	US 12,329,822 B2
	Antimicrobial tailored chitosan
Olivier Jordan, Prangins (CH); Viorica Patrulea, Le Grand-Saconnex (CH); Gerrit Borchard, Arzier (CH); Bee Ha Gan, La Chaux-de-Fonds (CH); and Jean-Louis Reymond, Bulle (CH)
Assigned to UNIVERSITÉ DE GENVE, Geneva (CH)
Appl. No. 17/608,595
Filed by UNIVERSITÉ DE GENÈVE, Geneva (CH)
PCT Filed May 5, 2020, PCT No. PCT/EP2020/062433 § 371(c)(1), (2) Date Nov. 3, 2021, PCT Pub. No. WO2020/225255, PCT Pub. Date Nov. 12, 2020.
Claims priority of application No. 19172726 (EP), filed on May 6, 2019.
Prior Publication US 2022/0193244 A1, Jun. 23, 2022
Int. Cl. A61K 47/00 (2006.01); A61K 47/61 (2017.01); A61K 47/69 (2017.01); A61P 31/04 (2006.01)

CPC A61K 47/61 (2017.08) [A61K 47/6903 (2017.08); A61P 31/04 (2018.01)]

19 Claims

1. A method for treating or decreasing the probability of developing a microbial infection in a patient in need thereof, the method comprising administering to the patient an active bio-conjugate comprising a chitosan derivative coupled to an antimicrobial peptide (AMP) according to the general formula (I):

C—S-L-Cys-AMP (I)

wherein:

C is a chitosan derivative selected from the group consisting of O-carboxymethyl chitosan (CMC), O-carboxymethyl-N,N,N-trimethyl chitosan (TMC), N-(4-N,N-dimethylamino cinnamyl) chitosan (DMCMC), and methylated N-(4-pyridylmethyl) chitosan chloride (MPyMeC);

S is a spacer consisting of a C₁-C₁₂aliphatic carbon chain terminated with one amino group at both ends;

L is a sulfo-crosslinker selected from the group consisting of: 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide (sulfo-SMCC); sulfosuccinimidyl 4-(N-maleimidophenyl)butyrate (sulfo-SMPB); sulfo-N-succinimidyl 4-maleimidobutyrate (sulfo-GMBS); N-(ε-maleimidocaproyloxy) sulfosuccinimide (sulfo-EMCS); N-(κ-maleimidoundecanoyloxy) sulfosuccinimide (sulfo-KMUS); sulfosuccinimidyl 6-[3′-(2-pyridyldithio)propionamido]hexanoate (sulfo-LC-SPDP), and sulfosuccinimidyl (4-iodoacetyl)aminobenzoate (sulfo-SIAB);

Cys is cysteine; and

AMP is a peptide or a peptide dendrimer, with the proviso that said peptide or peptide dendrimer is not a peptide consisting of arginine-glycine-aspartic acid (RGD); and

wherein said active bio-conjugate preserves its antimicrobial activity for at least 1 week when administered to the patient.