Compositions and Methods For Reducing Immune Intolerance
AssigneeLapix Therapeutics, Inc.
InventorsAnas Fathallah, Abdulraouf Ramadan
Life of this patent
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Abstract
Provided herein are compositions comprising amino acids, e.g., hydroxyamino acids, thioamino acids, or pharmaceutically acceptable salts thereof, that can be used to reduce immune intolerance in a subject. The compositions can be used, for example, to treat autoimmune disorders or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy.
Claims54
A method of immunotolerizing a subject in need thereof to an antigen, comprising administering to the subject a therapeutically effective amount of a composition comprising an amino acid, or a pharmaceutically acceptable salt thereof, wherein:
- (i) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted with -L(R)n;
- L is absent, or a (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- each R is independently a (C6-C15)aryl or (C5-C15)heteroaryl optionally substituted with one or more substituents independently selected from halo, (C1-C3)alkoxy, (C1-C3)haloalkoxy, (C1-C3)alkyl or (C1-C3)haloalkyl;
- and
- n is 1 or 2;
- or
- (ii) the amino acid is tyrosine;
- and
- the hydroxyl of the tyrosine is substituted with (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- or
- the hydroxyl of the tyrosine is replaced with —H;
- or
- (iii) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted or replaced with —PO3H2, —SO3H or —NO2;
- or
- (iv) the amino acid is a naturally-occurring hydroxyamino acid or thioamino acid, provided the amino acid is not O-phospho-L-serine.
A method of inhibiting or reducing an antigen-specific antibody titer in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising an amino acid, or a pharmaceutically acceptable salt thereof, wherein:
- (i) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted with -L(R)n;
- L is absent, or a (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- each R is independently a (C6-C15)aryl or (C5-C15)heteroaryl optionally substituted with one or more substituents independently selected from halo, (C1-C3)alkoxy, (C1-C3)haloalkoxy, (C1-C3)alkyl or (C1-C3)haloalkyl;
- and
- n is 1 or 2;
- or
- (ii) the amino acid is tyrosine;
- and
- the hydroxyl of the tyrosine is substituted with (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- or
- the hydroxyl of the tyrosine is replaced with —H;
- or
- (iii) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted or replaced with —PO3H2, —SO3H or —NO2;
- or
- (iv) the amino acid is a naturally-occurring hydroxyamino acid or naturally-occurring thioamino acid,
- provided the amino acid is not O-phospho-L-serine.
A method of inducing a population of regulatory T-cells or increasing the activity or level of tolerogenic T-cells in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising an amino acid, or a pharmaceutically acceptable salt thereof, wherein:
- (i) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted with -L(R)n;
- L is absent, or a (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- each R is independently a (C6-C15)aryl or (C5-C15)heteroaryl optionally substituted with one or more substituents independently selected from halo, (C1-C3)alkoxy, (C1-C3)haloalkoxy, (C1-C3)alkyl or (C1-C3)haloalkyl;
- and
- n is 1 or 2;
- or
- (ii) the amino acid is tyrosine;
- and
- the hydroxyl of the tyrosine is substituted with (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- or
- the hydroxyl of the tyrosine is replaced with —H;
- or
- (iii) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted or replaced with —PO3H2, —SO3H or —NO2;
- or
- (iv) the amino acid is a naturally-occurring hydroxyamino acid or naturally-occurring thioamino acid,
- provided the amino acid is not O-phospho-L-serine.
A method of treating an autoimmune disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising an amino acid, or a pharmaceutically acceptable salt thereof, wherein:
- (i) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted with -L(R)n;
- L is absent, or a (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- each R is independently a (C6-C15)aryl or (C5-C15)heteroaryl optionally substituted with one or more substituents independently selected from halo, (C1-C3)alkoxy, (C1-C3)haloalkoxy, (C1-C3)alkyl or (C1-C3)haloalkyl;
- and
- n is 1 or 2;
- or
- (ii) the amino acid is tyrosine;
- and
- the hydroxyl of the tyrosine is substituted with (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- or
- the hydroxyl of the tyrosine is replaced with —H;
- or
- (iii) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted or replaced with —PO3H2, —SO3H or —NO2;
- or
- (iv) the amino acid is a naturally-occurring hydroxyamino acid or naturally-occurring thioamino acid,
- provided the amino acid is not O-phospho-L-serine.
A method of treating a disease, disorder or condition in a subject in need thereof with an antigenic therapy, comprising administering to the subject the antigenic therapy and, in an amount sufficient to immunotolerize the subject to the antigenic therapy, a composition comprising an amino acid, or a pharmaceutically acceptable salt thereof, wherein:
- (i) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted with -L(R)n;
- L is absent, or a (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- each R is independently a (C6-C15)aryl or (C5-C15)heteroaryl optionally substituted with one or more substituents independently selected from halo, (C1-C3)alkoxy, (C1-C3)haloalkoxy, (C1-C3)alkyl or (C1-C3)haloalkyl;
- and
- n is 1 or 2;
- or
- (ii) the amino acid is tyrosine;
- and
- the hydroxyl of the tyrosine is substituted with (C1-C8)alkyl or (C2-C8)alkenyl optionally substituted with one or more fluoro;
- or
- the hydroxyl of the tyrosine is replaced with —H;
- or
- (iii) the amino acid is a hydroxyamino acid or thioamino acid;
- and
- the hydroxyl of the hydroxyamino acid or the thiol of the thioamino acid, respectively, is substituted or replaced with —PO3H2, —SO3H or —NO2;
- or
- (iv) the amino acid is a naturally-occurring hydroxyamino acid or naturally-occurring thioamino acid,
- provided the amino acid is not O-phospho-L-serine.
MPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine 18:0 (DSPC).
Dependencies are inferred from the claim text.