Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1997-03-14
1999-03-30
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530324, 514 12, 436 71, 552544, A61K 39385, A61K 3800, C07K 500, C07K 1700
Patent
active
058891536
DESCRIPTION:
BRIEF SUMMARY
This is a national stage application of PCT/JP95/00968 filed May 19, 1995.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel protein or polypeptide modified in bonding with a polyethylene glycol derivative, which is useful as a physiologically active or medically active substance or an intermediate compound therefor, and a method for producing the same. The present invention also relates a reactive polyethylene glycol derivative which is an intermediate compound for the novel protein or polypeptide above-mentioned.
2. Description of the Related Art
Many protein, polyaminoacid and peptide substances having a physiological or medical activity have recently been discovered, permitting expectation of more common application to medical substance. However, these protein and peptide substances have only a short half-life in blood when administered in vivo, giving a sufficient pharmacological effect in few cases. In order to utilize these substances as medical substance, therefore, it is believed to be absolutely necessary to improve behaviors in vivo by some method or other.
It is known that many of physiologically active or medically active substances administered in vivo, particularly into the blood flow, disappear from the biological body through glomerular filtration in the kidney. This glomerular filtration process may be considered a kind of molecular sieve in principle: substances of a molecular weight smaller than that of albumin (about 60,000) which is plasma protein indispensable for a biological body are excreted as a rule. In order to improve in vivo behaviors of protein and peptide medical substance disappearing from the body through glomerular filtration, therefore, it has conventionally been believed to be necessary to increase the molecular weight of medical substance through various chemical modifications.
As a method for improving behaviors in vivo of a protein or peptide medical substance, chemical modification using a water-soluble polymer typically represented by polyethylene glycol (hereinafter abbreviated as "PEG" as required) has popularly been applied. PEG has rather a long history: this substance has been utilized and studied widely in various areas since its synthesis in 1859. In the areas of biochemistry and medicines or medical drugs as well, it is confirmed that PEG exerts no interaction to protein except for physical stereo-hindrances, and no change is observed in protein CD spectrum even in a high-concentration aqueous PEG solution. This suggests that modification with PEG does not destroy the higher-order structure of protein. When, for example, PEG of a molecular weight of 4000 is administered to a dog at a rate of 90 mg/kg/day for a period of a year, no abnormality is observed in body weight or in a pathological or hemological inspection. Administration of PEG to a guinea pig does not cause an allergic symptom. Safety of PEG is thus commonly confirmed. By modifying protein with PEG having the unique properties as described above, it is expected to be possible to develop a protein or peptide medical substance having a long life in vivo, which is hard to be recognized not only by the immune system but also by the reticuloendothelial system.
When modifying a protein or peptide medical substance with PEG, the following advantages are available. When non-denatured protein is insoluble under a physiological pH condition or only partially soluble, it is possible to considerably improve solubility under the physiological pH condition by modifying protein with PEG, and also to reduce immune response of non-denatured protein. For these advantages, many types of protein or peptide medical substance have been modified with PEG to date Y., Yoshimoto, T., Matsushima, A. and Saito, Y. (1986) Trends Biotechno, 1, 4: 68-73!.
PEG derivatives so far used for modifying protein or peptide medical substance include: 2-(alkoxypolyethyleneglycoxy)-4,6-dechlorotriadine Biol. Chem. 252, 3578-3581!; T. P. and Weiner, C. (1980) Int. J. Peptide Protein Res. 16
REFERENCES:
patent: 4179337 (1979-12-01), Davis et al.
patent: 5359030 (1994-10-01), Ekwuribe
patent: 5468478 (1995-11-01), Saifer et al.
Abuchowski et al, Journal of Biology Chemistry, vol. 252, No. 11, 1977.
Sato Syuji
Suzuki Yosuke
Hisamitsu Pharmaceutical Co. Inc.
Marshall S. G.
Tsang Cecilia J.
LandOfFree
Protein or polypeptide, method for producing the same and interm does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Protein or polypeptide, method for producing the same and interm, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Protein or polypeptide, method for producing the same and interm will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1216264