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  Pharmaceutical Patents  

 

Title:  Compositions and methods for treatment of non-Hodgkin's lymphoma
United States Patent: 
7,410,772
Issued: 
August 12, 2008

Inventors: 
Ashkenazi; Avi J. (San Mateo, CA), Daniel; Dylan L. (San Francisco, CA), Shek; Theresa (San Mateo, CA)
Assignee: 
Genentech, Inc. (South San Francisco, CA)
Appl. No.: 
11/172,193
Filed: 
June 30, 2005


 

Executive MBA in Pharmaceutical Management, U. Colorado


Abstract

The present invention is directed to compositions of matter useful for the treatment of non-Hodgkin's lymphoma in mammals and to methods of using those compositions for the same.

Description of the Invention

The present invention relates to the identification of a cellular polypeptide (and its encoding nucleic acid, variant or fragments thereof) which is specifically, differentially and/or highly expressed by non-Hodgkin's tumors compared to normal counterpart cell types. Interestingly and significantly, this cellular polypeptide is highly expressed across a wide spectrum of non-Hodgkin's lymphomas, including B and T-cell lymphomas. The invention is also in part based on substantial insight (as described herein) into the differential regulation of the polypeptide with respect to specific subsets of non-Hodgkin's lymphoma types, which provides significant advantages in tailoring therapeutic approaches, if and where necessary, to selected subset(s) within the wide array of tumor types that collectively constitute the broad category of non-Hodgkin's lymphoma. This polypeptide is herein referred to as UNQ733 polypeptide and is expected to serve as an effective target for cancer therapy in mammals.

Accordingly, in one aspect, the invention provides a method for inhibiting the growth of a non-Hodgkin's lymphoma cell, wherein the method comprises contacting the cell with a UNQ733 antagonist which causes inhibition of the growth of the cell. In one embodiment, the UNQ733 antagonist binds to UNQ733 polypeptide. In one embodiment, the UNQ733 antagonist binds to UNQ733 on a non-Hodgkin's lymphoma cell. In one embodiment, the UNQ733 antagonist causes death of a cell expressing and/or responsive to UNQ733. In one embodiment, the UNQ733 antagonist is an antibody, an oligopeptide, inorganic or organic small molecule. In one embodiment, binding of the antibody, oligopeptide, inorganic or organic small molecule to the UNQ733 polypeptide causes inhibition of the growth of a cell expressing and/or responsive to the polypeptide. In one embodiment, the cell is a cancer cell and the UNQ733 antagonist causes death of the cell expressing and/or responsive to the UNQ733 polypeptide. In one embodiment, the cell is a cancer cell and binding of the antagonist to UNQ733 polypeptide causes death of the cell expressing and/or responsive to the polypeptide. In one embodiment, the UNQ733 antagonist is an antibody, oligopeptide, inorganic or organic small molecule and binding of the antibody, oligopeptide, inorganic or organic small molecule to the UNQ733 polypeptide causes death of the cell expressing the polypeptide. In one embodiment, a UNQ733 antagonist inhibits activation of UNQ733, e.g. by modulating enzymatic processing of UNQ733 protein (e.g., by inhibiting a proprotein convertase that cleaves UNQ733). In one embodiment, an antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, human antibody, multi-specific antibody or single-chain antibody. Antibodies, UNQ733 binding oligopeptides and UNQ733 binding inorganic or organic small molecules employed in the methods of the invention may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. In some embodiments of methods of the invention, a chemotherapeutic agent is also administered to the subject. The antibodies and UNQ733 binding oligopeptides employed in the methods of the invention may be produced in any suitable host cell, including for example CHO cells and bacterial cells.

