# US 10,307,457 B1 · Pristinamycin compositions, LpxC compositions, their improvements, and combinations thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,457 B1 - Document ID: US10307457B1 - Status: Granted - Kind: B1 - Application number: 15/877,338 - Filed: 2018-01-22 - Granted: 2019-06-04 - Earliest claimed: 2014-03-14 - Assignees: Fleurir Abx LLC - Applicants: Fleurir ABX LLC - Inventors: John Lee Pace - Web page: https://patentgrep.com/patent/US10307457B1 ## CPC - A61K 38/06: Tripeptides - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/0073: {Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M)} - A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol - A61K 31/4164: 1,3-Diazoles - A61K 31/4196: 1,2,4-Triazoles - A61K 31/424: condensed with heterocyclic ring systems, e.g. clavulanic acid - A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine - A61K 38/05: Dipeptides - A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} - A61K 38/15: Depsipeptides; Derivatives thereof - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - 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) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract New improved formulations are described, comprising at least a first composition, with or without a second composition, in which the first composition is an inhibitor of lipid A deacetylase resulting in permeabilization of an outer membrane of a susceptible microorganism to which it is provided to. The second composition is a streptogramin. Said first composition, alone or in combination, may be used to improve and/or treat a wide variety of bacterial infections, providing better efficacy, bioavailability, and/or pharmacokinetics, as compared with at least other inhibitors of lipid A deacetylase. When provided to a susceptible microorganism as a combination of the first composition and the second composition, the combination may be provided independently or may be provided together (co-combined in a same formulation, or in different formulations). Such combinations may also be provided via any route(s), and in any pharmaceutically acceptable form known, available, and/or suitable for use, such as to a subject in need thereof. ## Claims ### Claim 1 A composition effective in permeabilizing an outer membrane of a susceptible microorganism, the susceptible microorganism being one or more of a Gram positive bacteria and a Gram negative bacteria and having a UDP-3-O-(acyl)-N-acetyl glucosamine deacetylase enzyme involved in lipid A biosynthesis, the composition comprising a compound of formula I: wherein R1 includes any one or more of the group consisting of: and wherein R3 includes any one of the group comprising: ### Claim 2 (depends on 1) The composition of claim 1, wherein the composition is an antibacterial for use against the susceptible microorganism, the susceptible microorganism being a microorganism associated with one or more of a respiratory tract infection, a gastrointestinal infection, a systemic infection, a skin infection, and a genitourinary tract infection. ### Claim 3 (depends on 1) The composition of claim 1, wherein the composition is provided in a pharmaceutically acceptable form for an IV formulation. ### Claim 4 (depends on 1) The composition of claim 1, wherein the composition further comprises a suitable amount of a pharmaceutically acceptable excipient. ### Claim 5 (depends on 1) The composition of claim 1, wherein the composition is provided in a pharmaceutically acceptable form for an inhalation formulation. ### Claim 6 (depends on 1) The composition of claim 1, wherein the composition is provided in a formulation, the composition in a form for combining with at least one additional agent, the at least one additional agent comprising at least one of the group consisting of antibacterial agent, antiviral agent, antifungal agent, anti-parasitic agent, and anti-infective agent. ### Claim 7 (depends on 1) The composition of claim 1, wherein the composition is provided in a pharmaceutically acceptable form for an oral formulation. ### Claim 8 (depends on 1) The composition of claim 1, wherein the susceptible microorganism is one or more of Staphylococcus aureus, multi-drug resistant Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Chlamydia pneumoniae, Mycoplasma pneumoniae, Acinetobacter baumanii, Burkoholderia spp., Pseudomonas aeruginosa, Coxiella burnetii, Enterobacteriaceae including extended spectrum beta-lactamase producing Escherichia coli and extended spectrum carbapenemase producing Escherichia coli, Klebsiella pneumonia, Francisella tularensis, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophila, and Yersinia pestis. ### Claim 9 (depends on 1) The composition of claim 1, wherein the composition is an inhibitor of the UDP-3-O-(acyl)-N-acetyl glucosamine deacetylase enzyme in the susceptible microorganism, and when provided in a pharmaceutically acceptable form, and administered with a streptogramin to a subject having the susceptible microorganism, the composition provides an antimicrobial effect against the susceptible microorganism some time after administration of composition. ### Claim 10 (depends on 9) The composition of claim 9, wherein the streptogramin is a combination of a Group A compound comprising a polyunsaturated cyclic macrolactone, and a Group B compound comprising a cyclic hexadepsipeptide. ### Claim 11 (depends on 10) The composition of claim 10, wherein the streptogramin is pristinamycin. ### Claim 12 (depends on 9) The composition of claim 9, wherein the composition is provided with an effective amount of an excipient for any one of oral administration, inhalation administration, and IV administration. ### Claim 13 (depends on 1) The composition of claim 1 further comprising a phosphodiesterase inhibitor for providing the composition in a form for inhalation. ### Claim 14 (depends on 1) The composition of claim 1, wherein the composition is a first composition and is provided with an effective amount of a second composition, the second composition comprising a streptogramin, and wherein the first composition is further provided with an effective amount of an excipient. ### Claim 15 (depends on 14) The composition of claim 14, wherein the streptogramin is a combination of a Group A compound comprising a polyunsaturated cyclic macrolactone, and a Group B compound comprising a cyclic hexadepsipeptide. ### Claim 16 (depends on 14) The composition of claim 14, wherein the streptogramin is pristinamycin. ### Claim 17 (depends on 1) The composition of claim 1, wherein the composition is provided as an antibacterial agent for use against the susceptible microorganisms in a subject having the susceptible microorganism. ### Claim 18 A pharmaceutically acceptable formulation comprising at least a combination of a first composition and a second composition, the first composition comprising a streptogramin, and the second composition comprising a compound of formula I: wherein R1 includes any one or more of the group consisting of: and wherein R3 includes any one of the group comprising: ### Claim 19 (depends on 18) The pharmaceutically acceptable formulation-of claim 18, wherein the pharmaceutically acceptable formulation further comprises a suitable amount of one or more pharmaceutically acceptable excipients, and wherein the streptogramin is a combination of a Group A compound comprising a polyunsaturated cyclic macrolactone, and a Group B compound comprising a cyclic hexadepsipeptide. ### Claim 20 (depends on 18) The pharmaceutically acceptable formulation-of claim 18, wherein the pharmaceutically acceptable formulation further comprises a suitable amount of one or more pharmaceutically acceptable excipients, and wherein the streptogramin is pristinamycin.