WO 2008/116149 A2 - Apoptotic Anti-ige Antibodies - The Lens - Free & Open Patent and Scholarly Search

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WO 2008/116149 A2

Apoptotic Anti-ige Antibodies

Published: Sep 25, 2008
Earliest Priority: Mar 22 2007
Family: 55
Cited Works: 1
Cited by: 24
Cites: 0
Sequences: 112
Additional Info: Full text Published Sequence

Abstract

The present application relates to apoptotic anti-IgE antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use in the treatment of IgE-mediated disorders.

Claims

An anti-IgE/M 1 ' antibody that specifically binds the M 1 ' segment of IgE and which induces apoptosis in IgE-expressing B-cells.
The antibody of Claim 1 , wherein the antibody binds IgE that is of human, rhesus monkey and cynomolgus monkey in origin.
An anti-IgE/M 1 ' antibody that specifically binds the M 1 ' segment of IgE and specifically depletes IgE-producing B-cells when a therapeutically effective amount is administered in vivo to a mammal.
The antibody of Claim 3 that reduces total serum IgE.
The antibody of Claim 4 that reduces free serum IgE.
The antibody of Claim 4, wherein the IgE is allergen-specific.
The antibody of Claim 3 that is chimeric.
The antibody of Claim 3 that is humanized.
The antibody of Claim 3 that is human.
An anti-IgE/M 1 ' antibody that specifically binds to the same epitope as one bound by an antibody selected from the group consisting of: 47H4, 7A6, 26Al 1, 47H4v5, 7A6vl and 26Al Iv6.
The antibody of Claim 10 wherein the epitope corresponds to a peptide selected from the group consisting of: peptide 4 (SEQ ID NO: 8), peptide 5 (SEQ ID NO:9), peptide 7 (SEQ ID NO:11) or peptide 8 (SEQ ID NO: 12).
The antibody of Claim 11 , wherein the epitope corresponds to peptide 4 (SEQ ID NO:8).
A peptide selected from the group consisting of: peptide 4 (SEQ ID NO: 8), peptide 5 (SEQ ID NO:9), peptide 7 (SEQ ID NO: 11) or peptide 8 (SEQ ID NO: 12).
An anti-IgE/Ml ' antibody that specifically binds to an Ml ' segment of IgE with a Scatchard binding affinity that is equivalent to that of the murine anti-IgE/Ml ' antibody 47H4.
The antibody of Claim 14, wherein the affinity is between 0.30 and 0.83 nm.
An anti-IgE/Ml ' antibody that specifically binds to an Ml ' segment of IgE with a Scatchard binding affinity that is equivalent to that of humanized anti-IgE/M 1 ' antibody 47H4v5.
The antibody of Claim 16, wherein the affinity is about 1.5 nm.
An anti-IgE/Ml ' antibody comprising the heavy chain and light chain
HVRs of an antibody or antigen-binding fragment thereof selected from the group consisting of: 26Al 1, 26A11 v.1-16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The antibody of Claim 18 comprising variable regions of the heavy and light chains of the antibody or antigen-binding fragment thereof selected from the group consisting of: 26Al 1, 26Al 1 v.1-16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The antibody of Claim 18, comprising the heavy and light chain HVRs or an antibody or antigen-binding fragment thereof of 47H4v 1-6.
The antibody of Claim 18 that is afucosylated.
A composition comprising the antibody of any of claims 1-21 in combination with at least one pharmaceutically acceptable carrier.
A composition comprising the antibody of any of Claims 1-21 in combination with at least one pharmaceutically acceptable carrier and one or more drugs selected from the group consisting of: anti-IgE antibody, antihistamine, bronchodilator, glucocorticoid, NSAID, TNF-antagonist, integrin antagonist, immunosuppressive agent, IL-4 antagonist, IL- 13 antagonist, dual IL-4/IL-13 antagonist, DMARD, antibody that binds to a B-cell surface marker and BAFF antagonist.
An isolated nucleic that encodes an antibody or antigen-binding fragment thereof comprising the heavy and light chain HVRs of an apoptotic anti-IgE/Ml ' antibody or antigen-binding fragment thereof selected from the group consisting of: 26Al 1, 26Al 1 vl-16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The nucleic acid of Claim 24, further comprising nucleic acid encoding the variable regions of the heavy and light chains of the antibody sequence selected from the group consisting of: 26Al 1, 26Al lvl-16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The nucleic acid of Claim 25, wherein the encoded antibody is afucosylated.
A vector in which the nucleic acid of Claim 25 is operably linked.
A host cell comprising the vector of Claim 27.
The host cell of Claim 28 that is mammalian.
The host cell of Claim 29 that is Chinese Hamster Ovary.
A process for producing an apoptotic anti-IgE/Ml ' antibody or functional fragment comprising culturing the host cell of Claim 28 under conditions suitable for expression of the antibody or fragment, and recovering the antibody or fragment.
An article of manufacture enclosing the composition of Claim 22 and a package insert indicating use for the treatment of an IgE -mediated disorder.
The article of Claim 32 that is a vial.
The article of Claim 32 that is a pre-fϊlled syringe.
The article of Claim 34, further comprising an injection device.
The article of Claim 35 that is an auto-injector.
A method for specifically depleting IgE-producing B-cells, comprising administering to a mammal a therapeutically effective amount of an anti-IgE/Ml ' antibody that specifically binds to the Ml ' segment of IgE and induces apoptosis in IgE- expressing B-cells.
The method of Claim 37, wherein the antibody comprises the heavy and light chain HVRs of the antibody selected from the group consisting of: 26Al 1, 26Al 1 vl-16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The method of Claim 38, further comprising the reduction of total serum
IgE.
The method of Claim 39, further comprising the reduction of free serum IgE.
The method of Claim 39, wherein the IgE is allergen-specific.
