Human GLP-1 mimetibodies, compositions, methods and uses
First Claim
Patent Images
1. At least one GLP-1 CH1 deleted mimetibody nucleic acid, comprising at least one polynucleotide encoding the amino acid sequence of SEQ ID NOS:
- 2 or 4, or a polynucleotide complementary thereto.
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Accused Products
Abstract
The present invention relates to at least one novel human GLP-1 mimetibody or specified portion or variant, including isolated nucleic acids that encode at least one GLP-1 mimetibody or specified portion or variant, GLP-1 mimetibody or specified portion or variants, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.
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Citations
37 Claims
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1. At least one GLP-1 CH1 deleted mimetibody nucleic acid, comprising at least one polynucleotide encoding the amino acid sequence of SEQ ID NOS:
- 2 or 4, or a polynucleotide complementary thereto.
- View Dependent Claims (17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37)
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2. At least one GLP-1 CH1 deleted mimetibody nucleic acid, comprising at least one polynucleotide encoding the amino acid sequence comprising at least one selected from SEQ ID NOS:
- 7-14, or a polynucleotide complementary thereto.
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3. At least one GLP-1 CH1 deleted mimetibody nucleic acid, comprising at least one polynucleotide encoding a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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4. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising all of the contiguous amino acids of SEQ ID NOS:
- 2 or 4.
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5. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising all of the contiguous amino acids of at least one of SEQ ID NOS:
- 7-14.
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6. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide selected from SEQ ID NO;
1 and 6, L is selected from GS, GGS, GGGS (SEQ ID NO;
16), GSGGGS (SEQ ID NO;
17), GGSGGGS (SEQ ID NO;
18), GGSGGGSGG (SEQ ID NO;
19) and GGGSGGGSGG (SEQ ID NO;
20);
V is selected from GTLVTVSS (SEQ ID NO;
21), GTLVAVSS (SEQ ID NO;
22), GTAVTVSS (SEQ ID NO;
23), TVSS (SEQ ID NO;
24), and AVSS (SEQ ID NO;
25);
H is EPKSCDKTHTCPPCPAPELLGGP (SEQ ID NO;
26), CH2 is SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK (SEQ ID NO;
43), CH3 is GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO;
44), n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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7. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula.(I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide of SEQ ID NO;
6, L is selected from GS, GGS, GGGS (SEQ ID NO;
16), GSGGGS (SEQ ID NO;
17), GGSGGGS (SEQ ID NO;
18), GGSGGGSGG (SEQ ID NO;
19) and GGGSGGGSGG (SEQ ID NO;
20);
V is selected from GTLVTVSS (SEQ ID NO;
21), GTLVAVSS (SEQ ID NO;
22), GTAVTVSS (SEQ ID NO;
23), TVSS (SEQ ID NO;
24), and AVSS (SEQ ID NO;
25);
H is ESKYGPPCPSCPAPEFLGGP (SEQ ID NO;
27), CH2 is SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK (SEQ ID NO;
45), CH3 is GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO;
46), n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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8. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide of SEQ ID NO;
6, L is selected from GS, GGS, GGGS (SEQ ID NO;
16), GSGGGS (SEQ ID NO;
17), GGSGGGS (SEQ ID NO;
18), GGSGGGSGG (SEQ ID NO;
19) and GGGSGGGSGG (SEQ ID NO;
20);
V is selected from GTLVTVSS (SEQ ID NO;
21), GTLVAVSS (SEQ ID NO;
22), GTAVTVSS (SEQ ID NO;
23), TVSS (SEQ ID NO;
24), and AVSS (SEQ ID NO;
25);
H is ESKYGPPCPPCPAPEAAGGP (SEQ ID NO;
28), CH2 is SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK (SEQ ID NO;
45), CH3 is GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO;
46), n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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9. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK (SEQ ID NO;
43), CH3 is GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO;
44), n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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10. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK (SEQ ID NO;
45), CH3 is GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO;
46), n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.- View Dependent Claims (18)
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11. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide of SEQ ID NO;
6, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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12. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is selected from GS, GGS, GGGS (SEQ ID NO;
16), GSGGGS (SEQ ID NO;
17), GGSGGGS (SEQ ID NO;
18), GGSGGGSGG (SEQ ID NO;
19) and GGGSGGGSGG (SEQ ID NO;
20);
V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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13. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative;
L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties;
V is selected from GTLVTVSS (SEQ ID NO;
21), GTLVAVSS (SEQ ID NO;
22), GTAVTVSS (SEQ ID NO;
23), TVSS (SEQ ID NO;
24), and AVSS (SEQ ID NO;
25);
H is at least a portion of an immunoglobulin variable hinge region;
CH2 is at least a portion of an immunoglobulin CH2 constant region;
CH3 is at least a portion of an immunoglobulin CH3 constant region;
n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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14. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is selected from EPKSCDKTHTCPPCPAPELLGGP (SEQ ID NO;
26), ESKYGPPCPSCPAPEFLGGP (SEQ ID NO;
27), and ESKYGPPCPPCPAPEAAGGP (SEQ ID NO;
28), CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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15. At least one GLP-1 CH1 deleted mimetibody polypeptide, comprising a polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is selected from EPKSADKTHTCPPCPAPEAAGGP (SEQ ID NO;
29), EPKSADKTHTCPPCPAPELAGGP (SEQ ID NO;
30), EPKSADKTHTCPPCPAPEALGGP (SEQ ID NO;
31), EPKSADKTHTCPPCPAPELEGGP (SEQ ID NO;
32), EPKSSDKTHTCPPCPAPEFLGGP (SEQ ID NO;
33), EPKSADKTHACPPCPAPELLGGP (SEQ ID NO;
34), EPKSADKAHTCPPCPAPELLGGP (SEQ ID NO;
35), and EPKSADKTHTCPPCPAPELLGGP (SEQ ID NO;
36), ADKTHTCPPCPAPELLGGP (SEQ ID NO ;
37), THTCPPCPAPELLGGP (SEQ ID NO;
38), ESKYGPPCPSCPAPEAAGGP (SEQ ID NO;
39), ESKYGPPCPPCPAPELLGGP (SEQ ID NO;
40), CPPCPAPELLGGP (SEQ ID NO;
41), and CPPCPAPEAAGGP (SEQ ID NO;
42), CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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16. At least one GLP-1 CH1 deleted mimetibody polypeptide according to Formula (I):
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(Pep(n)-L(o)-V(p)-H(q)-CH2(r)-CH3(s))(t),wherein P is at least one bioactive GLP-1 peptide, variant or derivative, L is at least one linker sequence, which can be a polypeptide that provides structural flexibility by allowing the mimetibody to have alternative orientations and binding properties, V is at least one portion of a C-terminus of an immunoglobulin variable region, H is at least a portion of an immunoglobulin variable hinge region, CH2 is at least a portion of an immunoglobulin CH2 constant region, CH3 is at least a portion of an immunoglobulin CH3 constant region, n is an integer from 1 to 10, and o, p, q, r, s, and t can be independently an integer from 0 to 10.
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Specification