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US 2026/0062494 A1Published application
Antigen-binding molecules with increased penetration into and retention in brain, and methods for use thereof
OwnerYuki NOGUCHI, Naoka HIRONIWA +1inventors
InventorsYuki NOGUCHI, Naoka HIRONIWA, Kazuki SATO
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Abstract
The present invention relates to antigen-binding molecules with increased penetration into and/or retention in brain; methods for use thereof; and methods for producing or screening thereof.
Claims21
An antigen-binding molecule comprising a first antigen-binding domain and a second antigen-binding domain,
- wherein the first antigen-binding domain specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain, and
- the second antigen-binding domain specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain extracellular matrix (ECM) protein or a brain ECM polysaccharide.
A method for increasing the concentration of an antigen-binding molecule in the brain of a subject in need thereof, the method comprising:
- (a) providing a first antigen-binding molecule comprising:
- (a1) a first antigen-binding domain that specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain;
- or
- (a2) a second antigen-binding domain that specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain ECM protein or a brain ECM polysaccharide;
- (b) introducing
- in the case of (a1), to the first antigen-binding molecule at least one second antigen-binding domain that specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain ECM protein or a brain ECM polysaccharide, thereby obtaining a second antigen-binding molecule;
- or
- in the case of (a2), to the first antigen-binding molecule at least one first antigen-binding domain that specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain, thereby obtaining a second antigen-binding molecule;
- such that the concentration of said second antigen-binding molecule in the brain of said subject is increased upon administration to said subject as compared to the first antigen-binding molecule.
6 more elements
A method for increasing exposure of an antigen-binding molecule in the brain of a subject in need thereof, the method comprising:
- (a) providing a first antigen-binding molecule comprising:
- (a1) a first antigen-binding domain that specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain;
- or
- (a2) a second antigen-binding domain that specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain ECM protein or a brain ECM polysaccharide;
- (b) introducing
- in the case of (a1), to the first antigen-binding molecule at least one second antigen-binding domain that specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain ECM protein or a brain ECM polysaccharide, thereby obtaining a second antigen-binding molecule;
- or
- in the case of (a2), to the first antigen-binding molecule at least one first antigen-binding domain that specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain, thereby obtaining a second antigen-binding molecule;
- such that the exposure of said second antigen-binding molecule in the brain of said subject is increased upon administration to said subject as compared to the first antigen-binding molecule.
6 more elements
A method for the retention of an antigen-binding molecule in the brain of a subject in need thereof, the method comprising:
- (a) providing a first antigen-binding molecule comprising a first antigen-binding domain that specifically binds a first target that facilitates transfer of the antigen-binding molecule into a mammalian brain;
- (b) introducing to the first antigen-binding molecule at least one second antigen-binding domain that specifically binds a second target wherein the second target (i) is expressed on the cell membrane of brain cells, or (ii) is a brain ECM protein or a brain ECM polysaccharide, thereby obtaining a second antigen-binding molecule,
- such that the retention of said second antigen-binding molecule in the brain of said subject is increased upon administration to said subject as compared to the first antigen-binding molecule.
Dependencies are inferred from the claim text.