Baxalta Gmbh

Takeda Pharmaceutical Company Limited

Baxter International Inc.

Baxter Healthcare Sa

Lipoxen Technologies Incorporated

Nektar Therapeutics

Hanspeter Rottensteiner

Peter Turecek

Juergen Siekmann

Stefan Haider

Friedrich Scheiflinger

Katalin Varadi

Hans-Peter Schwarz

Franziska Horling

Jutta Schreiner

Johannes Lengler

Barbara Plaimauer

Falko-Günter Falkner

Eva-Maria Muchitsch

Alexandra Nathalie Kopic

Alfred Weber

Andreas Ivens

Sanjay Jain

Gregory Gregoriadis

Andrea Engelmaier

Dirk Voelkel

Werner Höllriegl

Werner Hoellriegl

Archana Dwivedi

Oliver Zoechling

Srijit Nath

Robert Pachlinger

Zhihao Fang

Mary J Bossard

Ping Zhang

Sean M Culbertson

Harold Zappe

Falko-Gunter Falkner

Heinz Anderle

Gerald Schrenk

Richard Sheinecker

Jürgen Siekmann

Richard Scheinecker

Silvia Ferrari

Bernadette Gruber

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.

Gene therapy of hemophilia a using viral vectors encoding recombinant FVIII variants with increased expression

Provided herein are anti-Factor IX Padua binding constructs, e.g., antibodies and antigen-binding fragments thereof. Related polypeptides, conjugates and kits are also provided. The inventions may be used in methods of detecting Factor IX Padua in a sample.

Anti-factor IX padua antibodies

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

Subcutaneous administration of ADAMTS13

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.

Viral vectors encoding recombinant FVIII variants with increased expression for gene therapy of hemophilia A

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

Gene therapy of hemophilia B using viral vectors encoding recombinant fix variants with increased expression

The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Nucleophilic catalysts for oxime linkage

Anti-factor IX Padua antibodies

The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBHto form an alkoxyamine linkage.

Blood coagulation protein conjugates

The invention generally relates to methods of testing the effectiveness of a von Willebrand factor (VWF) in treating von Willebrand disease (VWD) in a subject comprising measuring VWF cleavage fragments in a blood sample from the subject before and after treatment. In particular, the invention relates to methods of measuring VWF cleavage fragments, wherein an increase in VWF cleavage fragments after the treatment indicates that endogenous a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in the subject is cleaving the VWF and wherein a decrease or absence of VWF cleavage fragments after the treatment indicates that endogenous ADAMTS13 in the subject is not cleaving the VWF.

Methods for testing effectiveness of a von Willebrand factor used in treating von Willebrand disease (VWD)

Codon-altered polynucleotides encoding Factor IX variants for expression in mammalian cells are provided, including sequences with high nucleotide sequence identity to the CS02, CS03, CS04, CS05, and CS06 sequences. Mammalian gene therapy vectors, such as adeno-associated viral vectors, and methods for treating hemophilia B using those vectors are also provided.

Viral vectors encoding recombinant fix with increased expression for gene therapy of hemophilia B

A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety.

Glycopolysialylation of non-blood coagulation proteins

Growing community of inventors

Vienna, Austria

Hanspeter Rottensteiner