Senior Fitness - Exercise and Nutrition for Aging Men and Women
FREE Article Feed for your website.
Home Ownership Magazine
Party Planning Information
Article Marketing Resources
Bio-Medical Research Article Database
Informative Articles on Life, Love and Happiness
Tutorials on Business to Writing
Famous Quotes from Famous People
Song Lyric Information
New US Patent Information
Comprehensive List of Content by Category
Online Auctions and Shopping Related Articles
Article Search
Most Recent Articles
Title: Rocking motion charging device using faraday principle
Patent Number: 7,436,082 Issued on 10/14/2008 to Ruse,   et al.

Title: System for controlling a hybrid energy system
Patent Number: 7,436,081 Issued on 10/14/2008 to Lane

Title: Device for supplying power to a two-voltage vehicle electrical system equipped with safety-relevant components
Patent Number: 7,436,080 Issued on 10/14/2008 to Hackl,   et al.

Title: Power system for a telecommunications site
Patent Number: 7,436,079 Issued on 10/14/2008 to Meyers,   et al.

Title: Line layout structure of semiconductor memory device
Patent Number: 7,436,078 Issued on 10/14/2008 to Yang,   et al.

Title: Semiconductor device and method of manufacturing the same
Patent Number: 7,436,077 Issued on 10/14/2008 to Hasegawa

Title: Micromechanical component having an anodically bonded cap and a manufacturing method
Patent Number: 7,436,076 Issued on 10/14/2008 to Stahl,   et al.

Title: Ion beam irradiation apparatus and ion beam irradiation method
Patent Number: 7,436,075 Issued on 10/14/2008 to Ando

Title: Chip package without core and stacked chip package structure thereof
Patent Number: 7,436,074 Issued on 10/14/2008 to Pan,   et al.

Title: Junction structure for a terminal pad and solder, and semiconductor device having the same
Patent Number: 7,436,073 Issued on 10/14/2008 to Tanaka

Title: Protected chip stack
Patent Number: 7,436,072 Issued on 10/14/2008 to Hubner,   et al.

Title: Electronic component and semiconductor device, method of fabricating the same, circuit board mounted with the same, and electronic appliance comprising the circuit board
Patent Number: 7,436,071 Issued on 10/14/2008 to Hashimoto

Title: Semiconductor device
Patent Number: 7,436,070 Issued on 10/14/2008 to Uno,   et al.

Title: Semiconductor device, having a through electrode semiconductor module employing thereof and method for manufacturing semiconductor device having a through electrode
Patent Number: 7,436,069 Issued on 10/14/2008 to Matsui

Title: Components for film forming device
Patent Number: 7,436,068 Issued on 10/14/2008 to Hirata,   et al.

Title: Methods for forming conductive structures and structures regarding same
Patent Number: 7,436,067 Issued on 10/14/2008 to Basceri,   et al.

Title: Semiconductor element
Patent Number: 7,436,066 Issued on 10/14/2008 to Sonobe,   et al.

Title: Electrode contact structure
Patent Number: 7,436,065 Issued on 10/14/2008 to Ohno,   et al.

Title: Laser process for reliable and low-resistance electrical contacts
Patent Number: 7,436,064 Issued on 10/14/2008 to Lau,   et al.

Title: Packaging substrate and semiconductor device
Patent Number: 7,436,063 Issued on 10/14/2008 to Miyata,   et al.

Title: Semiconductor chip element, semiconductor chip element mounting structure, semiconductor chip element mounting device and mounting method
Patent Number: 7,436,062 Issued on 10/14/2008 to Kainuma,   et al.

Title: Semiconductor device, electronic device, electronic apparatus, and method of manufacturing semiconductor device
Patent Number: 7,436,061 Issued on 10/14/2008 to Nakayama

Title: Reactive solder material
Patent Number: 7,436,058 Issued on 10/14/2008 to Hua,   et al.

Title: Elastomer interposer with voids in a compressive loading system
Patent Number: 7,436,057 Issued on 10/14/2008 to Long,   et al.

Title: Electronic component package
Patent Number: 7,436,056 Issued on 10/14/2008 to Cheung,   et al.

Title: Packaging method of a plurality of chips stacked on each other and package structure thereof
Patent Number: 7,436,055 Issued on 10/14/2008 to Hu

Title: MEMS microphone with a stacked PCB package and method of producing the same
Patent Number: 7,436,054 Issued on 10/14/2008 to Zhe

Title: Optical device and method for fabricating the same
Patent Number: 7,436,053 Issued on 10/14/2008 to Minamio,   et al.

Title: Repatterned integrated circuit chip package
Patent Number: 7,436,052 Issued on 10/14/2008 to Gerstenhaber,   et al.

Title: Component for fabricating an electronic device and method of fabricating an electronic device
Patent Number: 7,436,051 Issued on 10/14/2008 to Noguchi,   et al.

Title: Semiconductor device having a flexible printed circuit
Patent Number: 7,436,050 Issued on 10/14/2008 to Yamazaki,   et al.

Title: Lead frame, semiconductor chip package using the lead frame, and method of manufacturing the semiconductor chip package
Patent Number: 7,436,049 Issued on 10/14/2008 to Youn,   et al.

Title: Multichip leadframe package
Patent Number: 7,436,048 Issued on 10/14/2008 to Ha,   et al.

