US2023090487A1PendingUtilityA1
Therapeutic Anti-IgE Antibodies and Methods and Compositions Thereof
Est. expiryJan 6, 2037(~10.4 yrs left)· nominal 20-yr term from priority
A61P 37/06A61P 37/08C07K 2317/56C07K 2317/24C07K 16/4291C07K 2317/76C07K 2317/92A61K 2039/505
68
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Disclosed herein are anti-IgE antibodies having low binding affinity to human IgE and compositions and methods thereof.
Claims
exact text as granted — not AI-modified1 - 20 . (canceled)
21 . A monoclonal antibody, which comprises
(1) a VH chain comprising
(SEQ ID NO: 15)
(X) 0-1 VQLXQSG(X) 5 PGXS(X) 3 SCXASGXTF(X) 6 WVRQAPGXGLEW(X) 3
I(X) 4 G(X) 3 Y(X) 6 R(X) 5 DXS(X) 2 T(X) 6 SL(X) 3 DTAVYYCAR(X) 9-11
WGXGTXVTVSSAS,
wherein each X is independently any amino acid, and the VH chain contains a region that has 100% sequence identity to PGX2SX3X4X5SCX6ASGX7TF (SEQ ID NO: 18), wherein X2 is A or R, X3 is L or V, X4 is K or R, X5 is L or V, X6 is A or K, and X7 is F or Y; and
(2) an amino acid sequence comprising
(a)
(SEQ ID NO: 16)
(X) 4 TQ(X) 0-1 PXS(X) 3 SXG(X) 3 TIXC(X) 2-3 S(X)V(X) 9-11 Q(X) 2 PG(X) 2 PKLXIY(X) 2-4
S(X) 3 S(X) 2-4 RFSGSXSG(X) 4 LTXSXLQAEDXAXYYC(X) 0-2 Q(X) 6-8 FGXGTKL(X) 3-7
AAPSV(X) 2 FPPSXEXL(X) 4 A(X) 2 VCL(X) 3 FYP(X) 4 VXWKXD(X) 5-6 G(X) 1-3 E(X) 2 T(X) 8
Y(X) 2 SSXLXL(X) 7 H(X) 2 YXCXVTHXG(X) 0-2 SXVXK(X) 5 EC(X) 0-1 ,
wherein each X is independently any amino acid;
(b)
(SEQ ID NO: 32)
DIVMTQSPDSLAVSLGERATINCRASQSVSTSX56HSYMHWYQQKPGQP
PKLLIYYASNLX57X58GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC
QHSWEIPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
EKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein X56 is A or
S, X57 is E or K, X58 is A or S;
(c)
(SEQ ID NO: 63)
DIVMTQSPDSLAVSLGERATINCRASQSVSTSSYSYMHWYQQKPGQPPK
LLIYYASNLKAGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQHSWEI
PWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY
ACEVTHQGLSSPVTKSFNRGEC;
or
(d)
(SEQ ID NO: 65)
QSAVTQPPSASGSPGQSVTISCTGTSSDVGAYDYVSWYQQHPGKAPKLM
IYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGRVD
VFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV
TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC
QVTHEGSTVEKTVAPTECS.
22 . The monoclonal antibody according to claim 21 , wherein the VH chain contains a region having 100% sequence identity to any one or more of the following sequences
(SEQ ID NO: 17)
VQLX1QSG,
(SEQ ID NO: 19)
WVRQAPGX8GLEW,
(SEQ ID NO: 20)
WGX9GTX10VTVSSA,
(SEQ ID NO: 21)
SLX11X12X13DTAVYYCAR,
and
(SEQ ID NO: 22)
RX14X15X16X17X18DX19SX20X21T,
wherein X1 to X21 are each independently any amino acid.
23 . The monoclonal antibody according to claim 21 , wherein the VH chain contains a region having 100% sequence identity to any one or more of the following sequences
(SEQ ID NO: 17)
VQLX1QSG,
(SEQ ID NO: 18)
PGX2SX3X4X5SCX6ASGX7TF,
(SEQ ID NO: 19)
WVRQAPGX8GLEW,
(SEQ ID NO: 20)
WGX9GTX10VTVSSA,
(SEQ ID NO: 21)
SLX11X12X13DTAVYYCAR,
and
(SEQ ID NO: 22)
RX14X15X16X17X18DX19SX20X21T,
wherein X1 is V or G, X2 is A or R, X3 is L or V, X4 is K or R, X5 is L or V, X6 is A or K, X7 is F or Y, X8 is K or Q, X9 is R or Q, X10 is L or T, X11 is T, K, or R, X12 is A or S, X13 is E or D, X14 is F or V, X15 is T or V, X16 is I, F, or M, X17 is S or T, X18 is L, R, or T, X19 is N or T, X20 is K, T, or V, and X21 is N or S.
