Anti-TLR7 agents and compositions and methods for making and using the same
Compositions and methods for making and using anti-TLR7 agents, for example, monoclonal antibodies, TLR7-binding antibody fragments, and derivatives are described, as are kits, nucleic acids encoding such molecules, diagnostic reagents and kits that include anti-TLR7 agents, and methods of making and using the same.
1 . An anti-TLR7 agent that binds Toll-like Receptor 7 (TLR7), comprising an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain, wherein the immunoglobulin heavy chain variable domain comprises a set of CDRH1, CDRH2, and CDRH3 amino acid sequences and the immunoglobulin light chain variable domain comprises a set of CDRL1, CDRL2, and CDRL3 amino acid sequences, wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain comprise sequences selected from one of sets 1-6:
CDRH1
CDRH2
CDRH3
CDRL1
CDRL2
CDRL3
set
(SEQ ID NO:)
(SEQ ID NO:)
(SEQ ID NO:)
(SEQ ID NO:)
(SEQ ID NO:)
(SEQ ID NO:)
1
DYWMS (1)
DIKYDGSFID
DLTTVVDGFAY
RASQSLSTSI
YASQPIS (24)
QQSYSSPYT
YAPSLKN (6)
(12)
H (19)
(29)
2
DYWMS (1)
DIKYDGTFI
DLTTVVDGFAY
RASQSLSTSI
YASQPIS (24)
QQSYSSPYT
DYAPSLKN
(12)
H (19)
(29)
(7)
3
NYYMA (2)
SITNSGRTTY
EGGDLYYSN
LPSEDIYNN
YASNLQD
LQDSDYPFT
YRDSVKG
YNYVRFAY
LA (18)
(23)
(28)
(8)
(13)
4
DYYMA (3)
SISYEGSSTH
HGGYPNWYFDF
RASEDIYNE
NANSLHT
QQYYDYPW
YGDSVKA
(14)
LA (17)
(22)
T (27)
(9)
5
DYCVH (4)
YINPYSGYT
GPYGGYSGDGFDY
RASEDIYNV
NANRLHN
QQYYDYPN
NYNEKFKS
(15)
LA (16)
(20)
T (25)
(10)
6
DYYIH (5)
FINPDSGYT
GPYGGYSGDGFDY
RASEDIYNV
NANNLHT
QQYYDYPH
NYNEKFKT
(15)
LA (16)
(21)
T (26)
and wherein all CDR amino acid sequences are from the same set.
2 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 1.
3 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 2.
4 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 3.
5 . The anti-TLR7 agent of claim 1 , wherein the immunoglobulin heavy chain variable domain (VH) comprises at least 90% identity to the sequence set forth in any one of SEQ ID NOS: 36-41.
6 . The anti-TLR7 agent of claim 1 , wherein the immunoglobulin heavy chain variable domain (VH) comprises at least 90% identity to the sequence set forth in SEQ ID NO:41.
7 . The anti-TLR7 agent of claim 1 , wherein the immunoglobulin light chain variable region comprises at least 90% identity to a sequence set forth in any of SEQ ID NOS: 42-47.
8 . The anti-TLR7 agent of claim 1 , wherein the immunoglobulin light chain variable region comprises at least 90% identity to a sequence set forth in SEQ ID NO:47.
9 . The anti-TLR7 agent of claim 1 , comprising two immunoglobulin heavy chain variable domains and two immunoglobulin light chain variable domains.
10 . The anti-TLR7 agent of claim 1 , wherein the agent comprises an antibody, or antigen-binding fragment thereof.
11 . The anti-TLR7 agent of claim 1 , wherein the agent comprises a humanized antibody, or a humanized antigen binding fragment thereof.
12 . The anti-TLR7 agent of claim 1 , further comprising one or more human framework regions.
13 . The anti-TLR7 agent of claim 1 , wherein the agent is conjugated to a detectable marker or label.
14 . The anti-TLR7 agent of claim 1 , wherein the agent is non-diffusively immobilized on a solid support.
15 . A diagnostic reagent comprising the anti-TLR7 agent of claim 1 .
16 . A kit comprising the anti-TLR7 agent of claim 1 .
17 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 4.
18 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 5.
19 . The anti-TLR7 agent of claim 1 , wherein the amino acid sequences for the immunoglobulin heavy chain variable domain and the immunoglobulin light chain variable domain are selected from set 6.