Antibodies

Patent metadata

Field	Value
Publication number	US-2022275059-A1
Application number	US-202017432745-A
Country	US
Kind code	A1
Filing date	Feb 20, 2020
Priority date	Feb 20, 2019
Publication date	Sep 1, 2022
Grant date	—

Abstract

The invention relates to antibodies and antigen-binding fragments thereof that recognize coronavirus spike proteins(CoV-S), such asthe spike protein of Middle East respiratory syndrome coronavirusspike protein(MERS-S). In some embodiments, the antibodiesbind to CoV-Swith high affinity, inhibit CoV infection of human cells, inhibit CoV sialic acid-binding activity and/or bind to multiple types of CoV-S. In some embodiments, the antibodies provide a means of preventing, treating or ameliorating CoV infection.

First claim

1 . An antibody that binds to Middle East Respiratory Syndrome coronavirus (MERS-CoV) spike protein (MERS-S), wherein the antibody is capable of inhibiting the infection of human cells by MERS-CoV.

2 . (canceled)

3 . The antibody of claim 1 , wherein the antibody binds to the S2 domain of MERS S.

4 - 5 . (canceled)

6 . The antibody of claim 3 , wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
(a)
i. SEQ ID NO: 83 for CDR1 of the heavy chain;
ii. SEQ ID NO: 84 for CDR2 of the heavy chain;
iii. SEQ ID NO: 85 for CDR3 of the heavy chain;
iv. SEQ ID NO: 86 for CDR1 of the light chain;
v. SEQ ID NO: 87 for CDR2 of the light chain; and
vi. SEQ ID NO: 88 for CDR3 of the light chain; or
(b)
i. SEQ ID NO: 89 for CDR1 of the heavy chain;
ii. SEQ ID NO: 90 for CDR2 of the heavy chain;
iii. SEQ ID NO: 91 for CDR3 of the heavy chain;
iv. SEQ ID NO: 92 for CDR1 of the light chain;
v. SEQ ID NO: 93 for CDR2 of the light chain; and
vi. SEQ ID NO: 94 for CDR3 of the light chain.

7 . The antibody of claim 6 , wherein the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 70 and a light chain variable region of the amino acid sequence of SEQ ID NO: 74; or wherein the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 69 and a light chain variable region of the amino acid sequence of SEQ ID NO: 72.

8 - 9 . (canceled)

10 . The antibody of claim 1 , wherein the antibody binds to the S1 domain of MERS S.

11 . (canceled)

12 . The antibody of claim 10 , wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
(a)
i. SEQ ID NO: 139 for CDR1 of the heavy chain;
ii. SEQ ID NO: 140 for CDR2 of the heavy chain;
iii. SEQ ID NO: 141 for CDR3 of the heavy chain;
iv. SEQ ID NO: 142 for CDR1 of the light chain;
v. SEQ ID NO: 143 for CDR2 of the light chain; and
vi. SEQ ID NO: 144 for CDR3 of the light chain; or
(b)
i. SEQ ID NO: 133 for CDR1 of the heavy chain;
ii. SEQ ID NO: 134 for CDR2 of the heavy chain;
iii. SEQ ID NO: 135 for CDR3 of the heavy chain;
iv. SEQ ID NO: 136 for CDR1 of the light chain;
v. SEQ ID NO: 137 for CDR2 of the light chain; and
vi SEQ ID NO: 138 for CDR3 of the light chain; or
(c)
i. SEQ ID NO: 127 for CDR1 of the heavy chain;
ii. SEQ ID NO: 128 for CDR2 of the heavy chain;
iii. SEQ ID NO: 129 for CDR3 of the heavy chain;
iv. SEQ ID NO: 130 for CDR1 of the light chain;
v. SEQ ID NO: 131 for CDR2 of the light chain; and
vi. SEQ ID NO: 132 for CDR3 of the light chain; or
(d)
i. SEQ ID NO: 95 for CDR1 of the heavy chain;
ii. SEQ ID NO: 96 for CDR2 of the heavy chain;
iii. SEQ ID NO: 97 for CDR3 of the heavy chain;
iv. SEQ ID NO: 98 for CDR1 of the light chain;
v. SEQ ID NO: 99 for CDR2 of the light chain; and
vi. SEQ ID NO: 100 for CDR3 of the light chain; or
(e)
i. SEQ ID NO: 101 for CDR1 of the heavy chain;
ii. SEQ ID NO: 102 for CDR2 of the heavy chain;
iii. SEQ ID NO: 103 for CDR3 of the heavy chain;
iv. SEQ ID NO: 104 for CDR1 of the light chain;
v. SEQ ID NO: 105 for CDR2 of the light chain; and
vi. SEQ ID NO: 106 for CDR3 of the light chain; or
(f)
i. SEQ ID NO: 109 for CDR1 of the heavy chain;
ii. SEQ ID NO: 110 for CDR2 of the heavy chain;
iii. SEQ ID NO: 111 for CDR3 of the heavy chain;
iv. SEQ ID NO: 112 for CDR1 of the light chain;
v. SEQ ID NO: 113 for CDR2 of the light chain; and
vi. SEQ ID NO: 114 for CDR3 of the light chain.

