# US 2023/0053631 A1 · Antibodies to lilrb2

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- Number: US 2023/0053631 A1
- Document ID: US20230053631A1
- Status: Published application
- Kind: A1
- Application number: 17/838,426
- Filed: 2022-06-13
- Published: 2023-02-23
- Earliest claimed: 2017-12-22
- Assignees: Jounce Therapeutics, Inc.
- Applicants: Jounce Therapeutics, Inc.
- Inventors: Heather B. COHEN; Lauren Pepper MACKENZIE; Yasmin RAMSAY; Donald Raymond SHAFFER; Jeffrey Yan-Fei SMITH; Kristin Shanea O'MALLEY; Kevin Patrick GUAY
- Web page: https://patentgrep.com/patent/US20230053631A1

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/3061: {Blood cells}
- C07K 16/46: Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00)
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C12Q 2600/158: Expression markers
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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

### Claim 1

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)2G(J)2 (SEQ ID NO: 171);
(b) a CDR-H2 comprising the amino acid sequence of (J)2W(J)11KJ (SEQ ID NO: 172);
(c) a CDR-H3 comprising the amino acid sequence of (J)2I(J)3TDYV(J)3 (SEQ ID NO: 173);
(d) a CDR-L1 comprising the amino acid sequence of (J)8DLJ (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)3YJYPLJ (SEQ ID NO: 176),
wherein each J is independently a naturally occurring amino acid.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the CDR-H2 comprises the amino acid sequence of SJW(J)11KJ (SEQ ID NO: 177) and/or the CDR-L3 comprises the amino acid sequence of (J)3YDYPLJ (SEQ ID NO: 178).

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 3)

The antibody of claim 3, wherein one or more of the CDRs comprises said additional J amino acid.

### Claim 11 (depends on 1)

The antibody of claim 1, wherein the CDR-H3 comprises the amino acid sequence of (J)2IJXJTDYV(J)3 (SEQ ID NO: 227), wherein X is not arginine.

### Claim 12 (depends on 11)

The antibody of claim 11, wherein X is selected from the group consisting of aspartate, glutamate, and alanine.

### Claim 13 (depends on 11)

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.

### Claim 14 (depends on 1)

The antibody of claim 1, 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: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, or 113, and/or 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: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, or 114.

### Claim 15 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a variable heavy chain (VH) 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 (VL) region comprising the amino acid sequence of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, or 114.

### Claim 16 (depends on 1)

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.

### Claim at position 17

17-49. (canceled)

### Claim 50 (depends on 1)

The antibody of claim 1, wherein the heavy chain additionally comprises a C-terminal lysine.

### Claim at position 19

51-66. (canceled)

### Claim 67 (depends on 1)

The antibody of claim 1, wherein the antibody binds to LILRB2 with a dissociation constant (KD) of less than 3.0 nM.

### Claim 68 (depends on 67)

The antibody of claim 67, wherein the antibody binds to LILRB2 with a KD of less than 1.5 nM.

### Claim 69 (depends on 68)

The antibody of claim 68, wherein the antibody binds to LILRB2 with a KD of less than 1.0 nM.

### Claim 70 (depends on 69)

The antibody of claim 69, wherein the antibody binds to LILRB2 with a dissociation constant (KD) less than 750 pM.

### Claim 71 (depends on 1)

The antibody of claim 1, wherein the antibody is a monoclonal antibody.

### Claim 72 (depends on 1)

The antibody of claim 1, wherein the antibody is a chimeric antibody, a humanized antibody, a CDR-grafted antibody, or a human antibody.

### Claim 73 (depends on 1)

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.

### Claim 74 (depends on 1)

The antibody of claim 1, wherein the antibody is a conjugate antibody or is detectably labeled.

### Claim 75 (depends on 1)

The antibody of claim 1, wherein the antibody is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody.

### Claim 76 (depends on 75)

The antibody of claim 75, which is an IgG4 antibody.

### Claim at position 30

77-96. (canceled)