The Salk Institute for Biological Studies

Other

Neurocrine Biosciences, Inc.

Nicholas C Ling

Amitabh Gaur

Paul J Conlon

Frederick S Esch

Roger C Guillemin

Peter Bohlen

Paul E Brazeau, Jr

Shao-Yao Ying

Lawrence Steinman

Andrew J Baird

Denis Gospodarowicz

Shunichi Shimasaki

Naoto Ueno

Theophil Staehelin

Fred S Esch

Paul D Crowe

Jean E Rivier

Wylie W Vale, Jr

Joachim Spiess

J Andrew Baird

Joan Vaughan

Anne Corrigan

R David Leslie

Marco Londei

Richard A McClintock

Solange Lavielle

Robert A Benoit

William B Wehrenberg

Paul E Brazeau

The present invention is directed toward peptide analogues of insulin B chain that are generally derived from peptides comprising residues 9 to 23 of the native B chain sequence. The analogues are altered from the native sequence at position 12, 13, 15 and/or 16, and may be additionally be altered at position 19 and/or other positions. Pharmaceutical compositions containing these peptide analogues are provided. The peptide analogues are useful for treating and inhibiting the development of diabetes.

Methods for treatment of diabetes using a peptide analogues of insulin

Peptide analogues of human myelin basic protein containing residues 87-99 are provided. Residue 91 of the peptide analogues is altered from the L-lysine residue found in the native protein to any other amino acid. Pharmaceutical compositions of the peptide analogues are provided. In addition, the peptide analogues are administered to patients with multiple sclerosis.

Methods for treatment of multiple sclerosis using peptide analogues at position 91 of human myelin basic protein

The present invention is directed toward peptide analogues of insulin B chain that are generally derived from peptides comprising residues 9 to 23 of the native B chain sequence. The analogues are altered from the native sequence at position 12, 13, 15 and/or 16, and may be additionally be altered at position 19 and/or other positions. Pharmaceutical compositions containing these peptide analogues arc provided. The peptide analogues are useful for treating and inhibiting the development of diabetes.

Methods for treatment of diabetes using peptide analogues of insulin

The present invention is directed toward peptide analogs of human myelin basic protein. The peptide analog is at least seven amino acids long and derived from residues 83 to 99 of human myelin basic protein. The analogs are altered from the native sequence at least at positions 91, 95, or 97. Additional alterations may be made at other positions. Pharmaceutical compositions containing these peptide analogs are provided. The peptide analogs are useful for treating multiple sclerosis.

Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein

The present invention is directed toward peptide analogues of human myelin basic protein. The peptide analogue is at least seven amino acids long and derived from residues 86 to 99 of human myelin basic protein. The analogues are altered from the native sequence at least at positions 91, 95, or 97. Additional alterations may be made at other positions. Pharmaceutical compositions containing these peptide analogues are provided. The peptide analogues are useful for treating multiple sclerosis.

Methods for treatment of multiple sclerosis using peptide analogues of human myelin basic protein

An insulin-like growth factor binding protein is isolated from rat serum and partially sequenced. Using nucleotide probes based upon the amino terminal sequence of the isolated protein, the complete sequence for the 233-residue rat protein, termed IGFBP-4, is deduced, and the homologous 237-residue sequence of the human protein is separately deduced. These proteins are useful in the inhibition of cell differentiation and/or proliferation requiring IGFs and are particularly useful in combating breast cancers. Antibodies to the proteins may be employed in diagnostic assays, in purification of the protein and in the modulation of bone growth.

DNA encoding IGFBP-4

The present invention is directed toward peptide analogues of human myelin basic protein for use in the treatment of multiple sclerosis. Within one aspect, peptide analogues suitable for treating multiple sclerosis are provided which are at least seven amino acids long and derived from residues 86 to 99 of human myelin basic protein. In addition, such analogues may be altered from the native sequence at positions 87, 88, 97, 98 or 99 to a D-amino acid. Additional alterations may be made at other positions. Pharmaceutical compositions containing these peptide analogues are also provided, as well as methods for treating multiple sclerosis.

Methods for treatment of multiple sclerosis utilizing peptide analogues

Peptides and peptide analogues of the 65 kD isoform of human glutamic acid decarboxylase are provided for use in the treatment and prevention of diabetes. Peptide analogues contain generally from one to three amino acid alterations. Peptides and analogues may be used to diagnose diabetes and detect a predisposition to diabetes.

Peptide analogues of the 65KD isoform of human glutamic acid

Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bovin bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.

Bovine basic fibroblast growth factor

Antagonists to basic fibroblast growth factor, a 146 amino acid residue polypeptide, are produced. These antagonists are generally between 10 and 45 residues in length and are characterized by their ability to interact with the FGF receptor and/or inhibit and therefore modulate endothelial and other cell growth in vitro and also in vivo. These antagonists includes the sequence of bovine basic FGF(106-115), namely Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr or a sequence having equivalent residues substituted therein. These peptides are also antagonistic to acidic FGF and other members of the family of FGF peptides. They are effective to combat FGF-promoted mitosis in melanomas and the like.

Fibroblast growth factor antagonists

Two follistatin proteins with inhibin-like activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then six steps of high-performance liquid chromatography. The larger protein has 315 residues and is believed to be glycosylated. The smaller protein is a 288-residue, C-terminally shortened version thereof. These proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The half-maximal effective dose for both is 2.5-6.0 ng/ml. Human and rat follistatins exhibit very high homology with the porcine protein, with the human differing from porcine in only 4 residues out of 315 and with the rat differing from porcine in only 8 residues out of 315. Using the porcine amino acid sequence information, cDNA clones encoding these proteins were identified from a porcine ovarian cDNA library. Then, using the porcine cDNA as a probe, the cloning and sequencing of the corresponding human and rat proteins were accomplished.

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San Diego, CA, United States of America

Nicholas C Ling