Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-7718174-B2
Publication Date
2010-05-18
Expiration Date
Abstract
The inventive anti-HGF/SF humanized antibody prepared by displaying on the surface of a phage an anti-HGF/SF chimeric Fab library comprising a set of human antibody light chain variable region (VL) and human antibody heavy chain variable region (VH) which are grafted with heavy chain complementary determining regions (HCDRs) of an anti-HGF/SF antibody of an animal other than human, has the equal or greater binding affinity than that of the parent anti-HGF/SF antibody, the neutralizing activity inhibiting the binding of HGF/SF to its receptor, cMET while having the reduced immunogenicity in human. Therefore, the inventive anti-HGF/SF humanized antibody can be used for preventing and treating diseases effectively, e.g., cancers, by the action of binding HGF/SF to cMET.
Core Innovation
The disclosed invention relates to an anti-HGF/SF humanized antibody generated by phage display using a human VH paired with a human VL, where the VH contains grafted HCDRs from an anti-HGF/SF non-human antibody (SFN 68). The resulting humanized Fab binds HGF/SF with equal or higher affinity than the parent antibody and inhibits HGF/SF binding to cMET.
The disclosed humanized antibody shows equal neutralizing activity while having reduced immunogenicity in humans. The structural definition is provided in terms of specific VH, VL, CDR, and human constant regions, including SEQ ID sequences and lead clones.
Selected lead clones include HSFN68-13, HSFN68-16, HSFN68-27, and HSFN68-41 with measured SPR Kd values and functional activity in cMET-binding inhibition and MDCK scattering assays. The document also describes pharmaceutical composition aspects, including formulation indications with a pharmaceutically acceptable carrier for cancer prevention and treatment.
Claims Coverage
The independent claim defines an anti-HGF/SF humanized antibody with three inventive elements: sequence-defined VH/VL variable regions, human constant regions, and specified SEQ ID NO combinations for the variable regions. Dependent claim coverage further limits the antibody format to a Fab and adds a pharmaceutical composition context with a pharmaceutically acceptable carrier.
Sequence-defined anti-HGF/SF humanized antibody with specified VH and VL SEQ ID combinations
An anti-HGF/SF humanized antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein VL and VH respectively have the amino acid sequences of SEQ ID NOs 4 and 5; SEQ ID NOs 8 and 9; SEQ ID NOs 12 and 13; or SEQ ID NOs 16 and 17.
Human antibody heavy-chain and light-chain constant regions
The antibody comprises a heavy chain constant region identical to the human antibody heavy chain constant region and a light chain constant region identical to the human antibody light chain constant region.
Fab format of the humanized antibody
The antibody of the independent claim is a Fab.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition comprising the humanized antibody of the independent claim as an active ingredient together with a pharmaceutically acceptable carrier.
Overall, the claim set covers a sequence-defined anti-HGF/SF humanized antibody using specified VH/VL SEQ ID combinations with human heavy- and light-chain constant regions, with dependent coverage limited to a Fab format and a pharmaceutical composition including a pharmaceutically acceptable carrier.
Stated Advantages
Equal or higher affinity binding to HGF/SF than the parent antibody.
Inhibition of HGF/SF binding to cMET.
Equal neutralizing activity.
Reduced immunogenicity in humans.
Documented Applications
Cancer prevention and treatment using a pharmaceutical composition with the humanized antibody together with a pharmaceutically acceptable carrier.
Interested in licensing this patent?