Anti-STAT3 specific antibody and the pharmaceutical composition comprising thereof
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12116403-B2
Publication Date
2024-10-15
Expiration Date
Abstract
An anti-STAT3 specific antibody and a pharmaceutical composition comprising the same is provided. The anti-STAT3 specific antibody includes a site that specifically binds to STAT3, and further includes a STAT3 site plus a DNA binding site that confer cell penetration ability, and the pharmaceutical composition includes the anti-STAT3 specific antibody as an active ingredient. The STAT3 specific antibody, and particularly the STAT3/DNA dual specific antibody having a dual specific characteristic, contains a DNA binding site that can penetrate cells and specifically bind to DNA in the nucleus, and thus can overcome the limitations of conventional antibody therapeutics that can target only extracellular proteins. The antibody can inhibit transcription factor activity of STAT3 by specifically binding to phosphorylated activated form of STAT3. Thus, the antibody could be used for the development of a therapeutic agent without side effects for various diseases caused by activation of STAT3.
Core Innovation
The invention relates to an anti-pSTAT3 antibody or antigen binding fragment thereof and a STAT3/DNA dual-specific pharmaceutical composition. The antibody comprises an antigen binding site that specifically binds STAT3 and is configured to bind phosphorylated STAT3, including phosphorylated STAT3 at tyrosine position 705 (pY705). The document describes an antibody design that includes a DNA binding site to enable intracellular and nuclear DNA binding in addition to STAT3 binding.
The antibody design is described as based on a 3E10 scFv with a D31N substitution, and includes complementary determining regions defined by specified amino acid sequences. The document characterizes binding to pY705 STAT3 using phage-display screening of pY705 STAT3-binding sequences and reports binding affinity values in the nanomolar range. The antibody is further described as showing recombinant bispecific antibody binding to pSTAT3 as validated using electrophoresis, and as demonstrating cell penetration and nuclear pSTAT3 binding.
The described STAT3/DNA dual-specific composition is stated to inhibit STAT3 transcription-factor activity selectively without affecting COX-2/other signaling. The document associates this selective inhibition with therapeutic use in cancer, including metastasis, and in inflammatory/autoimmune diseases, including rheumatoid arthritis and psoriasis or psoriatic dermatitis. Representative results are described for inhibition of pSTAT3 signaling in RAW264.7 and synoviocyte cells after LPS/TNFα stimulation, and for suppression of STAT3-RE luciferase reporter expression after IL-6 treatment in HepG2 cells.
Claims Coverage
The independent claim identified is clm-00001. It defines a STAT3 specific antibody or antigen binding fragment with antigen-binding-site specificity to STAT3 using sets of light-chain and heavy-chain CDR amino-acid sequences, with dependent claims additionally specifying functional and biochemical binding conditions.
Cdr-defined STAT3 specific antigen binding site
A STAT3 specific antibody or antigen binding fragment comprising an antigen binding site that specifically binds STAT3, where the antigen binding site specifically binds STAT3 with a light chain CDR represented by amino acid sequences of SEQ ID NO: 1 to 3 and a heavy chain CDR represented by amino acid sequences of SEQ ID NO: 4 to 6; or SEQ ID NO: 7 to 9 and SEQ ID NO: 10 to 12; or SEQ ID NO: 13 to 15 and SEQ ID NO: 16 to 18; or SEQ ID NO: 19 to 21 and SEQ ID NO: 22 to 24; or SEQ ID NO: 25 to 27 and SEQ ID NO: 28 to 30; or SEQ ID NO: 31 to 33 and SEQ ID NO: 34 to 36; or SEQ ID NO: 37 to 39 and SEQ ID NO: 40 to 42.
Cell-penetrating STAT3 specific antibody or antigen binding fragment
A STAT3 specific antibody or its antigen binding fragment characterized by ability to penetrate into cells.
Specified antibody fragment formats
The STAT3 specific antibody or its antigen binding fragment is selected from diabody, Fab, Fab′, F(ab)2, F(ab′)2, Fv, and scFv.
Polynucleotide encoding the STAT3 specific antibody
A polynucleotide encoding the STAT3 specific antibody or an antigen binding fragment of the antibody.
Production by culturing an expressing cell and recovering the polypeptide
A method producing a STAT3 specific antibody or an antigen binding fragment, comprising culturing a cell expressing a polynucleotide, producing a polypeptide having STAT3 antibody light chain variable regions and heavy chain variable regions, and recovering the polypeptide from the cell or culture medium.
Binding to STAT3 phosphorylated on tyrosine at position 705
The STAT3 protein bound by the STAT3 specific antibody or its antigen binding fragment is phosphorylated on tyrosine at position 705.
Across the independent claim and its dependent refinements shown, the core coverage is an antigen binding site defined by specific light-chain and heavy-chain CDR sequence sets that specifically bind STAT3, with additional defined features including cell penetration, selected antibody fragment formats, an encoding polynucleotide and expression-based production, and binding to STAT3 phosphorylated on tyrosine 705.
Stated Advantages
Selectively inhibits STAT3 transcription-factor activity without affecting COX-2/other signaling.
Enables intracellular and nuclear DNA binding in addition to STAT3 binding.
Documented Applications
Therapeutic use for cancer, including metastasis.
Therapeutic use for inflammatory/autoimmune diseases including rheumatoid arthritis.
Therapeutic use for inflammatory/autoimmune diseases including psoriasis and psoriatic dermatitis.
Interested in licensing this patent?