Specific delivery of toxins conjugated with antibodies to activate matripase

Disclosed are antibody drug conjugates (ADC) that include highly potent toxic agents with specific antibodies to target tumors. Also disclosed are related antibodies, polypeptides, nucleic acids, host cells, compositions, and uses.

Targeting tumor cells with chemotherapeutic agents conjugated to matriptase antibodies

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E(MMAE) and monomethyl auristatin F(MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Targeting matriptase expressing tumor cells with chemotherapeutic agents conjugated to matriptase antibodies

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as doxorubicin (DOX) are introduced, which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as doxorubicin (DOX) are introduced, which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers. 1. A method of treating a hematological malignancy , comprising administering to a subject in need of such a treatment a composition comprising a therapeutically effective amount of a matriptase antibody.2. The method of claim 1 , wherein the hematological malignancy is a cancer comprising cells that express matriptase.3. The method of claim 1 , wherein the hematological malignancy is selected from the group consisting of leukemias claim 1 , lymphomas claim 1 , and myelomas.4. The method of claim 1 , wherein the hematological malignancy is selected from the group consisting of acute lymphoblastic leukemia (ALL) claim 1 , acute myelogenous leukemia (AML) claim 1 , chronic lymphocytic leukemia (CLL) claim 1 , small lymphocytic lymphoma (SLL) claim 1 , chronic myelogenous leukemia (CML) claim 1 , acute monocytic leukemia (AMOL)) claim 1 , Hodgkin's lymphomas claim 1 , Non-Hodgkin's lymphomas ...

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as doxorubicin (DOX) are introduced, which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers. 117-. (canceled)18. A method of treating a malignancy comprising cells that express matriptase , the method comprising administering to a subject in need of such a treatment a therapeutically effective amount of a composition comprising an immunoconjugate between a matriptase antibody and a cytotoxic agent.19. (canceled)20. The method of claim 18 , wherein the malignancy is a matriptase-positive malignant B cell lymphoma or an epithelial carcinoma.21. The method of claim 20 , wherein the matriptase-positive malignant B cell lymphoma is selected from the group consisting of Mantle cell lymphoma (MCL) claim 20 , Burkitt's lymphoma (BL) claim 20 , and diffuse large B-cell lymphoma (DLBL).22. The method of claim 20 , wherein the epithelial carcinoma is selected from the group consisting of prostate claim 20 , breast claim 20 , brain claim 20 , kidney claim 20 , lung claim 20 , colon claim 20 , ...

Automatic Processing Apparatus

The present disclosure provides an automatic processing apparatus including a main body, a receiving portion, a working assembly, a workpiece magazine, a setting mechanism, a passivation bucket assembly, and a rotation driving assembly. The receiving portion is adapted for receiving a plurality of workpieces. The setting mechanism takes the workpieces to the receiving portion from the workpiece magazine. The working assembly is adapted for bringing the workpieces to the passivation bucket assembly for processing. The passivation bucket assembly includes a turning table and a plurality of passivation buckets moving when the turning table rotates. The rotation driving assembly drives one of the passivation buckets to rotate. Thereby, automatic processing can be achieved by the apparatus of the present invention, and the efficiency of processing is improved too.

Targeting tumor cells with chemotherapeutic agents conjugated to matriptase antibodies

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO ANTI-MATRIPTASE ANTIBODIES BY IN VIVO CLEAVABLE LINKING MOIETIES

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers. 1. An immunoconjugate selectively targeting cancer cells that express matriptase , comprising an anti-matriptase antibody or antigen-binding fragment thereof , and a cytotoxic agent , wherein said cytotoxic agent is selected from the group consisting of monomethyl auristatin E (MMAE) , monomethyl auristatin F (MMAF) , and auristatin PE , wherein the anti-matriptase antibody or antigen-binding fragment thereof is specific for activated matriptase.2. The immunoconjugate of claim 1 , wherein the anti-matriptase antibody comprises M69 monoclonal antibody or antigen-binding portion thereof.3. The immunoconjugate of claim 1 , wherein the immunoconjugate further comprises a linker comprising a cleavable linking moiety.4. (canceled)5. The immunoconjugate of claim 3 , wherein the cleavable ...

