The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Massachusetts Institute of Technology

Harvard College

Other

University System of Maryland

Alexion Pharmaceuticals, Inc.

National Institutes of Health

Whitehead Institute

Whitehead Insti.

Michael J Lenardo

Phillip A Sharp

Albert S Baldwin

David Baltimore

Thomas P Maniatis

Harinder Singh

Roger G Clerc

Jonathan H Lebowitz

Louis Staudt

Ranjan Sen

Lynn M Corcoran

Patrick A Baeuerle

Chen-Ming Fan

Richard M Siegel

Jae W Lee

Wei Lu

Francis Ka-Ming Chan

Jian Li

Lixin Zheng

Stephen P Squinto

Louis A Matis

Henry McFarland

Steven H Nye

John P Mueller

Eileen Elliott Mueller

James A Wilkins

Eric H Baehrecke

Stefen A Boehme

Kaan Boztug

Helen Su

Ahmet Oguzhan Ozen

William Andrew Comrie

Clara M Pelfrey

Rico Chandra Ardy

Ajjai Alva

Yu Li

Galen Fisher

Jeffrey Critchfield

Disclosed is a protein comprising no more than three human autoantigenic proteins, wherein a first human autoantigenic protein comprises a truncated myelin oligodendrocyte glycoprotein (MOG) amino acid sequence, a second human autoantigenic protein comprises a myelin basic protein (MBP) amino acid sequence, and a third human autoantigenic protein comprises a truncated proteolipid protein (PLP) amino acid sequence. Also disclosed are related nucleic acids, pharmaceutical compositions, methods of treating a demyelinating disease, and methods of producing the proteins.

Myelin oligodendrocyte glycoprotein, myelin basic protein, and proteolipid protein compositions and methods of use

Disclosed herein are methods of diagnosing, and treating and/or preventing CD55-deficiency, hyperactivation of complement, angiopathic thrombosis and protein-losing enteropathy (CHAPLE). The method of diagnosing includes: providing a sample from a patient; performing an assay detecting at least one of at least one mutation in a DNA sequence of a CD55 gene, at least one mutation in a RNA sequence of a CD55 transcript, at least one mutation in a DNA sequence of a CD55 complementary-DNA (cDNA), CD55 protein, CD55 protein binding, complement deposition or combination thereof, and diagnosing the patient with CHAPLE. The method of treating and/or preventing at least one symptom of CHAPLE includes: administering an effective amount of a composition comprising at least one complement inhibitor to a subject in need thereof, wherein the composition is effective in treating or preventing at least on symptom of CHAPLE. The disclosure further relates to compositions effective at treating and/or preventing CHAPLE.

Methods of diagnosing and treating CD55 deficiency, hyperactivation of complement, angiopathic thrombosis and protein losing enteropathy (CHAPLE), a newly identified orphan disease

The present invention provides a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD) of a TNF-like receptor. Also provided by this invention is a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD), wherein the PLAD is selected from the group consisting of: the PLAD of a TNF-R, the PLAD of p60, the PLAD of p80, the PLAD of Fas (CD95/APO-1), the PLAD of TRAIL receptors, the PLAD of LT&#x3b2;R, the PLAD of CD40, the PLAD of CD30, the PLAD of CD27, the PLAD of HVEM, the PLAD of OX40 and the PLAD of DR4. TNF-R, p60, p80, Fas, TRAIL receptor, LT&#x3b2;R, CD40, CD30, CD27, HVEM, OX40, DR4, TROY, EDAR, XEDAR, DCR3, AITR, 4-1BB, DR3, RANK, TACI, BCMA, DR6, DPG, DR5, DCR1 AND DCR2 are all members of the TNF receptor superfamily or the TNF-like receptor family. The invention also provides the PLAD for other members of the TNF receptor superfamily. The polypeptides of the present invention can be utilized to inhibit oligomerization of members of the TNF receptor superfamily. These polypeptides can also be utilized to inhibit ligand binding to members of the TNF receptor superfamily. The present invention also provides a composition comprising an inhibitor of TNF receptor oligomerization. Further provided by this invention are members of the TNF receptor superfamily that are lacking a PLAD.

