Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Lori C Morton

Dan Chalothorn

Jesper Gromada

KehDih Lai

Michael E Dunn

Lyndon Mitnaul

Andrew J Murphy

George D Yancopoulos

Lynn Macdonald

Aris N Economides

Brian Zambrowicz

Yajun Tang

Esther Latres

Chia-Jen Siao

Nicole M Alessandri-Haber

Vincent J Idone

Jason Mastaitis

Leah Sabin

Rachel Sattler

Daria Zamolodchikov

Jia Su

Qing Fang

Neil E Stahl

Tammy T Huang

Karolina Meagher

Douglas MacDonald

Jee Hwan Kim

Ashique Rafique

Jeffrey D Lee

Vishal Kamat

Kishor Devalaraja-Narashimha

Yinglin Gao

Yifan Luo

Scott Macdonnell

Bharathi Sundaram

Cong Huang

Isabella Del Priore

Jake Megna

Qin Ruan

Ishita Chatterjee

Sarah Casanova

Aris Economides

The present disclosure provides novel immunoglobulin proteins that bind to a human natriuretic peptide receptor 1 (NPR1) agonist, preferably an anti-NPR1 antibody. In certain embodiments, the proteins of the disclosure comprise at least one immunoglobulin variable domain that binds to an anti-NPR1 antibody. In certain embodiments, the proteins of the disclosure are useful in blocking and/or reversing the effect of an administered anti-NPR1 antibody. In certain embodiments, the antigen-binding proteins are useful for effective management of blood pressure and hemodynamics in humans.

Immunoglobulin proteins that bind to NPR1 agonists

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.

Method of using a genetically modified mouse that expresses human albumin

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.

Factor XI A2 domain-binding antibodies and methods of use thereof

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.

Non-human animals comprising a humanized coagulation factor 12 locus

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.

Anti-factor XII/XIIa antibodies and uses thereof

The present disclosure provides anti-Platelet-Derived Growth Factor Subunit B (PDGF-B) 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).

Anti-PDGF-B antibodies and pharmaceutical composition thereof

The present invention provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to NPR1. In some embodiments, the antibodies of the invention are useful for activating NPR1 activity, thus providing a means of treating or preventing a disease, disorder or condition associated with NPR1 in humans.

Anti-NPR1 antibodies and uses thereof

The present invention provides antibodies that bind to human gremlin-1 (GREM1), and methods of use. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to GREM1. The antibodies of the invention are useful for inhibiting or neutralizing GREM1 activity, thus providing a means of treating a GREM1-related disease or disorder such as fibrosis and cancer. In some embodiments, the antibodies of the present invention are used in treating at least one symptom or complication of fibrosis of the liver, lungs or kidney.

Human antibodies to GREM1

Genetically modified mouse that expresses human albumin

Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.

Humanized model of kidney and liver disorders

The present invention provides antibodies that bind to Activin A and methods of using the same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to Activin A with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders characterized by decreased muscle mass or strength, such as sarcopenia, cachexia, muscle injury, muscle wasting/atrophy, cancer, fibrosis, and weight loss. The antibodies of the invention are also useful in combination with Growth and Differentiation Factor 8 (GDF8) binding proteins for the treatment of diseases and disorders characterized by decreased muscle mass or strength. The antibodies of the invention are also useful for the prevention, treatment, or amelioration of disorders and diseases caused by, promoted by, exacerbated by, and/or aggravated by Activin A, such as renal fibrosis.

Anti-activin A antibodies and uses thereof

The present invention provides antibodies that bind big-endothelin-1 ('big-ET-1'), and methods of using same. According to certain embodiments of the invention, the antibodies specifically bind human big-ET-1 but do not bind human small-ET-1 (i.e., the active form of endothelin-1 that results from proteolytic cleavage of big-ET-1 by endothelin-converting enzyme-1 [ECE-1]). According to certain embodiments of the invention, the anti-big-ET-1 antibodies are capable of blocking cleavage of big-ET-1 by ECE-1. The antibodies of the invention are useful for the treatment of big-ET-1-related disorders, including hypertension disorders, fibrotic disorders, neurodegenerative disorders, retinal disorders, pain and cancers.

Anti-big-endothelin-1 (big-ET-1) antibodies and uses thereof

Growing community of inventors

Chappaqua, NY, United States of America

Lori C Morton