Anti-STAT3 bispecific antibody having cell-penetrating ability, and pharmaceutical composition containing same
Inventors
Assignees
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Publication Number
US-11186631-B2
Publication Date
2021-11-30
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 a STAT3/DNA bispecific antibody or antigen binding fragment thereof that has a STAT3-binding characteristic and a DNA-binding characteristic. The bispecific antibody comprises a first antigen binding site that specifically binds STAT3 and a second antigen-binding site specifically binding DNA, and this combined binding is defined as the STAT3/DNA bispecific characteristic.
The first antigen binding site is selected such that it specifically binds to STAT3 with light chain complementarity determining regions and heavy chain complementarity determining regions represented by specified amino acid sequence sets. The patent context further describes an anti-pSTAT3 antibody (phosphorylated STAT3 Tyr705) that includes a STAT3-binding site and a DNA-binding site (3E10 scFv domain including a D31N variant) for nuclear DNA binding.
By having both a STAT3-binding site and a DNA-binding site, the antibody is described as conferring cell penetration ability and enabling inhibition of STAT3 transcription factor activity. The described inhibition relates to phosphorylated STAT3 (pSTAT3) and is supported in the patent context by selective pSTAT3 inhibition without affecting COX-2, and suppression of STAT3-RE luciferase reporter gene expression.
Claims Coverage
The independent claim covers a STAT3/DNA bispecific antibody or antigen-binding fragment with two binding sites: one STAT3-binding site defined by multiple specified light- and heavy-chain CDR sequence sets and one DNA-binding site. The coverage includes one inventive feature centered on the dual binding format and the specified CDR-defined STAT3 binding.
STAT3/DNA bispecific characteristic with dual antigen-binding sites
A STAT3/DNA bispecific antibody or antigen binding fragment thereof comprising a first antigen binding site that specifically binds to STAT3 and a second antigen-binding site specifically binding to DNA.
STAT3 binding defined by specified light- and heavy-chain CDR sequences
The first antigen-binding site selected from the group that specifically binds to STAT3 with specified light chain CDR and heavy chain CDR amino acid sequence sets represented by the listed SEQ ID Nos.
The inventive coverage is centered on a STAT3/DNA bispecific antibody format that combines a DNA-binding site with a STAT3-binding site defined by specified light- and heavy-chain CDR amino acid sequence sets.
Stated Advantages
Inhibition of STAT3 transcription factor activity.
Selective pSTAT3 inhibition without affecting COX-2.
Suppression of STAT3-RE luciferase reporter gene expression.
Cell penetration ability.
Documented Applications
Therapeutic use in treating inflammatory diseases, specifically rheumatoid arthritis or psoriasis dermatitis.
Detection of a STAT3/DNA bispecific antibody or antigen-binding fragment thereof by contacting it with a sample and detecting the contacted bispecific antibody or fragment.
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