Abstract: Antibody formulations are described comprising a mixture of an anti-?4?7 antibody, an antioxidant or chelator, and at least one free amino acid. The disclosed formulations may have improved stability, reduced aggregate formation, or both. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-?4?7 antibody in vivo.

Abstract: Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

Abstract: The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.

Abstract: Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.

Abstract: The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

Abstract: Disclosed are chemical entities which are compounds of formula (I): or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra?, Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

Abstract: Systems and methods for distributing a filling fluid are discussed. More particularly an exemplary filling system may include a reservoir holding a filling fluid for distribution. The filling system may also include a pump and filling nozzle fluidly coupled to the reservoir. A processor executes a filling module that when executed receives at least one input fluid property of the filling fluid and generates at least one set of operating parameters for controlling operation of the pump during a filling operation based at least in part on the fluid property. The generated set of operating parameters enable control of the pump to distribute the filling fluid through the filling nozzle, such that a fluid interface with a stable resting profile forms in the filling fluid in the filling nozzle adjacent to the nozzle opening after the filling fluid is distributed from the filling nozzle.

Abstract: The present disclosure relates to methods or dosing regimens comprising a proteasome inhibitor of formula (I), or a pharmaceutically acceptable salt thereof, for treating cancer, or preventing cancer recurrence or progression; wherein ring A, Z1 and Z2 are as defined herein.

Abstract: The present invention is directed to cocrystal forms of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxcyclopentyl) methyl sulfamate of formula (I). The invention is also directed to methods of making cocrystal forms of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl) methyl sulfamate of formula (I). The invention is also directed to the pharmaceutical use of a cocrystal form as an E1 activating enzyme inhibitor, as well as a pharmaceutical composition comprising a cocrystal form. The invention is further directed to a method of treatment comprising administering a cocrystal form of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate of formula (I).

Abstract: This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.

Abstract: Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Abstract: Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

Abstract: The invention features new a method for treating inflammatory bowel disease, including Crohn's Disease (CD) or ulcerative colitis in a human patient, comprising administering to a patient a combination therapy comprising an anti-?4?7 antibody, a TNF? antagonist, and an immunomodulator.

Abstract: This invention provides novel solid pharmaceutical compositions and processes for the bulk production of said compositions. This invention also provides methods of using the pharmaceutical compositions in the treatment of cancer.

Abstract: Disclosed are chemical entities which are compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.

Abstract: Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

Abstract: Disclosed are chemical entities which are compounds of formula (I): or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra?, Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

Abstract: The present invention provides processes and synthetic intermediate (Ia) for the synthesis of 4-substituted ((1S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates. These sulfamate compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.