US2010003261A1PendingUtilityA1
agonist anti-trk-c monoclonal antibodies
Est. expiryJun 22, 2020(expired)· nominal 20-yr term from priority
A61P 9/00A61P 25/02A61P 25/00A61P 25/28C07K 16/2863C07K 2317/21C07K 16/32A61P 21/00C07K 2317/34A61K 2039/505C07K 16/28
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Claims
Abstract
The invention concerns agonist anti-trkC monoclonal antibodies which mimic certain biological activities of NT-3, the native ligand of trkC. The invention further concerns the use of such antibodies in the prevention andior treatment of cellular degeneration, including nerve cell damage associated with acute nervous cell system injury and chronic neurodegenerative diseases, including peripheral neuropathy.
Claims
exact text as granted — not AI-modified1 . An agonist anti-trkC monoclonal antibody which (a) shows no significant cross-reactivity with trkA or trkB; and (b) recognizes an epitope in domain 5 of trkC, wherein said agonist anti-trkC antibody binds trkC effective to activate a trkC receptor tyrosine kinase.
2 . The antibody of claim 1 which further recognizes an epitope in domain 4 of trkC.
3 . The antibody of claim 1 which binds both human and rat trkC.
4 . The antibody of claim 1 which is a human antibody.
5 . The antibody of claim 1 which is a murine antibody.
6 . The antibody of claim 5 which is humanized.
7 . The antibody of claim 1 effective in the treatment of cisplatin- or pyridoxine-induced neuropathy.
8 . The antibody of claim 1 effective in the treatment of diabetic neuropathy.
9 . The antibody of claim 1 which does not cause hyperalgesia when administered to a patient.
10 . The antibody of claim 1 which has increased bioavailability as compared to NT-3.
11 . The antibody of claim 1 which has a higher specific activity than NT-3.
12 . An anti-trkC antibody having a heavy chain comprising the following CDRs: a CDR1 defined by SEQ ID NO: 1; a CDR2 defined by SEQ ID NO: 6; and a CDR3 defined by SEQ ID NO: 12, and having a light chain comprising the following CDRs: a CDR1 defined by SEQ ID NO: 18; a CDR2 defined by SEQ ID NO: 25; and a CDR3 defined by SEQ ID NO: 31.
13 . An anti-trkC antibody having a heavy chain comprising the following CDRs: a CDR1 defined by SEQ ID NO: 1; a CDR2 defined by SEQ ID NO: 6; and a CDR3 defined by SEQ ID NO: 12; and having a light chain comprising the following CDRs: a CDR1 defined by SEQ ID NO: 19; a CDR2 defined by SEQ ID NO: 26; and a CDR3 defined by SEQ ID NO: 32.
14 - 15 . (canceled)
16 . The antibody of any of claims 12 , 13 , 70 , 71 , 72 , 73 , or 74 which is an agonist anti-trkC antibody.
17 . The antibody of claim 16 comprising human framework residues.
18 . The antibody of claim 17 which shows no significant cross-reactivity with trkA or trkB.
19 . The antibody of claim 17 having a homo-tetrameric structure composed of two disulfide-bonded antibody heavy chain-light chain pairs.
20 . The antibody of claim 17 which is an antibody fragment selected from the group consisting of Fv, Fab, Fab′ and F(ab′) 2 fragments.
21 . An anti-trkC agonist antibody of claim 16 which is a monoclonal antibody.
22 . The antibody of claim 21 which shows no significant cross-reactivity with trkA or trkB.
23 . The antibody of claim 22 having a homo-tetrameric structure composed of two disulfide-bonded antibody heavy chain-light chain pairs.
24 . The antibody of claim 22 which is an antibody fragment selected from the group consisting of Fv, Fab, Fab′ and F(ab′) 2 fragments.
25 . The antibody of claim 22 which is an IgG.
26 . The antibody of claim 25 which is an IgG-2 or IgG-4.
27 . A murine anti-trkC agonist antibody selected from the group consisting of antibodies 2248, 2250, 2253 and 2256.
28 . (canceled)
29 . The antibody of claim 16 that is a human anti-trkC agonist antibody selected from the group consisting of antibodies of any of claims 70 to 74 .
30 - 48 . (canceled)
49 . A pharmaceutical composition comprising an effective amount of an agonist anti-trkC monoclonal antibody of any one of claims 1 , 16 , and 21 , in admixture with a pharmaceutically acceptable carrier.
50 - 69 . (canceled)
70 . An anti-trkC antibody having a heavy chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:2; (b) a CDR2 defined by SEQ ID NO:7; and (c) a CDR3 defined by SEQ ID NO: 13, and having a light chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:20; (b) a CDR2 defined by SEQ ID NO:27; and (c) a CDR3 defined by SEQ ID NO:33.
71 . An anti-trkC antibody having a heavy chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:3; (b) a CDR2 defined by SEQ ID NO: 10; and (c) a CDR3 defined by SEQ ID NO: 16, and having a light chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:23; (b) a CDR2 defined by SEQ ID NO:30; and (c) a CDR3 defined by SEQ ID NO:36.
72 . An anti-trkC antibody having a heavy chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:3; (b) a CDR2 defined by SEQ ID NO:8; and (c) a CDR3 defined by SEQ ID NO:14, and having a light chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:21; (b) a CDR2 defined by SEQ ID NO:28; and (c) a CDR3 defined by SEQ ID NO:34.
73 . An anti-trkC antibody having a heavy chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:4; (b) a CDR2 defined by SEQ ID NO:9; and (c) a CDR3 defined by SEQ ID NO: 15, and having a light chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:22; (b) a CDR2 defined by SEQ ID NO:29; and (c) a CDR3 defined by SEQ ID NO:35.
74 . An anti-trkC antibody having a heavy chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:5; (b) a CDR2 defined by SEQ ID NO: 11; and (c) a CDR3 defined by SEQ ID NO: 17, and having a light chain comprising the following CDRs: (a) a CDR1 defined by SEQ ID NO:24; (b) a CDR2 defined by SEQ ID NO:30; and (c) a CDR3 defined by SEQ ID NO:36.Cited by (0)
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