# US 2021/0275480 A1 · Compositions and methods for the reduction or treatment of fibrosis

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0275480 A1
- Document ID: US20210275480A1
- Status: Published application
- Kind: A1
- Application number: 17/254,089
- Filed: 2019-06-19
- Published: 2021-09-09
- Earliest claimed: 2018-06-20
- Assignees: Axcella Health Inc.
- Applicants: Axcella Health Inc.
- Inventors: Michael Hamill; Raffi Afeyan; Chung-Wei Lee; Harry Luithardt; Luke S. Hamm; Svetlana Marukian; Nadine Daou
- Web page: https://patentgrep.com/patent/US20210275480A1

## CPC

- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61P 11/00: Drugs for disorders of the respiratory system
- A23L 33/175: Amino acids
- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- 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
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)

## Abstract

This disclosure provides compositions and methods for reducing or treating fibrosis, e.g., in a subject having a fibrotic condition or disorder.

## Claims

### Claim 1

A method for reducing fibrosis in a subject, comprising administering to the subject in need thereof an effective amount of a composition comprising:
a) a leucine amino acid entity,
b) an arginine amino acid entity,
c) glutamine amino acid entity; and
d) a N-acetylcysteine (NAC)-entity;
provided that:
the fibrosis is not liver fibrosis,
thereby reducing the fibrosis in the subject.

### Claim 2

A method of treating a fibrotic condition or disorder in a subject in need thereof, comprising administering to the subject an effective amount of a composition comprising:
a) a leucine-amino acid entity
b) an arginine-amino acid entity,
c) glutamine-amino acid entity; and
d) NAC-entity;
provided that:
the fibrotic condition or disorder is not a liver fibrotic condition or disorder,
thereby treating the fibrotic condition or disorder.

### Claim 3

A composition for use in reducing fibrosis in a subject, comprising an effective amount of a composition comprising:
a) a leucine amino acid entity,
b) an arginine amino acid entity,
c) glutamine amino acid entity; and
d) a N-acetylcysteine (NAC)-entity;
provided that:
the fibrosis is not liver fibrosis.

### Claim 4

A composition for use in intreating a fibrotic condition or disorder in a subject in need thereof, comprising an effective amount of a composition comprising:
a) a leucine-amino acid entity
b) an arginine-amino acid entity,
c) glutamine-amino acid entity; and
d) NAC-entity;
provided that:
the fibrotic condition or disorder is not a liver fibrotic condition or disorder.

### Claim 5 (depends on 1, 2, 3, 4)

The method of claim 1 or 2, or composition for use of claim 3 or 4, wherein the fibrotic condition or disorder is chosen from a lung fibrotic condition or disorder, a heart or vasculature fibrotic condition or disorder, a kidney fibrotic condition or disorder, a pancreas fibrotic condition or disorder, a skin fibrotic condition or disorder, a gastrointestinal fibrotic condition or disorder, a bone marrow or hematopoietic tissue fibrotic condition or disorder, a nervous system fibrotic condition or disorder, an eye fibrotic condition or disorder, or a combination thereof.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The method of any of claim 1, 2, or 5, or composition for use of any of claims 3-5, wherein administration of the composition results in a reduction or inhibition of one, two, three, four, five, six, or more (e.g., all) of:
(a) formation or deposition of tissue fibrosis;
(b) the size, cellularity, composition, or cellular content, of a fibrotic lesion;
(c) the collagen of a fibrotic lesion;
(d) the collagen or hydroxyproline content, of a fibrotic lesion;
(e) expression or activity of a fibrogenic protein;
(f) fibrosis associated with an inflammatory response; or
(g) weight loss associated with fibrosis.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The method of any of claim 1, 2, 5, or 6, or composition for use of any of claims 3-6, wherein the method further comprises determining the level of one, two, three, four, five, six, seven, eight, nine, ten, 11, or more (e.g., all) of the following: (a) Col1a1; (b) FGF-21; (c) hydroxyproline content; (d) IL-1β; (e) matrix metalloproteinase (MMP), e.g., MMP-13, MMP-2, MMP-9, MT1-MMP, MMP-3, or MMP-10; (f) N-terminal fragment of type III collagen (proC3); (g) PIIINP (N-Terminal Propeptide of Type III Collagen); (h) α-smooth muscle actin (aSMA); (i) TGF-β; (j) tissue inhibitor of metalloproteinase (TIMP); e.g., TIMP1 or TIMP2; (k) Acta2; or (l) Hsp47.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7)

The method of any of claim 1, 2, or 5-7, or composition for use of any of claims 3-7, wherein the total wt. % of (a)-(d) is greater than the total wt. % of one, two, or three of other amino acid entity components, non-amino acid entity protein components (e.g., whey protein), or non-protein components in the composition (e.g., in dry form).

