Novartis Ag

Mereo Biopharma 3 Limited

Shou-Ih Hu

David Jonathan Glass

Josef Prassler

Beate Diefenbach-Streiber

Christine Halleux

Michaela Kniessel

Michaela Kneissel

The present invention is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The Klotho fusion polypeptides of the invention include at least a Klotho protein or an active fragment thereof. In one embodiment, the fusion polypeptide comprises a Klotho polypeptide, a FGF (such as FGF23) and (optionally) a modified Fc fragment. The Fc fragment can, for example, have decreased binding to Fc-gamma-receptor and increased serum half-life. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23) and a modified Fc fragment.

Methods and compositions using a Klotho-FGF23 fusion polypeptide

The present invention is directed to fusion polypeptides comprising a Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.

Methods and compositions using Klotho-FGF fusion polypeptides

The present disclosure is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The fusion polypeptides of the disclosure include FGF23 or an active fragment thereof. In one embodiment, the fusion polypeptide comprises (a) a polypeptide comprising fibroblast growth factor 23 (FGF23), or a functionally active variant or derivative thereof, wherein FGF23 has a mutation at one or more of the positions Q156, C206 and C244; and (b) either a modified Fe fragment having decreased affinity for Fc-gamma-receptor and/or increased serum half-life, or a polypeptide comprising at least one extracellular subdomain of a Klotho protein, or a functionally active variant or derivative thereof; and, optionally (c) a linker. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23), or a functionally active variant or derivative thereof; and a modified Fe fragment, or a functionally active variant or derivative thereof. In various embodiments of the fusion polypeptides, FGF23 has mutations which decrease aggregation and protease-mediated cleavage.

Methods and compositions using FGF23 variant polypeptides with reduced aggregation and cleavage

Methods and compositions using Kloto-FGF23 fusion polypeptides

The present invention relates to antibodies against sclerostin and compositions and methods of use for said antibodies to treat a pathological disorder that is mediated by sclerostin or disease related to bone abnormalities such as osteoporosis.

Polynucleotides encoding antibodies against sclerostin and uses therefor

The present invention is directed to fusion polypeptides comprising Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.

Methods and compositions using FGF23 fusion polypeptides

Compositions and methods for use for antibodies against sclerostin

The present invention relates to antibodies against sclerostin and compositions and methods of use for said antibodies to treat disease related to bone abnormalities such as osteoporosis. An embodiment of the invention herein provides an antibody or a functional protein comprising an antigen-binding portion of said antibody for a target in sclerostin polypeptide, characterized in that the antibody or functional protein specifically binds to sclerostin polypeptide and can increase at least one of bone formation, bone mineral density, bone mineral content, bone mass, bone quality and bone strength in a mammal.

The subject invention is related to human MMP-8alt genes and gene products and their differential expression when comparing a patient with a disease state to a control. A further aspect of the invention concerns compounds which antagonize the biological activity of MMP-8alt protein and methods for identifying these compounds. Another aspect of the present invention concerns pharmaceutical compositions comprising such compounds for the treatment of arthritis, cancer, and disease caused by cellular apoptosis including but not limited to Parkinson's disease, Alzheimer's disease and Huntington's chorea.

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New Providence, NJ, United States of America

Shou-Ih Hu