Compositions and Methods For Treating or Preventing Endocrine FGF-Linked Diseases
First Claim
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1. A non-natural soluble construct that prevents or minimizes the binding of at least one selected from the group consisting of FGF receptor (FGFR), FGF19, and FGF21 to β
- -Klotho.
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Abstract
The present invention relates in one aspect to the discovery that β-Klotho is the primary cell-surface receptor for FGF21, with FGFR1c functioning as a catalytic subunit that ultimately mediates intracellular signaling. In one aspect, the invention provides compositions and methods that are useful in treating or preventing endocrine FGF-related diseases or disorders.
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Citations
48 Claims
- 1. A non-natural soluble construct that prevents or minimizes the binding of at least one selected from the group consisting of FGF receptor (FGFR), FGF19, and FGF21 to β
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4. (canceled)
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8. (canceled)
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9. (canceled)
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18. (canceled)
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28. A soluble construct comprising a FGF19 or FGF21 polypeptide that binds to β
- -Klotho more tightly than wild-type FGF19 or FGF21.
- View Dependent Claims (29, 30, 32, 33, 34)
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31. (canceled)
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35. A construct that simultaneously binds to an exposed epitope on FGF21CT and an exposed epitope on β
- -Klotho in a FGF21CT-β
-Klotho complex, thus stabilizing the FGF21CT-β
-Klotho complex. - View Dependent Claims (36, 38)
- -Klotho in a FGF21CT-β
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37. (canceled)
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39. A construct comprising a β
- -Klotho binder fused to at least one selected from the group consisting of a FGF19 polypeptide and FGF21 polypeptide, wherein the construct has at least one selected from the group consisting of FGF19 stimulatory activities and FGF 21 stimulatory activities.
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40. A method of treating endocrine FGF-related diseases or disorders in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a construct that modulates interaction of at least one selected from the group consisting of FGF19 and FGF21 with β
- -Klotho on the surface of a cell of the mammal.
- View Dependent Claims (41, 42, 43, 44, 45, 46, 47)
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48-49. -49. (canceled)
Specification