24 . The monoclonal antibody according to claim 21 , wherein
(1) the VH chain is QVQLVQSGSELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTGEPTYAD DFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARGAASHTMDYWGQGTTVTVSSAS (SEQ ID NO: 68) or the VH chain is provided as part of a sequence having a percent identity of about 75% to about 100% to QVQLVQSGSELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTGEPTYAD DFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARGAASHTMDYWGQGTTVTVSSASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW (SEQ ID NO: 2); and (2) the amino acid sequence contains a region having 100% sequence identity to a sequence selected from the group consisting of
(SEQ ID NO: 4)
YMHWYQQKPGQPPKLLIYYASNLESGVPDRFSGS,
(SEQ ID NO: 5)
YMHWYQQKPGQPPKLLIYYASNLKAGVPDRFSGS,
and
(SEQ ID NO: 6)
YVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGS.
25 . The monoclonal antibody according to claim 24 , wherein the VH chain is
(SEQ ID NO: 68)
QVQLVQSGSELKKPGASVKVSCKASGYTETNYGMNWVRQAPGQGLEWMG
WINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCAR
GAASHTMDYWGQGTTVTVSSAS,
(SEQ ID NO: 69)
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMG
WISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR
VSSWPYWYFDLWGRGTLVTVSSAS,
or
(SEQ ID NO: 70)
QVQLGQSGGGWQPGRSLRLSCAASGFTFSNYLIEWVRQAPGKGLEWVAV
INPGSGFTKYNEKFKQRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARE
DVYSWFAYWGQGTLVTVSAVTVSSAS.
26 . The monoclonal antibody according to claim 24 , wherein the VH chain is provided as part of a sequence having a percent identity of at least about 90% up to 100% to
(SEQ ID NO: 1)
QVQLVQSGSELKKPGASVKVSCKASGYTETNYGMNWVRQAPGQGLEWMG
WINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCAR
GAASHTMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP
PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
LSLSPGK.
27 . The monoclonal antibody according to claim 21 , wherein the amino acid sequence contains a region that has 100% sequence identity to any one or more of the following sequences
(SEQ ID NO: 24)
RFSGSX22SG,
(SEQ ID NO: 25)
LTX23SX24LQAEDX254AX26YY,
(SEQ ID NO: 26)
FGX27GTKL,
(SEQ ID NO: 27)
AAPSVX28X29FPPSX30EX31L,
(SEQ ID NO: 28)
AX32X33VCLX34X35X36FYP,
(SEQ ID NO: 29)
HX37X38YX39CX40VTHX41G,
(SEQ ID NO: 30)
PX42SX43X44X45SX45GX47X48X49TIX50C,
and
(SEQ ID NO: 31)
QX51X52PGX53X54PKLX55IY,
wherein X22 to X55 are each independently any amino acid.
28 . The monoclonal antibody according to claim 21 , wherein the amino acid sequence contains a region that has 100% sequence identity to any one or more of the following sequences
(SEQ ID NO: 24)
RFSGSX22SG,
(SEQ ID NO: 25)
LTX23SX24LQAEDX254AX26YY,
(SEQ ID NO: 26)
FGX27GTKL,
(SEQ ID NO: 27)
AAPSVX28X29FPPSX30EX31L,
(SEQ ID NO: 28)
AX32X33VCLX34X35X36FYP,
(SEQ ID NO: 29)
HX37X38YX39CX40VTHX41G,
(SEQ ID NO: 30)
PX42SX43X44X45SX45GX47X48X49TIX50C,
and
(SEQ ID NO: 31)
QX51X52PGX53X54PKLX55IY,
wherein X22 is G or K, X23 is I or V, X24 is G or S, X25 is E or V, X26 is D or V, X27 is G, S, or Q, X28 is F or T, X29 is I or L, X30 is D or S, X31 is E or Q, X32 is S or T, X33 is L or V, X34 is I or L, X35 is N or S, X36 is D or N, X37 is K or R, X38 is S or V, X39 is A or S, X40 is E or Q, X41 is E or Q, X42 is A, D, or P, X43 is A, L, or V, X44 is A or S, X45 is G or V, X46 is L or P, X47 is E or Q, X48 is R or S, X49 is A, I, or V, X50 is N or S, X51 is H or Q, X52 is H or K, X53 is K or Q, X54 is A or P, and X55 is L or M.