In another aspect, the invention provides a method of therapeutically treating a mammal having non-Hodgkin's lymphoma, wherein the method comprises administering to the mammal a therapeutically effective amount of a UNQ733 antagonist, thereby resulting in the effective therapeutic treatment of the lymphoma. In one embodiment, the UNQ733 antagonist is an antibody, an oligopeptide, inorganic or organic small molecule. In one embodiment, the UNQ733 antagonist binds to UNQ733 polypeptide, thereby resulting in the effective therapeutic treatment of the tumor. In one embodiment, a UNQ733 antagonist inhibits activation of UNQ733, for example by modulating enzymatic processing of UNQ733 protein (e.g., by inhibiting a proprotein convertase that cleaves UNQ733). In one embodiment, an antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, human antibody, multi-specific antibody or single-chain antibody. Antibodies, UNQ733 binding oligopeptides and UNQ733 binding inorganic or organic small molecules employed in the methods of the invention may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. In some embodiments of methods of the invention, a chemotherapeutic agent is also administered to the subject. The antibodies and UNQ733 binding oligopeptides employed in the methods of the invention may be produced in any suitable host cell, including for example CHO cells and bacterial cells.

In one aspect, the invention provides a method of inhibiting the growth of a non-Hodgkin's lymphoma comprising administering a UNQ733 antagonist to the lymphoma, whereby growth of the lymphoma is inhibited. In one aspect, the invention provides a method of inhibiting the growth of a non-Hodgkin's lymphoma comprising administering a UNQ733 antagonist to a cell that expresses and/or is responsive to UNQ733, whereby growth of the lymphoma is inhibited. In one aspect, the invention provides a method of inhibiting growth of a non-Hodgkin's lymphoma comprising administering a UNQ733 antagonist to a cell present in and/or adjacent to the lymphoma, whereby growth of the lymphoma is inhibited. In one embodiment, said cell is not a non-Hodgkin's lymphoma cell (e.g., it is not a T or B cell); for example, said cell may be a stromal cell. In one embodiment, the UNQ733 antagonist binds to UNQ733 polypeptide on a non-Hodgkin's lymphoma cell. In one embodiment, the UNQ733 antagonist causes death of a non-Hodgkin's lymphoma cell expressing and/or responsive to UNQ733. In one embodiment, the UNQ733 antagonist is an antibody, an oligopeptide, inorganic or organic small molecule. In one embodiment, binding of the antibody, oligopeptide, inorganic or organic small molecule to the UNQ733 polypeptide causes inhibition of the growth of a non-Hodgkin's lymphoma cell expressing and/or responsive to the polypeptide. In one embodiment, the UNQ733 antagonist is an antibody, oligopeptide, inorganic or organic small molecule and binding of the antibody, oligopeptide or organic small molecule to the UNQ733 polypeptide causes death of the non-Hodgkin's lymphoma cell expressing and/or responsive to the polypeptide. Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, human antibody, multi-specific antibody or single-chain antibody. Antibodies, UNQ733 binding oligopeptides and UNQ733 binding inorganic or organic small molecules employed in the methods of the invention may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. In one embodiment, a UNQ733 antagonist inhibits activation of UNQ733, for example by modulating enzymatic processing of UNQ733 protein (e.g., by inhibiting a proprotein convertase that cleaves UNQ733). In some embodiments of methods of the invention, a chemotherapeutic agent is also administered. The antibodies and UNQ733 binding oligopeptides employed in the methods of the invention may be produced in any suitable host cell, including for example CHO cells and bacterial cells.

In another aspect, the invention provides a method for treating or preventing a cell proliferative disorder associated with increased expression or activity of UNQ733, the method comprising administering to a subject in need of such treatment an effective amount of a UNQ733 antagonist. In one embodiment, the cell proliferative disorder is cancer and the UNQ733 antagonist is an anti-UNQ733 antibody, UNQ733 binding oligopeptide, UNQ733 binding inorganic or organic small molecule. In one embodiment, a UNQ733 antagonist inhibits activation of UNQ733, e.g. by modulating enzymatic processing of UNQ733 protein (e.g., by inhibiting a proprotein convertase that cleaves UNQ733). Effective treatment or prevention of the cell proliferative disorder may be a result of direct killing or growth inhibition of cells that express and/or are responsive to UNQ733 polypeptide or by antagonizing the cell growth potentiating activity of UNQ733 polypeptide. In one embodiment, the cell proliferative disorder is a non-Hodgkin's lymphoma. In one embodiment, the cell proliferative disorder is hyperplasia, which in one embodiment is diseased, non-malignant tonsilar tissue.

