Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: The present invention provides monoclonal antibodies that bind to the Factor XII (FXII) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to FXII and to the activated form of FXII (FXIIa). In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing FXII activity, thus providing a means of treating or preventing a disease, disorder or condition associated with thrombosis in humans.

Abstract: The present disclosure provides antibodies that bind to the catalytic domain of Factor XI (FXI) and methods of using the same. According to certain embodiments, the antibodies are antagonist antibodies that inhibit blood clot formation via the intrinsic pathway without affecting hemostasis, as shown by their effect on prolonging aPTT without affecting PT. As such, these antagonist antibodies may be used to treat blood clotting diseases or disorders or treatment regimens that have clot formation as a risk factor, such as, but not limited to atrial fibrillation. In certain embodiments, the disclosure includes antibodies that bind FXI and mediate clot formation or thrombogenesis. The antibodies of the disclosure may be fully human, non-naturally occurring antibodies.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Abstract: The present disclosure provides antibodies that bind to the A2 domain of Factor XI (FXI) and methods of using the same. According to certain embodiments, the antibodies are antagonist antibodies that inhibit blood clot formation via the intrinsic pathway without affecting hemostasis, as shown by their effect on prolonging aPTT without affecting PT. As such, these antagonist antibodies may be used to treat blood clotting diseases or disorders or treatment regimens that have clot formation as a risk factor, such as, but not limited to atrial fibrillation. In certain embodiments, the disclosure includes antibodies that bind FXI and mediate clot formation or thrombogenesis. The antibodies of the disclosure may be fully human, non-naturally occurring antibodies.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Abstract: An operational amplifier with totem pole connected output transistors having inputs coupled to multiplexers for selectable coupling of signals and voltage levels thereto. The high and low output transistors may be forced hard on or hard off in addition to normal coupling of signals thereto. The operation of the output transistors may be dynamically changed to pass only positive going signals, negative going signals, placed in a tristate high impedance state, hard connected to a supply voltage and/or hard connected to supply common return. A core independent peripheral (CIP) may also be coupled to the operational amplifier for dynamically changing the multiplexer inputs in real time, as can external control signals to a control circuit coupled to the multiplexers.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

Abstract: The present invention provides anti-Gremlin-1 (GREM1) antibodies, and antigen-binding fragments thereof, as well as methods of use of such antibodies, or antigen-binding fragments thereof, for treating a subject having pulmonary arterial hypertension (PAH).

Abstract: The present invention provides anti-Activin A antibodies, and antigen-binding fragments thereof, as well as methods of use of such antibodies, or antigen-binding fragments thereof, for treating a subject having pulmonary arterial hypertension (PAH).