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The method of any of claim 1, 2, or 5-8, or composition for use of any of claims 3-8, wherein the composition comprises a combination of 18 or fewer amino acid entities.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The method of any of claim 1, 2, or 5-9, or composition for use of any of claims 3-9, wherein the composition does not comprise a peptide of more than 20 amino acid residues in length (e.g., whey protein), or if a peptide of more than 20 amino acid residues in length is present, the peptide is present at less than: 10 weight (wt.) % of the total wt. of protein components or total components the composition (e.g., in dry form).

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The method of any of claim 1, 2, or 5-10, or composition for use of any of claims 3-10, wherein at least one, two, three, or four (e.g., all) of methionine (M), tryptophan (W), valine (V), or cysteine (C) is absent, or if present, are present at less than: 10 wt. % of the composition (e.g., in dry form).

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The method of any of claim 1, 2, or 5-11, or composition for use of any of claims 3-11, wherein at least one, two, three, or more (e.g., all) of (a)-(d) is selected from Table 1.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

The method of any of claim 1, 2, or 5-12, or composition for use of any of claims 3-12, wherein the composition further comprises one or both of (e) an isoleucine amino acid entity or (f) a valine amino acid entity.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

The method of any of claim 1, 2, or 5-13, or composition for use of any of claims 3-13, wherein the wt. ratio of the leucine amino acid entity, the arginine amino acid entity, the glutamine amino acid entity, and the NAC-amino acid entity is 1+/−20%:1.5+/−20%:2+/−20%:0.15+/−20%.

### Claim 15 (depends on 13, 14)

The method of claim 13 or 14, or composition for use of claim 13 or 14, wherein the wt. ratio of the leucine amino acid entity, the isoleucine amino acid entity, the valine amino acid entity, the arginine amino acid entity, the glutamine amino acid entity, and the NAC-amino acid entity is 1+/−20%:0.5+/−20%:0.5+/−20%:1.5+/−20%:2+/−20%:0.15+/−20%.

### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)

The method of any of claim 1, 2, or 5-15, or composition for use of any of claims 3-15, wherein the composition comprises:
a) an leucine amino acid entity chosen from:
i) L-leucine or a salt thereof,
ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine, or
iii) β-hydroxy-β-methylbutyrate (HMB) or a salt thereof;
b) an arginine amino acid entity chosen from:
i) L-arginine or a salt thereof,
ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-arginine,
iii) creatine or a salt thereof, or
iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising creatine;
c) the glutamine amino acid entity is L-glutamine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine; and
d) the NAC entity is NAC or a salt thereof or a dipeptide or salt thereof, comprising NAC.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The method of any of claim 1, 2, or 5-16, or composition for use of any of claims 3-16, wherein the composition further comprises one or both of:
e) L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine; or
f) L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

The method of any of claim 1, 2, or 5-17, or composition for use of any of claims 3-17, wherein the composition comprises:
a) the leucine amino acid entity is L-leucine or a salt thereof;
b) the arginine amino acid entity is L-arginine or a salt thereof;
c) the glutamine amino acid entity is L-glutamine or a salt thereof; and
d) the NAC entity is NAC or a salt thereof.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)

The method of any of claim 1, 2, or 5-18, or composition for use of any of claims 3-18, wherein the composition comprises:
a) the leucine amino acid entity is L-leucine or a salt thereof;
b) the arginine amino acid entity is L-arginine or a salt thereof;
c) the glutamine amino acid entity is L-glutamine or a salt thereof;
d) the NAC entity is NAC or a salt thereof;
e) the isoleucine amino acid entity is L-isoleucine or a salt thereof; and
f) the valine amino acid entity is L-valine or a salt thereof.

### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)

The method of any of claim 1, 2, or 5-19, or composition for use of any of claims 3-19, wherein the composition is formulated with a pharmaceutically acceptable carrier.

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)

The method of any of claim 1, 2, or 5-20, or composition for use of any of claims 3-20, wherein the composition is formulated as a dietary composition.

### Claim 22 (depends on 21)

The method of claim 21, or composition for use of claim 21, wherein the dietary composition is chosen from a medical food, a functional food, or a supplement.