T Cell Sciences, Inc.

Celldex Therapeutics Limited

Johns Hopkins University

The Brigham and Women's Hospital, Inc.

The University of Mississippi

Avant Immunotherapeutics, Inc.

University of Iowa Research Foundation

Smithkline Beecham Corporation

Celdara Medical, LLC

Henry C Marsh

Stephen H Ip

Michael F Concino

Lloyd B Klickstein

Douglas T Fearon

Savvas C Makrides

Gerald R Carson

Winnie W Wong

Tibor P Keler

Barton J Bradbury

Michael L Gosselin

Lawrence J Thomas

Robert D Sindelar

Richard A Smith

Chang-Jing Grace Yeh

Anne Mary Freeman

Laura A Vitale

Lizhen He

Joel Goldstein

Chew Lee

Richard J H Smith

Terrance A Stadheim

Karuna Sundarapandiyan

Jenifer Widger

John Lifter

Teodoro S Kaufman

Yuzhou Zhang

Teodoro Kaufman

Joana M Murad

Jake Reder

Li-Zhen He

Hua Gao

Xiaoxi Qiao

Richard Jh Smith

Richard JH Smith

The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).

Chimeric antigen receptors targeting TIM-1

Isolated monoclonal antibodies which bind to human CD27 and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic and diagnostic methods for using the antibodies.

Antibodies that bind human CD27 and uses thereof

A method is disclosed for treating nephropathies involving undesired alternative pathway complement activation by administration of a complement inhibitory protein such as soluble complement receptor type I (sCR1).

Treatment of chronic nephropathies using soluble complement receptor type I (sCR1)

A method is disclosed for treating diseases or disorders of the eye involving undesired neovascularization by administration of a complement inhibitory protein such as soluble complement receptor type I (sCR1). The present invention relates to the direct treatment of macular degeneration, particularly age-related macular degeneration (AMD), by administering a complement inhibitory protein intraocularly or systemically.

Treatment for age-related macular degeneration and other diseases of the eye

The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention also relates to CR1 nucleic acid sequences and fragments thereof comprising 70 nucleotides and their encoded peptides or proteins comprising 24 amino acids. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

Human C3b/C4b receptor (CR1)

Provided are methods of making preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms and therapeutic methods using them. The preparations are suitable for treatment of allograft or xenograft rejection, diseases involving inflammation or inappropriate complement activation, and thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of .ltoreq.5.1, or have a sialic acid: mannose molar ratio of .gtoreq.0.25.

Preparation and use of sialylated glycoforms of soluble complement

The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

Provided are therapeutic methods employing preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms. The methods are suitable for treatment of disease involving inflammation, inappropriate complement activation, and in thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of .ltoreq.5.1, or have a sialic acid:mannose molar ratio of .gtoreq.0.25.

Therapeutic methods employing sialylated glycoforms of soluble

Human complement receptor type 1 (CR1). Nucleic acid molecules encoding full-length CR1 protein and fragments thereof having complement regulatory activity are described, as well as recombinant CR1 protein and polypeptides, vectors for their expression, and cell lines expressing or bearing DNA molecules encoding such proteins and polypeptides, including a soluble CR1 polypeptide consisting of the extracellular 30 short consensus repeat domains of the mature CR1 protein. The nucleic acids and polypeptides described are useful in diagnosis and treatment of disorders involving complement activity and inflammation. Compositions useful in therapeutic applications are also disclosed.

Compounds that inhibit complement and/or suppress immune activity

Method of treating complement mediated disorders

The present invention relates to novel glycoforms and preparations of the soluble complement receptor type 1 (sCR1), and their uses in the therapy of complement mediated diseases and disorders involving inflammation and inappropriate complement activation and in thrombotic or shock state conditions. The invention provides novel glycoforms and methods for producing, detecting, enriching and purifying such glycoforms. The invention further provides methods of specifically producing a glycoform by recombinant or chemical means. Preferred embodiments of the invention include sialylated glycoforms and glycoforms with a pI.ltoreq.5.1 determined by chromatofocusing or with a sialic acid to mannose molar ratio of &gt;0.25. The glycoforms may be formulated alone in therapeutic compositions or in combination with thrombolytic agents.

Glycoform fractions of recombinant soluble complement receptor 1 (sCR1)

The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.

Compounds which inhibit complement and/or suppress immune activity

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Reading, MA, United States of America

Henry C Marsh