US2009162284A1PendingUtilityA1
Anti-igf-i receptor antibody
Est. expiryJun 14, 2022(expired)· nominal 20-yr term from priority
C07K 2317/56A61K 39/3955A61K 31/337C07K 2317/565A61K 31/4745C07K 16/2863A61K 45/06C07K 2317/76A61K 2039/505C07K 2317/73A61P 43/00C07K 2317/92C07K 2317/55A61P 35/00A61K 39/39558C07K 2317/24A61K 39/39541
67
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of these molecules with cytotoxic agents, which specifically bind to and inhibit insulin-like growth factor-I receptor, antagonize the effects of IGF-I and are substantially devoid of agonist activity toward the insulin-like growth factor-I receptor. These molecules can be conjugated to cytotoxic agents for use in the treatment of tumors that express elevated levels of IGF-I receptor, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer. These molecules can also be labeled for in vitro and in vivo diagnostic uses, such as in the diagnosis and imaging of tumors that express elevated levels of IGF-I receptor.
Claims
exact text as granted — not AI-modified1 . An antibody or antibody fragment that specifically binds to an insulin-like growth factor-I receptor, wherein said antibody or antibody fragment is an antagonist of said receptor and is substantially devoid of agonist activity toward said receptor.
2 . The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is resurfaced.
3 . The antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is humanized.
4 . An antibody or antibody fragment that specifically binds to an insulin-like growth factor-I receptor, wherein said antibody or antibody fragment is capable of inhibiting the growth of a cancer cell by greater than about 80% in the presence of a growth stimulant selected from the group consisting of serum, insulin-like growth factor-I and insulin-like growth factor-II.
5 . The antibody of claim 4 , wherein said cell is an MCF-7 human breast cancer cell.
6 . An antibody or antibody fragment comprising at least one complementarity-determining region having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-6:
SYWMH,
(SEQ ID NO:1)
EINPSNGRTNYNEKFKR,
(SEQ ID NO:2)
GRPDYYGSSKWYFDV,
(SEQ ID NO:3)
RSSQSIVHSNVNTYLE,
(SEQ ID NO:4)
KVSNRFS,
(SEQ ID NO:5)
FQGSHVPPT.
(SEQ ID NO:6)
7 . (canceled)
8 . An antibody or antibody fragment thereof, comprising at least one heavy chain, wherein said heavy chain has at least 90% sequence identity to an amino acid sequence represented by SEQ ID NO:7:
(SEQ ID NO:7)
QVQLQQSGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGE
INPSNGRTNYNEKFKRKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGR
PDYYGSSKWYFDVWGAGTTVTVSS.
9 . The antibody or antibody fragment of claim 8 , wherein said heavy chain has at least 95% sequence identity to said amino acid sequence represented by SEQ ID NO:7.
10 . (canceled)
11 . An antibody or antibody fragment thereof, comprising at least one light chain, wherein said light chain has at least 90% sequence identity to an amino acid sequence represented by SEQ ID NO:8:
(SEQ ID NO:8)
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNVNTYLEWYLQKPGQSPK
LLIYKVSNRFSGVPDRFSGSGSGTDFTLRISRVEAEDLGIYYCFQGSHVP
PTFGGGTKLEIKR.
12 . The antibody or antibody fragment of claim 11 , wherein said light chain has at least 95% sequence identity to said amino acid sequence represented by SEQ ID NO:8.
13 . (canceled)
14 . The antibody or antibody fragment of claim 1 , comprising at least one complementarity-determining region having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-6:
SYWMH,
(SEQ ID NO:1)
EINPSNGRTNYNEKFKR,
(SEQ ID NO:2)
GRPDYYGSSKWYFDV,
(SEQ ID NO:3)
RSSQSIVHSNVNTYLE,
(SEQ ID NO:4)
KVSNRFS,
(SEQ ID NO:5)
FQGSHVPPT.
(SEQ ID NO:6)
15 - 22 . (canceled)
23 . The antibody or fragment thereof of claim 1 , comprising a heavy chain variable region having a sequence represented by SEQ ID NO:13:
(SEQ ID NO:13)
QVQLVQSGAEVVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGE
INPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGR
PDYYGSSKWYFDVWGQGTTVTVSS.
24 . A pharmaceutical composition comprising the antibody or antibody fragment of claim 1 and a pharmaceutically acceptable carrier.
25 . A conjugate comprising the antibody or antibody fragment of claim 1 linked to a cytotoxic agent.
26 . The conjugate of claim 25 , wherein said cytotoxic agent is selected from the group consisting of a maytansinoid, a small drug, a prodrug, a taxoid, CC-1065 and a CC-1065 analog.
27 . A pharmaceutical composition comprising the conjugate of claim 26 and a pharmaceutically acceptable carrier.
28 . A diagnostic reagent comprising the composition of claim 24 or claim 27 , wherein said antibody or antibody fragment is labeled.
29 . The diagnostic reagent of claim 28 , wherein said label is selected from the group consisting of a radiolabel, a fluorophore, a chromophore, an imaging agent and a metal ion.
30 . A method for inhibiting the growth of a cancer cell comprising contacting said cell with the antibody or antibody fragment of claim 1 .
31 . A method for treating a patient having a cancer comprising administering to said patient an effective amount of the antibody or antibody fragment of claim 1 .
32 . The method of claim 31 further comprising administering to said patient a therapeutic agent.
33 . The method of claim 32 wherein said therapeutic agent is a cytotoxic agent.
34 . A method for treating a patient having a cancer comprising administering to said patient an effective amount of the conjugate of claim 25 .
