Introduction -- Targeting glucocerebrosidase to macrophages for effective treatment of patients with Gaucher disease: setting the paradigm of a "fit for purpose" approach to enzyme replacement therapy -- Challenges of Enzyme Replacement Therapy: Poor tissue distribution in lysosomal diseases using Pompe disease as a model -- Muscle targeting -- Blood-Brain Barrier Targeting of Therapeutic Lysosomal Enzymes -- Novel Methods for Addressing Immunogenicity in Therapeutic Enzymes -- Structure of monoclonal antibodies -- Prediction of aggregation in vivo by studies of therapeutic proteins in human plasma -- Effect of Hydrolytic Degradation on the In Vivo Properties of Monoclonal Antibodies -- Oxidation of proteins in the in-vivo environment: what we know; what we need to study and potential mitigation strategies -- Molecular assessment: balancing affinity, PK and manufacturability -- Perspectives on engineering biobetter therapeutic proteins with greater stability in inflammatory environments -- Antibody-like molecules designed for superior targeting and pharmacokinetics -- Alternative protein scaffolds as novel biotherapeutics -- Current strategies for pharmacokinetic optimization -- Biosimilar and Biobetter Scenarios for the US and Europe: What Should We Expect? -- Regulatory considerations for approval of biobetter products.

Over the last few decades, biopharmaceuticals have transformed many areas of healthcare and have given hope and extended the lives of many patients. Curative treatments, however, remain elusive in most cases. This book describes strategies to develop improved versions of biopharmaceuticals (“biobetters”) to bridge the gap between existing therapies and curative therapies. With an aim to stimulate research and development in a wide array of therapeutic areas, diverse topics are covered, including the following: tissue specific targeting of enzyme replacement therapies; the development of novel protein structures with the potential to improve upon critical attributes of current monoclonal antibodies; the modification of current monoclonal antibody designs to improve their in vivo stability; and finally, the economic and regulatory considerations for the development of biobetters.