Wylie W Vale

6353152, Mar 5, 2002

Jul 14, 2000

09/616937

Kuo-Fen Lee - Del Mar CA
Wylie W. Vale - La Jolla CA
Tracy L. Bale - San Diego CA
George W. Smith - Mason MI

Research Development Foundation - Carson City NV

A01K 67027

800 18, 800 3, 800 9

The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2. Corticotropin releasing factor is a critical integrator of the hypothalamic-pituitary-adrenal axis in response to stress. CRF and its related molecule urocortin bind CRF receptor 1 and CRFR2 with distinct affinities. CRFR2 mutant mice were hypersensitive to stress and displayed increased anxiety-like behavior. Mutant mice had normal basal feeding and weight gain, but exhibited decreased food intake following food deprivation. Intravenous UCN dramatically decreased the mean arterial pressure in the controls but had no effect in the mutants. A deficiency of CRFR2 results in a significant increase in urocortin mRNA in the rostral region of the Edinger Westphal and a significant increase in CRF mRNA in central nucleus of the amygdala. These results demonstrate that the CRFR2 mutant mice, opposed to CRFR1 mutant mice, have an increased sensitivity to stress and display anxiety-like behavior. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis.

6692744, Feb 17, 2004

Dec 15, 2000

09/738171

Wylie Vale - La Jolla CA
Kathy A. Lewis - San Diego CA
Peter C. Gray - Encinitas CA
Louise M. Bilezikjian - San Diego CA
Amy L. Blount - La Jolla CA

Research Development Foundation - Carson City NV

A61K 39395

4241581, 5303879, 5303881, 5303891, 530350

Inhibins and activins are protein hormones that reciprocally modulate a diversity of regulatory pathways. Competitive binding experiments revealed that betaglycan, the type III TGF- receptor, also functions as an inhibin receptor. Betaglycan augments the binding of inhibin to the ActRII activin receptor. By augmenting inhibin binding to ActRII, betaglycan effectively sequesters ActRII away from activin and thereby reduces activin signaling. In addition, the ActRII-betaglycan complex may generate novel signals distinct from those initiated by activin signaling via ActRII and ALK4. Betaglycan is produced in discrete nuclei of the rat brain and by specific cell types within the adult rat pituitary, testis, and ovary. The presence of betaglycan within inhibin-responsive tissues and cell types, together with the ability of this protoglycan to bind inhibin and to confer inhibin sensitivity, is consistent with a role of betaglycan as an inhibin-specific receptor mediating inhibin responses within various tissues.

7455839, Nov 25, 2008

Oct 29, 2003

10/696717

Wylie Vale - La Jolla CA, US
Kathy A. Lewis - San Diego CA, US
Peter C. Gray - Encinitas CA, US
Louise M. Bilezikjian - San Diego CA, US
Amy L. Blount - La Jolla CA, US

Research Development Foundation - Carson City NV

A61K 39/395
C07K 16/00
C12P 21/08

4241581, 530350, 5303879, 5303881, 5303891

Inhibins and activins are protein hormones that reciprocally modulate a diversity of regulatory pathways. Competitive binding experiments revealed that betaglycan, the type III TGF-β receptor, also functions as an inhibin receptor. Betaglycan augments the binding of inhibin to the ActRII activin receptor. By augmenting inhibin binding to ActRII, betaglycan effectively sequesters ActRII away from activin and thereby reduces activin signaling. In addition, the ActRII-betaglycan complex may generate novel signals distinct from those initiated by activin signaling via ActRII and ALK4. Betaglycan is produced in discrete nuclei of the rat brain and by specific cell types within the adult rat pituitary, testis, and ovary. The presence of betaglycan within inhibin-responsive tissues and cell types, together with the ability of this protoglycan to bind inhibin and to confer inhibin sensitivity, is consistent with a role of betaglycan as an inhibin-specific receptor mediating inhibin responses within various tissues.

