Monoclonal antibodies that bind to HGM-CSF and medical compositions comprising same
AssigneesEvec Inc., Boehringer Ingelheim International GmbH
InventorsKenzo Takada, Kantou Nakajima, Barbara Kistler, John Park
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Abstract
Disclosed herein are anti-hGM-CSF monoclonal antibodies and antigen-binding fragments of such antibodies, with improved neutralizing capacity to hGM-CSF activity. Pharmaceutical compositions comprising such an antibody or antigen-binding fragment are also provided. The present invention is useful for the treatment of various diseases that are associated with aberrant expression of hGM-CSF.
Claims64
An isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment thereof comprising:
- (a) a heavy chain comprising a VH-CDR1-containing sequence, a VH-CDR2-containing sequence, and a VH-CDR3-containing sequence, wherein:
- (i) the VH-CDR1-containing sequence is SYGMH (SEQ ID NO:
- 4),
- (ii) the VH-CDR2-containing sequence is LTYHHGNRKFYADSVRG (SEQ ID NO:
- 5), and
- (iii) the VH-CDR3-containing sequence is ESMGAINDN (SEQ ID NO:
- 6);
- and
- (b) a light chain comprising a VL-CDR1-containing sequence, a VL-CDR2-containing sequence, and a VL-CDR3-containing sequence, wherein:
- (i) the VL-CDR1-containing sequence is IGNNNNIGSHAVG (SEQ ID NO:
- 7),
- (ii) the VL-CDR2-containing sequence is GRSPPS (SEQ ID NO:
- 8), and
- (iii) the VL-CDR3-containing sequence is STWDSSLSAVV (SEQ ID NO:
- 9).
An isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment thereof comprising a heavy chain variable region having a heavy chain variable region sequence and a light chain variable region having a light chain variable region sequence, wherein the heavy chain variable region sequence is SEQ ID NO:
- 348, and wherein the light chain variable region sequence is SEQ ID NO:
- 365.
An isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment thereof comprising a heavy chain variable region having a heavy chain variable region sequence and a light chain variable region having a light chain variable region sequence, wherein the heavy chain variable region sequence is SEQ ID NO:
- 361, and wherein the light chain variable region sequence is SEQ ID NO:
- 365.
An isolated anti-hGM-CSF monoclonal antibody comprising a heavy chain having a heavy chain sequence and a light chain having a light chain sequence, wherein the heavy chain sequence is SEQ ID NO:
- 46, and wherein the light chain sequence is SEQ ID NO:
- 36.
An isolated anti-hGM-CSF monoclonal antibody comprising a heavy chain having a heavy chain sequence and a light chain having a light chain sequence, wherein the heavy chain sequence is SEQ ID NO:
- 51, and wherein the light chain sequence is SEQ ID NO:
- 36.
A vector comprising a DNA sequence encoding a heavy chain of an anti-hGM-CSF antibody comprising a VH-CDR1-containing sequence, a VH-CDR2-containing sequence, and a VH-CDR3-containing sequence, wherein:
- (i) the VH-CDR1-containing sequence is SYGMH (SEQ ID NO:
- 4),
- (ii) the VH-CDR2-containing sequence is LTYHHGNRKFYADSVRG (SEQ ID NO:
- 5), and
- (iii) the VH-CDR3-containing sequence is ESMGAINDN (SEQ ID NO:
- 6).
A vector comprising a DNA sequence encoding a light chain of an anti-hGM-CSF antibody comprising a VL-CDR1-containing sequence, a VL-CDR2-containing sequence, and a VL-CDR3-containing sequence, wherein:
- (i) the VL-CDR1-containing sequence is IGNNNNIGSHAVG (SEQ ID NO:
- 7),
- (ii) the VL-CDR2-containing sequence is GRSPPS (SEQ ID NO:
- 8), and
- (iii) the VL-CDR3-containing sequence is STWDSSLSAVV (SEQ ID NO:
- 9).
A method for producing an anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof that binds hGM-CSF, wherein the antibody or antigen-binding fragment thereof comprises at least a VH-CDR1-containing sequence, a VH-CDR2-containing sequence, a VH-CDR3-containing sequence, a VL-CDR1-containing sequence, a VL-CDR2-containing sequence, and a VL-CDR3-containing sequence, in an isolated host cell, the method comprising:
- (i) obtaining the isolated host cell comprising at least one DNA sequence encoding at least the VH-CDR1-containing sequence, the VH-CDR2-containing sequence, the VH-CDR3-containing sequence, the VL-CDR1-containing sequence, the VL-CDR2-containing sequence, and the VL-CDR3-containing sequence, wherein:
- (a) the VH-CDR1-containing sequence is SYGMH (SEQ ID NO:
- 4),
- (b) the VH-CDR2-containing sequence is LTYHHGNRKFYADSVRG (SEQ ID NO:
- 5),
- (c) the VH-CDR3-containing sequence is ESMGAINDN (SEQ ID NO:
- 6),
- (d) the VL-CDR1-containing sequence is IGNNNNIGSHAVG (SEQ ID NO:
- 7),
- (e) the VL-CDR2-containing sequence is GRSPPS (SEQ ID NO:
- 8), and
- (f) the VL-CDR3-containing sequence is STWDSSLSAVV (SEQ ID NO:
- 9);
- and
- (ii) culturing the isolated host cell under conditions suitable for expression of DNA and production of the antibody or antigen binding fragment thereof.
A composition comprising an isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof, said antibody or antigen-binding fragment thereof comprising:
- (a) a heavy chain comprising a VH-CDR1-containing sequence, a VH-CDR2-containing sequence, and a VH-CDR3-containing sequence, wherein:
- (i) the VH-CDR1-containing sequence is SYGMH (SEQ ID NO:
- 4),
- (ii) the VH-CDR2-containing sequence is LTYHHGNRKFYADSVRG (SEQ ID NO:
- 5), and
- (iii) the VH-CDR3-containing sequence is ESMGAINDN (SEQ ID NO:
- 6);
- and
- (b) a light chain comprising a VL-CDR1-containing sequence, a VL-CDR2-containing sequence, and a VL-CDR3-containing sequence, wherein:
- (i) the VL-CDR1-containing sequence is IGNNNNIGSHAVG (SEQ ID NO:
- 7),
- (ii) the VL-CDR2-containing sequence is GRSPPS (SEQ ID NO:
- 8), and
- (iii) the VL-CDR3-containing sequence is STWDSSLSAVV (SEQ ID NO:
- 9).
Dependencies are inferred from the claim text.