US2020207856A1PendingUtilityA1

Antibodies to lilrb2

59
Assignee: JOUNCE THERAPEUTICS INCPriority: Dec 22, 2017Filed: Mar 11, 2020Published: Jul 2, 2020
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 2317/33C07K 2317/32C07K 2317/515C07K 16/2818C07K 16/46C07K 2317/92C07K 16/3061C07K 16/2803C07K 2317/565C07K 16/2896A61K 45/06C07K 2317/51C07K 2317/76C12Q 1/6886A61P 35/00A61K 38/00C12Q 2600/158C07K 2317/24C07K 2317/31A61K 2039/505
59
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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-modified
1 - 16 . (canceled) 
     
     
         17 . An antibody that specifically binds to human LILRB2, wherein the antibody comprises the following six complementarity determining regions (CDRs):
 (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 15;   (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 16;   (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17;   (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 18;   (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 19; and   (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 20.   
     
     
         18 . The antibody of  claim 17 , wherein the antibody comprises a variable heavy chain (VH) region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 13 and a variable light chain (VL) region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 14, wherein the VH region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 15-17, and the VL region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20. 
     
     
         19 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 13 and a VL region comprising the amino acid sequence of SEQ ID NO: 14. 
     
     
         20 . The antibody of  claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 11 and a light chain comprising the amino acid sequence of SEQ ID NO: 12. 
     
     
         21 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 53 and a VL region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 54, wherein the VH region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 15-17, and the VL region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20. 
     
     
         22 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 53 and a variable light chain VL region comprising the amino acid sequence of SEQ ID NO: 54. 
     
     
         23 . The antibody of  claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 51 and a light chain comprising the amino acid sequence of SEQ ID NO: 52. 
     
     
         24 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 63 and a VL region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 64, wherein the VH region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 15-17, and the VL region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20. 
     
     
         25 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 63 and a VL region comprising the amino acid sequence of SEQ ID NO: 64. 
     
     
         26 . The antibody of  claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 61 and a light chain comprising the amino acid sequence of SEQ ID NO: 62. 
     
     
         27 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 73 and a VL region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 74, wherein the VH region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 15-17, and the VL region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20. 
     
     
         28 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 73 and a VL region comprising the amino acid sequence of SEQ ID NO: 74. 
     
     
         29 . The antibody of  claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 71 and a light chain comprising the amino acid sequence of SEQ ID NO: 72. 
     
     
         30 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 83 and a VL region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 84, wherein the VH region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 15-17, and the VL region comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20. 
     
     
         31 . The antibody of  claim 17 , wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 83 and a VL region comprising the amino acid sequence of SEQ ID NO: 84. 
     
     
         32 . The antibody of  claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 81 and a light chain comprising the amino acid sequence of SEQ ID NO: 82. 
     
     
         33 - 49 . (canceled) 
     
     
         50 . The antibody of  claim 17 , wherein the heavy chain additionally comprises a C-terminal lysine. 
     
     
         51 - 66 . (canceled) 
     
     
         67 . The antibody of  claim 17 , 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 μM. 
     
     
         71 . The antibody of  claim 17 , wherein the antibody is a monoclonal antibody. 
     
     
         72 . The antibody of  claim 17 , wherein the antibody is a chimeric antibody, a humanized antibody, a CDR-grafted antibody, or a human antibody. 
     
     
         73 . The antibody of  claim 17 , 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 17 , wherein the antibody is a conjugate antibody or is detectably labeled. 
     
     
         75 . The antibody of  claim 17 , 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 - 78 . (canceled) 
     
     
         79 . A pharmaceutical composition comprising the antibody of  claim 17 . 
     
     
         80 - 96 . (canceled) 
     
     
         97 . An antibody that specifically binds to human LILRB2, wherein the antibody comprises
 (a) a VH region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 13 and a VL region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 14;   (b) a VH region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 63 and a VL region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 64;   (c) a VH region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 73 and a VL region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 74; or   (d) a VH region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 83 and a VL region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 84.   
     
     
         98 . An antibody that specifically binds to human LILRB2, wherein the antibody comprises a VH region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 53 and a VL region comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 54.

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