US 2016/0237162 A1 · BINDING MOLECULES SPECIFIC FOR HER3 AND USES THEREOF

Abstract

Provided herein are antibodies and antigen binding fragments thereof that bind the extracellular domain of the HER3 receptor and inhibit various HER3 receptor related functions via ligand-dependent and/or ligand-independent mechanisms. Also provided are compositions with increased half-life, as well as compositions and methods for diagnosing and treating diseases associated with HER3 mediated signal transduction.

Claims104

Dependent claims

A method of resensitizing a tumor or tumor cell in a subject to a HER targeted therapy, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of resensitizing a HER2 amplified tumor or tumor cell in a subject to a HER2 targeted therapy, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of resensitizing a tumor in a subject to trastuzumab, comprising administering to a subject diagnosed as having a cancer resistant to treatment with trastuzumab a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of resensitizing a tumor or tumor cell in a subject to an EGFR targeted therapy, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of reducing or inhibiting growth of a tumor or tumor cell in a subject, comprising administering to a subject identified as having, or suspected of having, cancer resistant to treatment with a HER targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of reducing or inhibiting growth of a HER2 amplified tumor or tumor cell in a subject, comprising administering to a subject identified as having, or suspected of having, cancer resistant to treatment with a HER2 targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of reducing or inhibiting growth of a tumor resistant to trastuzumab in a subject, comprising administering to a subject diagnosed as having a cancer resistant to treatment with trastuzumab a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of reducing or inhibiting growth of a tumor or tumor cell in a subject, comprising administering to a subject identified as having, or suspected of having, cancer resistant to treatment with an EGFR targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising administering to a subject diagnosed as having, or suspected of having, a cancer resistant to treatment with a HER targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5G
EX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a tumor expressing HER3 and is resistant to treatment with a HER targeted therapy;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

A method of managing or treating cancer in a subject, comprising administering to a subject diagnosed as having, or suspected of having, a cancer resistant to treatment with a HER2 targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a HER2 amplified tumor which expresses HER3 and is resistant to treatment with a HER2 targeted therapy;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

A method of managing or treating cancer in a subject, comprising administering to a subject diagnosed as having, or suspected of having, a cancer resistant to treatment with trastuzumab a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising administering to a subject identified as having a cancer resistant to treatment with pertuzumab or the combination of pertuzumab and trastuzumab a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a HER2/HER3-positive cancer that is resistant to treatment with trastuzumab;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/023,858Filed 23 Sep 2014

Priority

24 Sep 2013

Published

18 Aug 2016

Term ends

Not estimatedThe source records don’t support an estimate.

Classification36 codes

A61K 39/39558
Against materials from animals: against tumor tissues, cells, antigens
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61K 39/39591
Antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum: stabilisation, fragmentation
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Abstract

Claims104

Dependent claims

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of reducing or inhibiting growth of a tumor or tumor cell in a subject, comprising administering to a subject identified as having, or suspected of having, cancer resistant to treatment with an EGFR targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5
GEX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI
[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5G
EX6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a tumor expressing HER3 and is resistant to treatment with a HER targeted therapy;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

A method of managing or treating cancer in a subject, comprising administering to a subject diagnosed as having, or suspected of having, a cancer resistant to treatment with a HER2 targeted therapy a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a HER2 amplified tumor which expresses HER3 and is resistant to treatment with a HER2 targeted therapy;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

18 more elements

A method of managing or treating cancer in a subject, comprising the steps of:

(a) identifying a subject with a HER2/HER3-positive cancer that is resistant to treatment with trastuzumab;
and
(b) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2;
or
(ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2;
or
(iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:
[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GE
X6[FW4]
wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and
wherein
(a) X1 represents amino acid residues Arginine (R) or Serine (S),
(b) X2 represents amino acid residues Serine (S) or Leucine (L),
(c) X3 represents amino acid residues Serine (S) or Glycine (G),
(d) X4 represents amino acid residues Leucine (L) or Proline (P),
(e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
(f) X6 represents amino acid residues Valine (V) or Alanine (A), and
(B) an antibody VH, wherein the VH comprises the amino acid sequence:
[FW5]YYYMQ[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFD
I[FW8]
wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and
wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).

21 more elements

Dependencies are inferred from the claim text.

Binding molecules specific for her3 and uses thereof

Life of this patent

Abstract

Claims104

Binding molecules specific for her3 and uses thereof

Life of this patent

Abstract

Claims104