In one aspect the invention provides a method of diagnosing a non-Hodgkin's lymphoma of interest comprising determining the level of UNQ733 in a test sample of tissue cells comprising cells of origin for the lymphoma of interest and in a control sample of known cells of the same tissue origin, wherein a higher level of UNQ733 in the test sample, as compared to the control sample, is indicative of the presence of the lymphoma. In another aspect, the invention provides a method of determining whether an individual is at risk for non-Hodgkin's lymphoma comprising determining the level of UNQ733 in a test sample of tissue cells comprising cells of origin for the lymphoma of interest from said individual and in a control sample of known cells of the same tissue origin, wherein a higher level of UNQ733 in the test sample, as compared to the control sample, is an indication that the individual is at risk for the lymphoma. In one embodiment of methods of the invention, the level of UNQ733 is determined based on level of UNQ733 RNA in the test sample. In one embodiment of methods of the invention, the level of UNQ733 is determined based on level of UNQ733 polypeptide in the test sample. In one embodiment of methods of the invention, the level of UNQ733 is determined based on the level of UNQ733 protein activity in the sample. In some embodiments, the method comprises exposing the sample to an antibody, oligopeptide, inorganic or organic small molecule that binds to the UNQ733 polypeptide and determining binding of the antibody, oligopeptide, inorganic or organic small molecule to the UNQ733 polypeptide in the sample. An antibody, UNQ733 binding oligopeptide, or UNQ733 binding inorganic or organic small molecule employed in the method may optionally be detectably labeled, attached to a solid support, or the like.

In one aspect, the invention provides a method for screening for biologically active agents for the treatment of non-Hodgkin's lymphoma comprising combining a candidate agent with a transgenic mammal having a genome comprising an integrated transgene encoding UNQ733 operably linked to a promoter, wherein said transgene results in said mammal acquiring non-Hodgkin's lymphoma and determining the effect of said agent on non-Hodgkin's lymphoma in said mammal. In yet another aspect, the invention provides a method for screening for biologically active agents for the treatment of non-Hodgkin's lymphoma comprising combining a candidate agent with a transgenic mammal cell culture, each cell of said culture comprising an integrated transgene encoding UNQ733 operably linked to a promoter, wherein said transgene results in said mammal acquiring non-Hodgkin's lymphoma, and determining the effect of said candidate agent on the transgenic mammal cell culture. In one embodiment of these methods, the candidate agent is an antibody or fragment thereof, an oligopeptide, or an inorganic or organic small molecule.

Yet another aspect of the present invention is directed to a method of binding an antibody, oligopeptide, inorganic or organic small molecule to a non-Hodgkin's lymphoma cell that expresses and/or is responsive to UNQ733, wherein the method comprises contacting said cell with said antibody, oligopeptide, inorganic or organic small molecule under conditions which are suitable for binding of the antibody, oligopeptide, or inorganic or organic small molecule to UNQ733 polypeptide and allowing binding therebetween. In one embodiment, binding of said antibody, oligopeptide, inorganic or organic small molecule to UNQ733 on the cell inhibits a UNQ733 biological function. In one embodiment, said antibody, oligopeptide, inorganic or organic small molecule does not compete with UNQ733 for binding to the cell. In one embodiment, said antibody, oligopeptide, inorganic or organic small molecule does not inhibit binding of UNQ733 to the cell. In one embodiment, said antibody, oligopeptide, inorganic or organic small molecule binds to UNQ733 bound on the cell and inhibits binding of free (unbound) UNQ733 to the cell. In one embodiment, the UNQ733 binding molecule is an antibody. In one embodiment, the antibody is designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)).

