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
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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
CPC Classifications
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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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Document History
- Publication: Sep 25, 2008
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Application:
Mar 21, 2008
US 2008/0057819 W
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Priority:
Mar 22, 2007
US 89633907 P