Anti-CD4 antibodies
Inventors
Sun, Ziyong • MA, Wencui • Ma, Hongli • Niu, Qian (Nicole) • Jin, Ying • Yu, Wen • Zhang, Huanhuan • Wang, Chengcheng • Wang, Yangzhou • Wery, Jean Pierre
Assignees
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Publication Number
US-11254745-B1
Publication Date
2022-02-22
Expiration Date
Abstract
The present disclosure provides herein anti-CD4 antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.
Core Innovation
The invention provides isolated antibodies specifically binding to human CD4 (hCD4) and antigen-binding fragments thereof, defined by particular VH and VL regions. The binding specificity is defined through named HCDR and LCDR sequences using specified SEQ ID NOs for HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, including alternative SEQ ID NO combinations for these CDR regions.
The disclosed antibodies include humanized variants and homologous variants having at least 80% identity, together with CDR/FR modifications described in the document. The invention also covers selection of immunoglobulin constant regions and optional constant-region engineering for IgG1, IgG2, IgG3, and IgG4 formats, including ADCC/CDC-enhancing Fc mutations such as S298A/E333A/K334A (3A) and other EU-numbered substitutions.
In addition to monovalent antibody formats, the document describes bispecific and epitope-competing formats and conjugates. The antibody system is positioned within pharmaceutical composition and kit contexts, together with therapeutic uses involving depletion of CD4-expressing cells, including Tregs, to enhance tumor microenvironment immunogenicity and improve immunotherapy efficacy, as well as methods for detecting and diagnosing CD4-related conditions.
Claims Coverage
The independent claim is directed to isolated human CD4-binding antibodies or antigen-binding fragments defined by specific HCDR/LCDR sequence selections, supported by dependent claim refinements that add allowable sequence sets, antibody formats, constant-region/Fc engineering including enumerated EU-numbered mutations, and pharmaceutical compositions/kits.
Human CD4-binding antibody defined by specific HCDR and LCDR SEQ ID NO sequences
An isolated antibody specifically binding to human CD4 (hCD4) or an antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH and VL regions include defined HCDR1/HCDR2/HCDR3 and LCDR1/LCDR2/LCDR3 sequences as set out by SEQ ID NO selections.
Additional selectable VH variable region SEQ ID NO options
The heavy chain variable region is selected from specified SEQ ID NO choices for the VH region listed in the dependent claim set.
Immunoglobulin constant region inclusion for the antibody construct
The antibody or antigen-binding fragment includes an immunoglobulin constant region, optionally including a human Ig constant region or a constant region of human IgG.
Defined enumerated EU-numbered Fc mutations
The antibody or antigen-binding fragment contains one or more mutations selected from a defined set of EU-numbered amino-acid substitutions.
Specific antibody formats and disulfide-stabilized or multispecific constructs
The antibody or antigen-binding fragment is provided in named antibody format types, including diabody, Fab, F(ab’)2, Fv fragment, dsFv, (dsFv)2, bispecific dsFv-dsFv, ds diabody, scFv, scFv dimer (bivalent diabody), multispecific antibody, and nanobody.
Pharmaceutical composition or kit comprising the antibody with a pharmaceutically acceptable carrier
A pharmaceutical composition or kit includes the antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier.
Overall, the claims cover CD4-binding antibody constructs whose core binding determinants are defined by specific HCDR/LCDR SEQ ID NO combinations, with claim refinements that further constrain selectable VH options, antibody-format implementations, optional constant-region inclusion, enumerated EU-numbered Fc mutation sets, and formulation as pharmaceutical compositions or kits.
Stated Advantages
Enhance tumor microenvironment immunogenicity.
Improve immunotherapy efficacy.
Deplete CD4-expressing cells, especially Tregs.
Documented Applications
Therapeutic use to deplete CD4-expressing cells, especially Tregs, to enhance tumor microenvironment immunogenicity and improve immunotherapy efficacy.
Detection and diagnosis of CD4-related conditions.
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