Inhibitors of pre-ligand assembly doman and function of the tumor necrosis factor receptor family

The present invention relates to a new molecular pathway in which activation of the receptor-interacting protein (RIP, a serine-threonine kinase) and Jun N-terminal kinase induce cell death with the morphology of autophagy. Further, autophagic death is induced by caspase 8 inhibition and expression of the mammalian genes ATG7 and beclin.

Function of autophagy genes in cell death

Identification of a novel domain in the tumor necrosis factor receptor family that mediates pre-ligand receptor assembly and function

Compositions and methods are provided for the clinical assessment, diagnosis, and treatment of multiple sclerosis. The compositions of the invention are molecules related to the 21.5 kDa fetal isoform of human myelin basic protein, and include nucleic acids and polypeptides. The nucleic acid molecules of the invention are useful in the efficient production of modified and unmodified 21.5 kDa myelin basic protein polypeptides, such polypeptides being useful for assaying T cells for responsiveness to myelin basic protein epitopes. The polypeptides of the invention are also useful as therapeutic agents that act by inducing T cell responses, including apoptosis, as a means of treating multiple sclerosis.

Modified myelin basic protein molecules

Constitutive and tissue-specific protein factors which bind to transcriptional regulatory elements of Ig genes (promoter and enhancer) are described. The factors were identified and isolated by an improved assay for protein-DNA binding. Genes encoding factors which positively regulate transcription can be isolated and employed to enhance transription of Ig genes. In particular, NF-kB, the gene encoding NF-kB, IkB and the gene encoding IkB and uses therefor.

Nuclear factors associated with transcriptional regulation

The present invention relates to an applicator system including an applicator, an applicator tube, an applicator tube system, and a cap system.

Applicator system

A method for the treatment or prevention of autoimmune diseases, allergic or atopic disorders, and graft rejection is provided, comprising inducing the death by apoptosis of a subpopulation of T lymphocytes that is capable of causing such diseases, while leaving substantially unaffected the majority of other T lymphocytes. Cell death is achieved by cycle(s) comprising challenging via immunization these T cells with antigenic substance at short time intervals, or by immunization followed by administering interleukin-2 (IL-2) when these T cells are expressing high levels of IL-2 receptor so as to cause these T cells to undergo apoptosis upon re-immunization with the antigenic peptide or protein. These methods are applicable to the treatment of autoimmune diseases such as, for example, multiple sclerosis, uveitis, arthritis, Type I insulin-dependent diabetes, Hashimoto's thyroiditis, Grave's thyroiditis, autoimmune myocarditis, etc., allergic disorders such as hay fever, extrinsic asthma, or insect bite and sting allergies, food and drug allergies, as well as for the treatment or prevention of graft rejection.

Interleukin-2 stimulated T lymphocyte cell death for the treatment of

A method for the treatment or prevention of allergic disorders is provided, comprising inducing the death by apoptosis of a subpopulation of T lymphocytes that is capable of causing such diseases, while leaving substantially unaffected the majority of other T lymphocytes. Cell death is achieved by cycle(s) comprising challenging via immunization these T cells with antigenic substance at short time intervals, or by immunization followed by administering interleukin-2 (IL-2) when these T cells are expressing high levels of IL-2 receptor so as to cause these T cells to undergo apoptosis upon re-immunization with the antigenic peptide or protein. These methods are applicable to the treatment of allergic disorders such as hay fever, extrinsic asthma, or insect bite and sting allergies, and food and drug allergies.

This invention discloses a method for the treatment or prevention of autoimmune diseases, allergic or atopic disorders and graft rejection. Specifically, it provides a means of killing a specific sub-population of T lymphocytes while leaving the majority of other T lymphocytes in the population unaffected. The sub-population of T lymphocytes are killed by repeatedly challenging the population with an antigen in conjunction with administration of interleukin-4.

Interleukin-4 stimulated T lymphocyte cell death for the treatment of

Nuclear factors associates with transcriptional regulation

Growing community of inventors

Potomac, MD, United States of America

Michael J Lenardo