# US 10,946,079 B2 · Glycotargeting therapeutics

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- Number: US 10,946,079 B2
- Document ID: US10946079B2
- Status: Granted
- Kind: B2
- Application number: 14/859,292
- Filed: 2015-09-19
- Published: 2016-08-25
- Granted: 2021-03-16
- Earliest claimed: 2014-02-21
- Assignees: Ecole Polytechnique Federale de Lausanne
- Applicants: Ecole Polytechnique Federale de Lausanne (EPFL)
- Inventors: Jeffrey A. Hubbell; David Scott Wilson
- Web page: https://patentgrep.com/patent/US10946079B2

## CPC

- A61K 39/001: {Preparations to induce tolerance to non-self, e.g. prior to transplantation}
- A61K 38/28: Insulins
- A61K 38/38: Albumins
- A61K 39/0002: {Fungal antigens, e.g. Trichophyton, Aspergillus, Candida}
- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 39/35: Allergens
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 47/555: {pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/555: {characterised by a specific combination antigen/adjuvant}
- A61K 2039/577: {tolerising response}
- A61K 2039/60: {characteristics by the carrier linked to the antigen}
- A61K 2039/6093: {Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine}
- A61K 2039/627: {characterised by the linker}
- C07K 2319/01: containing a localisation/targetting motif
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Glycotargeting therapeutics are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent.

## Claims

### Claim 1

A composition comprising a compound of Formula 1:
where:
m is an integer from 1 to 100;
X comprises a self-antigen which induces an unwanted immune response;
Y comprises one or more structures represented by one or more of the following Formulae:
where:
the left bracket “(” indicates the bond between X and Y;
the right or bottom bracket and “)” indicates the bond between Y and Z;
n, where present, is an integer from 1 to 100;
p, where present, is an integer from 2 to 150;
q, where present, is an integer from 1 to 44;
R8, where present, is —CH2— or —CH2—CH2—C(CH3)(CN)—; and
R9, where present, is a direct bond or —C(O)—NH—CH2—CH2—; and
Z comprises one or more liver-targeting moieties, wherein Z is selected from the group consisting of glucose, glucosamine or N-acetylglucosamine.

### Claim 2 (depends on 1)

The composition of claim 1 comprising Z conjugated at its C1, C2 or C6 to Y.

### Claim 3 (depends on 1)

The composition of claim 1 where Y is produced using N-hydroxysuccinamidyl linkers, malaemide linkers, vinylsulfone linkers, pyridyl di-thiol-poly(ethylene glycol) linkers, pyridyl di-thiol linkers, n-nitrophenyl carbonate linkers, NHS-ester linkers, or nitrophenoxy poly(ethylene glycol)ester linkers.

### Claim 4 (depends on 1)

The composition of claim 1 where:
n, where present, is 40 to 80;
p, where present, is 10 to 100;
q, where present, is 3 to 20;
R8, where present, is —CH2—CH2—C(CH3)(CN)—; and
R9, where present, is —C(O)—NH—CH2—CH2-, Z is glucose or N-acetylglucosamine conjugated at its C1.

### Claim 5 (depends on 4)

The composition of claim 4 where Y comprises Formula Ya, Formula Yb, Formula Ym or Formula Yn.

### Claim 6 (depends on 1)

The composition of claim 1 where Y comprises Formula Ya, Formula Yb, Formula Yh, Formula Yi, Formula Yk, Formula Ym or Formula Yn.

### Claim 7 (depends on 6)

The composition of claim 6, wherein X is selected from the group consisting of insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, glucose-6 phosphatase 2, insulinoma-associated protein 2, and insulinoma-associated protein 2β.

### Claim 8 (depends on 1)

The composition of claim 1 where Y comprises Formula Ym.

### Claim 9 (depends on 8)

The composition of claim 8, wherein X is selected from the group consisting of insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, glucose-6 phosphatase 2, insulinoma-associated protein 2, and insulinoma-associated protein 2β.

### Claim 10 (depends on 1)

The composition of claim 1 wherein X comprises a synthetic self-antigen.

### Claim 11 (depends on 1)

The composition of claim 1 where Y comprises Formula Ym, Formula Yn, or Formula Yp.

### Claim 12 (depends on 1)

The composition of claim 1 where Y comprises Formula Yp.

### Claim 13 (depends on 1)

The composition of claim 1 where Y further comprises the following:

### Claim 14 (depends on 1)

The composition of claim 1, wherein X is selected from the group consisting of insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, glucose-6 phosphatase 2, insulinoma-associated protein 2, and insulinoma-associated protein 2β.

### Claim 15 (depends on 1)

The composition of claim 1, wherein X is selected from the group consisting of myelin basic protein, myelin oligodendrocyte glycoprotein, myelin proteolipid protein, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13.

### Claim 16 (depends on 1)

The composition of claim 1, wherein X is transglutaminase.

### Claim 17

A compound comprising a compound of Formula 1:
where:
m is an integer from 1 to 100;
X is selected from the group consisting of insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, glucose-6 phosphatase 2, insulinoma-associated protein 2, and insulinoma-associated protein 20, myelin basic protein, myelin oligodendrocyte glycoprotein, myelin proteolipid protein, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13;
Y comprises one or more
structures represented by one or more of the following Formulae:
where:
the left bracket “(” indicates the bond between X and Y;
the right or bottom bracket and “)” indicates the bond between Y and Z;
n, where present, is an integer from 1 to 100;
p, where present, is an integer from 2 to 150;
q, where present, is an integer from 1 to 44;
R8, where present, is —CH2— or —CH2—CH2—C(CH3)(CN)—; and
R9, where present, is a direct bond or —C(O)—NH—CH2—CH2—; and
Z comprises one or more liver-targeting moieties.

### Claim 18 (depends on 17)

The compound of claim 17, wherein Z is selected from the group consisting of galactose, galactosamine, N-acetylgalactosamine, glucose, glucosamine or N-acetylglucosamine.

### Claim 19 (depends on 17)

The compound of claim 17 where Y comprises one or more of Ym, Yn, and Yp.

### Claim 20 (depends on 17)

The compound of claim 17 where Y comprises Formula Yp.

### Claim 21 (depends on 17)

The compound of claim 17 where Y further comprises the following:

### Claim 22 (depends on 17)

The compound of claim 17 where Y comprises Formula Ym.

### Claim 23

A composition comprising a compound of Formula 1:
where:
m is an integer from 1 to 100;
X comprises a synthetic self-antigen;
Y comprises a structure represented by one or more of the following Formulae:
where:
the left bracket “(” indicates the bond between X and Y;
the right or bottom bracket and “)” indicates the bond between Y and Z;
n is an integer from 1 to 100;
p is an integer from 2 to 150;
q is an integer from 1 to 44;
R8 is —CH2— or —CH2—CH2—C(CH3)(CN)—; and
R9 is a direct bond or —C(O)—NH—CH2—CH2—; and
Z comprises one or more liver-targeting moieties, wherein Z is selected from the group consisting of glucose, glucosamine or N-acetylglucosamine.

### Claim 24 (depends on 23)

The composition of claim 23, wherein the synthetic self-antigen is a of an antigen selected from the group consisting of insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, glucose-6 phosphatase 2, insulinoma-associated protein 2, and insulinoma-associated protein 2β.

### Claim 25 (depends on 24)

The composition of claim 24, for use in treating Type I diabetes.