Langerin+ cell targeting

Patent metadata

Field	Value
Publication number	US-12290535-B2
Application number	US-201916963107-A
Country	US
Kind code	B2
Filing date	Jan 16, 2019
Priority date	Jan 18, 2018
Publication date	May 6, 2025
Grant date	May 6, 2025

Abstract

The present invention relates to the use of a vehicle for specific molecular targeting of Langerin+ cells, wherein the vehicle is capable of specifically binding to a Langerin+ cell, said vehicle comprising (a) at least one carrier and (b) at least one saccharide moiety-based conjugate for a targeted cargo delivery into a Langerin+ cell, as well as pharmaceutical compositions and uses comprising the inventive vehicle.

First claim

The invention claimed is:

1. A method of targeting and delivering a cargo to Langerin + cells, comprising:
contacting a Langerin + cell with a composition comprising:
a vehicle capable of specifically binding to a Langerin + cell, said vehicle comprising (a) at least one carrier and (b) at least one conjugate of the general formula (I)

wherein
(i) R is independently selected from the group consisting of substituted or non-substituted alkyl, alkenyl, alkynyl, cycloalkyl, C 1 -C 8 alkyl cycloalkyl, aryl, C 1 -C 8 alkyl aryl, heteroaryl, C 1 -C 8 alkyl heteroaryl, biaryl and C 1 -C 8 alkyl biaryl,
wherein, when substituted, the substituents are independently selected from the group consisting of
—N(R a )(R b ), —OR a , —SR a , —C(O)R a , —C(O)OR a , —C(O)N(R a )(R b ), —N(R a )C(O)R b , —N(R a )S(O) 2 R b , —OS(O) 2 R a , halogen, —NO 2 , —CN, —NC, —N 3 , —NCO, —OCN, —NCS, —SCN, substituted or non-substituted alkyl, alkenyl, alkynyl, aryl and heteroaryl,
wherein R a and R b are independently selected from the group consisting of hydrogen, substituted or non-substituted C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-6 cycloalkyl, aryl-C 1-5 alkyl, heteroaryl-C 1-5 alkyl, aryl, heteroaryl;
(ii) R′ is independently selected from the group consisting of
—OR a , and —NHS(O) 2 R a ,
wherein R a is defined as above;

(iii) A-D-B-L is a linker group binding the glucose derivative of formula (I) covalently to the carrier or to a part of the carrier; and
a cargo,
thereby delivering the cargo to the Langerin + cell.

2. The method of claim 1 , wherein R is a substituted or non-substituted phenyl.

3. The method of claim 2 , wherein the substituted or non-substituted phenyl is a substituted phenyl that is mono-, di- or trisubstituted, and substituents of the phenyl are independently selected from the group consisting of:
—NH 2 , —OH, —OCH 3 , —C(O)CH 3 , C(O)NH 2 , —C(O)NHCH 3 , —CH 2 OH—NHC(O)CH 3 , —F, —Cl, —Br, —NO 2 , —CN, C 1 -C 4 alkyl, naphtyl and phenyl.

4. The method of claim 3 , wherein said conjugate is a conjugate of one of the following formulas (I-1) to (I-15):

5. The method of claim 1 , wherein said A-D-B-L linker group is a group consisting of a spacer A-D-B and a linker L, and wherein said linker L is a linker of the following general formula (L-1)

wherein
U 1 is a group connected via B with the spacer D, wherein U is selected from the group consisting of, —CH 2 —, —CH═CH—, or —C≡C—;
Z 1 is a moiety binding the linker to the carrier selected from the group consisting of —O—, —S—, —N(R d )—, —C(R d )(R e )—, —R d C═CR e —, —C(O)—, —C(O)O—, —OC(O)—, —C(O)S—, —C(O)N(R d )—, —N(R d )C(O)—, —N(R d )C(O)N(R e )—, —N(R d )C(S)N(R e )—, —N(R d )C(O)O—, —OC(O)N(R d )—, -cyclohexene-, -triazoles-, —NHS(O) 2 —, —S(O) 2 —, —OP(O)(H)O—, or —OP(O)(OH)O—;
wherein R d and R e are independently selected from the group consisting of hydrogen, substituted or non-substituted C 1-32 alkyl, C 2-32 alkenyl, C 3-8 cycloalkyl, aryl, C 1 -C 8 alkyl aryl, heteroaryl, C 1 -C 8 alkyl heteroaryl; and
d1 to d5 is each an integer from 0 to 50, d6 an integer from 1 to 50.

