Antibody molecules to dengue virus and uses thereof

• US 10,155,806 B2
• Filed: 05/16/2016
• Issued: 12/18/2018
• Est. Priority Date: 02/11/2014
• Status: Active Grant

• Current Assignee: Visterra, Inc. (Otsuka Holdings Company Limited)
• Original Assignee: Visterra, Inc. (Otsuka Holdings Company Limited)
• Inventors: Robinson, Luke, Shriver, Zachary, Myette, James R., Babcock, Gregory, Viswanathan, Karthik
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US15/155,620
• Publication Number:
  US 20160251413A1
• Time in Patent Office: 946 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/42 viral
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 16/1081 Togaviridae, e.g. flavivirus, rubella virus, hog cholera virus
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/90 characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: G01N 2333/185 Flaviviruses or Group B arboviruses, e.g. yellow fever virus, japanese encephalitis, tick-borne encephalitis, dengue
• CPC Class Codes: G01N 33/56983 Viruses
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Antibody molecules that specifically bind to dengue virus are disclosed. In certain embodiments, the antibody molecule bind to dengue virus serotypes DV-1, DV-2, DV-3, and DV-4. The antibody molecules can be used to treat, prevent, and/or diagnose dengue virus.

Claims

1. A nucleic acid molecule comprising a first nucleotide sequence encoding a heavy variable region of an antibody molecule capable of binding dengue virus, wherein the antibody molecule comprises:

(a) a heavy chain immunoglobulin variable region segment comprising;

a CDR1 comprising the sequence DVYMS (SEQ ID NO;

     3),

a CDR2 comprising the sequence RIDPENGDTKYDPKLQG (SEQ ID NO;

     4), and

a CDR3 comprising the sequence GWEGFAY (SEQ ID NO;

     5); and

(b) a light chain immunoglobulin variable region segment comprising;

a CDR1 comprising the sequence RASENVDKYGNSFMH (SEQ ID NO;

     6),

a CDR2 comprising the sequence RASELQW (SEQ ID NO;

     7), and

a CDR3 comprising the sequence QRSNEVPWT (SEQ ID NO;

     8).

2. An expression vector comprising the nucleic acid molecule of claim 1.

3. An isolated host cell comprising the nucleic acid molecule of claim 1.

4. The nucleic acid molecule of claim 1, wherein the antibody molecule comprises a VH FW1 having the sequence QVQLVQSGAEVKKPGASVKVSCKAGFNIK (SEQ ID NO:

11).

5. The nucleic acid molecule of claim 1, wherein the antibody molecule comprises a VH FW2 having the sequence WVRQAPGQGLEWMG (SEQ ID NO:

84) or WVRQAPEQGLEWMG (SEQ ID NO;

     85).

6. The nucleic acid molecule of claim 1, wherein the antibody molecule comprises a VH FW1 comprising a deletion of position 26 relative to SEQ ID NO:

33.

7. The nucleic acid molecule of claim 1, wherein the antibody molecule comprises a VH amino acid sequence at least 85% identical to SEQ ID NO:

1.

8. The nucleic acid molecule of claim 1, wherein the antibody molecule comprises the VH amino acid sequence of SEQ ID NO:

1.

9. The nucleic acid molecule of claim 1, wherein the first nucleotide sequence encodes a VH amino acid sequence at least 85% identical to SEQ ID NO:

1.

10. The nucleic acid molecule of claim 1, wherein the first nucleotide sequence encodes the VH amino acid sequence of SEQ ID NO:

1.

11. The nucleic acid molecule of claim 1, which comprises a VH nucleotide sequence at least 85% identical to SEQ ID NO:

37.

12. The nucleic acid molecule of claim 1, which comprises the VH nucleotide sequence of SEQ ID NO:

37.

13. The nucleic acid molecule of claim 1, further comprising a second nucleotide sequence encoding a light chain variable region of the antibody molecule.

14. The nucleic acid molecule of claim 13, wherein the antibody molecule comprises a VL amino acid sequence at least 85% identical to SEQ ID NO:

2.

15. The nucleic acid molecule of claim 13, wherein the antibody molecule comprises the VL amino acid sequence of SEQ ID NO:

2.

16. The nucleic acid molecule of claim 13, wherein the antibody molecule comprises the VH amino acid sequence of SEQ ID NO:

1 and the VL amino acid sequence of SEQ ID NO;

2.

17. The nucleic acid molecule of claim 13, wherein the second nucleotide sequence encodes a VL amino acid sequence at least 85% identical to SEQ ID NO:

2.

18. The nucleic acid molecule of claim 13, wherein the second nucleotide sequence encodes the VL amino acid sequence of SEQ ID NO:

2.

19. The nucleic acid molecule of claim 13, which the first nucleotide sequence encodes the VH amino acid sequence of SEQ ID NO:

1 and the second nucleotide sequence encodes the VL amino acid sequence of SEQ ID NO;

2.

20. The nucleic acid molecule of claim 13, which comprises a VL nucleotide sequence at least 85% identical to SEQ ID NO:

38.

21. The nucleic acid molecule of claim 13, which comprises the VL nucleotide sequence of SEQ ID NO:

38.

22. The nucleic acid molecule of claim 13, which comprises the VH nucleotide sequence of SEQ ID NO:

37 and the VL nucleotide sequence of SEQ ID NO;

38.

25. An expression vector comprising the nucleic acid molecule of claim 13.

28. An isolated host cell comprising the nucleic acid molecule of claim 13.

23. A nucleic acid molecule comprising a first nucleotide sequence encoding the VH amino acid sequence of SEQ ID NO:

1, a second nucleotide sequence encoding the VL amino acid sequence of SEQ ID NO;

2, or both.

26. An expression vector comprising the nucleic acid molecule of claim 23.

29. An isolated host cell comprising the nucleic acid molecule of claim 23.

24. A nucleic acid molecule comprising the VH nucleotide sequence of SEQ ID NO:

37, the VL nucleotide sequence of SEQ ID NO;

38, or both.

27. An expression vector comprising the nucleic acid molecule of claim 24.

30. An isolated host cell comprising the nucleic acid molecule of claim 24.