In one aspect, the invention provides a method of targeting a therapeutic agent to a non-Hodgkin's lymphoma in a host, the method comprising administering to the host said therapeutic agent in a form that is linked to a molecule that binds UNQ733, whereby the agent is targeted to the lymphoma in the host. The molecule that binds UNQ733 can be any molecule capable of specifically binding to UNQ733 protein in vivo, for example an antibody, an oligopeptide, an inorganic or organic small molecule. In one embodiment, the molecule that binds UNQ733 is a molecule capable of specifically binding to UNQ733 located on a cell (either in vitro or in vivo), for example where UNQ733 is bound to the surface of a non-Hodgkin's lymphoma cell. In one embodiment, the molecule is an antibody. In one embodiment, the antibody is designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)). In one embodiment, the therapeutic agent is linked to the molecule that binds UNQ733 in the form of a multi-specific (e.g., bi-specific) antibody.

Other embodiments of the invention are directed to the use of (a) a UNQ733 polypeptide (processed or unprocessed by a proprotein convertase, singly or in combination), (b) a nucleic acid encoding a processed or unprocessed UNQ733 polypeptide or a vector or host cell comprising that nucleic acid, (c) an anti-UNQ733 polypeptide antibody, (d) a UNQ733 binding oligopeptide, (e) a UNQ733 binding inorganic or organic small molecule, or (f) an inhibitor of an in vivo enzyme (such as a proprotein convertase) that cleaves UNQ733 protein, in the preparation of a medicament useful for the therapeutic treatment of a non-Hodgkin's lymphoma.

In one aspect, the invention provides a UNQ733 binding molecule useful in a method of the invention as herein described. For example, a UNQ733 binding molecule can be a molecule (such as an antibody) that binds to UNQ733 and inhibits binding of UNQ733 to its receptor. In another example, a UNQ733 binding molecule can be a molecule (such as an antibody) that binds UNQ733 that is bound to a cell. In one embodiment, the binding molecule binds UNQ733 that is bound to a cell but does not inhibit UNQ733 binding to a cell. In yet another example, a UNQ733 binding molecule is a molecule (such as an antibody) that binds UNQ733 only when said UNQ733 is bound to a cell. In one embodiment, the binding molecule binds a first UNQ733 polypeptide only when said first polypeptide is bound to a cell but does not inhibit binding of a second UNQ733 polypeptide to a cell. In some embodiments, it is advantageous for a UNQ733 binding molecule of the invention to be conjugated to a therapeutic agent (e.g., a toxin, etc. as described in greater detail hereinbelow). In one aspect, the invention provides a composition comprising a UNQ733 antagonist, wherein the composition is suitable for administration to a subject having non-Hodgkin's lymphoma. In one embodiment, the composition comprises a therapeutically effective amount of the UNQ733 antagonist. In one embodiment, the composition further comprises a carrier which in some embodiments is a pharmaceutically acceptable carrier. In one embodiment, the UNQ733 antagonist is an antibody. In one embodiment, the antibody is designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)).

In yet another aspect, the invention provides an article of manufacture comprising a container and a composition contained within the container, wherein the composition comprises a UNQ733 antagonist as described herein. The article may further optionally comprise a label affixed to the container, and/or a package insert included with the container, that refers to the use of the composition for therapeutic treatment of non-Hodgkin's lymphoma. In one embodiment, the invention provides a kit comprising a composition comprising a UNQ733 antagonist as described herein, optionally further comprising instruction for using the composition for treatment of non-Hodgkin's lymphoma.

In one aspect, the invention provides a composition comprising a UNQ733 polypeptide binding molecule, wherein the composition is suitable for detecting UNQ733 polypeptide in a test sample from an individual suspected of having non-Hodgkin's lymphoma. In one embodiment, the binding molecule is an antibody, oligopeptide, inorganic or organic small molecule. In one embodiment, the binding molecule is an antibody, wherein the antibody is capable of binding to UNQ733 in a detection assay such as western blot, immunoprecipitation and/or immunostaining. In one embodiment, the molecule is an antibody. In one embodiment, the antibody is designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)). In one embodiment, the composition further comprises a carrier.

