Hoffmann-la Roche Inc.

University of California

Waleed Danho

Jefferson Wright Tilley

Joseph Swistok

Wajiha Khan

Joseph Triscari

John K Bielicki

Jan Johansson

David Charles Fry

George Kenneth Ehrlich

Rolf Wagner

Nader Fotouhi

Arthur M Felix

Li Chen

Vincent Stewart Madison

David Robert Bolin

Xin-Jie Chu

Adrian Wai-Hing Cheung

Rebecca Taub

Keith A Yagaloff

Anish A Konkar

Karin Conde-Knape

Cristina Martha Rondinone

Robert Alan Goodnow, Jr

Gary L Olson

Shian-Jan Shiuey

Alain Fournier

Huifeng Niu

Yi Han

Francesca Milletti

Yao Wang

David J Nelson

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

The present invention provides compounds to disrupt the eIF4E-eIF4G interaction and pharmaceutically acceptable salts of such compounds. Generally, the compounds are cell-penetrating peptides which bind mammalian initiation factor eIF4E (CPP-eIF4E), wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 9-11, 12-26, 27-44 and 45-51. More preferably, the amino acid sequence comprises at least 9 to about 40 amino acids and the mammalian initiation factor eIF4E is human initiation factor eIF4E.

Cell penetrating peptides to target EIF4E

The present invention provides compounds which are analogs of glucose-dependent insulinotropic polypeptide (GIP) and pharmaceutically acceptable salts of such compounds. These compounds have activity as agonists of GIP receptor.

Glucose-dependent insulinotropic peptide analogs

Provided herein are neuropeptide-2 receptor agonists of the formula (I):Y&#x2014;R&#x2014;R&#x2014;X&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;NH&#x2003;&#x2003;(I) (SEQ ID NO: 1),as well as pharmaceutically acceptable salts, derivatives and fragments thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity and diabetes.

Neuropeptide-2 receptor (Y-2R) agonists

Provided herein are neuropeptide-2 receptor agonists of the formula (I): as well as pharmaceutically acceptable salts, derivatives and fragments thereof, wherein the substituents are as those disclosed in the specification. X is 4-oxo-6-(1-piperazinyl)-3(4H)-quinazoline-acetic acid (Pqa). These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity and diabetes.

Neuropeptide-2 receptor (Y-2R) agonists and uses thereof

Provided herein are neuropeptide-2 receptor agonists of the formula (I):Y&#x2014;R&#x2014;R&#x2014;X&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;R&#x2014;NH, &#x2003;&#x2003;(I)as well as pharmaceutically acceptable salts, derivatives and fragments thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.

Peptides cyclized via disulfide or lactam bridges are disclosed. The peptides exhibit melanocortin-4 receptor agonist activity and are useful for treating obesity.

Selective cyclic peptides with melanocortin-4 receptor (MC4-R) agonist activity

Peptides that selectively stimulate melanocortin-4 (MC-4) receptor activity are disclosed. In one embodiment, the peptides are of formula I:

Selective linear peptides with melanocortin-4 receptor (MC4-R) agonist activity

This invention relates to a novel process for the synthesis of vasoactive intestinal peptide analog Ac(1-31)-NH2 from four protected peptide fragments.

Synthesis of VIP analog

This invention relates to a novel process for the synthesis of vasoactive intestinal peptide analog Ac(1-31)--NH.sub.2 from four protected peptide fragments.

Analogs of Tyrosine Sulfate or Tyrosine Phosphate containing peptides, the novel intermediate compounds used in the preparation of these analogs, as well as a method for suppressing appetite in subjects by administering to the subject an effective amount of CCK analog wherein one or more of any Tyrosine Sulfate present is substituted with a radical of the invention.

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Del Mar, CA, United States of America

Waleed Danho