# US 11,433,115 B2 · Glycopeptide antibiotics liquid formulations and methods and uses thereof

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- Number: US 11,433,115 B2
- Document ID: US11433115B2
- Status: Granted
- Kind: B2
- Application number: 17/512,321
- Filed: 2021-10-27
- Published: 2022-05-05
- Granted: 2022-09-06
- Earliest claimed: 2020-10-30
- Assignees: Somerset Therapeutics, LLC
- Applicants: Somerset Therapeutics, LLC
- Inventors: Mandar V. Shah; Ilango Subramanian; Veerappan Subramanian
- Web page: https://patentgrep.com/patent/US11433115B2

## CPC

- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- 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 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61P 31/04: Antibacterial agents
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to formulations and compositions comprising one or more glycopeptide antibodies or a pharmaceutically acceptable salt thereof for parenteral administration. In particular, stable liquid formulations and compositions comprising vancomycin or a pharmaceutically acceptable salt thereof, N-acetyl-methionine and one or more pharmaceutically acceptable excipients. The invention also relates to a process of preparing such compositions and methods and uses thereof.

## Claims

### Claim 1

A method of treating one or more bacterial infections in a subject in need thereof, the method comprising administering to the subject a liquid formulation that comprises: (a) a therapeutically effective amount of a vancomycin antibiotic or a pharmaceutically acceptable salt thereof, (b) N-acetyl-methionine and (c) one or more pharmaceutically acceptable excipients, wherein the liquid formulation does not include N-acetyl D-alanine or polyethylene glycol-400 or both N-acetyl D-alanine and polyethylene glycol-400.

### Claim 2

A method of treating an infectious disease in a subject in need thereof, the method comprising administering to the subject a liquid formulation that comprises: (a) therapeutically effective amount of a vancomycin antibiotic or a pharmaceutically acceptable salt thereof, (b) N-acetyl-methionine, and (c) one or more pharmaceutically acceptable excipients, wherein the liquid formulation does not include N-acetyl D-alanine or polyethylene glycol-400 or both N-acetyl D-alanine and polyethylene glycol-400.

### Claim 3

A method of treating a subject suffering from an infection caused by Gram-positive organisms, the method comprising administering to the subject in need thereof a liquid formulation that comprises: (a) a therapeutically effective amount of a vancomycin antibiotic or a pharmaceutically acceptable salt thereof, (b) N-acetyl-methionine, and (c) one or more pharmaceutically acceptable excipients, wherein the liquid formulation does not include N-acetyl D-alanine or polyethylene glycol-400 or both N-acetyl D-alanine and polyethylene glycol-400.

### Claim 4

A method of treating a subject suffering from an inflammatory disease, the method comprising administering to the subject in need thereof a liquid formulation that comprises: (a) a therapeutically effective amount of a vancomycin antibiotic or a pharmaceutically acceptable salt thereof, (b) N-acetyl-methionine, and (c) one or more pharmaceutically acceptable excipients, wherein the liquid formulation does not include N-acetyl D-alanine or polyethylene glycol-400 or both N-acetyl D-alanine and polyethylene glycol-400.

### Claim 5 (depends on 1)

The method of claim 1, wherein the vancomycin antibiotic or the pharmaceutically acceptable salt thereof is present in an amount of about 0.1% by weight to about 1.000 by weight, and wherein the weight ratio of vancomycin antibiotic or the pharmaceutically acceptable salt thereof to N-acetyl-methionine in the liquid formulation is about 1:3 by weight to about 1:5 by weight, about 1:1 by weight to about 1:100 by weight, about 1:1 by weight to about 1:50 by weight, or about 1:1 by weight to about 1:10 by weight.

### Claim 6 (depends on 1)

The method of claim 1, wherein the vancomycin antibiotic or the pharmaceutically acceptable salt thereof is vancomycin or vancomycin hydrochloride, and the N-acetyl-methionine is N-acetyl-D-methionine, N-acetyl-L-methionine, or a combination thereof.

### Claim 7 (depends on 5)

The method of claim 5, wherein the vancomycin antibiotic or a pharmaceutically acceptable salt thereof is vancomycin or vancomycin hydrochloride, and the N-acetyl-methionine is N-acetyl-D-methionine.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject is mammal or human.

### Claim 9 (depends on 1)

The method of claim 1, wherein the one or more bacterial infections is one or more skin infections, one or more skin structure infections, one or more bone infections, one or more lower respiratory tract infections, or a combination thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administration is parenteral administration.

### Claim 11 (depends on 10)

The method of claim 10, wherein the parenteral administration is intramuscular injection, subcutaneous injection, intravenous injection, or intradermal injection.

### Claim 12 (depends on 2)

The method of claim 2, wherein the infectious disease is caused by Methicillin-resistant Staphylococcus aureus (MRSA), enterococci, vancomycin-resistant enterococci (VRE), coagulase negative staphylococci, or a combination thereof.

### Claim 13 (depends on 3)

The method of claim 3, wherein the Gram-positive organisms is Staphylococcus, Streptococcus spp., Enterococcus spp. or a combination thereof.

### Claim 14 (depends on 3)

The method of claim 3, wherein the infection caused by Gram-positive organisms is a staphylococcal infection.

### Claim 15 (depends on 14)

The method of claim 14, wherein the staphylococcal infection is staphylococcal endocarditis, staphylococcal septicemia, or a combination thereof.

### Claim 16 (depends on 4)

The method of claim 4, wherein the inflammatory disease is enterocolitis, rheumatic fever, endocarditis, colitis, or a combination thereof.

### Claim 17

A process for preparing a liquid composition for parenteral administration, the process comprising: (a) adding a vancomycin antibiotic or pharmaceutically acceptable salt to sterilized water; (b) stirring the solution until the vancomycin antibiotic or pharmaceutically acceptable salt is fully dissolved by visual inspection; (c) adding N-acetyl-D-methionine (NADM) to the solution and stirring until the NADM is fully dissolved by visual inspection; (d) adding sodium chloride and stirring until the components of the solution are fully dissolved by visual inspection; (e) adjusting the pH to about 5.0 using hydrochloric acid, sodium hydroxide, or both; (f) QS with sterilized water suitable for injection to a selected total volume; and (g) stirring for an additional selected amount of time to form a prepared composition.

### Claim 18 (depends on 17)

The process of claim 17, wherein the sterilized water is prepared by one or more of heat sterilization, gaseous sterilization, filtration sterilization, or radiation sterilization.

### Claim 19 (depends on 17)

The process of claim 17, further comprising the step of: (h) aseptically filling the prepared solution into sterile bags.

### Claim 20 (depends on 17)

The process of claim 17, wherein the relative amount of the vancomycin antibiotic or a pharmaceutically acceptable salt thereof in the prepared liquid composition is about 0.1% by weight to about 1.0% by weight.

### Claim 21 (depends on 17)

The process of claim 17, wherein the relative amount of the N-acetyl-methionine in the prepared liquid composition is about 1.5% to about 2.5% by weight.

### Claim 22 (depends on 17)

The process of claim 17, wherein the relative amount of the sodium chloride in the prepared solution is about 0.012% by weight.

### Claim 23 (depends on 17)

The process of claim 17, wherein the vancomycin antibiotic or the pharmaceutically acceptable salt thereof is vancomycin or vancomycin hydrochloride, and the N-acetyl-methionine is N-acetyl-D-methionine, N-acetyl-L-methionine, or a combination thereof.

### Claim 24 (depends on 17)

The process of claim 17, wherein the N-acetyl-methionine is N-acetyl-D-methionine, N-acetyl-L-methionine, or a combination thereof.