Harvard College

Children's Medical Center Corporation

Other

Best Doctors, Inc.

Nuchem Pharmaceuticals Inc.

Ion Pharmaceuticals, Inc.

Mellitus, LLC

Health Resources and Technology Inc.

Jose Alberto Halperin

Carlo Brugnara

Michael Chorev

Adel M Moussa

Ying-Duo Gao

Minghua Sun

Yesh P Sachdeva

Richard John Lombardy

John J Clifford

Reem M Haidar

Eugene W Kelleher

Heather N Taft

Emile M Bellott

Rudolf Fluckiger

Huseyin Aktas

Mark Froimowitz

Emile M Bellot, Jr

Falguni M Kher

Kenneth H Falchuk

Michael H Zeldin

Gerhard Wagner

Bertal Huseyin Aktas

Lawrence S Brewster

Harley Haynes

Juan A Acosta

Daniel J Goldstein

Nathan John Moerke

Evan J Falchuk

Evan Falchuk

The present invention provides glycated Amadori products of the CD59 peptide and fragments thereof to be used as tools and among methods for the diagnosis and prognosis of pre-diabetes and diabetes. Certain aspects of the invention include glycated Amadori products of CD59 and fragments thereof to be used for the generation of antibodies and antibody fragments. Still other aspects of the invention include methodologies for the preparation of glycated Amadori products of CD59, fragments thereof, the inventive antibodies, and antibody fragments.

Glycated CD59 peptides, their preparation, and uses thereof

Anti-CD59 and anti-glycated CD59 antibodies are disclosed. Assays, diagnostics, kits, and assay components including such antibodies are provided. Methods for the assessment of diabetes-related indications are included as well as inhibitors of CD59 glycation and methods of evaluating such inhibitors.

Anti-CD59 antibodies

The invention involves assays, diagnostics, kits, and assay components for determining levels of glycated CD59 in the assessment of gestational diabetes mellitus and/or related disorders and/or conditions.

Methods and reagents for the assessment of gestational diabetes

The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post-translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post-translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.

Surrogates of post-translationally modified proteins and uses thereof

A method for determining the translation initiation inhibitory potency of a composition having an unknown level of translation initiation inhibitory activity which comprises contacting an eI-F2&#x3b1;-WT cell with said composition for a time and at a temperature effective to inhibit proliferation of said cell, measuring the level of inhibition of proliferation of said eIF2&#x3b1;-WT cells induced by said sample and comparing the level of inhibition of proliferation induced by said sample with the level of inhibition of proliferation induced by a standard having a known amount of said activity, the amount of said translation initiation inhibitory activity in said sample being proportional to the level of inhibition of proliferation of said eIF2&#x3b1;-WT cell.

Cell based quality control bioassays for nutriceutical and medicinal products

Bioassays for detecting the ability of one sample of a food substance, nutritional supplement, therapeutic agent and/or disease preventive agent relative to that of a second sample of such a substance, supplement and/or agent to inhibit, upregulate or otherwise modulate translation initiation, and thereby demonstrate a disease curative and/or preventive effect in a human and/or animal that consumes a such substance, supplement and/or agent or to whom a such substance, supplement and/or agent is administered are provided.

Quality control bioassays for nutriceutical and medicinal products

Compositions and methods for inhibiting translation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, (4) disorders associated with viral infections, and/or (5) non-proliferative metabolic disorders such as type II diabetes where inhibition of translation initiation is beneficial using the compounds disclosed herein.

Compounds for the inhibition of cellular proliferation

The invention involves assays, diagnostics, kits, and assay components for mass spectrometry and other methods to determine levels of glycated CD59 in subjects.

Mass spectrometric methods and products

The invention involves assays, diagnostics, kits, and assay components for determining levels of K41-glycated CD59 in subjects. Treatments for subjects based upon levels of K41-glycated CD59 also are provided.

Methods, products and treatments for diabetes

Growing community of inventors

Brookline, MA, United States of America

Jose Alberto Halperin