Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1999-06-30
2001-02-13
Carlson, Karen Cochrane (Department: 1653)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S325000, C435S252300, C435S320100, C536S023100
Reexamination Certificate
active
06187560
ABSTRACT:
FIELD OF INVENTION
This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to the Uncoupling proteins family, hereinafter referred to as HNFCW60. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides.
BACKGROUND OF THE INVENTION
Uncoupling protein is a peptide that is believed to be located in the mitochondria of mammalian brown adipose tissue (BAT) and, more recently, in other tissues such as murine muscle (MUCP2, Ricquier et al., Genbank accessionnumber:U69135). It is predominant in rodent fat deposits (Saverio et al., The Endocrinology Journal, 138 (2), 1997), and leads to a dissipation of the proton gradient across the inner membrane of the mitochondrion. This, in turn, uncouples the oxidative phosphorylation chain, and “decontrols” the process. The roles played by uncoupling protein (UCP) are that of an important factor in the thermogenesis of tissue, and of energy expenditure as a whole. Therefore, this could be used to combat obesity and body weight -associated disorder by increasing BAT oxidation.
Human UCP is found predominantly in brown adipocytes (Cassard et al., Journal of Cell Biochemistry, 43, 1990). UCP mRNA is expressed at a higher rate when &bgr;-3 adrenoreceptors are agonized by, for example BRL 37344 (Chengjun et al., The Endocrinology Journal, 138(2), 1997), which suggests a use for the protein in controlling insulin dependent diabetes. Patent application no WO96/05861 disloses a gene sequence with high homology to MUCP2. Human UCP2 is described by Fleury et al. in Nature Genetics, 1997, 15, 269. More recently, a further member of the family, Uncoupling protein-3, has been described (Boss O et al., FEBS Lett, May 12, 1997, 408(1), 39-42; Vidal-Puig A et al., Biochem Biophys Rs Commun, Jun. 9, 1997, 235(1), 79-82). These papers were however published after the two priority dates (Mar. 5, 1997 and Mar. 18, 1997) claimed in the present application.
There is a need for identification and characterization of further members of the Uncoupling proteins family which can play a role in preventing, ameliorating or correcting dysfunction or diseases, including, but not limited to, obesity, diabetes, hyperlipidaemia and body weight disorder.
SUMMARY OF THE INVENTION
In one aspect, the invention relates to HNFCW60 polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such HNFCW60 polypeptides and polynucleotides. Such uses include the treatment of obesity, diabetes, hyperlipidaemia and body weight disorder, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with HNFCW60 imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate HNFCW60 activity or levels.
REFERENCES:
L. Hillier, et al., “Homo Sapiens clone 628529 similar to uncoupling protein”, Jan. 21, 1997, XP002067896, Accession No. AA192136.
O. Boss et al., “Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific Expression”, May 12, 1997, FEBS Letters 408, pp. 39-42.
Copy of International Search Report (PCT/GB98/00633) mailed Jul. 3, 1998.
Cinti et al. “Immunohistochemical Localization of Leptin and Uncoupling Protein in White and Brown Adipose Tissue”, Endocrinology, vol. 138(2) pp. 797-804 (1997).
Cassard et al. “Human Uncoupling Protein Gene: Structure, Comparison With Rat Gene, and Assignment To the Long Arm of Chromosome 4” Journal of Cellular Biochemistry, vol. 43(3) pp. 255-264 (1990).
Chengjun et al. “Leptin Is a Metabolic Gate for the Onset of Puberty in the Female Rat” The Endocrinology Journal, vol. 138(2) pp. 855-858 (1997).
Fleury et al. “Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia” Nature Genetics vol. 15 pp. 269-272 (1997).
Vidal-Puig et al. “UCP3 An Uncoupling Protein Homologue Expressed Preferentially and Abundantly in Skeletal Muscle and Brown Adipose Tissue.” Biochem Biosphys Res Comm, vol. 235(1) pp. 79-82 (1997).
GenBank Accession No. U69135.
GenBank Accession No. U76367.
Hillier et al. GI1781960, Jan. 1997.
Boss et al. #A, GI:2183020, Jan. 1997.
Boss et al. #B, GI:2183020, Jan. 1997.
Boss et al. #C, 2GI:183017, Dec. 1996.
Boss et al. #D, GI:2183017, Dec. 1996.
Beeley Lee James
Godden Robert James
Paine Kelly
Carlson Karen Cochrane
Han William T.
King William T.
Ratner & Prestia
SmithKline Beecham Plc
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