35 . The method of treatment of claim 31 , wherein said cancer is a cancer selected from the group consisting of breast cancer, colon cancer, ovarian carcinoma, osteosarcoma, cervical cancer, prostate cancer, lung cancer, synovial carcinoma and pancreatic cancer.
36 . A method for diagnosing a subject suspect of having a cancer, said method comprising:
administering to said subject the diagnostic reagent of claim 28 ; and detecting the distribution of said reagent within said subject.
37 . The method of diagnosis of claim 36 , wherein said cancer is a cancer selected from the group consisting of breast cancer, colon cancer, ovarian carcinoma, osteosarcoma, cervical cancer, prostate cancer, lung cancer, synovial carcinoma and pancreatic cancer.
38 . An improved antibody or antibody fragment that specifically binds to an insulin-like growth factor-I receptor, prepared by:
(a) providing a DNA encoding an antibody or fragment thereof comprising at least one sequence selected from the group consisting of SEQ ID NOS:1 to 8;
(SEQ ID NO:1)
SYWMH,
(SEQ ID NO:2)
EINPSNGRTNYNEKFKR,
(SEQ ID NO:3)
GRPDYYGSSKWYFDV,
(SEQ ID NO:4)
RSSQSIVHSNVNTYLE,
(SEQ ID NO:5)
KVSNRFS,
(SEQ ID NO:6)
FQGSHVPPT,
(SEQ ID NO:7)
QVQLQQSGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGE
INPSNGRTNYNEKFKRKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGR
PDYYGSSKWYFDVWGAGTTVTVSS,
(SEQ ID NO:8)
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNVNTYLEWYLQKPGQSPK
LLIYKVSNRFSGVPDRFSGSGSGTDFTLRISRVEAEDLGIYYCFQGSHVP
PTFGGGTKLEIKR;
(b) introducing at least one nucleotide mutation, deletion or insertion into said DNA such that the amino acid sequence of said antibody or antibody fragment encoded by said DNA is changed;
(c) expressing said antibody or antibody fragment;
(d) screening said expressed antibody or antibody fragment for said improvement, whereby said improved antibody or antibody fragment is prepared.
39 . The antibody or antibody fragment of claim 38 , wherein said improvement is an increased affinity for IGF-I receptor.
40 . The antibody or antibody fragment of claim 38 , wherein said at least one nucleotide mutation, deletion or insertion is made by a method selected from the group consisting of oligonucleotide-mediated site-directed mutagenesis, cassette mutagenesis, error-prone PCR, DNA shuffling and the use of mutator-strains of E. coli.
41 . A polynucleotide encoding the antibody or antibody fragment of any one of claims 6 , or 11 .
42 . A polynucleotide encoding a light or heavy chain of the antibody or antibody fragment of any one of claims 6 , or 11 .
43 . A vector comprising the polynucleotide of claim 41 .
44 . A vector comprising the polynucleotide of claim 42 .
45 . The vector of claim 43 , wherein said vector is an expression vector capable of expressing said antibody or antibody fragment.
46 . The vector of claim 44 , wherein said vector is an expression vector capable of expressing said antibody or antibody fragment.
47 . A murine antibody EM164 or an epitope-binding fragment thereof that specifically binds to an insulin-like growth factor-I receptor, wherein said antibody or fragment is an antagonist of said receptor and is substantially devoid of agonist activity toward said receptor.
48 . A humanized or resurfaced antibody EM164 or an epitope-binding fragment thereof that specifically binds to an insulin-like growth factor-I receptor, wherein said antibody or fragment is an antagonist of said receptor and is substantially devoid of agonist activity toward said receptor.
49 . (canceled)
50 . An isolated antibody or fragment thereof that specifically binds to IGF-IR, comprising at least one heavy chain variable region and at least one light chain variable region, wherein said heavy chain variable region comprises three complementarities-determining regions comprising the amino acid sequences of SEQ ID NOS:1, 54 and 3, and wherein said light chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:4-6.
51 . An antibody or fragment thereof, comprising a heavy chain variable region having a sequence selected from the group consisting of
SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO: 44, and SEQ ID NO:87.
52 . An antibody or fragment thereof, comprising a heavy chain variable region having a sequence selected from the group consisting of
SEQ ID NO:53, SEQ ID NO:54, and SEQ ID NO:55.
53 . An isolated humanized antibody or epitope-binding antibody fragment that specifically binds to IGF-IR, comprising at least one heavy chain variable region and at least one light chain variable region, wherein said heavy chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:1-3, and wherein said light chain variable region comprising a sequence selected from the group consisting of SEQ ID NO:9; SEQ ID NO:10; SEQ ID NO:11; SEQ ID NO:12; SEQ ID NO:83; SEQ ID NO:84; SEQ ID NO:85, and SEQ ID NO:86.
54 . An isolated humanized antibody or epitope-binding antibody fragment that specifically binds to IGF-IR, comprising at least one heavy chain variable region and at least one light chain variable region, wherein said light chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:4-6, and wherein said heavy chain variable region comprises a sequence selected from the group consisting of SEQ ID NO:13; and SEQ ID NO:88.
55 . An isolated humanized antibody or epitope-binding antibody fragment that specifically binds to IGF-IR, comprising a light chain variable region having a sequence selected from the group consisting of
SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and SEQ ID NO:86.
56 . An isolated humanized antibody or epitope-binding antibody fragment that specifically binds to IGF-IR, comprising a heavy chain variable region having the sequence of
SEQ ID NO:88.
57 . An antibody or fragment thereof, comprising a light chain variable region having a sequence selected from the group consisting of
SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, and SEQ ID NO:37.Join the waitlist — get patent alerts
Track US2009162284A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.