JP2014525939A5

JP2014525939A5 -

Info

Publication number: JP2014525939A5
Application number: JP2014527142A
Authority: JP
Filing date: 2012-03-01
Publication date: 2015-04-09

Claims

Formula I:

[Where
R is H or C _1-3 alkyl;
m is 1, 2, 3 or 4;
n is a positive integer selected in the range of 400-550 or 900-945;
L is a C _1-10 alkyl or heteroalkyl linker;
X is -O-, -NH- or -S-; and
IFNλ1 is interferon λ1]
A physiologically active PEG-IFNλ1 complex comprising a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof:

The complex of claim 1, wherein R is H or —CH ₃ , m is 1, L is —C (O) —, and X is —NH—.

The complex according to claim 1 or 2, wherein n is 900 to 945.

formula:

(Wherein INFλ1 is the interferon λ1 of SEQ ID 2;
n is 500 to 550 or 900 to 945)
The composite_body | complex of Claim 1 containing the compound shown by these.

5. The complex according to any one of claims 1 to 4, wherein the complex has a prolonged or prolonged serum half-life and duration compared to IFNλ1.

6. The complex according to any one of claims 1 to 5, wherein the PEG is bound to methionine at the N-terminus of IFNλ1.

A pharmaceutical composition for the treatment of hepatitis B and hepatitis, comprising the complex according to any one of claims 1 to 6, and pharmaceutically acceptable carriers and excipients.

Binding reaction:

(Wherein n is a positive integer selected in the range of 900 to 945 so that the molecular weight of the PEG moiety is about 40 kDa)
(Α-methoxy-ω- (4-nitrophenoxycarbonyl)) polyoxyethylene (PEG-pNC) 40 kDa covalently bound to IFNλ1 by isolating the complex; A method for producing the human recombinant complex according to 1.

Formula I:

[Where
R is H or C _1-3 alkyl;
m is 1, 2, 3 or 4;
n is a positive integer selected in the range of 400-550 or 900-945;
L is a C _1-10 alkyl or heteroalkyl linker;
X is -O-, -NH- or -S-; and
IFNλ1 is interferon λ1]
A method for producing a Peg-IFNλ1 complex containing a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof:
The production method comprising contacting IFNλ1 with a preactivated Peg under conditions sufficient to promote a covalent bond with an amino acid residue of IFNλ1.

A PEG-IFNλ1 complex produced by the production method according to claim 9.

A pharmaceutical composition for inhibiting cancer cell proliferation in a patient, comprising the complex according to any one of claims 1 to 4 and a pharmaceutically acceptable carrier and excipient, The pharmaceutical composition, wherein the body has a prolonged or prolonged serum half-life and duration compared to IFNλ1.

A pharmaceutical composition for treating a proliferative disease in a mammal comprising a therapeutically effective amount of the complex of claim 1 and a pharmaceutically acceptable carrier and excipient.

A therapeutically effective amount of Formula I:

[Where
R is H or C _1-3 alkyl;
m is 1, 2, 3 or 4;
n is a positive integer selected in the range of 500-550 or 900-945;
L is a C _1-10 alkyl or heteroalkyl linker;
X is -O-, -NH- or -S-; and
IFNλ1 is interferon λ1]
Or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier and excipient, and a pharmaceutical composition for treating a patient infected with or at risk of being infected with a virus .

14.R 13 is -CH ₃ , m is 1, L is -C (O)-, X is -NH-, and IFNλ1 is interferon λ1 of SEQ ID 2 The pharmaceutical composition as described.

The pharmaceutical composition according to claim 13 or 14, wherein the viral infection is caused by hepatitis C virus, or progressive cirrhosis is caused by the viral infection.

16. The pharmaceutical composition according to any one of claims 13 to 15, wherein the dose of PEG-IFNλ1 is 0.5 μg / kg to 10.0 μg / kg weekly.

The pharmaceutical composition according to any one of claims 13 to 16, further comprising a nucleoside analog selected from ribavirin or viramidine.

18. The pharmaceutical composition according to claim 17, wherein the dose of ribavirin is 5 mg / kg to 25 mg / kg daily.

The pharmaceutical composition according to any one of claims 13 to 18, wherein the patient is an HCV resistant or refractory patient.

Infected or at risk of infection comprising a therapeutically effective amount of the complex of any one of claims 1 to 4 in combination with a nucleoside analog selected from ribavirin or viramidine An agent for treating a patient.

R is -CH _3, m is 1, L is -C (O) -, X is -NH-, and, IFNramuda1 is an interferon λ1 of SEQ ID 2, in claim 20 The agent described.

The agent according to claim 20 or 21, wherein the viral infection is caused by hepatitis C virus, or progressive cirrhosis is caused by the viral infection.

The agent according to any one of claims 20 to 22, wherein the dose of PEG-IFNλ1 is from 0.5 µg / kg to 10.0 µg / kg weekly.

24. The agent according to any one of claims 20 to 23, wherein the ribavirin dose is 5 mg / kg to 25 mg / kg daily.

The agent according to any one of claims 20 to 24, wherein the patient is an HCV resistant or refractory patient.