Methods of treating gastrointestinal inflammatory disease
Inventors
Harwin, Peter Evan • Kiselak, Tomas • Shaheen, Hussam Hisham • ZHU, Eric Franklin
Assignees
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Publication Number
US-12404334-B2
Publication Date
2025-09-02
Expiration Date
Abstract
Provided herein are variant α4β7 integrin antibodies and methods of use.
Core Innovation
The invention relates to treatment of a gastrointestinal inflammatory disease in a subject in need thereof by administering a citrate-free pharmaceutical composition comprising a long acting anti- targeting molecule or long acting 7 integrin binding antibodies. The composition is an injectable liquid formulation with a high concentration of long acting anti- targeting molecule, comprising from about 150 mg/ml to about 200 mg/ml or at least about 180 mg/ml.
The long acting anti- targeting molecule is defined by a heavy chain consisting of an amino acid sequence according to SEQ ID NO: 1 and a light chain consisting of an amino acid sequence according to SEQ ID NO: 3. The method includes subcutaneous administration of the citrate-free pharmaceutical composition in a multi-dose regimen, with doses at least eight weeks apart and in representative regimens at least twelve weeks apart, and may be preceded by one or more additional doses.
The disclosure further describes induction versus maintenance regimens and associated serum pharmacokinetic targets, including maintenance trough concentrations (Ctrough) and average serum concentrations over defined windows. It also describes a longer serum half-life in cynomolgus monkeys, reduced cytotoxic and immune activation-related effects, and limited induction of T-cell activation/cytokines in connection with Fc-effector function considerations.
Claims Coverage
The document provides two independent claims. The main inventive features are the citrate-free formulation, the concentration constraints, the multi-dose interval constraint, and the anti- molecule or 7 targeting molecule defined by heavy and light chain sequences (SEQ ID NO: 1 and SEQ ID NO: 3).
Citrate-free subcutaneous anti- targeting composition for gastrointestinal inflammatory disease
Administering subcutaneously to the subject in need thereof a citrate-free pharmaceutical composition comprising at least about 180 mg/ml of a long acting anti- targeting molecule comprising a heavy chain according to SEQ ID NO: 1 and a light chain according to SEQ ID NO: 3.
Multi-dose citrate-free anti- treatment regimen with heavy and light chain sequences
Administering to the subject in need thereof two or more doses of a citrate-free pharmaceutical composition comprising from about 150 mg/ml to about 200 mg/ml of a long acting anti- targeting molecule, wherein the two or more doses are administered at least eight weeks apart, and wherein the long acting anti- targeting molecule comprises a heavy chain according to SEQ ID NO: 1 and a light chain according to SEQ ID NO: 3.
The independent claims cover treatment of a gastrointestinal inflammatory disease using a long acting anti- targeting molecule or 7 targeting molecule defined by heavy and light chain sequences (SEQ ID NO: 1 and SEQ ID NO: 3) formulated as a citrate-free pharmaceutical composition. The claims distinguish a multi-dose approach at least eight weeks apart with 150 200 mg/ml concentration and a subcutaneous approach with at least about 180 mg/ml concentration.
Stated Advantages
Long acting treatment profile supported by longer serum half-life in cynomolgus monkeys.
Achieves specified pharmacokinetic targets, including maintenance Ctrough and higher serum concentrations over defined windows.
Reduced safety/functional effects are described, including limited induction of T-cell activation/cytokines and reduced CDC/ADCC.
Documented Applications
Treating a gastrointestinal inflammatory disease in a subject in need thereof.
Applying the method to inflammatory bowel disease, including Crohns disease.
Applying the method to inflammatory bowel disease, including ulcerative colitis.
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