Human monoclonal antibodies against the middle east respiratory syndrome coronavirus (mers-cov) and engineered bispecific fusions with inhibitory peptides

Patent metadata

Field	Value
Publication number	US-2016264647-A1
Application number	US-201415030165-A
Country	US
Kind code	A1
Filing date	Oct 16, 2014
Priority date	Oct 18, 2013
Publication date	Sep 15, 2016
Grant date	—

Abstract

The invention provides polypeptides (e.g., antibodies) and fusion proteins that target a epitope in the receptor binding domain (RBD) of the spike (S) glycoprotein of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The polypeptides and fusion proteins can be used to treat and prevent MERS-CoV infection in mammals.

First claim

1 . A polypeptide comprising:
(a) the amino acid sequences of SEQ ID NOs: 3-8; (b) the amino acid sequences of SEQ ID NOs: 4 and 11-15; or (c) the amino acid sequences of SEQ ID NOs: 11 and 18-22.

2 . The polypeptide of claim 1 comprising the amino acid sequences of SEQ ID NOs: 3-8.

3 . The polypeptide of claim 2 , comprising the amino acid sequences of SEQ ID NOs: 1 and 2.

4 . The polypeptide of claim 1 comprising the amino acid sequences of SEQ ID NOs: 4 and 11-15.

5 . The polypeptide of claim 4 , comprising the amino acid sequences of SEQ ID NOs: 9 and 10.

6 . The polypeptide of claim 1 comprising the amino acid sequences of SEQ ID NOs: 11 and 18-22.

7 . The polypeptide of claim 6 , comprising the amino acid sequences of SEQ ID NOs; 16 and 17.

8 . The polypeptide of claim 1 , wherein the polypeptide is a monoclonal antibody or fragment thereof.

9 . The polypeptide of claim 1 , wherein the polypeptide is an Fab, Fab′, F(ab′)2, scFv, di-scFv, fusion molecule, or conjugate.

10 . The polypeptide of claim 9 , wherein the fusion molecule comprises an inhibitory peptide.

11 . The polypeptide of claim 9 , wherein the fusion molecule comprises a CH3 antibody dimerization domain sequence.

12 . The polypeptide of claim 9 , wherein the fusion molecule comprises the amino acid sequence of SEQ ID NO. 23.

13 . The polypeptide of claim 1 , wherein the polypeptide binds with an epitope of the receptor binding domain (RBD) of spike (S) glycoprotein of the Middle East Respiratory Syndrome Coronavirus (MERE-CoV).

14 . A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

15 . The composition of claim 14 , wherein the composition further comprises an additional active agent.

16 . The composition of claim 15 , wherein the additional active agent is selected from the group consisting of Cyclosporin A, inactivated virus, interleukin (IL)-2, IL-12, CD40 ligand and IL-12, IL-7, ribavirin, an interferon, and combinations thereof.

17 . A nucleic acid molecule comprising a non-genomic nucleic acid sequence that encodes the polypeptide of claim 1 .

18 . A vector comprising the isolated nucleic acid molecule of claim 17 .

19 . A cell comprising the nucleic acid molecule of claim 17 or a vector comprising the nucleic acid molecule.

20 . A pharmaceutical composition comprising (i) the nucleic acid molecule of claim 17 or a vector comprising the nucleic acid molecule and (ii) a pharmaceutically acceptable carrier.

21 . The composition of claim 20 , wherein the composition fu her comprises an additional active agent.

22 . The composition of claim 21 , wherein the additional active agent is selected from the group consisting of Cyclosporin A, inactivated virus, interleukin (IL)-2, IL-12, CD40 ligand and IL-12, IL-7, ribavirin, an interferon, and combinations thereof.

23 . A method of inhibiting a MERE -COV infection in a mammal, which method comprises administering to the mammal:
(a) the polypeptide of claim 1 ; (b) a pharmaceutical composition comprising the polypeptide and a pharmaceutically acceptable carrier; (c) a nucleic acid molecule comprising a non-genomic nucleic acid sequence that encodes the polypeptide; (d) a vector comprising the nucleic acid molecule; (e) a cell comprising the nucleic acid molecule or the vector; or (f) a pharmaceutical composition comprising (i) the nucleic acid molecule or the vector and (ii) a pharmaceutically carrier, wherein the MERS-COV infection is inhibited.

24 . The method of claim 23 , wherein the mammal is a human.

25 . A method of detecting MERS-CoV in a mammal comprising (a) contacting a sample obtained from the mammal with the polypeptide of claim 1 , thereby forming a complex of the polypeptide with an antigen of the mammal, and (h) detecting the complex, whereupon detection of the complex indicates presence of MERS-CoV in the mammal.

Assignees

• Us Health
• Univ Hong Kong

Inventors

• Dimitrov Dimiter S
• Ying Tianlei
• Ju Tina W
• Yuen Kwok Yung

Classifications

• C07K16/104 Primary

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• C12N2770/20033

  Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory · CPC title

• C07K2317/76

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

• C07K2317/526

  CH3 domain · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title