# US 2021/0277110 A1 · Antibodies specifically binding pd-1, tim-3 or pd-1 and tim-3 and their uses

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- Number: US 2021/0277110 A1
- Document ID: US20210277110A1
- Status: Published application
- Kind: A1
- Application number: 17/090,961
- Filed: 2020-11-06
- Published: 2021-09-09
- Earliest claimed: 2015-11-03
- Assignees: Janssen Biotech, Inc.
- Applicants: Janssen Biotech, Inc.
- Inventors: Raluca Verona; Gordon Powers; Nina Chi Sabins; Nikki A. DeAngelis; Sandra Santulli-Marotto; Karla R. Wiehagen; Sheng-Jiun Wu; Catherine Ferrante; Enrique Zudaire Ubani
- Web page: https://patentgrep.com/patent/US20210277110A1

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/1145: {Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/4258: {against anti-receptor Ig}
- 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 2317/31: 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 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/75: Agonist effect on antigen
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to antibodies specifically binding PD-1, TIM-3 or PD-1 and TIM-3, polynucleotides encoding the antibodies or fragments, and methods of making and using the foregoing.

## Claims

### Claim 1

1) (canceled)

### Claim 2

2) (canceled)

### Claim 3

3) (canceled)

### Claim 4

4) (canceled)

### Claim 5

5) (canceled)

### Claim 6

6) (canceled)

### Claim 7

7) (canceled)

### Claim 8

8) (canceled)

### Claim 9

9) (canceled)

### Claim 10

10) (canceled)

### Claim 11

11) A polynucleotide
a) encoding the VH of SEQ ID NOs: 41, 42, 43 or 48;
b) encoding the VL of SEQ ID NOs: 49, 50, 51, 52, 53, 54, 55 or 56;
c) encoding the VH of SEQ ID NOs: 41, 42, 43 or 48 and the VL of SEQ ID NOs: 49, 50, 51, 52, 53, 54, 55 or 56; or
d) comprising the polynucleotide sequence of SEQ ID NOs: 196 or 197.

### Claim 12 (depends on 11)

12) A vector comprising the polynucleotide of claim 11.

### Claim 13 (depends on 12)

13) A host cell comprising the vector of claim 12.

### Claim 14 (depends on 13)

14) A method of producing an antagonistic antibody specifically binding PD-1 or an antigen-binding portion thereof, comprising culturing the host cell of claim 13 in conditions that the antibody of the antigen-binding portion thereof is expressed, and recovering the antibody or the antigen-binding portion thereof produced by the host cell.

### Claim 15

15) (canceled)

### Claim 16

16) (canceled)

### Claim 17

17) A polynucleotide
a) encoding the VH of SEQ ID NO: 64;
b) encoding the VL of SEQ ID NO: 65;
c) encoding the VH of SEQ ID NO: 64 and the VL of SEQ ID NO: 65; or
d) comprising the polynucleotide sequence of SEQ ID NOs: 198 or 199.

### Claim 18 (depends on 17)

18) A vector comprising the polynucleotide of claim 17.

### Claim 19 (depends on 18)

19) A host cell comprising the vector of claim 18.

### Claim 20 (depends on 19)

20) A method of producing an antagonistic antibody specifically binding PD-1 or an antigen-binding portion thereof, comprising culturing the host cell of claim 19 in conditions that the antibody or the antigen-binding portion thereof is expressed, and recovering the antibody or the antigen-binding portion thereof produced by the host cell.

### Claim 21

21) A method of treating a cancer in a subject, comprising administering a therapeutically effective amount of an isolated antibody or the antigen-binding portion thereof to the subject in need thereof for a time sufficient to treat the cancer wherein the isolated antibody or the antigen-binding portion thereof comprises an HCDR1, HCDR2, and HCDR3, and an LCDR1, LCDR2, and LCDR3 of SEQ ID NOs:
(a) 10, 13, 16, 20, 26 and 31, respectively;
(b) 10, 13, 16, 21, 26 and 32, respectively;
(c) 10, 14, 16, 22, 27 and 33, respectively;
(d) 10, 14, 16, 22, 26 and 34, respectively;
(e) 10, 14, 16, 23, 28 and 35, respectively;
(f) 10, 13, 17, 20, 26 and 31, respectively;
(g) 10, 13, 17, 20, 26 and 36, respectively;
(h) 10, 13, 17, 21, 26 and 32, respectively;
(i) 10, 13, 17, 21, 27 and 37, respectively;
(j) 10, 13, 17, 23, 26 and 32, respectively;
(k) 10, 14, 17, 23, 28 and 35, respectively;
(l) 10, 14, 17, 22, 26 and 34, respectively; or
(m) 10, 14, 17, 23, 26 and 32, respectively.