Targeting tumor cells with chemotherapeutic agents conjugated to matriptase antibodies

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Gripper Module

The present disclosure provides a gripper module, including a base, an adapter holder, a collet holder, and an actuator. The base is adapted for an adapter to be detachably disposed thereon. The adapter holder is able to engage and to buckle the adapter. The collet holder is able to engage and to buckle a collet which is installed in the adapter. The actuator is connected to the collet holder. The actuator can pull the collet holder and the collet to move, causing pressing and retraction of the collet by the conical surface between the collet and the adapter. Therefore, sizes of collets may apply to the gripper module with the adapter. By sheathing the adapter, replacement and size alternation of the collets are made easier, and precisions of allocations of the collet and the gripped workpiece are improved. 1. A gripper module , adapted for an adapter and a collet to connect with , the collet being adapted for clamping a workpiece , the adapter having an axial hole , the collet being detachably inserted into the axial hole , the collect enclosing a clamping opening , the gripper module including:a base, having a receiving room, the receiving room having an opening, the receiving room defining an axis and an opening direction, the receiving room being adapted for the adapter to detachably insert into via the opening, the axial hole expanding along the opening direction when the adapter is inserted into the receiving room;an adapter holder, received in the receiving room, holding the adapter selectively so that the adapter is positioned in the receiving room;a collet holder, received in the receiving room, holding the collet so that the collet is positioned in the axial hole;an actuator, disposed on the base and connected to the collet holder, the actuator driving the collet holder to move along a direction opposite to the opening direction so as to drive the collet to move along a direction opposite to the opening direction and to fasten the collet into the clamping ...

Specific Delivery of Toxins Conjugated with Antiobodies to Activate Matripase

Disclosed are antibody drug conjugates (ADC) that include highly potent toxic agents with specific antibodies to target tumors. Also disclosed are related antibodies, polypeptides, nucleic acids, host cells, compositions, and uses. 1. An isolated antibody , or antigen binding portion thereof , comprising (i) a first sequence that is at least 70% identical to SEQ ID NO: 1 and (ii) a second sequence that is at least 70% identical to SEQ ID NO: 2 , wherein the antibody specifically recognizes the active form of matriptase and wherein the antibody or binding portion is conjugated with a cytotoxic agent.2. The isolated antibody of claim 1 , or antigen binding portion thereof claim 1 , wherein the first sequence is at least 80% identical to SEQ ID NO: 1.3. The isolated antibody of claim 2 , or antigen binding portion thereof claim 2 , wherein the first sequence is at least 90% identical to SEQ ID NO: 1.4. The isolated antibody of claim 1 , or antigen binding portion thereof claim 1 , wherein the second sequence is at least 80% identical to SEQ ID NO: 2.5. The isolated antibody of claim 4 , or antigen binding portion thereof claim 4 , wherein the second sequence is at least 90% identical to SEQ ID NO: 2.6. The isolated antibody of claim 1 , or antigen binding portion thereof claim 1 , comprising a heavy chain and a light chain that comprise the sequences of SEQ ID NOs: 1 and 2 claim 1 , respectively.76. The isolated antibody of any of - claims 1 , or antigen binding portion thereof claims 1 , wherein the antibody is a single-chain antibody claims 1 , a monoclonal antibody claims 1 , a humanized monoclonal antibody claims 1 , or a human monoclonal antibody.87. The isolated antibody of any of - claims 1 , or antigen binding portion thereof claims 1 , wherein cytotoxic agent is doxorubicin claims 1 , auristatin claims 1 , maytansinoid claims 1 , neocarzinostatin (NCS) claims 1 , or a derivative thereof.9. The isolated antibody of claim 8 , or antigen binding portion thereof ...

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO ANTI-MATRIPTASE ANTIBODIES BY IN VIVO CLEAVABLE LINKING MOIETIES

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers. 1. A method of treating a malignancy comprising cells that express matriptase , the method comprising administering to a subject in need of such a treatment a therapeutically effective amount of a composition comprising an immunoconjugate that comprises an anti-matriptase antibody or antigen-binding fragment thereof and a cytotoxic agent , wherein:the cytotoxic agent is selected from the group consisting of monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and auristatin PE;the anti-matriptase antibody or antigen-binding fragment thereof is specific for activated matriptase; andthe malignancy comprises a hematological malignancy selected from the group consisting of acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), ...

