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Now showing items 1 - 6 of 6


    Provided herein are methods and compositions for site-specific conjugation of antibodies.
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  • Design and Flight Performance of the Orion Prelaunch Navigation System

    Zanetti, Renato   Holt, Greg   Gay, Robert   D'Souza, Christopher   Sud, Jastesh   Mamich, Harvey   Gillis, Robert  

    The design of National Aeronautics and Space Administration Orion's prelaunch navigation system is introduced, both for the first flight test, Exploration Flight Test 1, and for the first planned Orion mission, Exploration Mission 1. A detailed tradeoff of possible design decisions is discussed, and the choices made by Orion are presented. The actual performance of the navigation system during Exploration Flight Test 1 is presented together with the navigation flight-software data provided by Orion to the ground controllers in telemetry.
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  • Absolute Navigation Performance of the Orion Exploration Flight Test 1

    Zanetti, Renato   Holt, Greg   Gay, Robert   D'Souza, Christopher   King, Ellis   Clark, Fred D.  

    Launched in December 2014 atop a Delta IV Heavy from the Kennedy Space Center, the Orion vehicle's Exploration Flight Test 1 successfully completed the objective to stress the system by placing the uncrewed vehicle on a high-energy parabolic trajectory, replicating conditions similar to those that would be experienced when returning from an asteroid or a lunar mission. Unique challenges associated with designing the navigation system for Exploration Flight Test 1 are presented with an emphasis on how redundancy and robustness influenced the architecture. Two inertial measurement units, one GPS receiver, and three barometric altimeters comprise the navigation sensor suite. The sensor data are multiplexed, using conventional integration techniques, and the state estimate is refined by the GPS pseudo- and delta-range measurements in an extended Kalman filter that employs UDU factorization. The performance of the navigation system during flight is presented to substantiate the design.
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  • Orion Rendezvous, Proximity Operations, and Docking Design and Analysis

    D'Souza, Christopher   Hanak, F Chad   Spehar, Pete   Clark, Fred D   Jackson, Mark  

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  • Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers

    Hickey, Carlos   Makonnen, Sosina   Coetzee, Sandra   Jalal, Sumreen   Wang, Yu   Delfino, Frank   Shan, Jing   Potocky, Terra B.   Chatterjee, Ishita   Andreev, Julian   Kunz, Arthur   D'Souza, Christopher   Giurleo, Jason T.   Nittoli, Thomas   Trail, Pamela A.   Thurston, Gavin   Kirshner, Jessica R.  

    The Prolactin Receptor (PRLR) is a type 1 cytokine receptor that is expressed in a subset of breast cancers and may contribute to its pathogenesis. It is relatively overexpressed in approximately 25% of human breast tumors while expressed at low levels in some normal human tissues including the mammary gland. We developed an anti-PRLR antibody-drug conjugate (ADC), to target PRLR-positive breast cancer. REGN2878-DM1 is comprised of a fully human high-affinity function-blocking anti-PRLR IgG1 antibody (REGN2878) conjugated via a noncleavable SMCC linker to the cytotoxic maytansine derivative DM1. Both unconjugated REGN2878 and conjugated REGN2878-DM1 block PRL-mediated activation in vitro and are rapidly internalized into lysosomes. REGN2878-DM1 induces potent cell-cycle arrest and cytotoxicity in PRLR-expressing tumor cell lines. In vivo, REGN2878-DM1 demonstrated significant antigen-specific antitumor activity against breast cancer xenograft models. In addition, REGN2878-DM1 showed additive activity when combined with the antiestrogen agent fulvestrant. These results illustrate promising antitumor activity against PRLR-positive breast cancer xenografts and support the evaluation of anti-PRLR ADCs as potential therapeutic agents in breast cancer.
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  • [American Institute of Aeronautics and Astronautics AIAA Guidance, Navigation, and Control Conference and Exhibit - Monterey, California ()] AIAA Guidance, Navigation, and Control Conference and Exhibit - An Optimal Guidance Law for Formation Flying and Stationkeeping

    D'Souza, Christopher  

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