### Claim 22

22) A method of treating a cancer in a subject, comprising administering a therapeutically effective amount of the isolated antibody or the antigen-binding portion thereof to the subject in need thereof for a time sufficient to treat the cancer wherein the isolated antibody or the antigen-binding fragment thereof comprises
(a) an HCDR1, HCDR2, and HCDR3, and an LCDR1, LCDR2, and LCDR3 of SEQ ID NOs: 66, 67, 68, 69, 70 and 71, respectively;
(b) a VH of SEQ ID NO: 64 and a VL of SEQ ID NO: 65; and/or
(c) a HC of SEQ ID NO: 74 and a LC of SEQ ID NO: 75.

### Claim 23 (depends on 21)

23) The method of claim 21, wherein the cancer is a solid tumor or a hematological malignancy.

### Claim 24 (depends on 23)

24) The method of claim 23, wherein the solid tumor is a melanoma, a lung cancer, a squamous non-small cell lung cancer (NSCLC), a non-squamous NSCLC, a colorectal cancer, a prostate cancer, a castration-resistant prostate cancer, a stomach cancer, an ovarian cancer, a gastric cancer, a liver cancer, a pancreatic cancer, a thyroid cancer, a squamous cell carcinoma of the head and neck, carcinomas of the esophagus or gastrointestinal tract, a breast cancer, a fallopian tube cancer, a brain cancer, an urethral cancer, a genitourinary cancer, an endometriosis, a cervical cancer or a metastatic lesion of the cancer.

### Claim 25 (depends on 23)

25) The method of claim 23, wherein the hematological malignancy is a lymphoma, a myeloma or a leukemia.

### Claim 26

26) A method of enhancing an immune response in a subject, comprising administering a therapeutically effective amount of an antibody or the antigen-binding portion thereof to the subject in need thereof for a time sufficient to enhance the immune response wherein the antibody or the antigen-binding portion thereof comprises an HCDR1, HCDR2, and HCDR3, and an LCDR1, LCDR2, and LCDR3 of SEQ ID NOs:
(a) 10, 13, 16, 20, 26 and 31, respectively;
(b) 10, 13, 16, 21, 26 and 32, respectively;
(c) 10, 14, 16, 22, 27 and 33, respectively;
(d) 10, 14, 16, 22, 26 and 34, respectively;
(e) 10, 14, 16, 23, 28 and 35, respectively;
(f) 10, 13, 17, 20, 26 and 31, respectively;
(g) 10, 13, 17, 20, 26 and 36, respectively;
(h) 10, 13, 17, 21, 26 and 32, respectively;
(i) 10, 13, 17, 21, 27 and 37, respectively;
(j) 10, 13, 17, 23, 26 and 32, respectively;
(k) 10, 14, 17, 23, 28 and 35, respectively;
(l) 10, 14, 17, 22, 26 and 34, respectively; or
(m) 10, 14, 17, 23, 26 and 32, respectively.

### Claim 27 (depends on 26)

27) The method of claim 26, wherein the subject has a cancer or a viral infection.

### Claim 28 (depends on 21)

28) The method of claim 21, wherein the antibody or the antigen-binding portion thereof is administered in combination with a second therapeutic agent.