29 . The monoclonal antibody according to claim 21 , wherein the amino acid sequence contains a region that has a percent sequence identity of at least about 65% up to 100% to
(SEQ ID NO: 4)
YMHWYQQKPGQPPKLLIYYASNLESGVPDRFSGS.
30 . The monoclonal antibody according to claim 21 , wherein the amino acid sequence contains a region that has 100% sequence identity to a sequence selected from the group consisting of:
(SEQ ID NO: 4)
YMHWYQQKPGQPPKLLIYYASNLESGVPDRFSGS,
(SEQ ID NO: 5)
YMHWYQQKPGQPPKLLIYYASNLKAGVPDRFSGS,
and
(SEQ ID NO: 6)
YVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGS.
31 . The monoclonal antibody according to claim 21 , wherein the amino acid sequence is
(SEQ ID NO: 32)
DIVMTQSPDSLAVSLGERATINCRASQSVSTSX56HSYMHWYQQKPGQPPKLLIYYASNLX57
X58GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQHSWEIPWTFGQGTKLEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST
LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC, wherein X56 is A or
S, X57 is E or K, X58 is A or S,
(SEQ ID NO: 65)
QSAVTQPPSASGSPGQSVTISCTGTSSDVGAYDYVSWYQQHPGKAPKLMIYEVSKRPSGVPD
RFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGRVDVFGGGTKLTVLGQPKAAPSVTLFPPS
SEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE
QWKSHRSYSCQVTHEGSTVEKTVAPTECS,
or
(SEQ ID NO: 67)
QSALTQPASVSGSPGQSITISCTRASESVDSYGNSFMHQHHPGKAPKLMIYEVRTSNLESSN
RFSGSKSGNTASLTISGLQAEDEADYYCSSQQSYEDPFTFGSGTKLGQPKAAPSVTLFPPSS
EELQANKATLVCLISDFYPGAVKVAWKADGSPVNTGVETTTPSKQSNNKYAASSYLSLTPEQ
WKSHRSYSCQVTHEGSTVEKTVAPAECS.
32 . The monoclonal antibody according to claim 21 , wherein the VH chain further comprises at least 10, 20, 30, 40, or 50 consecutive amino acid residues of
(SEQ ID NO: 23)
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGK at its C-terminus.
33 . The monoclonal antibody according to claim 24 , wherein the VH chain further comprises
(SEQ ID NO: 23)
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGK at its C-terminus.
34 . The monoclonal antibody according to claim 21 , wherein the monoclonal antibody binds to human IgE with a binding affinity of about 5×10 −5 to about 7×10 −8 M Kd as measured by the Biacore method.
35 . A composition comprising one or more monoclonal antibodies according to claim 21 .
36 . A method of treating a subject for a food allergy, asthma, allergic rhinitis, atopic dermatitis, urticaria, angioedema, or anaphylactic hypersensitivity, which comprises administering to the subject one or more monoclonal antibodies according to claim 21 or a composition comprising the one or more monoclonal antibodies.
37 . The method for treating a subject according to claim 36 , which comprises determining the binding affinity to human IgE of the one or more monoclonal antibodies using the Biacore method, and administering the one or more monoclonal antibodies which have a binding affinity of about 5×10 −5 to about 7×10 −8 M Kd to human IgE.
38 . A method for treating or inhibiting an allergic reaction in a subject, which comprises administering to the subject one or more monoclonal antibodies according to claim 21 or a composition comprising the one or more monoclonal antibodies.
39 . The method for treating or inhibiting an allergic reaction in a subject according to claim 38 , which comprises determining the binding affinity to human IgE of the one or more monoclonal antibodies using the Biacore method, and administering the one or more monoclonal antibodies which have a binding affinity of about 5×10 −5 to about 7×10 −8 M Kd to human IgE.Join the waitlist — get patent alerts
Track US2023090487A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.