IMPROVED FIBRONECTIN-BASED BINDING MOLECULES AND USES THEREOF
First Claim
1. A fibronectin type III (Fn3)-based binding molecule comprising an Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a specific target.
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Accused Products
Abstract
The invention provides fibronectin type III (Fn3)-based binding molecules that bind to a specific target antigen. The invention further provides bispecific Fn3-based binding molecules that bind to two or more targets simultaneously. The Fn3-based binding molecules of the invention can also be linked together to form multispecific Fn3-based binding molecules, and/or can be conjugated to a non-Fn3 moiety, such as, Human Serum Albumin (HSA), for improved half life and stability. The invention also provides methods for generating, screening and using Fn3-based binding molecules in a variety of therapeutic and diagnostic applications.
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Citations
48 Claims
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1. A fibronectin type III (Fn3)-based binding molecule comprising an Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a specific target.
- View Dependent Claims (2, 3, 4, 5, 6, 42, 43)
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7. A Fn3-based binding molecule comprising a first Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a first target, and wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of a second Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
1 to create a non-Fn3 binding sequence which binds to a second target. - View Dependent Claims (8, 9, 44)
- 1 to create a non-Fn3 binding sequence which binds to a first target, and wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of a second Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
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10. A Fn3-based binding molecule comprising a first Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD Or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a half-life extender, and wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of a second Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
1 to create a non-Fn3 binding sequence which binds to a second target. - View Dependent Claims (11, 12, 45)
- 1 to create a non-Fn3 binding sequence which binds to a half-life extender, and wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of a second Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
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13. A bispecific Fn3-based binding molecule comprising an Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a first target, and wherein at least one amino acid in one or more of the top BC, DE or FG loop regions of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
1 to create a non-Fn3 binding sequence which binds to a second target - View Dependent Claims (14, 15, 16, 17)
- 1 to create a non-Fn3 binding sequence which binds to a first target, and wherein at least one amino acid in one or more of the top BC, DE or FG loop regions of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
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18. A bispecific Fn3-based binding molecule comprising an Fn3 domain, wherein at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a half-life extender, and wherein at least one amino acid in one or more of the top BC, DE or FG loop regions of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
1 to create a non-Fn3 binding sequence which binds to a second target. - View Dependent Claims (19, 20, 46)
- 1 to create a non-Fn3 binding sequence which binds to a half-life extender, and wherein at least one amino acid in one or more of the top BC, DE or FG loop regions of the Fn3 domain are altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
- 21. A multispecific Fn3-based binding molecule comprising two or more Fn3-based binding molecules.
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25. The Fn3-based binding molecule which binds to a non-Fn3 moiety that increases the half-life of the Fn3-based binding molecule.
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26. A multispecific Fn3-based binding molecule comprising two or more monospecific Fn3-based binding molecules, wherein at least one monospecific Fn3-based binding molecule comprises at least one amino acid in one or more of the bottom AB, CD or EF loop regions or C-terminal of the Fn3 domain that is altered compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 to create a non-Fn3 binding sequence which binds to a first target; and
a second monospecific Fn3-based binding molecule having at least one amino acid in one or more of the top BC, DE or FG loop regions of the Fn3 domain that is altered compared to the wild-type Fn3 domain comprising SEQ ID NO;
1 to create a non-Fn3 binding sequence which binds to a second target, wherein the first and second monospecific Fn3-based binding molecules are connected by a linker sequence. - View Dependent Claims (27, 28, 29, 30, 31, 48)
- 1 to create a non-Fn3 binding sequence which binds to a first target; and
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32. An Fn3-based binding molecule comprising SEQ ID NO:
- 119 (clone
87)
- 119 (clone
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33. An Fn3-based binding molecule comprising SEQ ID NO:
- 120 (clone
89)
- 120 (clone
- 34. A conjugate comprising an Fn3-based binding molecule linked to one or more non-Fn3 moieties.
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37. The Fn3-based binding molecule or conjugate which further comprises at least one modified amino acid residue compared to the wild-type Fn3 domain comprising SEQ ID NO:
- 1 for attaching a functional moiety.
- View Dependent Claims (38)
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39. The Fn3-based binding molecule or conjugate comprising beta strands from two or more different Fn3 domains.
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40. A composition comprising the Fn3-based binding molecule or conjugate and a carrier.
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41. A method of treating a subject for a disease selected from the group consisting of an autoimmune disease, a cancer, and an infectious disease, the method comprising administering to the subject a Fn3-based binding molecule, conjugate, or composition comprising an Fn3-based binding molecule.
Specification