Regeneron Pharmaceuticals, Inc.

Stanley J Wiegand

Jingtai Cao

George D Yancopoulos

James P Fandl

Andrew J Murphy

Nicholas J Papadopoulos

Ying Hu

Alexander O Mujica

Ivan Borisovich Lobov

Adrianna Latuszek

Thomas Daly

Mark W Sleeman

Neil E Stahl

Claus Cursiefen

Lynn Macdonald

John R McWhirter

Daniel B Dix

Karolina Meagher

Peter Anthony Campochiaro

Kenneth S Graham

Li-Hsien Wang

Nikos Panayotatos

Susan D Croll

Ronald M Lindsay

Karen W Chu

Robert L Vitti

John Mcwhirter

Saurabh Wadhwa

Kristine A Erickson

Hsin Chieh Lin

Philip D Lambert

Keith D Anderson

Ivan B Lobov

Cao Jingtai

Wang Li-Hsien

Chieh Lin Hsin

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

Humanized C5 animals

The present invention provides methods for treating, preventing or reducing the severity of an eye disease. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an angiopoietin-2 (Ang-2) inhibitor such as an anti-Ang-2 antibody in combination with a vascular endothelial growth factor (VEGF) antagonist (e.g., aflibercept).

Methods and formulations for treating vascular eye diseases using aflibercept and nesvacumab

Humanized C3 animals

The present invention provides antibodies that bind to platelet derived growth factor receptor beta (PDGFR-beta) and methods of using the same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PDGFR-beta with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders associated with PDGFR-beta signaling and/or PDGFR-beta cellular expression, such as ocular diseases, fibrotic diseases, vascular diseases and cancer.

Anti-PDGFR-beta antibodies and uses thereof

Methods of reducing or treating angiogenesis and/or inflammation associated with eye injury in a subject in need thereof, comprising administering an agent capable of blocking or inhibiting vascular endothelial growth factor (VEGF) are provided. The methods are useful for inhibiting or ameliorating eye injury, particularly acute or subacute corneal injury and feature local administration (for example, subconjunctival injection or eye drops).

Ophthalmic composition of a VEGF antagonist

Modified chimeric polypeptides with improved pharmacokinetics and improved tissue penetration are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.

Use of VEGF inhibitors for treatment of eye disorders

Methods of treating diabetes in mammals, particularly humans, by blocking or inhibiting VEGF-mediated activity. A preferred inhibitor of VEGF-mediated activity is a VEGF antagonist such as the VEGF fusion protein trap of SEQ ID NO:2 capable of binding and blocking VEGF. The method of the invention may be combined with other therapies, such as with insulin therapy.

Methods of treating type I diabetes by blocking VEGF-mediated activity

The invention provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.

Method of treatment using Tie2 ligand2

Method of treating eye injury with local administration of a VEGF inhibitor

Modified chimeric polypeptides with improved pharmacokinetics are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.

Methods of treating eye disorders with modified chimeric polypeptides

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Croton-on-Hudson, NY, United States of America

Stanley J Wiegand