# US 10,500,254 B2 · Method for reducing flu-like symptoms associated with intramuscular administration of interferon using a fast titration escalating dosing regimen

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- Number: US 10,500,254 B2
- Document ID: US10500254B2
- Status: Granted
- Kind: B2
- Application number: 15/695,587
- Filed: 2017-09-05
- Published: 2017-12-21
- Granted: 2019-12-10
- Earliest claimed: 2011-03-15
- Assignees: Biogen MA Inc.
- Applicants: Biogen MA Inc.
- Inventors: Aaron Deykin
- Web page: https://patentgrep.com/patent/US10500254B2

## CPC

- A61K 38/21: Interferons {[IFN]}
- 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 38/215: {IFN-beta}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/565: IFN-beta
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention provides a method for treating multiple sclerosis (MS), and for reducing flu-like symptoms associated with administration of an interferon to a patient with MS. The method involves intramuscularly administering the interferon to the MS patient according to an escalating dosing regimen in weeks 1 to 3, and a full therapeutically effective dose of interferon in week 4. In one embodiment of the invention, the escalating dosing regimen comprises administering one quarter of the therapeutically effective dose in week 1, half of the therapeutically effective dose in week 2, and three-quarters of the therapeutically effective dose in week 3. Also provided are titration packages for enabling compliance with a regimen of changing dosage of an interferon over a period of time.

## Claims

### Claim 1

A method for reducing the severity of flu-like symptoms associated with treating a patient having multiple sclerosis with intramuscularly administered interferon-β-1a, comprising:
providing a kit comprising interferon-β-1a in lyophilized form in a vial, interferon-β-1a in liquid form in a pre-filled syringe, and interferon-β-1a in liquid form in a pre-filled pen;
administering 7.5 micrograms of interferon-β1a to the patient intramuscularly in week one;
administering 15 micrograms of interferon-β1a to the patient intramuscularly in week two;
administering 22.5 micrograms of interferon-β1a to the patient intramuscularly in week three; and
administering 30 micrograms of interferon-β1a to the patient intramuscularly in week four and each week thereafter,
thereby reducing severity of flu-like symptoms experienced by the patient, wherein the severity of flu-like symptoms experienced by the patient is reduced at 4-6 hours and at 12-15 hours after each intramuscular administration of interferon-β-1a throughout an eight week period which includes once a week intramuscular administration of 30 micrograms of interferon-β-1a to the patient in weeks four through eight when compared to the severity of flu-like symptoms at 4-6 hours and at 12-15 hours after each intramuscular administration of interferon-β-1a to a patient having multiple sclerosis according to:
(i) a second schedule comprising once a week intramuscular administration of 30 micrograms of interferon-β-1a to the patient having multiple sclerosis for eight weeks; and
(ii) a third schedule comprising intramuscular administration of 7.5 micrograms of interferon-β-1a to the patient in weeks one and two, intramuscular administration of 15 micrograms of interferon-β-1a to the patient in weeks three and four, intramuscular administration of 22.5 micrograms of interferon-β-1a to the patient in weeks five and six and intramuscular administration of 30 micrograms of interferon-β-1a to the patient in week seven and each week thereafter.

### Claim 2 (depends on 1)

The method of claim 1, wherein fever, muscle aches, chills, sweating, fatigue, headache, and/or malaise in said patient are reduced.

### Claim 3 (depends on 1)

The method of claim 1, further comprising administration of an analgesic or anti-inflammatory drug, or a mixture thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the drug is a steroid.

### Claim 5 (depends on 3)

The method of claim 3, wherein the drug is a non-steroidal anti-inflammatory agent.

### Claim 6 (depends on 3)

The method of claim 3, wherein the drug is acetaminophen.

### Claim 7 (depends on 3)

The method of claim 3, wherein the drug is ibuprofen.

### Claim 8 (depends on 1)

The method of claim 1, wherein the flu-like symptoms are reduced by at least 40% at 4-6 hours post-injection.

### Claim 9 (depends on 1)

The method of claim 1, wherein the flu-like symptoms are reduced by at least 10% at 12-15 hours post-injection.

### Claim 10 (depends on 1)

The method of claim 1, further comprising providing a vial adapter.

### Claim 11 (depends on 1)

The method of claim 1, wherein the pre-filled pen comprises an auto-injector.

### Claim 12 (depends on 1)

The method of claim 1, further comprising a needle stick prevention device.

### Claim 13 (depends on 12)

The method of claim 12, wherein the needle-stick prevention device comprises a needle shield.

### Claim 14 (depends on 13)

The method of claim 13, wherein the shield is activated manually by the patient.

### Claim 15 (depends on 13)

The method of claim 13, wherein the shield is automated.

### Claim 16 (depends on 15)

The method of claim 15, wherein the automated shield is activated by the patient.

### Claim 17 (depends on 15)

The method of claim 15, wherein the needle is automatically shielded without any action by the patient.

### Claim 18 (depends on 15)

The method of claim 15, wherein the needle is shielded without any action by the patient.

### Claim 19 (depends on 1)

The method of claim 1, wherein the kit further comprises a dose-limiting titration device.