US2023053631A1PendingUtilityA1
Antibodies to lilrb2
Est. expiryDec 22, 2037(~11.4 yrs left)· nominal 20-yr term from priority
Inventors:Heather B. CohenLauren Pepper MackenzieYasmin RamsayDonald ShafferJeffrey Yan-Fei SmithKristin Shanea O'MalleyKevin Patrick Guay
C07K 2317/76C12Q 1/6886C07K 16/2896C07K 16/46A61P 35/00C12Q 2600/158C07K 2317/24A61K 45/06C07K 2317/565C07K 16/2803C07K 2317/33C07K 2317/92C07K 2317/32C07K 2317/31C07K 16/2818C07K 2317/51A61K 38/00C07K 16/3061C07K 2317/515A61K 2039/505
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Claims
Abstract
Provided herein are various embodiments relating to antibodies that bind LILRB2. Anti-LILRB2 antibodies can be used in methods to treat disease, for example, cancer.
Claims
exact text as granted — not AI-modified1 . An antibody that specifically binds to human LILRB2, wherein the antibody comprises the following complementarity determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence of JY(J) 2 G(J) 2 (SEQ ID NO: 171); (b) a CDR-H2 comprising the amino acid sequence of (J) 2 W(J) 11 KJ (SEQ ID NO: 172); (c) a CDR-H3 comprising the amino acid sequence of (J) 2 I(J) 3 TDYV(J) 3 (SEQ ID NO: 173); (d) a CDR-L1 comprising the amino acid sequence of (J) 8 DLJ (SEQ ID NO: 174); (e) a CDR-L2 comprising the amino acid sequence of (J) 7 (SEQ ID NO: 175); and (f) a CDR-L3 comprising the amino acid sequence of (J) 3 YJYPLJ (SEQ ID NO: 176), wherein each J is independently a naturally occurring amino acid.
2 . The antibody of claim 1 , wherein the CDR-H2 comprises the amino acid sequence of SJW(J) 11 KJ (SEQ ID NO: 177) and/or the CDR-L3 comprises the amino acid sequence of (J) 3 YDYPLJ (SEQ ID NO: 178).
3 . The antibody of claim 1 , wherein the CDR-H1 comprises the amino acid sequence of:
(i)
(SEQ ID NO: 15)
TYAMGVS;
(ii)
(SEQ ID NO: 179)
JYAMGVS;
(iii)
(SEQ ID NO: 180)
TYJMGVS;
(iv)
(SEQ ID NO: 181)
TYAJGVS;
(v)
(SEQ ID NO: 182)
TYAMGJS;
(vi)
(SEQ ID NO: 183)
TYAMGVJ;
or
(vii) a variant of any one of (ii) to (vi) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 171.
4 . The antibody of claim 1 , wherein the CDR-H2 comprises the amino acid sequence of:
(i)
(SEQ ID NO: 16)
SIWWNGNKYNNPSLKS;
(ii)
(SEQ ID NO: 184)
SJWWNGNKYNNPSLKS;
(iii)
(SEQ ID NO: 185)
SIWJNGNKYNNPSLKS;
(iv)
(SEQ ID NO: 186)
SIWWJGNKYNNPSLKS;
(v)
(SEQ ID NO: 187)
SIWWNJNKYNNPSLKS;
(vi)
(SEQ ID NO: 188)
SIWWNGJKYNNPSLKS;
(vii)
(SEQ ID NO: 189)
SIWWNGNJYNNPSLKS;
(viii)
(SEQ ID NO: 190)
SIWWNGNKJNNPSLKS;
(ix)
(SEQ ID NO: 191)
SIWWNGNKYJNPSLKS;
(x)
(SEQ ID NO: 192)
SIWWNGNKYNJPSLKS;
(xi)
(SEQ ID NO: 193)
SIWWNGNKYNNJSLKS;
(xii)
(SEQ ID NO: 194)
SIWWNGNKYNNPJLKS;
(xiii)
(SEQ ID NO: 195)
SIWWNGNKYNNPSJKS;
(xiv)
(SEQ ID NO: 196)
SIWWNGNKYNNPSLKJ;
or
(xv) a variant of any one of (ii) to (xiv) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 172.
5 . The antibody of claim 1 , wherein the CDR-H3 comprises the amino acid sequence of:
(ix)
(SEQ ID NO: 204)
SRIIRFTDYVMDJ;
(i)
(SEQ ID NO: 17)
SRHRFTDYVMDA;
(ii)
(SEQ ID NO: 197)
JRIIRFTDYVMDA;
(iii)
(SEQ ID NO: 198)
SJIIRFTDYVMDA;
(iv)
(SEQ ID NO: 199)
SRIJRFTDYVMDA;
(v)
(SEQ ID NO: 200)
SRIIJFTDYVMDA;
(vi)
(SEQ ID NO: 201)
SRIIRJTDYVMDA;
(vii)
(SEQ ID NO: 202)
SRIIRFTDYVJDA;
(viii)
(SEQ ID NO: 203)
SRIIRFTDYVMJA;
or
(x) a variant of any one of (ii) to (ix) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 173.
