# US 7,745,421 B2 · Methods and compositions for treating diseases and disorders associated with Siglec-8 expressing cells

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- Number: US 7,745,421 B2
- Document ID: US7745421B2
- Status: Granted
- Kind: B2
- Application number: 11/597,336
- Filed: 2005-05-24
- Published: 2008-06-12
- Granted: 2010-06-29
- Earliest claimed: 2004-05-25
- Assignees: The Johns Hopkins University
- Inventors: Bruce S. Bochner; Ronald L. Schnaar
- Web page: https://patentgrep.com/patent/US7745421B2

## CPC

- C07H 3/06: Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 35/02: specific for leukemia
- C07H 5/04: to nitrogen
- C07H 5/06: Aminosugars
- C07H 7/00: Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
- C07H 7/02: Acyclic radicals
- C07H 11/00: Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof (halo-sugars C07H5/02; thio-, seleno-, or telluro-sugars C07H5/08)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides therapeutic methods and compositions for the prevention and treatment of Siglec-8 associated diseases and disorders such as asthma and allergic reactions. In particular, the invention provides methods and compositions for the prevention and treatment of diseases and disorders associated with Siglec-8 expressing cells in humans, as well as other animals, through the administration of one or more novel, carbohydrate-based compounds.

## Claims

### Claim 1

The compound NeuAcα2-3(6-O-sulfo)Galβ1-4(Fucα1-3)GlcNAcβ-O—(CH2)3—NH—CO(CH2)5NH-M, where M is a hydrogen or amide linkage; or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising any of the compounds of claim 1 and a pharmaceutically acceptable solvent.

### Claim 3

A method for treating a subject suffering from or susceptible to a disease or disorder involving activation of Siglec-8 on Siglec-8 expressing cells comprising administering to the subject an effective amount of one or more compounds represented by the formula:
in which
A is a sialic acid residue or an analog thereof;
B is a galactose residue or an analog thereof, and is substituted with an anionic moiety at the 6-position;
C is an N-acetylglucosamine residue or an analog thereof;
D is a fucose residue or an analog thereof; and
R together with the O atom to which it is attached, is an aglycone;
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The method of claim 3 wherein the subject is suffering from or susceptible to asthma, allergic diseases, atopic dermatitis, hypereosinophilic syndromes, mastocytosis, leukemias, lymphomas, urticaria, Churg-Strauss syndrome, eosinophilic esophagitis, eosinophilic gastroenteritis, anaphylaxis, and nasal polyposis.

### Claim 5 (depends on 3)

The method of claim 3 wherein the subject is a human.

### Claim 6 (depends on 1)

A pharmaceutical composition kit comprising i) one or more compounds of claim 1; and ii) directions for use of the one or more compounds of claim 1 to treat a disease or disorder involving activation of Siglec-8 on Siglec-8 expressing cells.

### Claim 7

A compound represented by the formula:
in which
A is a sialic acid residue or an analog thereof;
B is a galactose residue or an analog thereof, and is substituted with an anionic moiety at the 6-position;
C is an N-acetylglucosamine residue or an analog thereof;
D is a fucose residue or an analog thereof; and
wherein R, together with the O atom to which it is attached is an aglycone represented by the structure —O—(CH2)3—NH—CO(CH2)5NH-M, where M is a hydrogen or an amide linkage;
or a pharmaceutically acceptable salt thereof.

### Claim 8

A compound represented by the formula:
wherein R together with the O atom to which it is attached is an aglycone represented by the structure —O—(CH2)3—NH—CO(CH2)5NH-M, where M is a hydrogen or an amide linkage; and
Y is independently for each occurrence an anionic group selected from the group consisting of carboxylate, sulfate, sulfonate, phosphate, phosphonate and hydroxamate;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound of claim 1, wherein the compound binds to Siglec-8 protein with an affinity of less than 10 μM.

### Claim 10 (depends on 7)

The compound of claim 7, wherein the compound binds to Siglec-8 protein with an affinity of less than 10 μM.

### Claim 11 (depends on 8)

The compound of claim 8, wherein the compound binds to Siglec-8 protein with an affinity of less than 10 μM.

### Claim 12 (depends on 1, 7)

A pharmaceutical composition comprising any of the compounds of claim 1, 7, or 8; and a pharmaceutically acceptable solvent.

### Claim 13 (depends on 1, 7)

A method for treating a subject suffering from or susceptible to a disease or disorder involving activation of Siglec-8 on Siglec-8 expressing cells comprising administering to the subject an effective amount of one or more compounds of claim 1, 7, or 8.

### Claim 14 (depends on 13)

The method of claim 13 wherein the subject is suffering from or susceptible to asthma, allergic diseases, atopic dermatitis, hypereosinophilic syndromes, mastocytosis, leukemias, lymphomas, urticaria, Churg-Strauss syndrome, eosinophilic esophagitis, eosinophilic gastroenteritis, anaphylaxis, and nasal polyposis.

### Claim 15 (depends on 13)

The method of claim 13 wherein the subject is a human.

### Claim 16 (depends on 1, 7)

A pharmaceutical composition kit comprising
i) one or more compounds of claim 1, 7, or 8; and
ii) directions for use of the one or more compounds of claim 1, 7, or 8 to treat a disease or disorder involving activation of Siglec-8 on Siglec-8 expressing cells.