Oregon Health & Science University

State of Oregon

Imperial Innovations Limited

New England Medical Center Hospitals. Inc.

Imperial College Innovations Limited

Roger D Cone

Kathleen G Mountjoy

Michael Alexander Cowley

Andrew A Butler

Malcolm J Low

Stephen Robert Bloom

Caroline Jane Small

Rachel Louise Batterham

Linda Roselli-Rehfuss

Linda S Robbins

Wenbiao Chen

Mohammad Ali Ghatei

Bruce A Boston

Dongsi Lu

Wei Fan

Robert A Kesterton

Mohammad Ali Ghatel

Malcolm James Duncan Low

Michael Cowley

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, thereby decreasing the calorie intake of the subject.

Modification of feeding behavior

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering PYY or an agonist thereof and GLP-1 or an agonist thereof to the subject, simultaneously or sequentially, thereby decreasing the calorie intake of the subject.

Modification of feeding behavior using PYY and GLP-1

Screening methods of use in identifying agents that affect caloric intake, food intake, appetite, and energy expenditure are disclosed herein. These methods are used to identify agents of use in treating obesity, or that can be used to decrease the weight of a subject. These methods can also be used to identify agents of use in treating anorexia or cachexia and can be used to increase appetite and to increase the weight and lean body mass of a subject.

Method for screening for agents that affect food intake

The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically-detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which is associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

Methods and reagents for discovering and using mammalian melanocortin receptor agonists and antagonists to modulate feeding behavior in animals

The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adrenocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTH receptor gene. The invention specifically provides human and bovine ACTH genes.

Mammalian adrenocorticotropic hormone receptor nucleic acids

This invention provides methods and reagents for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor, and the use of such agonists and antagonists for treatment and alleviation of dysfunction and disease. The invention specifically provides reagents and methods for developing naturally-occurring and synthetic agonists and antagonists specific for a mammalian melanocortin receptor termed MC5-R. The naturally-occurring and synthetic agonists and antagonists specific for the MC5-R receptor are provided by the invention for the treatment, control, amelioration and alleviation of diseases, and dysfunctional and abnormal states related to thermoregulatory disorders, as well as other diseases relating to exocrine gland disorders, including lacrimal gland dysfunction and sebaceous gland disorders including acne and other skin problems. Also provided by the invention are nucleic acids, constructs, vectors and methods for producing an animal bearing a genetically-disrupted endogenous MC5-R melanocortin receptor, in both the heterozygous and homozygous condition, preferably a rodent and most preferably a mouse. Rodents bearing genetically disrupted MC5-R genes homozygously, termed &ldquo;gene knockout&rdquo;rodents in the art, are also advantageously provided.

Mammalian melanocortin receptors and uses

The present invention relates to a mammalian melanocyte stimulating hormone receptor (MSH-R). The invention is directed toward the isolation, characterization and pharmacological use of a mammalian melanocyte stimulating hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian melanocyte stimulating hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian melanocyte stimulating hormone receptor. The invention also provide methods for screening MSH-R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the MSH-R receptor gene. The invention specifically provides human and mouse MSH-R genes.

Melanocyte stimulating hormone receptor and uses

The present invention relates to a mammalian melanocortin receptor. The invention is directed toward the isolation, characterization and pharmacological use of a mammalian melanocortin receptor (MC3-R). The invention specifically provides a particular melanocortin receptor, termed MC3-R, isolated as a complementary DNA copy of mRNA corresponding to the gene for this receptor in rats. Also provided is a eukaryotic recombinant expression construct capable of expressing a mammalian melanocortin receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize a mammalian melanocortin receptor. The invention also provides methods for screening in vitro agonists and antagonists of such a melanocortin receptor using preparations of receptor protein from such cultures of eukaryotic cells transformed with a recombinant expression construct.

Rat melanocortin receptor MC3-R

The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian melanocortin receptors. The invention provides a panel of such transformed mammalian cells expressing melanocortin receptors for screening compounds for receptor agonist and antagonist activity. The invention also provides methods for using such panels of melanocortin receptor-expressing mammalian cells to specifically detect and identify agonists and antagonists for each melanocortin receptor, as well as patterns of agonist and antagonist activity of said compounds for the class of melanocortin receptors. Such screening methods provide a means for identifying compounds with patterns of melanocortin agonist and antagonist activity which are associated with the capacity to influence or modify metabolism and behavior, particularly feeding behavior.

Methods and reagents for discovering and using mammalian melanocortin

The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adreocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH-R agonists and antagonists in vitro using prerations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTH-R receptor gene. The invention specifically provides human and bovine ACTH-R genes.

Mammalian adrenocorticotropic hormone receptors and uses

The present invention relates to a mammalian alpha-melanocyte stimulating hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian melanocyte stimulating hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian melanocyte stimulating hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian melanocyte stimulating hormone receptor. The invention also provides methods for screening MSH-R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the MSH-R receptor gene. The invention specifically provides human and mouse MSH-R genes.

.alpha.-melanocyte stimulating hormone receptor

Nucleic acids encoding the .gamma.-MSH receptor MC3-R

The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adrenocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH.sup.R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the ACTH.sup.R receptor gene. The invention specifically provides human and bovine ACTH.sup.R genes.

Growing community of inventors

Oregon City, OR, United States of America

Roger D Cone