Markers for Abnormal Cells

The present invention relates to methods of determining the presence or absence of abnormal lymphoid cells or abnormal myeloid cells in a cell sample, with the methods comprising subjecting the cell sample to conditions that will activate any inactive matriptase present in the cell sample and measuring the levels of activated matriptase in the cell sample. Once measured, these levels can then be compared to control levels of active matriptase to determine if the cell sample has elevated levels of activated matriptase over control levels of active matriptase. An elevation in the levels of activated matriptase in the cell sample is indicative that the cell sample contains abnormal lymphoid cells or abnormal myeloid cells. 1. A method of determining the presence or absence of abnormal lymphoid cells or abnormal myeloid cells in a cell sample , the method comprisinga) subjecting the cell sample to conditions that will activate any inactive matriptase present in the cell sample,b) measuring the levels of activated matriptase in the cell sample, andc) comparing these determined activated levels of matriptase to control levels of active matriptase to determine if the cell sample has elevated levels of activated matriptase over control levels of active matriptasewherein an elevation in the levels of activated matriptase in the cell sample is indicative that the cell sample contains abnormal lymphoid cells or abnormal myeloid cells.2. The method of claim 1 , where the measuring of the levels of activated matriptase in the cell sample comprises measuring the activity of the activated matriptase.3. The method of claim 2 , wherein measuring the activity of activated matriptase comprises placing a fluorogenic peptide in contact with at least a portion of the cell sample to form a mixture of fluorgenic peptide and cell sample portion claim 2 , wherein the activated matriptase will act upon the fluorogenic peptide in the mixture and the fluorescence intensity of the mixture will ...

TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers. 130.-. (canceled)31. An immunoconjugate comprising an antibody or antigen-binding fragment thereof that binds matriptase in a form selectively expressed on cancer cells , said antibody or fragment covalently linked to a chemotherapeutic agent , wherein said antibody or fragment binds a complex between activated matriptase and its inhibitor HAI-1.32. The immunoconjugate of wherein the chemotherapeutic agent is doxorubicin or an auristatin.33. The immunoconjugate of which comprises a chimeric antibody claim 31 , humanized antibody claim 31 , or human antibody.34. A method to treat a malignancy in a subject which method comprises administering to a subject in need of such treatment an effective amount of the immunoconjugate of .35. The method of wherein the malignancy is cancer of the breast claim 34 , prostate claim ...

Targeting tumor cells with chemotherapeutic agents conjugated to anti-matriptase antibodies by in vivo cleavable linking moieties

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti- matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Matriptase, a serine protease and its applications

The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of a concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.

Matriptase, a serine protease and its applications

The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.

Matriptase, a serine protease and its applications

The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of a concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.

Rotating table device

Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions

The present invention relates to a method of inhibiting carcinoma progression wherein matriptase plays a role in a subject in need of such inhibition including administering to a subject an effective amount of a compound comprising two positively charged groups, which are the same or different. The groups are linked by a chemical group having a length of between 5 and 30 A, and preferably between 15 and 24 A. Diagnostic methods based on matriptase action and therapeutic methods involving inhibition of matriptase activity are provided.

Horizontal turning machine for milling machines (1)

Horizontal cutting device of milling machine

Targeting tumor cells with chemotherapeutic agents conjugated to matriptase antibodies

The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as doxorubicin (DOX) are introduced, which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Embedded multiband detecting device in vivo

發光控制模組

Targeting tumor cells with chemotherapeutic agents conjugated to anti-matriptase antibodies by in vivo cleavable linking moieties

The present disclosure relates to an immunoconjugate comprising an antibody or antigen-binding fragment thereof that selectively binds activated matriptase expressed on tumor cells, where the antibody or antigen-binding fragment thereof is coupled to a cytotoxic agent via a linker. The cytotoxic agent is selected from the group consisting of monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and auristatin PE, and the anti-matriptase antibody comprises M69 or an antigen-binding fragment thereof or is a chimeric or humanized form thereof. The linker comprises a first linking component and a second linking component and the first linking component comprises PEG and the second linking component comprises PEG. The first linking component is bound to the second linking component through a triazole moiety, and the cytotoxic agent is bound to the second linking component; and further, the linker is covalently bound to a lysine residue on the anti-matriptase antibody.

Inhibitors of matriptase for the treatment of cancer

The present invention relates to a method of inhibiting carcinoma progression wherein matriptase plays a role in a subject in need of such inhibition including administering to a subject an effective amount of a compound comprising two positively charged groups, which are the same or different. The groups are linked by a chemical group having a length of between 5 and 30 A, and preferably between 15 and 24 A. Diagnostic methods based on matriptase action and therapeutic methods involving inhibition of matriptase activity are provided. Exemplary compounds are pentamidine and analogs thereof.

