Humanized anti-human neurotensin receptor 1 antibodies and their uses
Inventors
YU, CHENG-CHOU • YEH, SHU-PING • Huang, Chao-Yang • LAI, SZU-LIANG • HSIAO, SHIH-LIANG • HOU, MEI-LING • YANG, TZUNG-JIE • Sun, Wei-Ting • HSIA, LIANG-YU • YUEH, Andrew • Chen, Chiung-Tong • Wu, Ren-Huang • Wu, Pei-Shan • Hu, Han-Shu • Wu, Tzu-Chin • TIAN, JIA-NI
Assignees
Development Center for Biotechnology • National Health Research Institutes
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12091454-B2
Publication Date
2024-09-17
Expiration Date
Abstract
A humanized anti-neurotensin receptor 1 (NTSR1) antibody or an antigen-binding fragment thereof. Also, a method for treating, prophylactic treating and/or preventing diseases and/or disorders caused by or related to NTSR1 activity and/or signaling, and a method or kit for detecting NTSR1 in a sample.
Core Innovation
The invention relates to a humanized anti-NTSR1 antibody or antigen-binding fragment that binds neurotensin receptor 1 (NTSR1). The antibodies are defined by specific pairing combinations of a VH sequence and a VL sequence using SEQ ID NOs, including VH comprising SEQ ID NO: 16 with VL comprising SEQ ID NO: 17 or 15, VH comprising SEQ ID NO: 13 with VL comprising SEQ ID NO: 12 or 14, and VH comprising SEQ ID NO: 11 with VL comprising SEQ ID NO: 12 or 14.
The disclosed humanized antibodies and antigen-binding fragments are presented in multiple formats, including full-length antibody and antigen-binding fragments such as Fab, F(ab')2, ScFv, chimeric antibodies, and nanobody formats. The invention also includes multi-specific antibodies, antibody conjugates including antibody-drug conjugates (ADCs), polynucleotides and vectors encoding the antibody or antigen-binding fragment, genetically engineered cells for expression, and pharmaceutical compositions containing an effective amount of the antibody or antigen-binding fragment with a pharmaceutically acceptable carrier.
The document frames use in treating or preventing disease or disorders associated with NTSR1 activity or signaling, and it also discloses NTSR1 detection kits for detecting NTSR1 in a sample by contacting the sample with the antibody or antigen-binding fragment, optionally labeled. The example content describes humanization of a parental 7C3 mAb to humanized variants and evaluates binding characteristics and cell binding using assays such as ELISA with reported KD values and FACS-based binding.
The examples further evaluate affinity maturation to AKT2 and humanized AKT2 variants, including reported kinetic parameters, and report in vivo half-life improvements in mice. The examples also include ADC cytotoxicity measurements and xenograft efficacy trends for ADCs in FaDu head-and-neck tumors.
Claims Coverage
The independent claim family covers at least one independent claim directed to a humanized anti-NTSR1 antibody or antigen-binding fragment with defined VH/VL sequence combinations. The inventive features are the defined VH/VL pairings by SEQ ID NO, together with dependent features such as constant region isotype options, selectable antibody/fragment formats, pharmaceutical compositions, treatment, and detection kits.
Defined VH/VL sequence pairings for humanized anti-NTSR1 binding
A humanized anti-NTSR1 antibody or antigen-binding fragment wherein the VH comprises SEQ ID NO: 16 and the VL comprises SEQ ID NO: 17 or 15, or the VH comprises SEQ ID NO: 13 and the VL comprises SEQ ID NO: 12 or 14, or the VH comprises SEQ ID NO: 11 and the VL comprises SEQ ID NO: 12 or 14.
Specified heavy- and light-chain constant-region isotypes
The humanized anti-NTSR1 antibody or antigen-binding fragment wherein the heavy-chain constant region is selected from IgG1, IgG2, or IgG4 and the light-chain constant region is selected from κ or λ isotypes.
Selected antibody/fragment format
The humanized anti-NTSR1 antibody or antigen-binding fragment provided as an Fab fragment, F(ab')2 fragment, ScFv fragment, a chimeric antibody, or a nanobody format.
Pharmaceutical composition with effective amount and carrier
A pharmaceutical composition comprising an effective amount of a humanized anti-NTSR1 antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier.
Treatment method for NTSR1-associated disease or disorder
A method for treating a disease or disorder associated with NTSR1 activity or signaling by administering an effective amount of a humanized anti-NTSR1 antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier.
NTSR1 detection kit
A detection kit that detects NTSR1 in a sample using a humanized anti-NTSR1 antibody or antigen-binding fragment.
Overall, the claim coverage is grounded in the defined humanized anti-NTSR1 VH/VL SEQ ID NO pairings, and is extended through dependent features specifying constant-region isotype options and selectable antibody/fragment formats. The dependent coverage further includes a pharmaceutical composition, a treatment method for NTSR1-associated disease or disorder, and an NTSR1 detection kit.
Stated Advantages
Improved in vivo half-life for the disclosed humanized antibody variants as reported in the examples.
ADC cytotoxicity and in vivo xenograft efficacy trends are reported for ADCs using the disclosed humanized antibodies.
Documented Applications
Therapeutic use: treating or preventing a disease or disorder associated with NTSR1 activity or signaling by administering an effective amount of the humanized anti-NTSR1 antibody or antigen-binding fragment.
Diagnostic/detection use: detecting NTSR1 in a sample using a humanized anti-NTSR1 antibody or antigen-binding fragment, optionally labeled.
Interested in licensing this patent?