7488865, Feb 10, 2009

May 19, 2003

10/440636

Kuo-Fen Lee - Del Mar CA, US
Wylie Vale - La Jolla CA, US
Chien Li - San Diego CA, US
Lingyun Zhao - San Diego CA, US
Douglas E. Vetter - Boston MA, US

Research Development Foundation - Carson City NV

A01K 67/00
A01K 67/027
A01K 67/033

800 18, 800 13

The present invention provides transgenic mice deficient in urocortin. Urocortin null mutant mice are hypersensitive to stress and display heightened anxiety-like behaviors in the elevated plus maze and open field tests. These mice also demonstrate physiological alterations in auditory thresholds and distortion product otoacoustic emissions. These results indicate that urocortin plays a modulatory role in anxiety-related behaviors and in contributing to the establishment of auditory thresholds. Such urocortin deficient mutant mice can provide useful models in the study of anxiety pathology and hearing physiology at the biochemical and molecular levels.

7507794, Mar 24, 2009

Feb 8, 2006

11/350411

Alon Chen - Rehovot, IL
Marilyn Perrin - La Jolla CA, US
Wylie Vale - La Jolla CA, US

Research Development Foundation - Carson City NV

C07K 1/00
C07K 14/00
C07K 17/00
A01N 37/18
A61K 38/00

530350, 514 2

The present invention is directed to compositions and methods related to soluble G-protein coupled receptors (sGPCR). In ceratin aspects the invention includes compositions and methods related to a soluble corticotropin releasing factor receptor related protein, sCRFR2, as well as its effects on CRFR signaling and interaction between CRF family ligand and CRFR receptors, including but not limited to CRFR2, CRFR1 and functional or signaling capable variants thereof.

7575751, Aug 18, 2009

Apr 27, 2005

11/115877

Wylie Vale - La Jolla CA, US
Craig Harrison - Nunawading, AU
Peter Gray - Encinitas CA, US
Wolfgang Fischer - Encinitas CA, US
Senyon Choe - Solana Beach CA, US

Research Development Foundation - Carson City NV

A61K 39/00
C07K 14/00

4241981, 530350

Members of the TGF-β superfamily control many physiologic and pathophysiologic processes in multiple tissues and signal via type II and type I receptor serine kinases. Type II activin receptors are promiscuous and known to bind 12 TGF-β ligands including activins, myostatin, BMPs and nodal. Methods are described for the screening and identification of antagonist for TGF-β superfamily members, in particular activin-A antagonist.

7674463, Mar 9, 2010

Nov 16, 2000

09/714692

Kuo-Fen Lee - Del Mar CA, US
Wylie W. Vale - La Jolla CA, US
Tracy L. Bale - San Diego CA, US
George W. Smith - Mason MI, US

Research Development Foundation - Carson City NV

A61K 38/16
C07K 14/435

4241841, 4241981, 514 2, 514 12, 530350

The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2 (CRFR2). Mice deficient for CRFR1 exhibit decreased anxiety-like behavior and a decreased stress response. In contrast, CRFR2 null mutant mice are hypersensitive to stress and display increased anxiety-like behavior. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis. CRFR2 null mutant mice also exhibit increased angiogenesis in all tissues examined. Thus, CRFR2 antagonists may be used to stimulate angiogenesis for the treatment of various conditions. In contrast, CRFR2 agonists may be used to inhibit angiogenesis. A combination of urocortin and bFGF was observed to stimulate rapid hair growth.

7815905, Oct 19, 2010

Jan 29, 2007

11/668047

Alon M. Chen - Rehovot, IL
Kuo-Fen Lee - Del Mar CA, US
Chien Li - Charlottesville VA, US
Wylie W. Vale - La Jolla CA, US

Research Development Foundation - Carson City NV

A61K 39/395
A61K 39/00

4241301, 4241391

In some aspects, the invention relates to methods for increasing insulin-sensitivity and/or decreasing insulin secretion in an individual by reducing or inhibiting corticotropin releasing factor 2 (CRFR2) signaling. CRFR2 antagonists may block agonism by one or more CRFR2 agonist, for example Ucn 2 or Ucn 3. Methods according to the invention may be use to treat a variety of metabolic diseases such as type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease, polycystic ovarian syndrome and obesity.