Producing process for the head of golf clubs

自動化処理機

【課題】丸み付けの加工効率を大幅に上昇させることができ、全自動化プロセスの目標を達成した自動化処理機を提供する。【解決手段】本発明の自動化処理機は、本体１０、材料配置部２０、作業セット３０、保管装置４０、材料配置機構５０、研磨槽セット６０及び自転駆動セットを含む。前記材料配置部２０は複数のワークを保持し、前記材料配置機構５０は前記保管装置４０から前記ワークを前記材料配置部２０に誘導し、前記作業セット３０は前記材料配置部２０から前記ワークを前記研磨槽セット６０に誘導して加工する。前記研磨槽セット６０は回転テーブル６２及び複数の研磨槽６３を含み、前記研磨槽６３は回転テーブル６２の回転に伴って移動し、前記自転駆動セットがこのうちの１つの研磨槽６３を加工に有利なように回転させる。これにより本発明は全自動化加工プロセスを達成することができ、生産効率を大幅に高める。【選択図】図１

Automatisierte Bearbeitungseinrichtung

Die Erfindung betrifft eine automatisierte Bearbeitungseinrichtung, die einen Hauptkörper (10), eine Materialablage (20), eine Betriebseinheit (30), eine Lagervorrichtung (40), eine Materialabstelleinrichtung (50), eine Schleifgefässeinheit (60) und automatisierte Antriebseinheit (70) umfasst, wobei die Materialablage (20) dem Tragen einer Vielzahl von Werkstücken (300) dient, wobei die Materialabstelleinrichtung (50) die Werkstücke (300) von der Lagervorrichtung (40) bis zu der Materialablage (20) transportiert, wobei die Betriebseinheit (30) die Werkstücke (300) von der Materialablage (20) zu der Schleifgefässeinheit (60) transportiert, um die Werkstücke (300) bearbeiten zu lassen, wobei die Schleifgefässeinheit (60) eine Drehscheibe (62) und eine Vielzahl von Mahlgefässen (63) umfasst, wobei sich die Mahlgefässe (63) mit dem Drehen der Drehscheibe (62) verschieben, wobei die automatisierte Antriebseinheit (70) eine der Mahlgefässe (63) zum Drehen veranlasst, damit die Bearbeitung erfolgt. Mit der erfindungsgemäßen Bearbeitungseinrichtung wird ein vollautomatisiertes Bearbeitungsverfahren erzielt, das zu einer Steigerung der Herstellungsleistung beiträgt.

具有廣告推播功能的社區管理系統

Spindle Structure

OF THE DISCLOSURE The present disclosure provides a spindle structure including a base, a spindle, a sliding member, a restoring mechanism, and a restriction member. The spindle is rotatably received in the base and forms a receiving room. An end of the receiving room is a blind 5 end communicating exterior via a gas channel. The sliding member is slidably received in the receiving room, and two ends thereof are a piston and a driving portion respectively. A gas cavity is defined between the piston and the blind end. The sliding member tends to move toward the blind end due to the restoring mechanism. The restriction member is connected to the driving portion and radially deforms when the sliding member slides so as 0 to fix or to release the tool-holder. The sliding member slides outward when the gas cavity is injected with gas via the gas channel. 17 2/5 ICAD C.CAD

Targeting tumor cells with chemotherapeutic agents conjugated to anti-matriptase antibodies by in vivo cleavable linking moieties

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti- matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Grinding wheels changing structure

A grinding wheel changing structure of grinding machines includes a base to which a clamping device, a grinding device, a storage device, a gripping device are mounted thereon. The clamping device clamps workpieces. The grinding device is movable along two axes and includes a grinding wheel and a guard. The grinding wheel is located inside the guard. A lid is pivotably connected to the guard. The storage device has multiple grinding wheels detachably stored therein. The gripping device is located between the grinding device and the storage device. The gripping device is linearly movable and includes a gripping unit which is rotatable. By using the gripping device with its gripping unit to grasp the grinding wheel and shuttle back and forth, rotate between the grinding device and the storage device, to load and unload the grinding wheel.

