RSV-specific binding molecules and means for producing them

Patent metadata

Field	Value
Publication number	US-10059757-B2
Application number	US-201615047306-A
Country	US
Kind code	B2
Filing date	Feb 18, 2016
Priority date	Jun 1, 2007
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The invention provides antibodies and functional equivalents thereof which are capable of specifically binding RSV, and means and methods for producing them.

First claim

The invention claimed is:

1. An isolated nucleic acid molecule which comprises:
a nucleic acid sequence encoding a heavy chain CDR1 comprising the amino acid sequence NYIIN (SEQ ID NO:1), and
a nucleic acid sequence encoding a heavy chain CDR2 comprising the amino acid sequence GIIPVLGTVHYAPKFQG (SEQ ID NO:2), and
a nucleic acid sequence encoding a heavy chain CDR3 comprising the amino acid sequence ETALVVSTTYLPHYFDN (SEQ ID NO:3).

2. The isolated nucleic acid molecule of claim 1 further comprising:
a nucleic acid sequence encoding a light chain CDR1 comprising the amino acid sequence QASQDIVNYLN (SEQ ID NO:4), and
a nucleic acid sequence encoding a light chain CDR2 comprising the amino acid sequence VASNLET (SEQ ID NO:5), and
a nucleic acid sequence encoding a light chain CDR3 comprising the amino acid sequence QQYDNLP (SEQ ID NO:6).

3. The isolated nucleic acid molecule according to claim 2 , wherein the nucleic acid molecule comprises a cDNA sequence and/or the nucleic acid sequence has been codon optimized to maximize translation into protein.

4. A vector comprising an exogenous nucleic acid molecule of claim 2 .

5. A method for producing an antibody or antigen binding fragment thereof that binds to a respiratory syncytial virus (RSV) F protein, the method comprising providing a cell with a vector according to claim 4 and allowing the cell to translate the nucleic acid sequence.

6. An isolated host cell genetically engineered to express the exogenous nucleic acid molecule of claim 2 .

7. A method for producing an antibody or antigen binding fragment thereof that binds to a respiratory syncytial virus (RSV) F protein, the method comprising allowing the host cell according to claim 6 to translate the nucleic acid molecule.

8. A method for producing an antibody or antigen binding fragment thereof that binds to a respiratory syncytial virus (RSV) F protein, the method comprising providing a cell with a nucleic acid sequence according to claim 2 and allowing the cell to translate the nucleic acid sequence.

9. The isolated nucleic acid molecule according to claim 1 which comprises a nucleic acid sequence encoding a heavy chain variable region having:
an amino acid sequence at least 70% identical to

(SEQ ID NO: 7)

QVQLVQSGAEVKKPGSSVMVSCQASGGPLRNYIINWLRQAPGQGPEWMGG

IIPVLGTVHYAPKFQGRVTITADESTDTAYIHLISLRSEDTAMYYCATET

ALVVSTTYLPHYFDNWGQGTLVTVSS;

an amino acid sequence at least 80% identical to SEQ ID NO:7,
an amino acid sequence at least 85% identical to SEQ ID NO:7,
an amino acid sequence at least 90% identical to SEQ ID NO:7,
an amino acid sequence at least 95% identical to SEQ ID NO:7, or
the amino acid sequence SEQ ID NO:7.

10. The nucleic acid molecule according to claim 1 , wherein:
the nucleic acid sequence encoding the heavy chain CDR1 sequence comprising the amino acid sequence NYIIN (SEQ ID NO:1) comprises SEQ ID NO:60,
the nucleic acid sequence encoding the heavy chain CDR2 sequence comprising the amino acid sequence GIIPVLGTVHYAPKFQG (SEQ ID NO:2) comprises SEQ ID NO:62, and/or
the nucleic acid sequence encoding the heavy chain CDR3 sequence comprising the amino acid sequence ETALVVSTTYLPHYFDN (SEQ ID NO:3) comprises SEQ ID NO:64.

11. The nucleic acid molecule according to claim 1 , wherein:
the nucleic acid sequence comprises SEQ ID NO:9, SEQ ID NO:139, or SEQ ID NO:140.

12. The isolated nucleic acid molecule according to claim 1 , further comprising a nucleic acid sequence encoding an IgG heavy chain constant region.

13. The isolated nucleic acid molecule according to claim 12 , wherein the IgG molecule comprises the IgG1 isotype.

14. The isolated nucleic acid molecule according to claim 1 , wherein the nucleic acid molecule comprises a cDNA sequence and/or the nucleic acid sequence has been codon optimized to maximize translation into protein.

15. The isolated nucleic acid molecule according to claim 14 , wherein the nucleic acid sequence codon optimized to maximize translation into protein comprises SEQ ID NO:140.

16. A vector comprising an exogenous nucleic acid molecule of claim 1 .

17. An isolated host cell comprising the vector of claim 16 .

18. An isolated host cell genetically engineered to express the exogenous nucleic acid molecule of claim 1 .

19. The isolated host cell according to claim 18 , further genetically engineered to express a nucleic acid molecule comprising:
a nucleic acid sequence encoding a light chain CDR1 comprising the amino acid sequence QASQDIVNYLN (SEQ ID NO:4), and
a nucleic acid sequence encoding a light chain CDR2 comprising the amino acid sequence VASNLET (SEQ ID NO:5), and
a nucleic acid sequence encoding a light chain CDR3 comprising the amino acid sequence QQYDNLP (SEQ ID NO:6).

20. The isolated host cell of claim 19 , wherein the isolated host cell is a producer cell adapted to commercial antibody production.

21. The isolated host cell according to claim 19 , wherein the host cell comprises:
a first expression vector comprising a nucleic acid sequence encoding a heavy chain region comprising SEQ ID NO:140, and
a second expression vector comprising a nucleic acid sequence encoding a light chain variable region comprising SEQ ID NO:142.

22. A method for producing an antibody or antigen binding fragment thereof that binds to a respiratory syncytial virus (RSV) F protein, the method comprising allowing the host cell according to claim 21 to translate the nucleic acid molecule.

23. A method for producing an antibody or antigen binding fragment thereof that binds to a respiratory syncytial virus (RSV) F protein, the method comprising allowing the host cell according to claim 19 to translate the nucleic acid molecule.

24. An isolated nucleic acid molecule which comprises:
a nucleic acid sequence encoding a light chain CDR1 comprising the amino acid sequence QASQDIVNYLN (SEQ ID NO:4), and
a nucleic acid sequence encoding a light chain CDR2 comprising the amino acid sequence VASNLET (SEQ ID NO:5), and
a nucleic acid sequence encoding a light chain CDR3 comprising the amino acid sequence QQYDNLP (SEQ ID NO:6).

25. The isolated nucleic acid molecule according to claim 24 which comprises a nucleic acid sequence encoding a light chain variable region having:
an amino acid sequence at least 70% identical to

(SEQ ID NO: 8)

DIQMTQSPSSLSAAVGDRVTITCQASQDIVNYLNWYQQKPGKAPKLLIY

VASNLETGVPSRFSGSGSGTDFSLTISSLQPEDVATYYCQQYDNLPLTF

GGGTKVEIKRTV;

an amino acid sequence at least 80% identical

Assignees

• Medimmune Ltd

Inventors

• Spits Hergen
• Beaumont Tim
• Kwakkenbos Mark Jeroen
• Yasuda Etsuko

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title