RSV-specific binding molecule

Patent metadata

Field	Value
Publication number	US-10035843-B2
Application number	US-201615042656-A
Country	US
Kind code	B2
Filing date	Feb 12, 2016
Priority date	Oct 6, 2009
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The invention provides antibodies and functional equivalents thereof which are capable of specifically binding RSV. Nucleic acid sequences encoding said antibody, as well as antibody producing cells and methods for producing said antibody are also provided.

First claim

The invention claimed is:

1. A method for treating and/or preventing a RSV-related disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of an antibody, or functional part thereof, wherein the antibody or functional part thereof specifically binds to a Respiratory Syncytial Virus (RSV) F protein and comprises:
a heavy chain CDR1 sequence comprising the sequence KLSIH (SEQ ID NO:4), a heavy chain CDR2 sequence comprising the sequence GYEGEVDEIFYAQKFQH (SEQ ID NO:8), a heavy chain CDR3 sequence comprising the sequence LGVTVTEAGLGIDDY (SEQ ID NO:12), a light chain CDR1 sequence comprising the sequence RASQIVSRNHLA (SEQ ID NO:20), a light chain CDR2 sequence comprising the sequence GASSRAT (SEQ ID NO:24), and a light chain CDR3 sequence comprising the sequence LSSDSSI (SEQ ID NO:28).

2. The method of claim 1 , the antibody or functional part thereof having a heavy chain sequence comprising a sequence which is at least 70% identical to the sequence

(SEQ ID NO: 16)

QVQLVQSGAEVKKPGATVKVSCKISGHTLIKLSIHWVRQAPGKGLEWMGG

YEGEVDEIFYAQKFQHRLTVIADTATDTVYMELGRLTSDDTAVYFCGTLG

VTVTEAGLGIDDYWGQGTLVTVSS

and/or having a light chain sequence which is at least 70% identical to the sequence

(SEQ ID NO: 32)

EIVLTQSPGTLSLSPGERATLSCRASQIVSRNHLAWYQQKPGQAPRLLIF

GASSRATGIPVRFSGSGSGTDFTLTINGLAPEDFAVYYCLSSDSSIFTFG

PGTKVDFK.

3. The method of claim 1 , wherein the antibody, or functional part thereof, comprises an IgG1 heavy chain.

4. The method of claim 1 , wherein the antibody, or functional part thereof, comprises a Fc region comprising a modification at one or more positions selected from the group consisting of 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 251, 252, 254, 255, 256, 262, 263, 264, 265, 266, 267, 268, 269, 279, 280, 284, 292, 296, 297, 298, 299, 305, 313, 316, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 339, 341, 343, 370, 373, 378, 392, 416, 419, 421, 440 and 443 as numbered by the EU index of Kabat, said modification comprising an amino acid substitution, and/or an amino acid insertion, and/or an amino acid deletion.

5. The method of claim 4 , wherein the Fc region modification comprises amino acid substitutions at amino acid positions 252, 254, and/or 256.

6. The method of claim 5 , wherein the amino acid substitution at amino acid position 252 is a substitution with tyrosine, the amino acid substitution at amino acid position 254 is a substitution with threonine, and/or the amino acid substitution at amino acid position 256 is a substitution with glutamic acid.

7. The method of claim 1 , wherein the antibody or functional part thereof is administered to the individual before infection with RSV.

8. The method of claim 1 , wherein the antibody or functional part thereof is administered to the individual after infection with RSV.

9. The method of claim 1 , wherein the individual is at an increased risk of complications from an RSV infection.

10. The method of claim 9 , wherein an increased risk of complications from an RSV infection comprises premature birth, otherwise healthy but younger than six weeks of age, elderly, chronic lung disease, congenital heart disease, hospitalized, or with compromised immunity.

11. The method of claim 1 further comprising administering palivizumab, AM14, AM16, AM23, and/or D25.

12. The method of claim 1 , further comprising administering at least one other RSV-specific antibody.

13. The method of claim 1 , wherein the antibody or functional part thereof comprises:
a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:16; or
a light chain sequence comprising the amino acid sequence of SEQ ID NO:32; or
a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:16 and a light chain sequence comprising the amino acid sequence of SEQ ID NO:32.

14. The method of claim 1 , wherein the antibody or functional part thereof comprises a humanized antibody.

15. The method of claim 1 , wherein the antibody or functional part thereof comprises a human antibody.

16. The method of claim 1 , wherein the antibody or functional part thereof comprises a human IgG1 heavy chain.

17. The method of claim 13 , wherein the antibody or functional part thereof comprises a human IgG1 heavy chain.

18. The method of claim 17 , wherein the antibody, or functional part thereof, comprises a Fc region comprising a modification at one or more positions selected from the group consisting of 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 251, 252, 254, 255, 256, 262, 263, 264, 265, 266, 267, 268, 269, 279, 280, 284, 292, 296, 297, 298, 299, 305, 313, 316, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 339, 341, 343, 370, 373, 378, 392, 416, 419, 421, 440 and 443 as numbered by the EU index of Kabat, said modification comprising an amino acid substitution, and/or an amino acid insertion, and/or an amino acid deletion.

19. The method of claim 18 , wherein the Fc region modification comprises amino acid substitutions at amino acid positions 252, 254, and/or 256.

20. The method of claim 19 , wherein the amino acid substitution at amino acid position 252 is a substitution with tyrosine, the amino acid substitution at amino acid position 254 is a substitution with threonine, and/or the amino acid substitution at amino acid position 256 is a substitution with glutamic acid.

Assignees

• Medimmune Ltd

Inventors

• Beaumont Tim
• Bakker Adrianus Q
• Yasuda Etsuko

Classifications

• C07K2317/76

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

• A61K39/42

  viral · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07K2317/92

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

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title