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(12) Patent Application Publication (10) Pub. No.: US 2011/0185439 A1 Gaitanaris Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2011/0185439 A1 Gaitanaris Et Al US 2011 0185439A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0185439 A1 Gaitanaris et al. (43) Pub. Date: Jul. 28, 2011 (54) GPROTEIN COUPLED RECEPTORS AND Publication Classification USES THEREOF (51) Int. Cl. (75) Inventors: George A. Gaitanaris, Seattle, WA GOIN 33/48 (2006.01) (US); John E. Bergmann, Mercer AOIK 67/027 (2006.01) Island, WA (US); Alexander CI2N 15/87 (2006.01) Gragerov, Seattle, WA (US); John CI2N 5/10 (2006.01) Hohmann, Seattle, WA (US); C07K I4/47 (2006.01) Fusheng Li, Seattle, WA (US); C7H 2L/04 (2006.01) Linda Madisen, Seattle, WA (US); A63L/7088 (2006.01) Kellie L. McIlwain, Washington, A6IP 25/00 (2006.01) DC (US); Maria N. Pavlova, A6IP3/00 (2006.01) Seattle, WA (US); Demetri CI2O I/68 (2006.01) Vassilatis, Seattle, WA (US); A6IP 9/00 (2006.01) Hongkui Zeng, Shoreline, WA A6IP 700 (2006.01) (US) GOIN 33/53 (2006.01) (52) U.S. Cl. ..................... 800/3; 800/18: 800/8: 800/21: (73) Assignee: OMEROS CORPORATION, 435/325; 530/350,536/23.5; 514/44 R; 435/6.11; Seattle, WA (US) 435/6.13:435/7.1 (21) Appl. No.: 12/970,094 (57) ABSTRACT (22) Filed: Dec. 16, 2010 The present invention provides GPCR polypeptides and poly nucleotides, recombinant materials, and transgenic mice, as Related U.S. Application Data well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diag (63) Continuation of application No. 12/243,731, filed on nosis and treatment of diseases and disorders. The invention Oct. 1, 2008, now abandoned, which is a continuation also provides methods for identifying compounds (e.g., ago of application No. 10/527,265, filed on Jan. 26, 2006, nists or antagonists) using the GPCR polypeptides and poly now abandoned, filed as application No. PCT/US03/ nucleotides of the invention, and for treating conditions asso 28226 on Sep. 9, 2003. ciated with GPCR dysfunction with the GPCR polypeptides, (60) Provisional application No. 60/409,303, filed on Sep. polynucleotides, or identified compounds. The invention also 9, 2002, provisional application No. 60/461.329, filed provides diagnostic assays for detecting diseases or disorders on Apr. 9, 2003. associated with inappropriate GPCR activity or levels. Patent Application Publication Jul. 28, 2011 Sheet 1 of 31 US 2011/O185439 A1 O e Seqeed ysselo Patent Application Publication Jul. 28, 2011 Sheet 2 of 31 US 2011/O185439 A1 s Patent Application Publication Jul. 28, 2011 Sheet 3 of 31 US 2011/0185439 A1 £SSBIO Vsselo Patent Application Publication Jul. 28, 2011 Sheet 4 of 31 US 2011/0185439 A1 W W W W W W N |N M M W W W W W W N W Patent Application Publication Jul. 28, 2011 Sheet 5 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 6 of 31 US 2011/O185439 A1 „HI'50|| Patent Application Publication Jul. 28, 2011 Sheet 7 of 31 US 2011/0185439 A1 |N W W W W W W YN W W’H H Patent Application Publication Jul. 28, 2011 Sheet 8 of 31 US 2011/0185439 A1 SSSSSSSSSS 8 Patent Application Publication Jul. 28, 2011 Sheet 9 of 31 US 2011/0185439 A1 II'50|| Patent Application Publication Jul. 28, 2011 Sheet 10 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 11 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 12 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 13 of 31 US 2011/O185439 A1 s s Patent Application Publication Jul. 28, 2011 Sheet 14 of 31 US 2011/O185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 15 of 31 US 2011/0185439 A1 SSEEIGN ?Ndrioffiueqd?G Patent Application Publication Jul. 28, 2011 Sheet 16 of 31 US 2011/0185439 A1 FIC, 1P Patent Application Publication Jul. 28, 2011 Sheet 17 of 31 US 2011/0185439 A1 Peptide æuouujoHDI Patent Application Publication Jul. 28, 2011 Sheet 18 of 31 US 2011/0185439 A1 Patent Application Publication US 2011/0185439 A1 ueudio§B?HS |eºupy[Jo,d?oou Patent Application Publication Jul. 28, 2011 Sheet 20 of 31 US 2011/0185439 A1 HowD Joideoou?una Patent Application Publication Jul. 28, 2011 Sheet 21 of 31 US 2011/0185439 A1 Neurotransmitter Peptide : - - - - - - - - in n Patent Application Publication Jul. 28, 2011 Sheet 22 of 31 US 2011/0185439 A1 plouesoola? Patent Application Publication Jul. 28, 2011 Sheet 23 of 31 US 2011/0185439 A1 Peptide £8ue?duo Z?ue?duO H_id #:: *.No.??ae» }}}}-----------FLU ±&********************************************* z***************w****** ********************************&&~~ ? ESS’e|O +--~~~~--~~~~*…*…***************************************************************** Patent Application Publication Jul. 28, 2011 Sheet 24 of 31 US 2011/0185439 A1 g-ºgÝ5)t######\*** **?¢) ?