# US 12,005,061 B2 · Ophthalmic formulations of methotrexate

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- Number: US 12,005,061 B2
- Document ID: US12005061B2
- Status: Granted
- Kind: B2
- Application number: 17/932,453
- Filed: 2022-09-15
- Published: 2023-01-19
- Granted: 2024-06-11
- Earliest claimed: 2019-09-13
- Assignees: Aldeyra Therapeutics, Inc.
- Applicants: Aldeyra Therapeutics, Inc.
- Inventors: Dean Eliott; Pramod Sarpotdar; Stephen Gitu Machatha; Tomasz Stryjewski
- Web page: https://patentgrep.com/patent/US12005061B2

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/0051: {Ocular inserts or implants}
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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)

## Abstract

The present disclosure provides formulations of methotrexate for ocular administration, including intravitreal administration, and use of the formulations for treating proliferative vitreoretinopathy (PVR), intraocular lymphoma (e.g., PVRL), and intraocular inflammation.

## Claims

### Claim 1

A composition suitable for intravitreal administration, comprising methotrexate at a concentration of about 7 mg/mL to about 9 mg/mL; sucrose at a concentration of about 7% w/v to about 12% w/v; and a phosphate buffer, wherein the composition has an administration volume of about 40 μL, about 45 μL, about 50 μL, or about 60 μL.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the methotrexate is at a concentration of about 8 mg/mL.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the sucrose is at a concentration of about 7% w/v to about 9% w/v.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the sucrose is at a concentration of about 7.5% w/v.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the phosphate buffer is sodium phosphate dibasic dihydrate.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the sodium phosphate dibasic dihydrate is at a concentration of about 0.113 mg/mL to 0.142 mg/mL.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the sodium phosphate dibasic dihydrate is at a concentration of about 0.113 mg/mL.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the composition has a pH of about 6 to 8.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the composition is in a pre-filled syringe and has an administration volume of about 50 μL.

### Claim 10 (depends on 1)

A method of treating intraocular lymphoma, comprising administering intravitreally to a subject in need thereof the composition of claim 1.

### Claim 11 (depends on 10)

The method of claim 10, wherein the intraocular lymphoma is primary vitreoretinal lymphoma (PVRL), intraocular lymphoma accompanied by primary cerebral nervous system lymphoma (PCNSL), or diffuse large B-cell lymphoma.

### Claim 12 (depends on 10)

The method of claim 10, wherein the intraocular lymphoma is primary vitreoretinal lymphoma (PVRL).

### Claim 13 (depends on 10)

The method of claim 10, wherein the composition is administered during treatment once a month, once every two weeks, once a week, two times a week, three times a week, or four times a week.

### Claim 14 (depends on 10)

The method of claim 10, wherein treatment includes an induction phase, and optionally a consolidation phase, and/or optionally a maintenance phase.

### Claim 15 (depends on 14)

The method of claim 14, wherein the induction phase is administration of the composition two times a week, or up to four times a week.

### Claim 16 (depends on 14)

The method of claim 14, wherein the consolidation phase, when present, comprises administration once a week or once every two weeks.

### Claim 17 (depends on 14)

The method of claim 14, wherein the maintenance phase, when present, comprises administration once every two weeks or once every month.

### Claim 18 (depends on 14)

The method of claim 14, wherein the method includes the consolidation phase immediately following the initiation phase and the consolidation phase comprises administration once a week or once every two weeks, and wherein the method further includes the maintenance phase immediately following the consolidation phase and the maintenance phase comprises administration once every two weeks or once every month.

### Claim 19 (depends on 10)

The method of claim 10, wherein the volume of composition administered is about 50 μL.

### Claim 20 (depends on 1)

A method of treating primary vitreoretinal lymphoma (PVRL), comprising administering intravitreally to a subject in need thereof the composition of claim 1; wherein the composition comprises methotrexate at a concentration of about 8 mg/mL; the composition comprises sucrose at a concentration of about 7.5% w/v; and the composition is at a pH of about 6 to about 8.

### Claim 21 (depends on 20)

The method of claim 20, wherein the buffer comprises sodium phosphate dibasic dihydrate at a concentration of about 0.113 mg/mL to about 0.142 mg/mL and the pH of the composition is 7.4±0.2.

### Claim 22 (depends on 20)

The method of claim 20, wherein the composition has an osmolarity of 250 mOsm/L to 350 mOsm/L.

### Claim 23 (depends on 20)

The method of claim 20, wherein the volume of composition administered is about 50 μL.

### Claim 24 (depends on 20)

The method of claim 20, wherein the composition is administered during treatment once every 4 weeks, once every two weeks, once a week, two times a week, three times a week, or four times a week.

### Claim 25 (depends on 20)

The method of claim 20, wherein the treatment includes an induction phase, and optionally a consolidation phase, and/or optionally a maintenance phase.

### Claim 26 (depends on 25)

The method of claim 25, wherein the induction phase is administration of the composition two times a week, or up to four times a week.

### Claim 27 (depends on 26)

The method of claim 26, wherein the method includes the consolidation phase immediately following the initiation phase and the consolidation phase comprises administration once a week or once every two weeks, and wherein the method further includes the maintenance phase immediately following the consolidation phase and the maintenance phase comprises administration once every two weeks or once every month.