The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.

The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.

The present invention relates to compositions and methods of use of anti-ADAMTS13 autoantibodies and fragments thereof. In one aspect, the invention includes a composition comprising an isolated anti-ADAMTS13 autoantibody or fragment thereof. In other aspects, methods are described for generating an in vivo model of thrombotic thrombocytopenic purpura (TTP) comprising introducing at least one anti-ADAMTS13 autoantibody or fragment thereof into a model organism and identifying an anti-autoimmune reagent for treating TTP.

Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange/hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration/diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

This invention relates to ADAMTS13 variants and methods of administering ADAMTS13 variants to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction.

Provided herein are methods and compositions for treating a coronavirus disease, and particularly its complications, in a subject infected with a pathogenic coronavirus, such as a subject infected with a SARS-CoV-2 or suffering from one or more signs or symptoms of COVID-19. The composition comprises a therapeutically effective amount of an isolated or recombinant disintegrin and metalloproteinase with a thrombospondin type 1 motif (ADAMTS13) protein. The present disclosure further relates to methods for diagnosing a coagulopathy in subject infected with a coronavirus disease, particularly SARS-CoV-2, or suffering from one or more signs or symptoms of COVID-19. The method comprises testing for elevated levels of VWF, depressed levels of ADAMTS13, and the presence of UHMW VWF multimers. These factors, in combination, indicate the presence of a coagulopathy.

Methods are provided for determining the presence of antibodies in blood or a blood product, using immobilized self-assembled polypeptides comprising an ectodomain and being recognized by the antibodies. The self-assembled polypeptide comprises at least a first chimeric polypeptide. In the methods the functionality and active conformation of the immobilized and self-assembled polypeptides is preserved. Processes for making the immobilized self-assembled polypeptides are also provided.

The invention includes a chimeric autoantibody receptor (CAAR) comprising an extracellular domain comprising an ADAMTS13 autoantigen or fragment thereof, compositions comprising the CAAR, nucleic acids encoding the CAAR, vectors comprising a nucleic acid encoding the CAAR, and recombinant cells comprising the CAAR.

The present invention provides culture mediums that are useful for the expression of ADAMTS proteins, such as ADAMTS13. Methods for the expression and purification of ADAMTS proteins are also provided. In some embodiments, the mediums and methods of the invention are useful for the expression of ADAMTS proteins having high specific activities. Also provided are ADAMTS, e.g., ADAMTS13, protein compositions with high specific activities, which are expressed and purified according to the methods provided herein.

Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange/hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration/diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.