}+\######********************************************···---···---··· ??UITEEosselo Patent Application Publication Jul. 28, 2011 Sheet 25 of 31 US 2011/0185439 A1 FIG. 2I Patent Application Publication Jul. 28, 2011 Sheet 26 of 31 US 2011/O185439 A1 Genes : i Hypothalamus Amygdala i Brain Stem Cerebellum Cortex Frontal Cortex Hippocampus Adrenal Colon intestine Kidney Liver Lung is . Muscle Ovary PBL Prostate Skin Spleen Stornach Testis Thymus Thyroid Uterus Patent Application Publication Jul. 28, 2011 Sheet 27 of 31 US 2011/O185439 A1 8 i : : i polkul snukul SESL upeLoS ueeds US eyesold 19d AJeNO eSW 5un Keup'sJe. eugseu U000 eupy Sueye Line S Srdueodd H X900 euo Keio) uneqe.80 LeSueelepbuy Shujeelodh Patent Application Publication Jul. 28, 2011 Sheet 28 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 29 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 30 of 31 US 2011/0185439 A1 Patent Application Publication Jul. 28, 2011 Sheet 31 of 31 US 2011/O185439 A1 US 2011/O 185439 A1 Jul. 28, 2011 GPROTEIN COUPLED RECEPTORS AND and modulating compounds for use in the treatment and diag USES THEREOF nosis of a wide variety of disorders and diseases. SUMMARY OF THE INVENTION CROSS-REFERENCES TO RELATED APPLICATIONS 0007. The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic 0001. This application is a continuation of U.S. patent mice, as well as methods for their production. The polypep application Ser. No. 12/243,731, filed Oct. 1, 2008, now tides and polynucleotides are useful, for example, in methods pending, which is a continuation of U.S. patent application of diagnosis and treatment of diseases and disorders. The Ser. No. 10/527,265, filed Jan. 26, 2006, now abandoned, invention also provides methods for identifying compounds which is a U.S. national stage application of PCT Patent (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating condi Application No. PCT/US03/28226, filed Sep. 9, 2003, which tions associated with GPCR dysfunction with the GPCR claims the benefit under 35 U.S.C. S 119(e) of U.S. Provi polypeptides, polynucleotides, or identified compounds. The sional Patent Application No. 60/409,303, filed Sep. 9, 2002, invention also provides diagnostic assays for detecting dis and U.S. Provisional Patent Application No. 60/461,329, filed eases or disorders associated with inappropriate GPCR activ Apr. 9, 2003, where all of the above applications are incor ity or levels. porated herein by reference in their entireties. 0008. In one aspect, the invention features a variety of substantially pure GPCR polypeptides. Such polypeptides STATEMENT REGARDING SEQUENCE include: (a) polypeptides including a polypeptide sequence LISTING having at least 90%, 95%, 97%, 98%, or 99% identity to a polypeptide listed in Table 2; (b) polypeptides that include a 0002 The Sequence Listing associated with this applica polypeptide listed in Table 2; (c) polypeptides having at least tion is provided in text format in lieu of a paper copy, and is 90%.95%,97%.98%, or 99% sequence identity to a polypep hereby incorporated by reference into the specification. The tide listed in Table 2; and (d) polypeptides listed in Table 2. name of the text file containing the Sequence Listing is 0009 Polypeptides of the present invention also include variants of the aforementioned polypeptides, including all NG 1 0058 US3 SEQUENCELISTING..txt. The text file allelic forms and splice variants. Such polypeptides vary from is 4.87 MB, was created on Dec. 13, 2010, and is being the reference polypeptide by insertions, deletions, and sub submitted electronically via EFS-Web, concurrent with the stitutions that may be conservative or non-conservative, or filing of the specification. any combination thereof. Particularly desirable variants are those in which several, for instance from 50 to 30, from 30 to BACKGROUND OF THE INVENTION 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, or from 2 to 1 amino acids are inserted. Substituted, or deleted, in 0003. The invention relates to the fields of medicine and any combination. drug discovery. 0010 Polypeptides of the present invention also include 0004 Mammalian G protein coupled receptors (GPCRs) polypeptides that include an amino acid sequence having at least 30, 50, or 100 contiguous amino acids from any of the constitute a superfamily of diverse proteins with thousands of polypeptides listed in Table 2. Polypeptides of the invention members. GPCRs act as receptors for a multitude of different are desirably biologically active or are antigenic or immuno signals. Chemosensory GPCRs (csGPCR) are receptors for genic in an animal, especially in a human. sensory signals of external origin that are sensed as odors, 0011. The polypeptides of the present invention may be in pheromones, or tastes. Most other GPCRs respond to endog the form of the “mature' polypeptide, or may be a part of a enous signals, such as peptides, lipids, neurotransmitters, or larger polypeptide Such as a precursor or a fusion protein.
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