### Claim 29 (depends on 28)

29) The method of claim 28, wherein the second therapeutic agent is
a) a standard of care drug for treatment of the solid tumor or the hematological malignancy;
b) an agonist of a T cell activating molecule;
c) an agonist of CD86 (SEQ ID NO: 264), CD80 (SEQ ID NO: 265), CD28 (SEQ ID NO: 266), ICOS (SEQ ID NO: 267), ICOS ligand (SEQ ID NO: 268), TMIGD2 (SEQ ID NO: 269), CD40 (SEQ ID NO: 270), GITR (SEQ ID NO: 271), 4-1BB ligand (SEQ ID NO: 271), OX40 ligand (SEQ ID NO: 272), CD70 (SEQ ID NO: 274), CD40L (SEQ ID NO: 275), TNFRSF25 (SEQ ID NO: 264), LIGHT (SEQ ID NO: 277), GITR ligand (SEQ ID NO: 278), OX-40 (SEQ ID NO: 279), CD27 (SEQ ID NO: 280), CD137 (SEQ ID NO: 281), NKG2D (SEQ ID NO: 282), CD48 (SEQ ID NO: 283), CD226 (SEQ ID NO: 284), or MICA (SEQ ID NO: 285);
d) an inhibitor of a T cell inhibitory molecule;
e) an inhibitor of PD-1 (SEQ ID NO: 1), PD-L1 (SEQ ID NO: 5), PD-L2 (SEQ ID NO: 8), VISTA (SEQ ID NO: 286), BTNL2 (SEQ ID NO: 287), B7-H3 (SEQ ID NO: 288), B7-H4 (SEQ ID NO: 289), HVEM (SEQ ID NO: 290), HHLA2 (SEQ ID NO: 291), CTLA-4 (SEQ ID NO: 292), LAG-3 (SEQ ID NO: 293), TIM-3 (SEQ ID NO: 138), BTLA (SEQ ID NO: 294), CD160 (SEQ ID NO: 295), CEACAM-1 (SEQ ID NO: 296), LAIR1 (SEQ ID NO: 297), TGFβ (SEQ ID NO: 298), IL-10 (SEQ ID NO: 299), CD96 (SEQ ID NO: 300), TIGIT (SEQ ID NO: 301), NKG2A (SEQ ID NO: 302), CD112 (SEQ ID NO: 303), CD47 (SEQ ID NO: 304), SIRPA (SEQ ID NO: 305) or CD244 (SEQ ID NO: 306);
f) an antagonistic antibody specifically binding TIM-3;
g) an antagonistic antibody specifically binding TIM-3 comprising the VH and the VL of
i) SEQ ID NOs: 145 and 155, respectively;
ii) SEQ ID NOs: 146 and 156, respectively;
iii) SEQ ID NOs: 148 and 157, respectively;
iv) SEQ ID NOs: 147 and 155, respectively;
v) SEQ ID NOs: 149 and 158, respectively;
vi) SEQ ID NOs: 150 and 159, respectively;
vii) SEQ ID NOs:151 and 160, respectively;
viii) SEQ ID NOs: 152 and 161, respectively;
ix) SEQ ID NOs: 153 and 162, respectively;
x) SEQ ID NOs: 154 and 163, respectively; or
xi) SEQ ID NOs: 172 and 173, respectively;
h) a fibroblast growth factor receptor (FGFR) inhibitor;
i) a vaccine;
j) an agonistic antibody specifically binding GITR;
k) an agonistic antibody specifically binding OX40;
l) an agonistic antibody specifically binding OX40, comprising the VH and the VL of SEQ ID NOs: 309 and 310, respectively;
m) an agonistic antibody specifically binding OX40, comprising the VH and the VL of SEQ ID NOs: 311 and 312, respectively;
n) an agonistic antibody specifically binding CD137;
o) radiation therapy; or
p) surgery.

### Claim 30 (depends on 29)

30) The method of claim 29, wherein the antibody or the antigen-binding portion thereof and the second therapeutic agent are administered simultaneously, sequentially or separately.

### Claim 31

31) An anti-idiotypic antibody binding to an antibody or the antigen-binding portion thereof wherein the antibody or the antigen-binding portion thereof comprises an HCDR1, HCDR2, and HCDR3, and an LCDR1, LCDR2, and LCDR3 of SEQ ID NOs:
(a) 10, 13, 16, 20, 26 and 31, respectively;
(b) 10, 13, 16, 21, 26 and 32, respectively;
(c) 10, 14, 16, 22, 27 and 33, respectively;
(d) 10, 14, 16, 22, 26 and 34, respectively;
(e) 10, 14, 16, 23, 28 and 35, respectively;
(f) 10, 13, 17, 20, 26 and 31, respectively;
(g) 10, 13, 17, 20, 26 and 36, respectively;
(h) 10, 13, 17, 21, 26 and 32, respectively;
(i) 10, 13, 17, 21, 27 and 37, respectively;
(j) 10, 13, 17, 23, 26 and 32, respectively;
(k) 10, 14, 17, 23, 28 and 35, respectively;
(l) 10, 14, 17, 22, 26 and 34, respectively; or
(m) 10, 14, 17, 23, 26 and 32, respectively.