13 . The antibody of claim 12 , wherein
the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 17 and a light chain variable region of the amino acid sequence of SEQ ID NO: 67, or the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 32 and a light chain variable region of the amino acid sequence of SEQ ID NO: 56; or the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 22 and a light chain variable region of the amino acid sequence of SEQ ID NO: 59; or the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 28 and a light chain variable region of the amino acid sequence of SEQ ID NO: 63; or the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 26 and a light chain variable region of the amino acid sequence of SEQ ID NO: 65; or the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 107 and a light chain variable region of the amino acid sequence of SEQ ID NO: 108.

14 - 24 . (canceled)

25 . The antibody of claim 1 , wherein the antibody binds to the S1 domain of MERS-S and inhibits the sialic acid-binding activity of MERS-S.

26 . The antibody of claim 25 , wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
SEQ ID NO: 145 for CDR1 of the heavy chain; SEQ ID NO: 146 for CDR2 of the heavy chain; SEQ ID NO: 147 for CDR3 of the heavy chain; SEQ ID NO: 148 for CDR1 of the light chain; SEQ ID NO: 149 for CDR2 of the light chain; and SEQ ID NO: 150 for CDR3 of the light chain.

27 . The antibody of claim 26 , wherein the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 18 and a light chain variable region of the amino acid sequence of SEQ ID NO: 58.

28 . The antibody of claim 1 , wherein the antibody binds to MERS-S and to one or more spike proteins from Coronaviruses other than MERS-CoV.

29 . (canceled)

30 . The antibody of claim 28 , wherein the antibody comprises complementarity determining regions (CDRs) with the sequences of:
i. SEQ ID NO: 617 for CDR1 of the heavy chain; ii. SEQ ID NO: 618 for CDR2 of the heavy chain; iii. SEQ ID NO: 619 for CDR3 of the heavy chain; iv. SEQ ID NO: 614 for CDR1 of the light chain; v. SEQ ID NO: 615 for CDR2 of the light chain; and vi. SEQ ID NO: 616 for CDR3 of the light chain.

31 . The antibody of claim 30 , wherein the antibody comprises a heavy chain variable region of the amino acid sequence of SEQ ID NO: 480 and a light chain variable region of the amino acid sequence of SEQ ID NO: 458.

32 . The antibody of claim 1 , wherein the antibody is a heavy chain-only antibody.

33 . The antibody of claim 1 , wherein the antibody is an Fab, Fab′, F(ab′)2, Fd, Fv, a single-chain Fv (scFv) or a disulfide-linked Fv (sdFv).

34 . (canceled)

35 . An isolated nucleic acid encoding the antibody of claim 1 .

36 - 37 . (canceled)

38 . A method of producing antibodies that binding to two or more Coronaviruses, wherein the method comprises immunizing an animal sequentially with spike proteins from the two or more Coronaviruses.

39 . The method of claim 38 , wherein:
(a) interval between sequential immunizations is one week, two weeks, three weeks or four weeks, and/or (b) the method comprises one, two, three or four rounds of sequential immunizations, and/or (c) the animal is immunized sequentially with spike proteins from OC43, MERS and SARS, optionally wherein the method further comprises a booster immunization in which each of the spike proteins from OC43, MERS and SARS is administered to the animal, and/or (d) the B-cells are harvested from spleen and lymph nodes four days after the last immunization, and/or

Assignees

• Harbour Antibodies Bv
• Univ Utrecht Holding Bv
• Univ Erasmus Med Ct Rotterdam

Inventors

• Grosveld Franklin Gerardus
• Van Haperen Marinus Johannes
• Drabek Dubravka
• Bosch Berend Jan
• Widjaja Ivy
• Wang Chunyan
• Van Dieren Brenda
• Li Wentao
• Van Kuppeveld Frank J M
• Haagmans Bart L
• Okba Nisreen M A

Classifications

• C07K16/102

  Coronaviridae (F) · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title