antibody of claim 1 , which is an antibody comprising heavy chains each consisting of the amino acid sequence of SEQ ID NO:93, and light chains each consisting of the amino acid sequence of SEQ ID NO:100.