Antibodies specifically binding to HER3

Patent metadata

Field	Value
Publication number	US-10179815-B2
Application number	US-201615083686-A
Country	US
Kind code	B2
Filing date	Mar 29, 2016
Priority date	Oct 4, 2013
Publication date	Jan 15, 2019
Grant date	Jan 15, 2019

Abstract

The present invention relates to isolated antibodies, or an antigen portions thereof, which bind to human HER3. The novel antibodies are of great utility since they allow for the sensitive and specific detection of human HER3. Detection of human HER3 is, e.g., possible in a tissue sample, even when such tissue sample is a formalin-fixed paraffin embedded tissue (FFPET) sample.

First claim

The invention claimed is:

1. An isolated antibody, or an antigen binding portion thereof, which binds to human HER3, wherein
the heavy chain variable domain comprises
a CDR1H region comprising the amino acid sequence of SEQ ID NO: 1,
a CDR2H region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 3,
and a CDR3H region comprising the amino acid sequence of SEQ ID NO: 4,
and the light chain variable domain comprises
a CDR1L region comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2L region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 6 and SEQ ID NO: 7,
and a CDR3L region comprising the amino acid sequence of SEQ ID NO: 8.

2. The antibody, or an antigen binding portion thereof, according to claim 1 , wherein
the heavy chain variable domain comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 9 and SEQ ID NO: 10, and the light chain variable domain comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 11 and SEQ ID NO: 12.

3. An isolated antibody, or an antigen binding portion thereof, which binds to human HER3, wherein
the heavy chain variable domain comprises
a CDR1H region comprising the amino acid sequence of SEQ ID NO: 1,
a CDR2H region comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3,
and a CDR3H region comprising the amino acid sequence of SEQ ID NO: 4,
and the light chain variable domain comprises
a CDR1L region comprising the amino acid sequence of SEQ ID NO: 5 modified by a conservative amino acid substitution, wherein the conservative amino acid substitution is a threonine/serine substitution at position 5 of SEQ ID NO: 5,
a CDR2L region comprising the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7,
and a CDR3L region comprising the amino acid sequence of SEQ ID NO: 8.

4. The antibody, or an antigen binding portion thereof, according to claim 1 , wherein the antibody is a monoclonal antibody.

5. A method for performing immunohistochemistry the method comprising the steps of
a) incubating a tissue sample with an antibody, or an antigen binding portion thereof, according to claim 1 , whereby binding of said antibody to HER3 in said tissue takes place and
b) staining said tissue sample for the anti-HER3 antibody bound in step (a).

6. The method according to claim 5 , wherein said tissue sample is a tissue sample that had been formaldehyde-fixed and paraffin-embedded (FFPE).

7. The method according to claim 5 , wherein steps a) and b) are performed using an automated instrument.

8. A kit for the detection of human HER3 in a formaldehyde-fixed paraffin-embedded tissue (FFPET) sample, said kit comprising:
an antibody, or an antigen binding portion thereof, according to claim 1 ; and
reagents for the detection of said antibody, or an antigen binding portion thereof.

9. A nucleic acid encoding a heavy and light chain of an antibody binding to human HER3, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain according to claim 1 .

10. An isolated antibody, or an antigen binding portion thereof, which binds to human HER3, wherein
the heavy chain variable domain comprises
a CDR1H region comprising the amino acid sequence of SEQ ID NO: 1,
a CDR2H region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 3,
and a CDR3H region comprising the amino acid sequence of SEQ ID NO: 4,

and the light chain variable domain comprises a CDR1L region comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2L region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6 and SEQ ID NO: 7,
and a CDR3L region comprising an amino acid sequence modified from SEQ ID NO: 8 by one or two conservative amino acid substitutions, wherein the one or two conservative amino acid substitutions is/are a valine/alanine substitution at position 6 of SEQ ID NO: 8 and/or an alanine/threonine substitution at position 9 of SEQ ID NO: 8.

11. The antibody, or an antigen binding portion thereof, according to claim 3 , wherein the antibody is a monoclonal antibody.

12. A method for performing immunohistochemistry the method comprising the steps of
a) incubating a tissue sample with an antibody, or an antigen binding portion thereof, according to claim 3 , whereby binding of said antibody to HER3 in said tissue takes place and
b) staining said tissue sample for the anti-HER3 antibody bound in step (a).

13. The method according to claim 12 , wherein said tissue sample is a tissue sample that had been formaldehyde-fixed and paraffin-embedded (FFPE).

14. The method according to claim 12 , wherein steps a) and b) are performed using an automated instrument.

15. A kit for the detection of human HER3 in a formaldehyde-fixed paraffin-embedded tissue (FFPET) sample, said kit comprising:
an antibody, or an antigen binding portion thereof, according to claim 3 ; and
reagents for the detection of said antibody, or an antigen binding portion thereof.

16. The antibody, or an antigen binding portion thereof, according to claim 10 , wherein the antibody is a monoclonal antibody.

17. A method for performing immunohistochemistry the method comprising the steps of
a) incubating a tissue sample with an antibody, or an antigen binding portion thereof, according to claim 10 , whereby binding of said antibody to HER3 in said tissue takes place and
b) staining said tissue sample for the anti-HER3 antibody bound in step (a).

18. The method according to claim 17 , wherein said tissue sample is a tissue sample that had been formaldehyde-fixed and paraffin-embedded (FFPE).

19. The method according to claim 17 , wherein steps a) and b) are performed using an automated instrument.

20. A kit for the detection of human HER3 in a formaldehyde-fixed paraffin-embedded tissue (FFPET) sample, said kit comprising:
an antibody, or an antigen binding portion thereof, according to claim 10 ; and
reagents for the detection of said antibody, or an antigen binding portion thereof.

Assignees

• Roche Molecular Systems Inc
• Ventana Med Syst Inc

Inventors

• Soukupova Monika
• Schraeml Michael
• Bossenmaier Birgit
• Roche Patrick C
• Gerg Michael
• Dziadek Sebastian

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• G01N2333/71

  for growth factors; for growth regulators · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title