US2011268727A1PendingUtilityA1
Anti-interferon-alpha antibodies
Est. expiryFeb 22, 2021(expired)· nominal 20-yr term from priority
A61P 37/06A61P 3/10A61P 5/14A61P 7/06A61P 37/02A61P 5/50A61P 37/00C07K 2317/567C07K 16/249C07K 2317/55G01N 2800/24C07K 2319/00A61K 2039/505G01N 33/6866A61P 19/04A61P 17/00G01N 33/564C07K 2317/92C07K 2317/24C07K 2317/565C07K 2317/76G01N 2800/042G01N 2333/56C07K 16/24
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Claims
Abstract
The present invention relates generally to the generation and characterization of neutralizing anti-IFN-α monoclonal antibodies with broad reactivity against various IFN-α subtypes. The invention further relates to the use of such anti-IFN-α antibodies in the diagnosis and treatment of disorders associated with increased expression of IFN-α, in particular, autoimmune disorders such as insulin-dependent diabetes mellitus (IDDM) and systemic lupus erythematosus (SLE).
Claims
exact text as granted — not AI-modified1 . An anti-IFN-α monoclonal antibody which binds to and neutralizes a biological activity of at least IFN-α subtypes, IFN-α1, IFN-α2, IFN-α4, IFN-α5, IFN-α8, IFN-α10, and IFN-α21.
2 . The antibody of claim 1 which is a murine antibody.
3 . The antibody of claim 1 which is a humanized antibody.
4 . The antibody of claim 1 which is a human antibody.
5 . The antibody of claim 1 wherein said biological activity is antiviral activity.
6 . The antibody of claim 5 wherein said antibody is capable of neutralizing at least 70% of the antiviral activity of said IFN-α subtypes.
7 . The antibody of claim 5 wherein said antibody is capable of neutralizing at least 80% of the antiviral activity of said IFN-α subtypes.
8 . The antibody of claim 5 wherein said antibody is capable of neutralizing at least 90% of the antiviral activity of said IFN-α subtypes.
9 . The antibody of claim 5 wherein said antibody is capable of neutralizing at least 99% of the antiviral activity of said IFN-α subtypes.
10 . The antibody of claim 1 which binds essentially the same IFN-α epitope as murine anti-human IFN-α monoclonal antibody 9F3 or a humanized or chimeric form thereof.
11 . The antibody of claim 1 which is murine anti-human IFN-α monoclonal antibody 9F3 or a humanized or chimeric form thereof.
12 . The antibody of claim 11 which is humanized anti-human IFN-α monoclonal antibody 9F3 version 13 (V13).
13 . The antibody of claim 1 which binds essentially the same IFN-α epitope as the anti-IFN-α antibody produced by the hybridoma cell line deposited with ATCC on Jan. 18, 2001 and having accession No. PTA-2917.
14 . The antibody of claim 1 which is of the IgG class.
15 . The antibody of claim 14 which has an IgG 1 , IgG 2 , IgG 3 , or IgG 4 isotype.
16 . The antibody of claim 1 which is an antibody fragment.
17 . The antibody of claim 16 which is a Fab fragment.
18 . The antibody of claim 16 which is a F(ab′) 2 fragment.
19 . The antibody of claim 16 which is a Fab′ fragment.
20 . An anti-IFN-α antibody light chain or a fragment thereof, comprising the following CDR's:
(a) L1 of the formula RASQSVSTSSYSYMH (SEQ ID NO: 7);
(b) L2 of the formula YASNLES (SEQ ID NO: 8); and
(c) L3 of the formula QHSWGIPRTF (SEQ ID NO: 9).
21 . The anti-IFN-α antibody light chain fragment of claim 20 which is the light chain variable domain.
22 . An anti-IFN-α antibody heavy chain or a fragment thereof, comprising the following CDR's:
(a) H1 of the formula GYTFTEYIIH (SEQ ID NO: 10);
(b) H2 of the formula SINPDYDITNYNQRFKG (SEQ ID NO: 11); and
(c) H3 of the formula WISDFFDY (SEQ ID NO: 12).
23 . The anti-IFN-α antibody heavy chain fragment of claim 22 which is the heavy chain variable domain.
