The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

The subject of this invention is point mutants of human proteins constituting the complement system's C3 and C5 convertases, where the mutation are as follows: For the factor B: —D279G, F286L, K323E, Y363A; D279G_F286L_K323E_Y363A—quadruple mutant; For the C2 protein: —C261A, Q.263G, Y347A, L348A; T442Q, double mutants C261A_Q263G and Y347A_Q263G, triple mutant Y347A_Q263G_T442Q The subject of this invention is the method of enhancing the activity of the anti-cancer antibodies, which includes the addition of mutants defined above. The subject of this invention is the pharmaceutical composition, which includes the therapeutically effective number of mutants defined above. The subject of this invention is the use of mutants defined above to enhance the cytotoxic activity of anti-cancer antibodies in therapy and in the treatment of neoplastic diseases.

The present invention features inter alia nucleic acid molecules which encode polypeptides comprising a single chain Fc region and the polypeptides they encode. The Fc moieties of these constructs are linked by a cleavable scFc linker which is adjacent to at least one enzymatic cleavage site, e.g., an intracellular processing site. The resulting processed molecules comprise two polypeptide chains and substantially lack the extraneous amino acid sequence found in single chain Fc linker molecule. Methods of making and using these dimeric molecules are also described.

The subject of this invention is point mutants of human proteins constituting the complement system's C3 and C5 convertases, where the mutation are as follows: For the factor B:—D279G, F286L, K323E, Y363A; D279G_F286L_K323E_Y363A-quadruple mutant; For the C2 protein:—C261A, Q.263G, Y347A, L348A; T442Q, double mutants C261A_Q263G and Y347A_Q263G, triple mutant Y347A_Q263G_T442Q The subject of this invention is the method of enhancing the activity of the anti-cancer antibodies, which includes the addition of mutants defined above. The subject of this invention is the pharmaceutical composition, which includes the therapeutically effective number of mutants defined above. The subject of this invention is the use of mutants defined above to enhance the cytotoxic activity of anti-cancer antibodies in therapy and in the treatment of neoplastic diseases.

The invention relates to commercially viable methods for producing biologically active vitamin K dependent protein, particularly Factor IX. Factor IX is produced at a level of at least about 15 mg/L and is at least 25% biologically active. The method relies upon co-expression of one or more of paired basic amino acid converting enzyme (PACE), vitamin K dependent epoxide reductase (VKOR) and vitamin K dependent γ-glutamyl carboxylase (VKGC) at a preferred ratio so that the vitamin K dependent protein is efficiently produced and processed by a recombinant cell.

Chimeric clotting factors which localize the therapeutic to sites of coagulation (e.g., by being targeted to platelets or being activatable at sites of coagulation), have reduced clearance rates, have improved manufacturability, have reduced thrombogenicity, have enhanced activity, or have more than one of these characteristics are described as are methods for making chimeric clotting factors and methods for improving hemostasis using these clotting factors.

The present invention features inter alia nucleic acid molecules which encode polypeptides comprising a single chain Fc region and the polypeptides they encode. The Fc moieties of these constructs are linked by a cleavable scFc linker which is adjacent to at least one enzymatic cleavage site, e.g., an intracellular processing site. The resulting processed molecules comprise two polypeptide chains and substantially lack the extraneous amino acid sequence found in single chain Fc linker molecule. Methods of making and using these dimeric molecules are also described.

Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.