# US 11,993,797 B2 · Thrombin solution and methods of use thereof

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

- Number: US 11,993,797 B2
- Document ID: US11993797B2
- Status: Granted
- Kind: B2
- Application number: 17/546,447
- Filed: 2021-12-09
- Published: 2022-03-31
- Granted: 2024-05-28
- Earliest claimed: 2012-12-03
- Assignees: Omrix Biopharmaceuticals Ltd.
- Applicants: Omrix Biopharmaceuticals Ltd.
- Inventors: Roberto Meidler; Oleg Belyaev; Liliana Bar; Israel Nur
- Web page: https://patentgrep.com/patent/US11993797B2

## CPC

- C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 38/4833: {Thrombin (3.4.21.5)}
- 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 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- C12N 9/6429: {Thrombin (3.4.21.5)}
- C12Y 304/21005: Thrombin (3.4.21.5)
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- C12Y: ENZYMES
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided are methods for lyophilization of an aqueous thrombin solution, thrombin solutions for use in such lyophilization methods, and solid thrombin compositions produced by such methods.

## Claims

### Claim 1

A solid composition consisting of a powder, said powder being obtained by powdering a monolithic block, the composition comprising: thrombin; a single saccharide or sugar alcohol, said single saccharide or sugar alcohol comprising one member selected from the group consisting of sucrose, maltose, and mannitol, at a concentration of about 19.5% to about 78%, by total weight of the solid composition; sodium acetate at a concentration of about 1% to about 20%, by total weight of the solid composition; albumin at a concentration of about 2% to about 53%, by total weight of the solid composition; calcium chloride at a concentration of about 2.5% to about 31%, by total weight of the solid composition; and sodium chloride at a concentration of about 6% to about 45%, by total weight of the solid composition, wherein the solid composition has a water content of less than 3%, by total weight of the solid composition.

### Claim 2 (depends on 1)

The solid composition of claim 1, wherein said single saccharide or sugar alcohol comprises mannitol.

### Claim 3 (depends on 1)

The solid composition of claim 1, comprising about 22% to about 66% mannitol, by total weight of the solid composition.

### Claim 4 (depends on 1)

The solid composition of claim 1, comprising about 1.5% to about 10% sodium acetate, by total weight of the solid composition.

### Claim 5 (depends on 1)

The solid composition of claim 1, comprising about 2.5% to about 43% albumin, by total weight of the solid composition.

### Claim 6 (depends on 1)

The solid composition of claim 1, comprising about 4% to about 17% calcium chloride, by total weight of the solid composition.

### Claim 7 (depends on 1)

The solid composition of claim 1, comprising about 9.5% to about 25% sodium chloride, by total weight of the solid composition.

### Claim 8 (depends on 1)

The solid composition of claim 1, comprising mannitol at a concentration of about 22% to about 66%, by total weight of the solid composition; sodium acetate at a concentration of about 1.5% to about 10% by total weight of the solid composition; albumin at a concentration of about 2.5% to about 43%, by total weight of the solid composition; calcium chloride at a concentration of about 4% to about 17%, by total weight of the solid composition; and sodium chloride at a concentration of about 9.5% to about 25%, by total weight of the solid composition.

### Claim 9 (depends on 1)

The solid composition of claim 1, having thrombin activity recovery of at least 95%.

### Claim 10 (depends on 1)

The solid composition of claim 1, having a water content of not more than about 1.5%, by total weight of the solid composition, and a thrombin activity recovery of at least 98%.

### Claim 11 (depends on 1)

The solid composition of claim 1, being stable for at least 2 years under non-freezing storage conditions.

### Claim 12 (depends on 1)

The solid composition of claim 1, being stable for at least 2 years at room temperature.