Bioverativ Therapeutics Inc.

Lonza Sales Ag

Codiak Biosciences, Inc.

Other

John D Kulman

Douglas E Williams

Ke Xu

Robert T Peters

Tongyao Liu

Ekta Seth Chhabra

Damian J Houde

Nikki Ross

Pei-yun Chang

Sonya Haupt

Russell E McConnell

Rane A Harrison

Kevin P Dooley

Haiyan Jiang

Sriram Sathyanarayanan

Shelly Martin

Yu Zhou

Nuruddeen D Lewis

Volker Schellenberger

Leonid A Gaydukov

Joshua A Silverman

Willem P Stemmer

Deping Wang

Chia-wei Wang

Nathan C Geething

Benjamin Spink

Sheng Ding

Baisong Mei

Chia-Wei Wang

Garabet G Toby

Young Jun Choi

Arjan Van Der Flier

Marisol Acosta

Russell E Mcconnell

Fatbardha Varfaj

Lily Zhu

Anxhela Kole

Ayman Ismail

David R Light

Zhiqian Liu

Pei-Yun Chang

Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Exosomes for immuno-oncology and anti-inflammatory therapy

The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Preparation of therapeutic exosomes using membrane proteins

Described herein are novel rapid and reliable methods of detection of extracellular vesicles and quantifying extracellular vesicle concentrations and absolute number from various sources, including raw cell harvest. The methods described herein comprise detection of intrinsic fluorescence of extracellular vesicles in biological samples. Extracellular vesicles analyzed by the methods of this application have a stereotypical elution profile distinct from known contaminants. The methods described herein are a significant improvement over the state of the art and fulfills an unmet need in the field of extracellular vesicle manufacturing and quality control.

Methods of measuring exosomes using intrinsic fluorescence

Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.

Recombinant factor VIII proteins

The present invention provides a chimeric protein comprising a first polypeptide which comprises a FVIII protein and a first Ig constant region or a portion thereof and a second polypeptide which comprises a VWF protein comprising the D' domain and D3 domain of VWF, a XTEN sequence having less than 288 amino acids in length, and a second Ig constant region or a portion thereof, wherein the first polypeptide and the second polypeptide are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the chimeric proteins.

Factor VIII chimeric proteins and uses thereof

The present invention provides a chimeric protein comprising a VWF protein comprising the D' domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof

The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.

Purification of chimeric FVIII molecules

The present invention provides Factor IX (FIX) fusion proteins comprising at least one heterologous moiety, such as an XTEN. The present invention further discloses methods of making and using the FIX fusion proteins.

Factor IX fusion proteins and methods of making and using same

The present invention provides chimeric proteins comprising a Factor VIII (FVIII) polypeptide and XTEN polypeptides. The FVIII polypeptide can have a reduced affinity for von Willebrand Factor (VWF). XTEN polypeptides of appropriate sizes are inserted into the FVIII polypeptide at particular locations in order to extend the half-life of the FVIII polypeptide. The invention also includes nucleotides, vectors, host cells, and methods of using the chimeric proteins, e.g., to treat bleeding diseases and disorders.

Factor VIII-XTEN fusions and uses thereof

The present invention relates to compositions comprising factor VIII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of factor VIII-related diseases, disorders, and conditions.

Factor VIII compositions and methods of making and using same

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Belmont, MA, United States of America

John D Kulman