6. The method of claim 5 , wherein said at least one carrier is a soft particle selected from the group consisting of a liposome, a niosome, a micelle, a hydrophilic deformable phospholipid vesicle, and a transferosome and wherein the conjugate is directly bound via Z 1 to one part of the soft particle, wherein said one part of the soft particle is a lipid, a modified lipid, a phospholipid, 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), a membrane lipid, or a modified phosphatidylcholine.

7. The method of claim 6 , wherein the conjugate is bound to one part of a soft particle carrier resulting in the following structure (II):

wherein n is an integer from 0 to 150.

8. The method of claim 1 , wherein said carrier comprises, or is associated to the cargo.

9. The method of claim 8 , wherein said cargo is located within the carrier, is linked to the outside of the carrier, and/or is integrated into a mono- or bilayer structure of the carrier.

10. The method of claim 1 , wherein said cargo is a small molecule, a peptide, a protein, a cytotoxic substance, a nucleic acid, a pigment, a dye, a metal, a radionuclide, a virus, a modified virus, a viral vector, an inoculant, a plasmid, and/or a multicomponent system; or is a pharmaceutically active compound or an immunologically active compound; or wherein said cargo comprises, essentially consists of or consists of (i) a cancer antigen or epitope or comprises a cancer antigen or epitope, (ii) an autoimmune disease antigen or epitope or comprises an autoimmune disease antigen or epitope, (iii) a bacterial antigen or comprises a bacterial antigen or epitope, (iv) a viral antigen or comprises a viral antigen or epitope, (v) a parasitic antigen or comprises a parasitic antigen or epitope, or (vi) an allergen, or an epitope of an allergen, or comprises an allergen or an epitope of an allergen.

11. A pharmaceutical composition comprising:
a vehicle comprising (a) at least one carrier and (b) at least one conjugate of the general formula (I)

wherein
(i) R is independently selected from the group consisting of
substituted or non-substituted alkyl, alkenyl, alkynyl, cycloalkyl, C 1 -C 8 alkyl cycloalkyl, aryl, C 1 -C 8 alkyl aryl, heteroaryl, C 1 -C 8 alkyl heteroaryl, biaryl and C 1 -C 8 alkyl biaryl,
wherein, when substituted, the substituents are independently selected from the group consisting of
—N(R a )(R b ), —OR a , —SR a , —C(O)R a , —C(O)OR a , —C(O)N(R a ) (R b ), —N(R a )C(O)R b , —N(R a )S(O) 2 R b , —OS(O) 2 R a , halogen, —NO 2 , —CN, —NC, —N 3 , —NCO, —OCN, —NCS, —SCN, substituted or non-substituted alkyl, alkenyl, alkynyl, aryl and heteroaryl,
wherein R a and R b are independently selected from the group consisting of hydrogen, substituted or non-substituted C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-6 cycloalkyl, aryl-C 1-5 alkyl, heteroaryl-C 1-5 alkyl, aryl, heteroaryl;
(ii) R′ is independently selected from the group consisting of
—OR a , and —NHS(O) 2 R a ,
wherein R a is defined as above;

(iii) A-D-B-L is a linker group binding the glucose derivative of formula (I) covalently to the carrier or to a part of the carrier;
a cargo,
wherein the carrier comprises or is associated to a pharmaceutically active cargo, and
a pharmaceutically acceptable carrier substance or a pharmaceutical adjuvant.

12. The method of claim 1 , for use in the treatment or prevention of cancer, an autoimmune disease, a bacterial infection, a viral infection, a parasitic infection or a graft-vs. host disease, a local or systemic inflammation, allergy, or for hyposensitization.

13. The pharmaceutical composition of claim

Assignees

• Max Planck Gesellschaft
• Humboldt Univ Zu Berlin

Inventors

• Rademacher Christoph
• Wamhoff Eike-Christian
• Schulze Jessica
• Wawrzinek Robert Carsten Willi
• Seitz Oliver
• Bachem Gunnar

Classifications

• A61K40/46

  Viral antigens · CPC title

• A61K40/42

  Cancer antigens · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title

• A61K40/19

  Dendritic cells · CPC title

• C12N5/0639

  Dendritic cells, e.g. Langherhans cells in the epidermis · CPC title