The method of Claim 38, wherein the antibody has ADCC activity.
A method of treating an IgE-mediated disorder comprising administering a therapeutically effective amount of an anti-IgE/Ml ' antibody that specifically binds to the Ml ' segment of IgE induces apoptosis of IgE-expressing B-cells.
The method of Claim 43, wherein the antibody specifically depletes IgE- expressing B-cells.
The method of Claim 43 , wherein the antibody reduces total serum IgE.
The method of Claim 45, wherein the antibody reduce free serum IgE.
The method of Claim 45, wherein the IgE is allergen-specific.
The method of Claim 43, wherein the antibody comprises the heavy and light chain HVRs or an antibody selected from the group consisting of 26Al 1, 26Al IvI- 16, 7A6, 7A6vl, 47H4, 47H4vl-6.
The method of Claim 43 wherein the IgE-mediated disorder is selected from the group consisting of: allergic rhinitis, allergic asthma, non-allergic asthma, atopic dermatitis, allergic gastroenteropathy, anaphylaxis, urticaria, food allergies, allergic bronchopulmonary aspergillosis, parasitic diseases, interstitial cystitis, hyper-IgE syndrome, ataxia-telangiectasia, Wiskott-Aldrich syndrome, athymic lymphoplasia, IgE myeloma, graft- versus-host reaction and allergic purpura.
A method of treating an IgE-mediated disorder comprising a therapeutically effective amount of an anti-IgE/Ml ' antibody that specifically binds to the Ml ' segment of IgE and that induces apoptosis of IgE-expressing B-cells in combination with a therapeutically effective amount of at least one drug selected from the group consisting of: anti-IgE antibody, antihistamine, bronchodilator, glucocorticoid, NSAID, decongestant, cough suppressant, analgesic, TNF-antagonist, integrin antagonist, immunosuppressive agent, IL-4 antagonist, IL- 13 antagonist, dual IL-4/IL-13 antagonist, DMARD, antibody that binds to a B-cell surface marker and BAFF antagonist. In a specific aspect, the antibody specifically depletes IgE -producing B-cells.
A method of treating an IgE -mediated disorder comprising a combined treatment regimen of administering a therapeutically effective amount of an anti-IgE/Ml ' antibody that specifically binds to the Ml ' segment of IgE and that induces apoptosis of IgE-expressing B-cells prior to, simultaneous with or after the administration of a known method of treatment for allergic disorders.
The method of Claim 51, wherein the known treatment for allergic disorder comprises the administration of an anti-IgE antibody antihistamine, a bronchodilator, a glucocorticoid, a non-steroidal anti-inflammatory drug, an immunosuppressant, a IL-4 antagonist, a IL- 13 antagonist, a dual IL-4/IL-13 antagonist, a decongestant, a cough suppressant or an analgesic.
The method of Claim 51, wherein the known treatment for allergic disorder comprises a treatment regimen of allergen densitization.
A method for preventing allergen-induced IgE production, comprising administering a therapeutically effective amount of an anti-IgE/Ml ' antibody that that specifically binds to the Ml ' segment of IgE and induces apoptosis of IgE-expressing B- cells.
A method for reducing allergen-induced IgE production, comprising administering a therapeutically effectgive amount of an anti-IgE/Ml ' antibody that that specifically binds to the Ml ' segment of IgE and induces apoptosis of IgE-expressing B- cells.
A murine hybridoma deposited at the ATCC on March 21, 2007 selected from the group consisting of: PTA-8260, PTA-8261, PTA-8262, PTA-8263, PTA-8264, PTA-8265, PTA-8266, PTA-8267, PTA-8268, PTA-8269, PTA-8270.
An antibody that is secreted by the hybridoma of Claim 52.
A transgenic animal that expresses the human Ml ' segment of IgE.

Applicants

Genentech Inc
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Wu Lawren
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Balazs Mercedesz
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Brightbill Hans
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Chan Andrew
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Chen Yvonne
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Chuntharapai Anan
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Dennis Mark
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Wong Terence
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Inventors

Wu Lawren
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Balazs Mercedesz
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Brightbill Hans
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Chan Andrew
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Chen Yvonne
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Chuntharapai Anan
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Dennis Mark
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Wong Terence
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CPC Classifications

A01K2217/072
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A01K2227/105
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A01K2267/0387
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A01K67/0278
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A61K2039/505
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C07K16/4291
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C07K2317/21
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C07K2317/24
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C07K2317/41
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C07K2317/73
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IPC Classifications

A61P37/06
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C07K16/42
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Document History

Publication: Sep 25, 2008
WO 2008/116149 A2
Application: Mar 21, 2008
US 2008/0057819 W
Priority: Mar 22, 2007
US 89633907 P