Antibody specifically binding to FOLR1 and uses thereof
Inventors
Park, Soon Jae • Chung, Hye-Shin • Lee, Sunbae
Assignees
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Publication Number
US-11866492-B2
Publication Date
2024-01-09
Expiration Date
Abstract
A modified antibody that binds specifically to folate receptor alpha (FOLR1) and blocks the activity of FOLR1 with an increased binding affinity, an antigen-binding fragment thereof, a composition containing the antibody or fragment, and their uses are disclosed. The modified antibody or antigen-binding fragment thereof may be used for the prevention or treatment of cancer proliferative disorder associated with an increased FOR1 expression, and may also be used for diagnosis of the disease. The proliferative disorder may be cancer.
Core Innovation
The invention relates to an antibody or antigen-binding fragment thereof that binds specifically to folate receptor-a (FOLR1). The antibody or antigen-binding fragment comprises a heavy-chain variable region and a light-chain variable region restricted to defined SEQ ID NO combinations, including heavy-chain variable region of SEQ ID NO: 1 with light-chain variable regions of SEQ ID NO: 32, 33, or 34, and heavy-chain variable region of SEQ ID NO: 31 with light-chain variable regions of SEQ ID NO: 2 or 32.
The invention further provides FOLR1 activity blockade with enhanced affinity, including identification and selection using CDR diversity libraries and phage display. CDR/variable-region definitions are described in relation to a parent antibody, and vAb variants are generated based on selected diversity outcomes. Characterization is provided showing improved binding versus the parent antibody, including ELISA EC50-based comparisons and SPR measurements including dissociation constant (KD) values.
Beyond the binding and blockade, the document discloses uses of the FOLR1-binding antibody or antigen-binding fragment in the context of antibody-drug conjugate concepts and diagnostic or therapeutic use for FOLR1-associated cancers. The disclosure includes linker and drug class concepts and diagnostic detection approaches directed to FOLR1-related disease and cancer.
Claims Coverage
The independent claim covers an antibody or antigen-binding fragment with specified heavy- and light-chain variable-region SEQ ID NO combinations that specifically bind FOLR1. Dependent claims further define ADC embodiments and diagnostic methods, including comparative test-versus-control detection based on increased FOLR1 expression.
FOLR1-binding antibody with defined variable-region SEQ ID NO combinations
An antibody or antigen-binding fragment thereof that binds specifically to folate receptor-a (FOLR1), comprising selected heavy-chain variable region and light-chain variable region combinations among: heavy-chain variable region of SEQ ID NO: 1 with light-chain variable regions of SEQ ID NO: 32, 33, or 34; or heavy-chain variable region of SEQ ID NO: 31 with light-chain variable regions of SEQ ID NO: 2 or 32.
Antibody-drug conjugate of the defined FOLR1-binding antibody
An antibody-drug conjugate where a drug is conjugated to the antibody or antigen-binding fragment defined for FOLR1 binding.
Linker-mediated conjugation in the antibody-drug conjugate
An antibody-drug conjugate in which the antibody or an antigen-binding fragment is conjugated to the drug through a linker.
Selected drug payload classes for the ADC
An antibody-drug conjugate in which the attached drug is selected from chemotherapeutic agents, toxins, microRNA (miRNA), siRNA, shRNA, or radioactive isotopes.
Diagnostic detection of cancer with increased FOLR1 expression using test versus control comparison
A method of diagnosing cancer with increased FOLR1 expression by contacting a test cell with an antibody or antigen-binding fragment, detecting binding to measure FOLR1 expression, and comparing that level to a control cell where higher FOLR1 expression indicates the presence of such cancer.
Cancer-type limitation for the diagnostic or therapeutic embodiment
Cancers selected from ovarian, breast, lung, kidney, colon, brain, rectal, cervical, or endometrial cancer.
Overall, claim coverage centers on an antibody or antigen-binding fragment that specifically binds FOLR1 using defined heavy- and light-chain variable-region SEQ ID NO combinations, and extends to ADC embodiments and diagnostic use based on detecting increased FOLR1 expression via test-versus-control comparison.
Stated Advantages
Enhanced affinity and improved binding versus a parent antibody, including ELISA EC50-based comparisons and SPR KD measurements.
FOLR1 activity blockade.
Documented Applications
Use of the FOLR1-binding antibody or antigen-binding fragment in antibody-drug conjugate concepts for FOLR1-associated cancers.
Diagnosing cancer with increased FOLR1 expression by contacting test cells with an antibody or antigen-binding fragment, detecting binding to measure FOLR1 expression, and comparing to control cells.
Diagnostic or treatment embodiment for cancers selected from ovarian, breast, lung, kidney, colon, brain, rectal, cervical, or endometrial cancer.
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