Patent application EP19386020A (EP), filed 2019-03-27
Publication number: EP3714904A1
Title: IMINODIACETIC ACID SUBSTITUTED CYCLODEXTRINS AS POTENTIATORS OF BETA-LACTAM ANTIBIOTICS
Abstract: [0001]    Combinatorial therapeutic regimens based on iminodiacetic acid-substituted cyclodextrins (IDACYDs) are used to treat infections caused by Gram-negative pathogens. IDACYDs fully restore the activity of β-lactam antibiotics against Gram-negative clinical isolates producing the three main MBL enzymes. IDACYDs have a non-toxic profile both in-vitro and in-vivo and high bioavailability and a well-tolerated and potent pharmaceutical profile.
IPC codes: A61K  47/    40            A I
A61P  31/    04            A I
C08B  37/    16            A I
A61K  47/    02            A I
A61K   9/    00            A I
A61K   9/    08            A I
Claims: number: 1
text: A compound of Formula I
number: 2
text: A compound according to claim 1, wherein R is CH<3> and n is 2.
number: 3
text: A compound according to claim 1 or 2, wherein the β-lactam antimicrobial agent is a cephalosporin or a carbapenem.
number: 4
text: A compound according to claim 3, wherein the β-lactam antimicrobial agent is meropenem or imipenem.
number: 5
text: A compound according to any one of the preceding claims, wherein the bacterial infection is selected from blood stream infection, septicemia, sepsis, septic shock, upper respiratory tract infection, lower respiratory tract infection, lung abscess, urinary tract infection, intra-abdominal infection, surgical wound infection, endocarditis, skin and soft tissue infection, thrombophlevitis, osteomyelitis, septic arthritis, endophthalmitis, cystic fibrosis lung infection, brain abscess.
number: 6
text: A compound according to any one of the preceding claims, wherein the compound is administered at a dosage of 5 to 500 mg/kg.
number: 7
text: A compound according to claim 6, wherein the compound is administered at a dosage of 10 to 120 mg/kg.
number: 8
text: A compound according to any one of the preceding claims, wherein the ratio between the administered amount of the β-lactam antimicrobial agent and the compound according to Formula I is from 1/0.3 to 1/15.
number: 9
text: A compound according to claim 8, wherein the ratio between the administered amount of the β-lactam antimicrobial agent and the compound according to Formula I is from 1/0.7 to 1/12.
number: 10
text: A compound according to any one of the preceding claims, wherein the compound is administered via the oral or the parenteral route.
number: 11
text: A compound according to any one of the preceding claims, wherein the compound and the β-lactam antimicrobial agent are administered simultaneously or successively.
number: 12
text: A pharmaceutical composition comprising a compound according to Formula I for use in the treatment of a bacterial infection according to any one of claims 1 to 10.
number: 13
text: A pharmaceutical composition according to claim 11, wherein the composition further comprises a β-lactam antimicrobial agent.
number: 14
text: A pharmaceutical composition according to claim 12, wherein the β-lactam antimicrobial agent is a cephalosporin or a carbapenem, preferably meropenem or imipenem.
number: 15
text: A compound according to Formula I,
Office action: search_report, dated 2020-09-30
Rejection reasons: inventive_step_epc_56
Prior art cited: ref_id: GR1006924B
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ref_type: npl
severity: background
ref_id: GR1006924
ref_type: patent
severity: obviousness
ref_id: WO2018091668
ref_type: patent
severity: background
ref_id: - DAVIDE MAFFEO ET AL, "Novel polycarboxylated EDTA-type cyclodextrins as ligands for lanthanide binding: study of their luminescence, relaxivity properties of Gd(iii) complexes, and PM3 theoretical calculations", ORGANIC & BIOMOLECULAR CHEMISTRY, (20100101), vol. 8, no. 8, doi:10.1039/b924980j, ISSN 1477-0520, page 1910, XP055626401 [I] 15 * scheme 1 * [Y] 1-3,5-15
ref_type: npl
severity: obviousness
ref_id: - JING-ZHEN DENG, "Methicillin/per-6-(4-methoxylbenzyl)-amino-6-deoxy-[beta]-cyclodextrin 1:1 complex and its potentiation in vitro against methicillin-resistant Staphylococcus aureus", THE JOURNAL OF ANTIBIOTICS, GB, (20130529), vol. 66, no. 9, doi:10.1038/ja.2013.51, ISSN 0021-8820, pages 517 - 521, XP055626404 [Y] 1-3,5-15 * abstract *
ref_type: npl
severity: obviousness
ref_id: - DAVIDE MAFFEO ET AL, "Positive effect of natural and negatively charged cyclodextrins on the stabilization of penicillins towards [beta]-lactamase degradation due to inclusion and external guest-host association. An NMR and MS study", ORGANIC & BIOMOLECULAR CHEMISTRY, (20060101), vol. 4, no. 7, doi:10.1039/b517275f, ISSN 1477-0520, page 1297, XP055626400 [Y] 1-3,5-15 * page  1297, column  r, paragraph  l  - page  1298, column  l, line  3 *
ref_type: npl
severity: obviousness
Final disposition: pending (2020-09-30)