# US 2022/0033501 A1 · Anti-human tim-3 monoclonal antibody and application thereof

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- Number: US 2022/0033501 A1
- Document ID: US20220033501A1
- Status: Published application
- Kind: A1
- Application number: 17/298,817
- Filed: 2019-12-02
- Published: 2022-02-03
- Earliest claimed: 2018-11-30
- Assignees: Shanghai Pharmaexplorer Co., Ltd.; Pharmaexplorer Limited
- Applicants: Shanghai Pharmaexplorer Co., Ltd.; Pharmaexplorer Limited
- Inventors: Ningning SONG; Qing DUAN; Lile LIU; Tatchi Teddy YANG; Lina XU; Hu LIU; Peipei WEI; Qian WANG; Yuangdong WANG; Xiaohui SHAO; Shaoping HU; Yu ZHANG; Jian WU; Meilling WANG; Dongxu WANG; Chaohui DAI; Mengying WANG
- Web page: https://patentgrep.com/patent/US20220033501A1

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/2818: {against CD28 or CD152}
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/85: for animal cells
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/74: Inducing cell proliferation
- 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
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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 a high-affinity full human monoclonal antibody highly specifically targeting to TIM-3 and a preparation method therefor. The monoclonal antibody has a remarkable antitumor activity, and can be used for preparing a related diagnostic reagent or a pharmaceutical composition preventing or treating diseases related to TIM-3 dysfunction.

## Claims

### Claim 1

A heavy chain variable region of an antibody, wherein the heavy chain variable region comprises the following three complementarity determining regions or CDRs:
VH-CDR1 shown in SEQ ID NO. 10n+3,
VH-CDR2 shown in SEQ ID NO. 10n+4, and
VH-CDR3 shown in SEQ ID NO. 10n+5;
wherein each n is independently 0, 1, 2, 3, 4, 5 or 6;
wherein any one of the above amino acid sequences further comprises a derivative sequence which is obtained through optional addition, deletion, modification and/or substitution of at least one amino acid and is capable of retaining the binding affinity to TIM-3.

### Claim at position 2

2-4. (canceled)

### Claim 5 (depends on 1)

An antibody, wherein the antibody comprises:
(1) the heavy chain variable region of claim 1; and/or
(2) the light chain variable region comprising the following three complementarity determining regions or CDRs:
VL-CDR1 shown in SEQ ID NO. 10n+8,
VL-CDR2 shown in SEQ ID NO. 10n+9, and
VL-CDR3 shown in SEQ ID NO. 10n+10;
wherein each n is independently 0, 1, 2, 3, 4, 5 or 6;
wherein any one of the above amino acid sequences further comprises a derivative sequence which is obtained through optional addition, deletion, modification and/or substitution of at least one amino acid and is capable of retaining the binding affinity to TIM-3.

### Claim 6 (depends on 5)

The antibody of claim 5, wherein the antibody comprises the heavy chain variable region and the light chain variable region;
wherein, the heavy chain variable region and the light chain variable region comprise CDRs selected from the group consisting of:
VH-CDR1
VH-CDR2
VH-CDR3
VL-CDR1
VL-CDR2
VL-CDR3
Sequence
Sequence
Sequence
Sequence
Sequence
Sequence
number
number
number
number
number
number
3
4
5
8
9
10
13
14
15
18
19
20
23
24
25
28
29
30
33
34
35
38
39
40
43
44
45
48
49
50
53
54
55
58
59
60
63
64
65
68
69
70
wherein any one of the above amino acid sequences further comprises a derivative sequence which is obtained through optional addition, deletion, modification and/or substitution of at least one amino acid and is capable of retaining the binding affinity to TIM-3.

### Claim 7 (depends on 5)

The antibody of claim 5, wherein the heavy chain variable region of the antibody comprises the amino acid sequence shown in SEQ ID NO. 1, 11, 21, 31, 41, 51 or 61; and/or the light chain variable region of the antibody comprises the amino acid sequence shown in SEQ ID NO. 6, 16, 26, 36, 46, 56 or 66.

### Claim 8 (depends on 6)

The antibody of claim 6, wherein the antibody is selected from the group consisting of:
VH
VL
sequence
sequence
Antibody number
clone
number
number
1
7A4F10
1
6
2
18D2H2
11
16
3
134H3G6
21
26
4
215A8F2
31
36
5
34B6D8
41
46
6
39E5H1
51
56
7
57F4E5
61
66.

### Claim 9 (depends on 5)

A recombinant protein, wherein the recombinant protein comprises:
(i) the antibody of claim 5; and
(ii) an optional tag sequence that assists expression and/or purification.

### Claim 10 (depends on 5)

A polynucleotide, wherein the polynucleotide encodes a polypeptide selected from group consisting of:
(1) the antibody of claim 5; and
(2) the recombinant protein comprising the antibody.

### Claim 11 (depends on 10)

The polynucleotide of claim 10, wherein the polynucleotide encoding the heavy chain variable region is shown in SEQ ID NO. 2, 12, 22, 32, 42, 52 or 62; and/or, the polynucleotide encoding the light chain variable region is shown in SEQ ID NO. 7, 17, 27, 37, 47, 57 or 67.

### Claim 12 (depends on 11)

The polynucleotide of claim 11, wherein the polynucleotide encoding the heavy chain variable region and the polynucleotide encoding the light chain variable region are selected from the group consisting of:
Sequence number of
Sequence number of
the polynucleotide
the polynucleotide
Clone
encoding VH
encoding VL
7A4F10
2
7
18D2H2
12
17
134H3G6
22
27
215A8F2
32
37
34B6D8
42
47
39E5H1
52
57
57F4E5
62
67.

### Claim 13 (depends on 10)

A vector, wherein the vector comprises the polynucleotide of claim 10.

### Claim 14 (depends on 13)

A genetically engineered host cell, wherein the host cell contains the vector of claim 13.

### Claim 15 (depends on 5)

An antibody conjugate, wherein the antibody conjugate comprises:
(a) an antibody moiety, which is selected from the group consisting of: the antibody of claim 5; and
(b) a coupling moiety coupled to the antibody moiety, and the coupling moiety is selected from the group consisting of a detectable label, a drug, a toxin, a cytokine, a radionuclide, an enzyme, and a combination thereof.

### Claim 16 (depends on 5)

An immune cell, which expresses or is exposed outside the cell membrane with the antibody of claim 5.

### Claim 17 (depends on 5)

A pharmaceutical composition, wherein the pharmaceutical composition comprises:
(i) an active ingredient, wherein the active ingredient is selected from the group consisting of: the antibody of claim 5, the recombinant protein comprising the antibody, the antibody conjugate comprising the antibody, the immune cell expressing the antibody, and a combination thereof; and
(ii) a pharmaceutically acceptable carrier.

### Claim 18 (depends on 5)

A method for the treatment of diseases associated with abnormal TIM-3 expression or function, comprising administering an effective amount of the antibody of claim 5, the recombinant protein comprising the antibody, the antibody conjugate comprising the antibody, the immune cell expressing the antibody, and a combination thereof, to a subject in need.

### Claim 19 (depends on 18)

The method of claim 18, the disease associated with abnormal TIM-3 expression or function is cancer.