6 . The antibody of claim 1 , wherein the CDR-L1 comprises the amino acid sequence of:
(i)
(SEQ ID NO: 18)
RASEDIYNDLA;
(ii)
(SEQ ID NO: 205)
JASEDIYNDLA;
(iii)
(SEQ ID NO: 206)
RJSEDIYNDLA;
(iv)
(SEQ ID NO: 207)
RAJEDIYNDLA;
(v)
(SEQ ID NO: 208)
RASJDIYNDLA;
(vi)
(SEQ ID NO: 209)
RASEJIYNDLA;
(vii)
(SEQ ID NO: 210)
RASEDJYNDLA;
(viii)
(SEQ ID NO: 211)
RASEDIJNDLA;
(ix)
(SEQ ID NO: 212)
RASEDIYJDLA;
(x)
(SEQ ID NO: 213)
RASEDIYNDLJ;
or
(xi) a variant of any one of (ii) to (x) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 174.
7 . The antibody of claim 1 , wherein the CDR-L2 comprises the amino acid sequence of:
(i)
(SEQ ID NO: 19)
NANSLHT;
(ii)
(SEQ ID NO: 214)
JANSLHT;
(iii)
(SEQ ID NO: 215)
NJNSLHT;
(iv)
(SEQ ID NO: 216)
NAJSLHT;
(v)
(SEQ ID NO: 217)
NANJLHT;
(vi)
(SEQ ID NO: 218)
NANSJHT;
(vii)
(SEQ ID NO: 219)
NANSLJT;
(viii)
(SEQ ID NO: 220)
NANSLHJ;
or
(ix) a variant of any one of (ii) to (viii) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 175.
8 . The antibody of claim 1 , wherein the CDR-L3 comprises the amino acid sequence of:
(i)
(SEQ ID NO: 20)
QQYYDYPLT;
(ii)
(SEQ ID NO: 221)
JQYYDYPLT;
(iii)
(SEQ ID NO: 222)
QJYYDYPLT;
(iv)
(SEQ ID NO: 223)
QQJYDYPLT;
(v)
(SEQ ID NO: 224)
QQYYDYPLJ;
or
(vi) a variant of any one of (ii) to (v) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 176.
9 . The antibody of claim 1 , wherein the CDR-H2 comprises the amino acid sequence of JIWWNGNKYNNPSLKS (SEQ ID NO: 225), or a variant thereof comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 172, and/or the CDR-L3 comprises the amino acid sequence of QQYYJYPLT (SEQ ID NO: 226), or a variant thereof comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 176.
10 . The antibody of claim 3 , wherein one or more of the CDRs comprises said additional J amino acid.
11 . The antibody of claim 1 , wherein the CDR-H3 comprises the amino acid sequence of (J) 2 IJXJTDYV(J) 3 (SEQ ID NO: 227), wherein X is not arginine.
12 . The antibody of claim 11 , wherein X is selected from the group consisting of aspartate, glutamate, and alanine.
13 . The antibody of claim 11 , wherein the CDR-H3 comprises the sequence of:
(i)
(SEQ ID NO: 228)
JRIIXFTDYVMDA;
(ii)
(SEQ ID NO: 229)
SJIIXFTDYVMDA;
(iii)
(SEQ ID NO: 230)
SRIJXFTDYVMDA;
(iv)
(SEQ ID NO: 231)
SRIIXFTDYVMDA;
(v)
(SEQ ID NO: 232)
SRIIXJTDYVMDA;
(vi)
(SEQ ID NO: 233)
SRIIXFTDYVJDA;
(vii)
(SEQ ID NO: 234)
SRIIXFTDYVMJA;
(viii)
(SEQ ID NO: 235)
SRIIXFTDYVMDJ;
or
(ix) a variant of any one of (ii) to (iii) or (v) to (viii) comprising an additional J amino acid in place of a recited amino acid that is represented by a J in SEQ ID NO: 173.
14 . The antibody of claim 1 , wherein the antibody comprises a variable heavy chain (V H ) region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, or 113, and/or a variable light chain (V L ) region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, or 114.
15 . The antibody of claim 1 , wherein the antibody comprises a variable heavy chain (V H ) region comprising the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, or 113, and/or a variable light chain (V L ) region comprising the amino acid sequence of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, or 114.
16 . The antibody of claim 1 , wherein the antibody comprises a heavy chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, or 111, and/or a light chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2, 22, 32, 42, 52, 62, 72, 82, 92, 102, or 112.
17 - 49 . (canceled)
50 . The antibody of claim 1 , wherein the heavy chain additionally comprises a C-terminal lysine.
51 - 66 . (canceled)
67 . The antibody of claim 1 , wherein the antibody binds to LILRB2 with a dissociation constant (K D ) of less than 3.0 nM.
68 . The antibody of claim 67 , wherein the antibody binds to LILRB2 with a K D of less than 1.5 nM.
69 . The antibody of claim 68 , wherein the antibody binds to LILRB2 with a K D of less than 1.0 nM.
70 . The antibody of claim 69 , wherein the antibody binds to LILRB2 with a dissociation constant (K D ) less than 750 pM.
71 . The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
72 . The antibody of claim 1 , wherein the antibody is a chimeric antibody, a humanized antibody, a CDR-grafted antibody, or a human antibody.
73 . The antibody of claim 1 , wherein the antibody comprises an Fc region selected from the group consisting of a native Fc region, a variant Fc region, and a functional Fc region.
74 . The antibody of claim 1 , wherein the antibody is a conjugate antibody or is detectably labeled.
75 . The antibody of claim 1 , wherein the antibody is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody.
76 . The antibody of claim 75 , which is an IgG4 antibody.
77 - 96 . (canceled)Cited by (0)
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