Shire Human Genetic Therapies, Inc.

Genzyme Corporation

Takeda Pharmaceutical Company Limited

Eyetech Inc.

Imotik Biosolutions LLC

The Brigham and Women's Hospital, Inc.

Tufts University

Synageva Biopharma Corporation

Translate Bio, Inc.

Pericles Calias

Jing Pan

Zahra Shahrokh

Teresa Leah Wright

Lawrence Charnas

Richard Pfeifer

Gaozhong Zhu

Robert J Miller

Jan Powell

Thomas Mccauley

Kris Lowe

Katherine Taylor

Paul Campolieto

James Christian

Nazila Salamat-Miller

Michael F Concino

Paolo Martini

Muthuraman Meiyappan

Alla Romashko

Farah Natoli

Jennifer Terew

Yuan Jiang

Jamie Tsung

Brian Vernaglia

Angela Norton

Bettina Strack-Logue

Bohong Zhang

Kevin Holmes

Andrea Iskenderian

Dianna Lundberg

Huang Yan

Mary Alessandrini

Michel Morency

Michael W Heartlein

Gary Paul Cook

James R Olson

Arthur O Tzianabos

Andrew B Onderdonk

Sujit Basu

Richard L Fahrner

Frank Derosa

Kathleen M Campbell

Brian Felice

Keethkumar Jain

Rick Fahrner

Brian Pescatore

Nancy Savioli

Mary A Ganley

Marc d'Alarcao

Richard Fahmer

David T Shima

Gregory S Robinson

John P Wing

Lori M Mullin

Lillian M Smith

Ervin Sinani

Richard Fahrner

Yan Huang

The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

CNS delivery of therapeutic agents

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

Methods and compositions for CNS delivery of arylsulfatase A

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Methods and compositions for CNS delivery of heparan N-sulfatase

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Methods and compositions for CNS delivery of iduronate-2-sulfatase

Described herein is an implantable access port device with a catheter compartment which permits lengthening or shortening the catheter in response to changes in tension of the distal catheter. Implantable access port devices are used extensively in the medical field to facilitate the performance of recurrent therapeutic tasks such as repeated drug delivery, drainage, blood sampling, transfusions, or total parental nutrition. In current access port systems, the catheter is rigidly attached to the access port via a connection ring. As such, the system does not provide any flexibility or ability for catheter length adjustments, which can lead to long-term complications such as dislodgement of catheters, migration of catheters, port separation with extravasation, suture disruption, and mechanical failure of the access port system. These catheter-related complications carry serious risks for the patients. The implantable access port system described herein permits self-adjusting catheter length, thereby reducing catheter-related complications.

Access port system for intrathecal drug delivery with self-adjusting catheter length

Access port system with self-adjusting catheter length

Methods and compositions for CNS delivery of heparan n-sulfatase

Among other things, the present invention provides methods and compositions of treating Sanfilippo syndrome type B (Sanfilippo B) by, e.g., intrathecal (IT) administration of a Naglu protein. A suitable Naglu protein can be a recombinant, gene-activated or natural protein. In some embodiments, a suitable Naglu protein is a recombinant Naglu protein. In some embodiments, a recombinant Naglu protein is a fusion protein containing a Naglu domain and a lysosomal targeting moiety. In some embodiments, the lysosomal targeting domain is an IGF-II moiety.

Therapeutic fusion protein comprising an alpha-n-acetylglucosaminidase and a lysosomal targeting moiety

The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease), In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.

Stable formulations for CNS delivery of arylsulfatase A

Treatment of Sanfilippo syndrome type B by intrathecal administration of alpha-n-acetylglucosaminidase

Growing community of inventors

Melrose, MA, United States of America

Pericles Calias