A serum albumin variant, or functional fragment thereof, comprising, one or more amino acid substitutions selected from (i) glycine, isoleucine, lysine, methionine, phenylalanine, tryptophan, tyrosine, valine and leucine substituted for glutamine at position (522); (ii) valine substituted for alanine at position (552); and (iii) alanine, glutamic acid, histidine, serine, lysine and arginine substituted for glycine at position (572).

Provided herein are methods for managing host immune responses to improve therapeutic outcomes in adeno-associated virus (AAV)-mediated gene therapy. Such methods may include administering a recombinant adeno-associated vims (rAAV) to a subject following administration of a CD 19 inhibitor, e.g., an anti-CD 19 antibody. The methods described herein can facilitate improved transgene expression, help overcome pre-existing NAbs, and/or permit redosing with the same or substantially similar rAAV or transgene.

Provided herein are methods for managing host immune responses to improve therapeutic outcomes in adeno-associated virus (AAV)-mediated gene therapy. Such methods may include administering a recombinant adeno-associated vims (rAAV) to a subject following administration of a CD 19 inhibitor, e.g., an anti-CD 19 antibody. The methods described herein can facilitate improved transgene expression, help overcome pre-existing NAbs, and/or permit redosing with the same or substantially similar rAAV or transgene.

Disclosed is a method for preparing a composition comprising factor VIII (FVIII) and von Willebrand factor (vWF), wherein the content of the von Willebrand factor (vWF) can be controlled by mixing the factor VIII (FVIII) with the von Willebrand factor (vWF) at an appropriate ratio after separately purifying the factor VIII (FVIII) and the von Willebrand factor (vWF) from plasma in a single process. The method can prepare and purify a composition comprising factor VIII (FVIII) and a varying content of von Willebrand factor (vWF) without increasing the amount of impurities other than the von Willebrand factor (vWF) compared to a method of purifying factor VIII (FVIII) separately, without significantly increasing the processing time (within 3 hours) compared to a method of purifying factor VIII (FVIII), and without changing the yield of factor VIII (FVIII).

Disclosed is a method for preparing a composition comprising factor VIII (FVIII) and von Willebrand factor (vWF), wherein the content of the von Willebrand factor (vWF) can be controlled by mixing the factor VIII (FVIII) with the von Willebrand factor (vWF) at an appropriate ratio after separately purifying the factor VIII (FVIII) and the von Willebrand factor (vWF) from plasma in a single process. The method can prepare and purify a composition comprising factor VIII (FVIII) and a varying content of von Willebrand factor (vWF) without increasing the amount of impurities other than the von Willebrand factor (vWF) compared to a method of purifying factor VIII (FVIII) separately, without significantly increasing the processing time (within 3 hours) compared to a method of purifying factor VIII (FVIII), and without changing the yield of factor VIII (FVIII).

Methods and materials for effective dosages of AAV gene therapy for the treatment and prophylaxis of hemophilia A.

Methods and materials for effective dosages of AAV gene therapy for the treatment and prophylaxis of hemophilia A.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

A highly glycosylated human blood-clotting factor VIII (FVIII) fusion protein, and a manufacturing method and application of same. The fusion protein comprises, from the N-terminus to the C-terminus, a human (FVIII), a flexible peptide connector, at least one rigid unit of a human chorionic gonadotropin β-subunit carboxyl terminal peptide, and a half-life extending portion (preferentially selected from a human IgG Fc variant). The fusion protein has a similar level of biological activity as a recombinant (FVIII) and an extended in vivo half-life, thereby improving pharmacokinetics and drug efficacy.