Binding molecule having influenza A virus-neutralizing activity produced from human B cell

Patent metadata

Field	Value
Publication number	US-9475861-B2
Application number	US-201214348284-A
Country	US
Kind code	B2
Filing date	Sep 27, 2012
Priority date	Sep 30, 2011
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

The present invention relates to a binding molecule having influenza A virus-neutralizing activity derived from a human B cell, and the binding molecule having the influenza A virus-neutralizing activity, according to the present invention, is a binding molecule that is derived from a B cell that is selected from the blood of a patient infected with an influenza A virus, and has neutralizing activity against influenza A viruses, and thus is useful in preventing and treating disease derived from the influenza A virus, and can be useful in diagnosing the influenza A virus by using the binding molecule according to the present invention.

First claim

The invention claimed is:

1. A binding molecule comprising:
(a) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 18, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 19, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 20, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 21, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 22, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 23;
(b) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 24, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 25, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 26, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 27, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 28, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 29;
(c) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 30, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 25, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 26, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 31, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 32, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 33; or
(d) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 34, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 35, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 26, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 31, a CDR2 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 36, and a CDR3 region comprising a polypeptide encoded by a polynucleotide sequence set forth in SEQ ID NO: 29.

2. The binding molecule of claim 1 , wherein the binding molecule is composed of a light chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 45, and a heavy chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 46.

3. The binding molecule of claim 1 , wherein the binding molecule is composed of a light chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 47, and a heavy chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 48.

4. The binding molecule of claim 1 , wherein the binding molecule is composed of a light chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 49, and a heavy chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 50.

5. The binding molecule of claim 1 , wherein the binding molecule is composed of a light chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 51, and a heavy chain comprising a polypeptide encoded by polynucleotide sequence set forth in SEQ ID NO: 52.

6. A composition for diagnosis of influenza A virus, the composition comprising a conjugate comprising a tag linked to a binding molecule having neutralizing activity against influenza A virus, wherein the binding molecule is:
(a) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 1, a CDR2 region set forth in SEQ ID NO: 2, and a CDR3 region set forth in SEQ ID NO: 3, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 4, a CDR2 region set forth in SEQ ID NO: 5, and a CDR3 region set forth in SEQ ID NO: 6;
(b) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 7, a CDR2 region set forth in SEQ ID NO: 8, and a CDR3 region set forth in SEQ ID NO: 9, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 10, a CDR2 region set forth in SEQ ID NO: 11, and a CDR3 region set forth in SEQ ID NO: 12;
(c) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 13, a CDR2 region set forth in SEQ ID NO: 8, and a CDR3 region set forth in SEQ ID NO: 9, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 10, a CDR2 region set forth in SEQ ID NO: 14, and a CDR3 region set forth in SEQ ID NO: 6; or
(d) a binding molecule composed of a light chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 15, a CDR2 region set forth in SEQ ID NO: 16, and a CDR3 region set forth in SEQ ID NO: 9, and a heavy chain comprising, as determined according to the Kabat method, a CDR1 region set forth in SEQ ID NO: 10, a CDR2 region set forth in SEQ ID NO: 17, and a CDR3 region set forth in SEQ ID NO: 12.

7. The composition of claim 6 , wherein the tag is any one selected from the group consisting of enzymes, luciferases, radioactive isotopes, and toxin.

8. The binding molecule of claim 1 , wherein the binding molecule is an antibody.

9. The binding molecule of claim 8 , wherein the antibody is a Fab fragment, a Fv fragment, a diabody, a chimeric antibody, a humanized antibody or a human antibody.

10. A composition comprising a binding molecule having neutralizing activity against influenza A virus according to claim 1 .

11. The composition of claim 10 , wherein the influenza A virus is selected from the group consisting of H1, H3, H5, H7 and H9 subtypes.

12. A composition for preventing and treating a disease caused by influenza A virus, the composition comprising a binding molecule having neutralizing activity against influenza A virus according to claim 1 .

13. A kit for diagnosis of influenza A virus, comprising:
i) a binding molecule having neutralizing activity against influenza A virus according to claim 1 ; and
ii) a container.

14. The kit of claim 13 , wherein the influenza A virus is selected from the group consisting of H1, H3, H5, H7 and H9 subtypes.

15. The binding molecule of claim 1 ,

Assignees

• Celltrion Inc

Inventors

• Chang Shin Jae
• Kwon Ki Sung
• Yi Kye Sook
• Lee Hyun Joo
• Jeon Jae Won
• Jun Hwang Keun
• Chang Min Seok

Classifications

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C07K16/108 Primary

  Orthomyxoviridae (F), e.g. influenza virus · CPC title

• C07K2317/76

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

• G01N33/577

  involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)} · CPC title

• G01N2500/00

  Screening for compounds of potential therapeutic value · CPC title