Polyethylene-protein conjugates

• US 5,747,646 A
• Filed: 06/01/1995
• Issued: 05/05/1998
• Est. Priority Date: 03/25/1991
• Status: Expired due to Term

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Rosen, Perry, Hakimi, John, Kilian, Patricia
• Primary Examiner(s): Sayala, Chhaya D.
• Application Number:
  US08/457,058
• Time in Patent Office: 1,069 Days
• Field of Search: 564/23, 530/350, 530/351, 530/403, 530/405, 530/409, 530/408, 424/85.1, 424/85.2, 424/85.4, 424/85.7, 435/188
• US Class Current: 530/351
• 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: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y10S 435/964 including enzyme-ligand conjugate production, e.g. reducing rate of nonproductive linkage
• CPC Class Codes: Y10S 530/816 Attached to the carrier via a bridging agent

Abstract

The present invention is a physiologically active, substantially non-immunogenic water soluble polyethylene glycol protein conjugate having the same utility as the protein which forms the conjugate, without having the same properties of producing an immunogenic response possessed by the protein which forms this conjugate.

Claims

1. A physiologically active protein conjugate of the formula ##STR10## wherein R is lower alkyl;

m and n form any combination of numbers such that the conjugate has at least a portion of the biological activity of the protein which forms the conjugate.

2. The protein conjugate of claim 1 wherein R is CH₃.

3. The protein conjugate of claim 1 wherein the protein is IL-1.

4. The protein conjugate of claim 1 wherein the protein is IL-1ra.

5. The protein conjugate of claim 1 wherein the protein is IFN-alpha.

6. The protein conjugate of claim 1 wherein the protein is IL-2.

7. A physiologically active protein conjugate of the formula ##STR11## wherein R is lower alkyl;

and m and n are selected from any combination of numbers such that the molecular weight of the conjugate excluding the protein is from 300 to 30,000 daltons and the conjugate has at least a portion of the biological activity of the protein which forms the conjugate.

8. The protein conjugate of claim 7 wherein R is CH₃.

9. The protein conjugate of claim 7 wherein the protein is IL-1.

10. The protein conjugate of claim 7 wherein the protein is IL-Ira.

11. The protein conjugate of claim 7 wherein the protein is IFN-alpha.

12. The protein conjugate of claim 7 wherein the protein is IL-2.