園區資訊整合管理系統

Crushing and wringing device for plastic recycling

Spindelanordnung

Die Erfindung betrifft eine Spindelanordnung, die einen Sockel (10), einen Spindelhauptkörper (20), ein Gleitelement (30), ein Rückstellmittel, einen Abstandhalter (50) und eine Düse (60) umfasst, wobei der Spindelhauptkörper (20) in dem Sockel (10) drehbar aufgenommen ist und eine Aufnahmekammer aufweist, deren eines Ende als blindes Ende ausgebildet ist, wobei an der Aufnahmekammer ein Gaskanal (21) ausgebildet ist, der mit dem äußeren Umfeld in Verbindung steht. Das Gleitelement (30) ist in der Aufnahmekammer verschiebbar angeordnet und weist zwei Enden auf, die jeweils als Kolben (311) und Sperrteil ausgebildet sind, wobei zwischen dem Kolben (311) und dem blinden Ende der Aufnahmekammer eine Gaskammer (22) abgegrenzt ist, wobei das Gleitelement (30) durch die elastische Kraft des Rückstellmittels dazu tendiert, sich zu dem blinden Ende der Aufnahmekammer zu verschieben. Der Abstandhalter (50) ist mit dem Sperrteil verbunden und greift somit optional einen Werkzeughalter (80) störend axial ein, wobei sich der Abstandhalter (50) durch Gleiten des Gleitelements (30) radial verformt, um den Werkzeughalter (80) zu positionieren oder freizugeben. Die Düse (60) ist an dem Sockel (10) angeordnet, wobei der Gaskanal (21) über die Düse (60) mit Gas befüllt wird, wobei das Gleitelement (30) unter Einwirkung des Gases zum Verschieben nach außen gebracht wird, damit der Werkzeughalter (80) freigegeben wird.

Spindle Structure

OF THE DISCLOSURE The present disclosure provides a spindle structure including a base, a spindle, a sliding member, a restoring mechanism, and a restriction member. The spindle is rotatably received in the base and forms a receiving room. An end of the receiving room is a blind 5 end communicating exterior via a gas channel. The sliding member is slidably received in the receiving room, and two ends thereof are a piston and a driving portion respectively. A gas cavity is defined between the piston and the blind end. The sliding member tends to move toward the blind end due to the restoring mechanism. The restriction member is connected to the driving portion and radially deforms when the sliding member slides so as 0 to fix or to release the tool-holder. The sliding member slides outward when the gas cavity is injected with gas via the gas channel. 17 2/5 ICAD C.CAD

具切削液流通結構之主軸裝置

一種具切削液流通結構之主軸裝置，其係於本體內架設一可由動力源驅動旋轉之轉軸，於該轉軸內穿設一具軸孔之拉刀桿，並於該拉刀桿之頂端連接一具軸孔之轉接件，於該本體之頂部設有具伸縮桿之壓缸，並以該壓缸之伸縮桿凸伸壓抵轉接件，而帶動該拉刀桿作下移鬆刀動作，另該壓缸之伸縮桿內係設有軸孔，並於該伸縮桿之軸孔與該轉接件之軸孔間設有迴轉接頭組件，該迴轉接頭組件係於該伸縮桿之軸孔底部設有套管，並於該套管之底端設有第一抵接環，該轉接件之軸孔頂端則設有第二抵接環，並使該第一抵接環與該第二抵接環保持相互抵接，而形成一流通切削液之通道；藉此，其不僅可減少組裝之零組件，於驅動轉軸旋轉時，更可大幅降低偏擺及振動現象，而達到提昇加工精度及降低組裝成本之實用效益。

Targeting tumor cells with chemotherapeutic agents conjugated to anti-matriptase antibodies by in vivo cleavable linking moieties

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Workpiece Spindle

A workpiece spindle comprises a spindle, a spindle motor and an actuator. The spindle is dynamically connected to the spindle motor and has a first channel and a second channel connected to the first channel. The first channel is assembled with a lathe center, the actuator is provided with an actuating rod disposed outside the spindle corresponding to the second channel. The workpiece spindle limits rotation of the spindle by displacing the actuating rod of the actuator by a first actuation distance relative to the second channel, and the workpiece spindle drives the lathe center to displace in the first channel by displacing the actuating rod of the actuator by a second actuation distance relative to the second channel. Thereby, machining statuses of the lathe center are integrated for convenient operation, and the lathe center is driven and displaced in the channel to facilitate replacement.

Single polysilicon process for dram

A method of fabricating a DRAM cell, comprising the following steps. A substrate is provided. An isolation structure is formed within the substrate. The substrate is patterned to form nodes adjacent the isolation structure. Doped regions are formed with the substrate adjacent the nodes. A gate dielectric layer is formed over the patterned substrate, lining the nodes. A conductive layer is formed over the gate dielectric layer, filling the nodes. The conductive layer is patterned to form: a top electrode capacitor within the nodes; and respective word lines over the substrate adjacent the top electrode capacitor; each word line having exposed side walls. Source/drain regions are formed adjacent the word lines.

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