Composition comprising coagulation factor VIII formulation, proc

Details Composition comprising coagulation factor VIII formulation, proc Composition comprising coagulation factor VIII formulation, proc

1994-05-20

1998-03-31

Degen, Nancy

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 21, 514834, 530383, 530417, 530830, A61K 3837, A61K 3836, C07K 14745, C07K 14755

Patent

active

057338736

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a novel formulation comprising coagulation factor VIII and a non-ionic surfactant such as block co-polymers, e.g. polyoxamers or polyoxyethylene (20) sorbitan fatty acid esters e.g. polysorbate 20 or polysorbate 80. The composition can also comprise sodium chloride, calcium chloride, L-histidine and/or sugars and/or sugar alcohols.
Haemophilia is an inherited disease which has been known for centuries but it is only within the last three decades that it has been possible to differentiate between the various forms; haemophilia A, haemophilia B and haemophilia C. Haemophilia A is the most frequent form. It affects only males with an incidence of one or two individuals per 10,000 live-born males. The disease is caused by strongly decreased level or absence of biologically active coagulation factor VIII (antihaemophilic factor) which is a protein normally present in plasma. The clinical manifestation of haemophilia A is a strong bleeding tendency and before treatment with factor VIII concentrates was introduced, the mean age of those patients was less than 20 years. Concentrates of factor VIII obtained from plasma have been available for about three decades. This has improved the situation for treatment of haemophilia patients considerably and given them possibility to live a normal life.
Therapeutic factor VIII concentrates have until now been prepared by fractionation of plasma. However, there are now methods available for production of factor VIII in cell culture using recombinant DNA techniques as reported in e.g. J Gitschier et al. Nature 312, 330-37, 1984 and EP 160 457.
Factor VIII concentrates derived from human plasma contain several fragmented fully active factor VIII forms (Andersson et al, Proc. Natl. Acad. Sci. USA, Vol 83,2979-83, May 1986). The smallest active form has a molecular mass of 170 kDa and consists of two chains of 90 kDa and 80 kDa held together by a metal ion bridge. Reference is here made to EP 197 901. Kabi Pharmacia has developed a recombinant factor VIII product which corresponds to the 170 kDa plasma factor VIII form in therapeutic factor VIII concentrates. The truncated recombinant factor VIII molecule is termed r-VIII SQ and is produced by Chinese Hamster Ovary (CHO) cells in a cell culture process in serum free medium at finite passage.
The specific activity of r-VIII SQ could be more than 12,000 IU/mg protein and preferably more than 14,000 IU/mg. Activity of about 15,000 IU/mg has been measured. About 10,000 IU VIII:C per mg protein has earlier been known for our r-VIII SQ.
Recombinant factor VIII SQ is indicated for treatment of classical haemophilia. The dosage is similar to the dosage of the plasma factor VIII concentrates. Due to the high concentration now obtainable only small volumes are needed for injection.
The structure and biochemistry of recombinant factor VIII-products in general have been described by Kaufman Tibtech, Vol 9,1991 and Hematology, 63, 155-65, 1991. The structure and biochemistry of r-VIII SQ have been described in WO 91/09122.
The stability of proteins is generally a problem in pharmaceutical industry. It has often been solved by drying of the protein in different drying processes, such as freeze drying. The protein has thereafter been distributed and stored in dried form. The solution before drying or freeze-drying, the dried material and the reconstituted product should all be stable, so that not too much activity is lost during the drying process, the storage or during handling.
Factor VIII which has been fractionated from plasma is normally sold as lyophilized powder which should be reconstituted with water.
A formulation with a low amount of protein will generally loose activity during purification, sterile manufacturing, in the package and during the administration. This problem is usually solved by the addition of human albumin which reduces the activity loss of the active protein considerably. Human albumin functions as a general stabilizer during purification, sterile manufacturing and freeze-drying (see

REFERENCES:
patent: 4165370 (1979-08-01), Coval
patent: 4597966 (1986-07-01), Zolton et al.
patent: 4783441 (1988-11-01), Thurow
patent: 4877608 (1989-10-01), Lee et al.
patent: 5118794 (1992-06-01), Grangeorge et al.
patent: 5328694 (1994-07-01), Schwinn

Affiliated with

Also associated with

Rating

Composition comprising coagulation factor VIII formulation, proc does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Composition comprising coagulation factor VIII formulation, proc, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition comprising coagulation factor VIII formulation, proc will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-51894