### Claim 32

32) (canceled)

### Claim 33

33) (canceled)

### Claim 34

34) (canceled)

### Claim 35

35) (canceled)

### Claim 36

36) (canceled)

### Claim 37

37) (canceled)

### Claim 38

38) (canceled)

### Claim 39

39) (canceled)

### Claim 40

40) (canceled)

### Claim 41

41) (canceled)

### Claim 42

42) (canceled)

### Claim 43

43) (canceled)

### Claim 44

44) (canceled)

### Claim 45

45) (canceled)

### Claim 46

46) (canceled)

### Claim 47

47) (canceled)

### Claim 48

48) (canceled)

### Claim 49

49) (canceled)

### Claim 50

50) (canceled)

### Claim 51

51) (canceled)

### Claim 52

52) (canceled)

### Claim 53

53) (canceled)

### Claim 54

54) (canceled)

### Claim 55

55) (canceled)

### Claim 56

56) (canceled)

### Claim 57

57) (canceled)

### Claim 58

58) (canceled)

### Claim 59

59) (canceled)

### Claim 60

60) (canceled)

### Claim 61

61) (canceled)

### Claim 62

62) (canceled)

### Claim 63

63) (canceled)

### Claim 64

64) (canceled)

### Claim 65

65) (canceled)

### Claim 66

66) (canceled)

### Claim 67

67) (canceled)

### Claim 68

68) (canceled)

### Claim 69

69) (canceled)

### Claim 70

70) (canceled)

### Claim 71

71) (canceled)

### Claim 72

72) (canceled)

### Claim 73

73) (canceled)

### Claim 74

74) (canceled)

### Claim 75

75) (canceled)

### Claim 76

76) (canceled)

### Claim 77

77) (canceled)

### Claim 78

78) (canceled)

### Claim 79

79) (canceled)

### Claim 80

80) (canceled)

### Claim 81

81) (canceled)

### Claim 82

82) (canceled)

### Claim 83

83) (canceled)

### Claim 84

84) (canceled)

### Claim 85

85) (canceled)

### Claim 86

86) (canceled)

### Claim 87

87) (canceled)

### Claim 88

88) (canceled)

### Claim 89

89) (canceled)

### Claim 90 (depends on 21)

90) The method of claim 21, wherein the antibody or the antigen-binding portion thereof comprises
a) a heavy chain variable region (VH) of SEQ ID NOs: 41, 42, 43 or 48;
b) a light chain variable region (VL) of SEQ ID NOs: 49, 50, 51, 52, 53, 54, 55 or 56; or
c) a VH of SEQ ID NOs: 41, 42, 43 or 48 and a VL of SEQ ID NOs: 49, 50, 51, 52, 53, 54, 55 or 56.

### Claim 91 (depends on 21)

91) The method of claim 21, wherein the antibody or the antigen-binding portion thereof comprises
a) a VH of SEQ ID NO: 41 and a VL of SEQ ID NO: 49;
b) a VH of SEQ ID NO: 41 and a VL of SEQ ID NO: 50;
c) a VH of SEQ ID NO: 42 and a VL of SEQ ID NO: 51;
d) a VH of SEQ ID NO: 42 and a VL of SEQ ID NO: 52;
e) a VH of SEQ ID NO: 42 and a VL of SEQ ID NO: 53;
f) a VH of SEQ ID NO: 43 and a VL of SEQ ID NO: 49;
g) a VH of SEQ ID NO: 43 and a VL of SEQ ID NO: 54;
h) a VH of SEQ ID NO: 43 and a VL of SEQ ID NO: 50;
i) a VH of SEQ ID NO: 43 and a VL of SEQ ID NO: 55;
j) a VH of SEQ ID NO: 43 and a VL of SEQ ID NO: 56;
k) a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 53;
l) a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 52; or
m) a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 56.

### Claim 92 (depends on 91)

92) The method of claim 91, wherein the antibody or the antigen-binding portion thereof comprises a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 53.

### Claim 93 (depends on 91)

93) The method of claim 91, wherein the antibody or the antigen-binding portion thereof comprises a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 52.

### Claim 94 (depends on 91)

94) The method of claim 91, wherein the antibody or the antigen-binding portion thereof comprises a VH of SEQ ID NO: 48 and a VL of SEQ ID NO: 56.

### Claim 95 (depends on 21)

95) The method of claim 21, wherein the antibody or the antigen-binding portion thereof comprises a HC of SEQ ID NO: 72 and a LC of SEQ ID NO: 73.

### Claim 96 (depends on 29)

96) The method of claim 29, wherein the standard of care drug is capecitabine.