In yet another aspect, the invention provides an article of manufacture comprising a container and a composition contained within the container, wherein the composition comprises a UNQ733 polypeptide binding molecule and is suitable for detecting UNQ733 polypeptide in a test sample from an individual suspected of having non-Hodgkin's lymphoma. The article may further optionally comprise a label affixed to the container, and/or a package insert included with the container, that refers to the use of the composition for detection of non-Hodgkin's lymphoma. In one embodiment, the invention provides a kit comprising a composition comprising a UNQ733 polypeptide binding molecule, optionally further comprising instruction for using the composition for detecting non-Hodgkin's lymphoma. In one embodiment, the binding molecule is an antibody, wherein the antibody is capable of binding to UNQ733 in a detection assay such as western blot, immunoprecipitation and/or immunostaining. In one embodiment, the antibody is In one embodiment, the molecule is an antibody. In one embodiment, the antibody is designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, the antibody competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)).

As described herein, an antibody of the invention can be in any suitable form for use in a method of the invention. For example, an antibody of the invention can be human, humanized or chimeric. In one embodiment, an antibody of the invention is the humanized or chimeric form of the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, an antibody of the invention is a humanized, chimeric or human antibody that binds to the same epitope on UNQ733 as the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, an antibody of the invention is a humanized, chimeric or human antibody that competes with the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) and/or 12H4.11.3 (ATCC deposit no. PTA-6034) for binding to UNQ733 (e.g., where UNQ733 is located in a cell free environment, is a secreted protein in vivo or in vitro, or is bound to a cell (in vitro or in vivo)). In one embodiment, an antibody of the invention comprises one, two, three, four, five or all of the hypervariable regions, hypervariable loops and/or complementarity determining region (CDR) sequences of the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034). In one embodiment, an antibody of the invention comprises one or both variable domains, or portion thereof, of the antibody designated 3E7.9.20 (ATCC deposit no. PTA-6026), 3F10.11.2 (ATCC deposit no. PTA-6027), 3H1.4.8 (ATCC deposit no. PTA-6028), 4A9.12.12 (ATCC deposit no. PTA-6029), 5A8.11.6 (ATCC deposit no. PTA-6030), 5F2.6.14 (ATCC deposit no. PTA-6031), 9D6.11.15 (ATCC deposit no. PTA-6032), 10G10.15.16 (ATCC deposit no. PTA-6033) or 12H4.11.3 (ATCC deposit no. PTA-6034).

In some embodiments, methods and compositions of the invention are directed to a non-Hodgkin's lymphoma that is a B-cell lymphoma (not-otherwise-specified--"NOS"), diffuse large B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, malignant lymphoma (NOS), malignant T cell lymphoma, anaplastic large cell lymphoma or mucosal associated lymphoid tissue lymphoma.
 

Claim 1 of 15 Claims

1. A method for inhibiting the growth of a non-Hodgkin's lymphoma cell in vitro that overexpresses a polypeptide, wherein the polypeptide comprises an amino acid sequence selected from (i) the amino acid sequence of SEQ ID NO:2, (ii) the amino acid sequence of SEQ ID NO:2, lacking its siginal peptide, and (iii) an amino acid sequence resulting from enzymatic cleavage of (i) or (ii) with a proprotein convertase, the method comprising contacting the non-Hodgkin's lymphoma cell with an antibody that (a) specifically binds to the polypeptide that is bound to the surface of the non-Hodgkin's lymphoma cell and (b) does not inhibit binding of the polypeptide to the non-Hodgkin's lymphoma cell, and wherein the antibody is conjugated to a therapeutic agent that inhibits the growth of the non-Hodgkin's lymphoma cell.

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