New factor VIII coagulant polypeptides

Claim 2

The active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR3## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at least two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity.

Claim 3

An active coagulant polypeptide of the sequence: ##STR4##

Claim 4

An active coagulant polypeptide of the sequence: ##STR4##

Claim 5

An active factor VIII:C coagulant fragment having a molecular weight in the range of about 79,000-80,000 and having a partial protein amino acid sequence as follows: ##STR5## wherein Z, A, B, C, D and E are amino acids Z, C, D, and E being SER, SER, SER and PHE, respectively, said coagulant fragment being cleavable by thrombin, and capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity.

Claim 6

An active factor VIII:C coagulant fragment having a molecular weight in the range of about 79,000-80,000 and having a partial protein amino acid sequence as follows: ##STR5## wherein Z, A, B, C, D and E are amino acids Z, C, D, and E being SER, SER, SER and PHE, respectively, said coagulant fragment being cleavable by thrombin, and capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity.

Claim 7

An active coagulant polypeptide of the sequence: ##STR6## wherein A and B are as defined in claim 3.

Claim 8

A factor VIII:C coagulant fragment, thrombin-derived from the fragment of claim 4, having a molecular weight in the range of about 71,000-72,000 and having a partial protein amino acid sequence substantially as shown in claim 3.

Claim 9

An active factor VIII:C coagulant polypeptide composition consisting essentially of the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR7## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at last two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the fragment recited in claim 3.

Claim 10

An active factor VIII:C coagulant polypeptide composition consisting essentially of the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR8## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at least two epitopes being capable of binding with monoclonal antibody that neutralizes human factor VIII:C activity and the fragment recited in claim 5.

Claim 11

An active factor VIII:C coagulant polypeptide composition consisting essentially of the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR9## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at least two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and an active factor VIII:C coagulant fragment having a molecular weight in the range of about 79,000-80,000 and having a partial protein amino acid sequence as follows: wherein Z, A, B, C, D and E are amino acids Z, C, D and E being SER, SER, SER and PHE, respectively, said coagulant fragment being cleavable by thrombin, and capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the fragment recited in claim 5. ##STR10##

Claim 12

An active coagulant polypeptide composition consisting essentially of an active coagulant polypeptide of the sequence: ##STR11## and the polypeptide recited in claim 4.

Claim 13

An active coagulant polypeptide composition consisting essentially of the polypeptides recited in claims 2 or 4.

Claim 14

A biological preparation suitable for treatment of hemophilia-related clotting disorders which contains the fragment of claim 3 and an inert carrier therefor.

Claim 15

A biological preparation suitable for treatment of hemophilia-related clotting disorders which contains the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR12## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at least two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the fragment of claim 3 and an inert carrier therefor.

Claim 16

A biological preparation suitable for treatment of hemophilia-related clotting disorders which contains the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR13## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C precursor, said coagulant fragment having at least two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the fragment of claim 5 and an inert carrier therefor.

Claim 17

A biological preparation suitable for treatment of hemophilia-related clotting disorders which contains the active factor VIII:C coagulant fragment having a molecular weight of about 92,000 and having the partial protein amino acid sequence at the N-terminus as follows: ##STR14## wherein X and Y are amino acids ALA and SER, respectively, and terminating at the thrombin cleavage site of a factor VIII:C recursor, said coagulant fragment having at least two epitopes being capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the active factor VIII:C coagulant fragment having a molecular weight in the range of about 79,000-(80,000 and having a partial protein amino acid sequence as follows: ##STR15## wherein Z, A, B, C, D and E are amino acids Z, C, D and E being SER, SER, SER and PHE, respectively, said coagulant fragment dbeing cleavable by thrombin, and capable of binding with a monoclonal antibody that neutralizes human factor VIII:C activity and the fragment of claim 5 and an inert carrier therefor.

Claim 18

A biological preparation as claimed in claim 12 which exhibits specific coagulant activity higher than 1800 units/mg.

Claim 19

A biological preparation as claimed in claim 13 which exhibits specific coagulant activity higher than 1800 units/mg.

Claim 20

A biological preparation as claimed in claim 14 which exhibits specific coagulant activity higher than 1800 units/mg.

Claim 21

The method of treating hemophilia-related clotting disorders, comprising administering to a host in need of such treatment an effective amount of a biological preparation as claimed in claim 10 or 11.

Claim 22

The method of treating hemophilia-related clotting disorders, comprising administering to a host in need of such treatment an effective amount of a biological preparation as claimed in claim 12.

Claim 23

The method of treating hemophilia-related clotting disorders, comprising administering to a host in need of such treatment an effective amount of a biological preparation as claimed in claim 13.

Claim 24

The method of treating hemophilia-related clotting disorders, comprising administering to a host in need of such treatment an effective amount of a biological preparation as claimed in claim 14.