α4β7 integrin binding proteins and methods of use
Inventors
ZHU, Eric Franklin • Shaheen, Hussam Hisham • Milligan, Jacob Cole
Assignees
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Publication Number
US-12606627-B2
Publication Date
2026-04-21
Expiration Date
Abstract
Provided herein are α4β7 binding proteins (e.g., antibodies that bind α4β7) and methods of use.
Core Innovation
The document describes anti-b14b27 binding protein antibody sequences, including heavy-chain variable domains and light-chain variable regions, with specific example VH/VL sequence pairings. It also specifies CDR definitions mapped to SEQ ID ranges and presents anti-b14b27 binding antibody defined by specific heavy chain variable domain (VH) and light chain variable region (VL) amino acid sequences.
The document further specifies Fc engineering using the EU numbering convention. Modified Fc regions with amino-acid substitutions are described, including YTE (M252Y/S254T/T256E), LAGA (L234A/G237A), LALA, LALAGA, N297A, D265A, and variant combinations such as LALA/YTE, LAGA/YTE, and LALAGA/YTE.
The document states that the described Fc changes can alter half-life and effector functions, including ADCC, ADCP, and CDC. It further ties the b14b27 binding antibodies with modified Fc variants to methods of treatment and pharmaceutical compositions for inflammatory bowel disease, including Crohn92s disease and ulcerative colitis, and inflammatory disease including hidradenitis suppurativa.
Claims Coverage
The independent claims cover anti-b14b27 binding antibodies defined by specific heavy-chain and light-chain variable region amino acid sequences, with dependent claim coverage extending to Fc engineering features and pharmaceutical composition formulation. Across the independent claims, three main inventive feature areas are recited: defined VH/VL sequence pairs, Fc modifications for engineered Fc variants, and pharmaceutical compositions containing an effective amount with a pharmaceutically acceptable carrier. In total, 3 independent claims are present (clm-00001, clm-00005, clm-00009).
Defined heavy and light variable region sequence pair
A heavy chain variable domain (VH) comprising the amino acid sequence of SEQ ID NO: 1909 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 2015, or a VH comprising the amino acid sequence of SEQ ID NO: 1910 and a VL comprising the amino acid sequence of SEQ ID NO: 2016.
Modified Fc to extend half-life
A modified Fc region designed to extend the antibody half-life compared to an anti-b14b27 binding antibody lacking the modified Fc.
YTE Fc amino-acid substitutions under EU numbering
A modified Fc region containing the amino acid substitutions M252Y, S254T, and T256E (YTE) per the EU numbering system.
LAGA Fc substitution under EU numbering
A modified Fc region further including the L234A/G237A (LAGA) substitution per the EU numbering system.
Pharmaceutical composition with effective amount and carrier
A pharmaceutical composition containing an effective amount of an anti-b14b27 binding antibody together with a pharmaceutically acceptable carrier.
The claim set first defines anti-b14b27 binding antibodies by specific VH/VL sequence pairings (SEQ ID NOs for VH and VL). Dependent coverage then specifies Fc engineering, including half-life extension via a modified Fc, with YTE substitutions (M252Y/S254T/T256E) and LAGA (L234A/G237A) using EU numbering. Further dependent claims recast the antibody into a pharmaceutical composition comprising an effective amount and a pharmaceutically acceptable carrier.
Stated Advantages
Extend antibody half-life.
Provide a basis for altered effector functions including ADCC, ADCP, and CDC as associated with the described Fc changes.
Extend half-life via a modified Fc (YTE and/or LAGA).
The modified Fc is designed to extend the antibody half-life compared to an antibody lacking the modified Fc.
Documented Applications
Treatment methods for inflammatory bowel disease, including Crohn92s disease and ulcerative colitis, using b14b27 integrin binding proteins bearing specified CDR sets and modified Fc variants.
Subcutaneous administration and intravenous administration routes for the b14b27 integrin binding proteins in inflammatory bowel disease treatment.
Pharmaceutical compositions containing an effective amount of the b14b27 binding antibody with a pharmaceutically acceptable carrier for use in the disclosed treatment context.
Treatment of inflammatory disease, including hidradenitis suppurativa, using the b14b27 binding antibody.
Subcutaneous administration of the therapeutic composition.
Intravenous administration of the therapeutic composition.
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