Biogen Ma Inc.

Biogen Idec Ma Inc.

University of California

Other

Kenneth J Simon

Mia Marie Rushe

Paul H Weinreb

Shelia Marie Violette

Alexey Alexandrovich Lugovskoy

Meena Subramanyam

Leonid Gorelik

Jose William Saldanha

Dean Sheppard

Diane R Leone

Justin Andrew Caravella

Herman Van Vlijmen

Karl Hanf

Thomas O Cameron

Louise A Koopman

Herman W T Van Vlijmen

You Li

Ellen A Garber

Deping Wang

Joseph Arndt

George Campbell Kaynor

Eric Day

The invention relates to methods and reagents for analyzing samples for the presence of JC virus antibodies.

Assay for JC virus antibodies

The disclosure relates to methods and reagents for analyzing samples for the presence of JC virus antibodies. Disclosed is a method that includes obtaining a biological sample from a subject (e.g., plasma, serum, blood, urine, or cerebrospinal fluid), contacting the sample with highly purified viral-like particles (HPVLPs) under conditions suitable for binding of a JCV antibody in the sample to an HPVLP, and detecting the level of JCV antibody binding in the sample to HPVLP. In one embodiment, determining the level of anti-JCV antibodies in the subject sample provides a method of identifying PML risk in a subject.

Monoclonal antibodies that specifically bind to M.96. Also included are methods of using these antibodies to treat mammals having or at risk of having 006-mediated diseases, or to diagnose % Qmediated diseases.

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In one aspect, the disclosure provides neutralizing antibodies against JCV and methods for the treatment of PML. In some embodiments, aspects of the invention relate to an isolated JC-virus neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-virus. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VPI. In some embodiments, the antibody binds JCV-VP 1 comprising one or more of the following mutations: S269F, S269Y, S267F, N265D, Q271 H, D66H, K60E, K60N and L55F.

JCV neutralizing antibodies

In one aspect, the disclosure provides neutralizing antibodies against JCV and methods for the treatment of PML. In some embodiments, aspects of the invention relate to an isolated JC-vims neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-vims. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VP1.

The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize &#x3b1;&#x3b2;integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-&#x3b1;&#x3b2;antibodies of the invention. The invention also relates to the identification of differential expression of the integrin &#x3b1;&#x3b2;on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin &#x3b1;&#x3b2;.

The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.

Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues

Monoclonal antibodies that specifically bind to &#x25a1;v&#x25a1;&#x25a1;. Also included are methods of using these antibodies to treat mammals having or at risk of having &#x25a1;v&#x25a1;6-mediated diseases, or to diagnose &#x25a1;V&#x25a1;6-mediated diseases.

This invention concerns humanized antibodies specific for the lymphotoxin beta receptor (LT-&#x3b2;-R), cell lines that produce these antibodies, immunochemicals made from the antibodies, and diagnostic methods that use the antibodies. The invention also relates to the use of the antibodies alone or in combination with chemotherapeutic agent(s) in therapeutic methods.

Growing community of inventors

Cambridge, MA, United States of America

Kenneth J Simon