24 . An anti-IFN-α antibody comprising
(A) at least one light chain or a fragment thereof, comprising the following CDR's:
(a) L1 of the formula RASQSVSTSSYSYMH (SEQ ID NO: 7);
(b) L2 of the formula YASNLES (SEQ ID NO: 8); and
(c) L3 of the formula QHSWGIPRTF (SEQ ID NO: 9); and
(B) at least one heavy chain or a fragment thereof, comprising the following CDR's:
(a) H1 of the formula GYTFTEYIIH (SEQ ID NO: 10);
(b) H2 of the formula SINPDYDITNYNQRFKG (SEQ ID NO: 11); and
(c) H3 of the formula WISDFFDY (SEQ ID NO: 12).
25 . The antibody of claim 24 having a homo-tetrameric structure composed of two disulfide-bonded antibody heavy chain-light chain pairs.
26 . The antibody of claim 24 which is a linear antibody.
27 . The antibody of claim 24 which is a murine antibody.
28 . The antibody of claim 24 which is a chimeric antibody.
29 . The antibody of claim 24 which is a humanized antibody.
30 . The antibody of claim 24 which is a human antibody.
31 . An isolated nucleic acid molecule encoding an antibody of claim 1 .
32 . An isolated nucleic acid molecule encoding an antibody of claim 11 .
33 . An isolated nucleic acid molecule encoding an antibody of claim 12 .
34 . An isolated nucleic acid molecule encoding an antibody of claim 24 .
35 . An isolated nucleic acid molecule encoding an antibody light chain or light chain fragment of claim 20 .
36 . An isolated nucleic acid molecule encoding an antibody heavy chain or heavy chain fragment of claim 22 .
37 . An isolated nucleic acid molecule comprising the light chain polypeptide-encoding nucleic acid sequence of the vector deposited with ATCC on Jan. 9, 2001 and having accession No. PTA-2882.
38 . An isolated nucleic acid molecule comprising the heavy chain polypeptide-encoding nucleic acid sequence of the vector deposited with ATCC on Jan. 9, 2001 and having accession No. PTA-2881.
39 . A vector comprising a nucleic acid molecule according to any one of claims 31 to 38 .
40 . A host cell transformed with a nucleic acid molecule according to any one of claims 31 to 38 .
41 . A method of producing the antibody of any one of claims 1 , 11 , 12 and 24 comprising culturing a host cell comprising a nucleic acid sequence encoding the antibody under conditions wherein the nucleic acid sequence is expressed to produce the antibody.
42 . A hybridoma cell line comprising a nucleic acid molecule according to any one of claims 31 to 38 .
43 . A hybridoma cell line deposited with ATCC on Jan. 18, 2001 and having accession No. PTA-2917.
44 . An antibody produced by the hybridoma cell line of claim 42 .
45 . A pharmaceutical composition comprising an effective amount of the antibody of claim 1 in admixture with a pharmaceutically acceptable carrier.
46 . A pharmaceutical composition comprising an effective amount of the antibody of claim 11 in admixture with a pharmaceutically acceptable carrier.
47 . A pharmaceutical composition comprising an effective amount of the antibody of claim 12 in admixture with a pharmaceutically acceptable carrier.
48 . A pharmaceutical composition comprising an effective amount of the antibody of claim 24 in admixture with a pharmaceutically acceptable carrier.
49 . A method for diagnosing a condition associated with the expression of IFN-α in a cell, comprising contacting said cell with an anti-IFN-α antibody of claim 1 , and detecting the presence of IFN-α.
50 . A method for the treatment of a disease or condition associated with the expression of IFN-α in a patient, comprising administering to said patient an effective amount of an anti-IFN-α antibody of claim 1 .
51 . The method of claim 50 wherein said patient is a mammalian patient.
52 . The method of claim 51 wherein said patient is human.
53 . The method of claim 52 wherein said disease is an autoimmune disease.
54 . The method of claim 53 wherein said disease is selected from the group consisting of insulin-dependent diabetes mellitus (IDDM); systemic lupus erythematosus (SLE); and autoimmune thyroiditis.Join the waitlist — get patent alerts
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