# US 11,028,164 B2 · Anti-CXCL13 antibodies

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- Number: US 11,028,164 B2
- Document ID: US11028164B2
- Status: Granted
- Kind: B2
- Application number: 16/963,130
- Filed: 2019-09-18
- Published: 2020-12-24
- Granted: 2021-06-08
- Earliest claimed: 2018-09-18
- Assignees: I-Mab Biopharma US Limited
- Applicants: I-Mab Biopharma US Limited
- Inventors: Haijuan Gu; Qiumei Yang
- Web page: https://patentgrep.com/patent/US11028164B2

## CPC

- A61P 37/00: Drugs for immunological or allergic disorders
- C07K 16/24: against cytokines, lymphokines or interferons
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- 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
- G01N 2333/521: Chemokines
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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 are antibodies or fragments thereof having binding specificity to the human chemokine (C-X-C motif) ligand 13 (CXCL 13) protein. In various examples, the antibodies or fragments thereof include a VH and VL CDRs as disclosed herein, or variants thereof. Methods of using the antibodies or fragments thereof for treating autoimmune diseases and disorders are also provided.

## Claims

### Claim 1

An antibody or fragment thereof having specificity to a human chemokine (C-X-C motif) ligand 13 (CXCL13) protein, wherein the antibody or fragment thereof comprises a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:
the HCDR1 comprises the amino acid sequence of SEQ ID NO: 127 (RYWMS);
the HCDR2 comprises the amino acid sequence of SEQ ID NO: 128 (EINPDSSTINY APSLKD);
the HCDR3 comprises the amino acid sequence of SEQ ID NO: 130 (QDDYEYYAMDY);
the LCDR1 comprises the amino acid sequence of SEQ ID NO: 131 (KASQDVNTGVA);
the LCDR2 comprises the amino acid sequence of SEQ ID NO: 132 (SASYRYT);
and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 133 (QQYYSTPLT), or
the HCDR1 comprises the amino acid sequence of SEQ ID NO: 127 (RYWMS);
the HCDR2 comprises the amino acid sequence of SEQ ID NO: 129 (EINPESSTINYAPSLKD);
the HCDR3 comprises the amino acid sequence of SEQ ID NO: 130 (QDDYEYYAMDY);
the LCDR1 comprises the amino acid sequence of SEQ ID NO: 131 (KASQDVNTGVA);
the LCDR2 comprises the amino acid sequence of SEQ ID NO: 132 (SASYRYT);
and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 133 (QQYYSTPLT), or
the HCDR1 comprises the amino acid sequence of SEQ ID NO: 127 (RYWMS);
the HCDR2 comprises the amino acid sequence of SEQ ID NO: 129 (EINPESSTINYAPSLKD);
the HCDR3 comprises the amino acid sequence of SEQ ID NO: 359 (QDDYEYYTMDY);
the LCDR1 comprises the amino acid sequence of SEQ ID NO: 360 (KVSQDVNTGVA),
The LCDR2 comprises the amino acid sequence of SEQ ID NO: 132 (SASYRYT);
the LCDR3 comprises the amino acid sequence of SEQ ID NO: 361 (QQYWSTPLT), or
the HCDR1 comprises the amino acid sequence of SEQ ID NO: 127 (RYWMS);
the HCDR2 comprises the amino acid sequence of SEQ ID NO: 129 (EINPESSTINYAPSLKD);
the HCDR3 comprises the amino acid sequence of SEQ ID NO: 359 (QDDYEYYTMDY);
the LCDR1 comprises the amino acid sequence of SEQ ID NO: 360 (KVSQDVNTGVA),
the LCDR2 comprises the amino acid sequence of SEQ ID NO: 132 (SASYRYT);
and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 133 (QQYYSTPLT), or
the HCDR1 comprises the amino acid sequence of SEQ ID NO: 127 (RYWMS);
the HCDR2 comprises the amino acid sequence of SEQ ID NO: 129 (EINPESSTINYAPSLKD);
the HCDR3 comprises the amino acid sequence of SEQ ID NO: 367 (QDDYETYTMDY),
the LCDR1 comprises the amino acid sequence of SEQ ID NO: 360 (KVSQDVNTGVA),
the LCDR2 comprises the amino acid sequence of SEQ ID NO: 132 (SASYRYT); and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 133 (QQYYSTPLT).

### Claim 2 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCD2 and LCDR3 comprise SEQ ID NO:127, 129, 367, 360, 132 and 133, respectively.

### Claim 3 (depends on 2)

The antibody or fragment thereof of claim 2, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:181 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:181, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:179 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:179.

### Claim 4 (depends on 3)

The antibody or fragment thereof of claim 3, which is humanized and wherein the heavy chain variable region comprises one or more back mutations selected from the group consisting of 5Q, 47I, 48G, and 85V, according to Kabat numbering, and combinations thereof, or wherein the light chain variable region comprises a mutation 78V according to Kabat numbering.

### Claim 5 (depends on 2)

The antibody or fragment thereof of claim 2, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:181, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:179.

### Claim 6 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCD2 and LCDR3 comprise SEQ ID NO:127, 129, 359, 360, 132 and 133, respectively.

### Claim 7 (depends on 6)

The antibody or fragment thereof of claim 6, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:174 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:174, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:179 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:179.

### Claim 8 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCD2 and LCDR3 comprise SEQ ID NO:127, 129, 359, 360, 132 and 361, respectively.

### Claim 9 (depends on 8)

The antibody or fragment thereof of claim 8, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:174 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:174, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:175 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:175.

### Claim 10 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCD2 and LCDR3 comprise SEQ ID NO:127, 129, 130, 131, 132 and 133, respectively.

### Claim 11 (depends on 10)

The antibody or fragment thereof of claim 10, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:156 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:156, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:138 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:138.

### Claim 12 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCD2 and LCDR3 comprise SEQ ID NO:127, 128, 130, 131, 132 and 133, respectively.

### Claim 13 (depends on 12)

The antibody or fragment thereof of claim 12, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:134 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:134, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:138 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:138.

### Claim 14 (depends on 6)

The antibody or fragment thereof of claim 6, which is humanized and wherein the heavy chain variable region comprises one or more back mutations selected from the group consisting of 5Q, 47I, 48G, and 85V, according to Kabat numbering, and combinations thereof, or wherein the light chain variable region comprises a mutation 78V according to Kabat numbering.