Branched polyalkylene glycols

• US 7,691,367 B2
• Filed: 12/22/2000
• Issued: 04/06/2010
• Est. Priority Date: 12/24/1999
• Status: Expired due to Fees

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Inventors: Kuwabara, Takashi, Sakurai, Noriko, Mukai, Mayumi, Ohta, So, Suzuwa, Toshiyuki, Yamashita, Kinya, Miki, Ichiro, Yamasaki, Motoo, Murakami, Tatsuya
• Primary Examiner(s): Witherspoon; Sikarl A
• Assistant Examiner(s): Nwaonicha; Chukwuma O
• Application Number:
  US10/168,956
• Publication Number:
  US 20030219404A1
• Time in Patent Office: 3,392 Days
• Field of Search: 568/852, 424/85.4, 424/85.3, 435/183, 514/12, 530/399, 548/960
• US Class Current: 424/85.4
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 47/6889 Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: 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
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08L 2203/02 for biomedical use

Abstract

The present invention provides branched polyalkylene glycols useful as a chemically modifying agent for physiologically active polypeptides, wherein two single-chain polyalkylene glycols are linked to a group having a cyclic structure other than a plane structure, and wherein a group having reactivity with an amino acid side chain, an N-terminal amino group or a C-terminal carboxyl group in a polypeptide or a group convertible into the group having reactivity is linked to the group having a structure other than a plane structure.

Claims

1. A branched polyalkylene glycol represented by formula (I):

(R¹-M_n-X¹)₂L(X²—

X³—

R²)_q 

 

(I)

wherein L represents a nonplanar cyclic group represented by formula (II) or (III);

2. The branched polyalkylene glycol according to claim 1, wherein u is 4.

3. The branched polyalkylene glycol according to claim 2, wherein q is 1.

4. The branched polyalkylene glycol according to claim 1, wherein the molecular weight is 500 to 1,000,000.

10. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 2,000 or more.

11. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 5,000 or more.

12. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 10,000 or more.

13. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 20,000 or more.

14. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 2,000 or more.

15. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of the moiety of M_n is 5,000 or more.

16. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 10,000 or more.

17. The branched polyalkylene glycol according to claim 1, wherein the average molecular weight of M_n is 20,000 or more.

5. A compound, comprising a branched polyalkylene glycol represented by formula (I):

(R¹-M_n-X¹)₂L(X²—

X³—

R²)_q 

 

(I)

wherein L represents a nonplanar cyclic group represented by formula (II) or (III);

6. The compound according to claim 5, wherein the physiologically active polypeptide is an enzyme, a cytokine or a hormone.

7. A pharmaceutical composition comprising the compound according to claim 5 and a pharmaceutically acceptable excipient.

8. The pharmaceutical composition according to claim 7, wherein the physiologically active polypeptide is an interferon.

9. A method for treating multiple scleroses which comprises administering, to a patient in need thereof, a compound comprising a branched polyalkylene glycol represented by formula (I):

(R¹-M_n-X¹)₂L(X²—

X³—

R²)_q 

 

(I)

wherein L represents a nonplanar cyclic group represented by formula (II) or (III);