Title: Wafer having scribe lanes suitable for sawing process, reticle used in manufacturing the same, and method of manufacturing the same
Patent Number: 7,436,047 Issued on 10/14/2008 to Yang

Title: Semiconductor device and manufacturing method of the same
Patent Number: 7,436,046 Issued on 10/14/2008 to Kondo,   et al.

Title: Gallium nitride-based semiconductor device
Patent Number: 7,436,045 Issued on 10/14/2008 to Kobayakawa,   et al.

Title: Electrical fuses comprising thin film transistors (TFTS), and methods for programming same
Patent Number: 7,436,044 Issued on 10/14/2008 to Khan,   et al.

Title: N-well and N.sup.+ buried layer isolation by auto doping to reduce chip size
Patent Number: 7,436,043 Issued on 10/14/2008 to Sung,   et al.

Title: Circuit for driving gate of power MOSFET
Patent Number: 7,436,042 Issued on 10/14/2008 to Ryoo,   et al.

Title: Electrostatic discharge protection circuit using a double-triggered silicon controlling rectifier
Patent Number: 7,436,041 Issued on 10/14/2008 to Ker,   et al.

Title: Method and apparatus for diverting void diffusion in integrated circuit conductors
Patent Number: 7,436,040 Issued on 10/14/2008 to Allman,   et al.

Title: Gallium nitride semiconductor device
Patent Number: 7,436,039 Issued on 10/14/2008 to Zhu,   et al.

Title: Visible/near infrared image sensor array
Patent Number: 7,436,038 Issued on 10/14/2008 to Engelmann,   et al.

Title: Moisture resistant pressure sensors
Patent Number: 7,436,037 Issued on 10/14/2008 to Kurtz,   et al.

Title: PMOS transistor of semiconductor device, semiconductor device comprising the same, and method for manufacturing the same
Patent Number: 7,436,036 Issued on 10/14/2008 to Lee

Title: Method of fabricating a field effect transistor structure with abrupt source/drain junctions
Patent Number: 7,436,035 Issued on 10/14/2008 to Murthy,   et al.

Title: Metal oxynitride as a pFET material
Patent Number: 7,436,034 Issued on 10/14/2008 to Callegari,   et al.

Title: Tri-gated molecular field effect transistor and method of fabricating the same
Patent Number: 7,436,033 Issued on 10/14/2008 to Park,   et al.

Title: Semiconductor integrated circuit comprising read only memory, semiconductor device comprising the semiconductor integrated circuit, and manufacturing method of the semiconductor integrated cir
Patent Number: 7,436,032 Issued on 10/14/2008 to Kato

Title: Device for implementing an inverter having a reduced size
Patent Number: 7,436,031 Issued on 10/14/2008 to Kitabatake,   et al.

Title: Strained MOSFETs on separated silicon layers
Patent Number: 7,436,030 Issued on 10/14/2008 to Yang,   et al.

Title: High performance CMOS device structures and method of manufacture
Patent Number: 7,436,029 Issued on 10/14/2008 to Doris,   et al.

Title: One-time programmable read only memory and operating method thereof
Patent Number: 7,436,028 Issued on 10/14/2008 to Yang,   et al.

Title: Semiconductor device and fabrication method for the same
Patent Number: 7,436,027 Issued on 10/14/2008 to Ogawa,   et al.

Title: Semiconductor device comprising a superlattice channel vertically stepped above source and drain regions
Patent Number: 7,436,026 Issued on 10/14/2008 to Kreps

Title: Termination structures for super junction devices
Patent Number: 7,436,025 Issued on 10/14/2008 to Zhu,   et al.

Title: Semiconductor device and method of manufacturing the same
Patent Number: 7,436,024 Issued on 10/14/2008 to Kumagai,   et al.

Title: High blocking semiconductor component comprising a drift section
Patent Number: 7,436,023 Issued on 10/14/2008 to Hirler,   et al.

Title: Enhancing Schottky breakdown voltage (BV) without affecting an integrated MOSFET-Schottky device layout
Patent Number: 7,436,022 Issued on 10/14/2008 to Bhalla,   et al.

Title: Dense trench MOSFET with decreased etch sensitivity to deposition and etch processing
Patent Number: 7,436,021 Issued on 10/14/2008 to Hao,   et al.

Title: Flash memory with metal-insulator-metal tunneling program and erase
Patent Number: 7,436,020 Issued on 10/14/2008 to Forbes

Title: Non-volatile memory cells shaped to increase coupling to word lines
Patent Number: 7,436,019 Issued on 10/14/2008 to Lutze,   et al.

Title: Discrete trap non-volatile multi-functional memory device
Patent Number: 7,436,018 Issued on 10/14/2008 to Bhattacharyya

Title: Semiconductor integrated circuit using a selective disposable spacer
Patent Number: 7,436,017 Issued on 10/14/2008 to Lee,   et al.

Title: MIM capacitor with a cap layer over the conductive plates
Patent Number: 7,436,016 Issued on 10/14/2008 to Barth,   et al.

Title: Driver for driving a load using a charge pump circuit
Patent Number: 7,436,015 Issued on 10/14/2008 to Tanaka,   et al.

Title: Method of fabricating storage capacitor in semiconductor memory device, and storage capacitor structure
Patent Number: 7,436,014 Issued on 10/14/2008 to Son

Title: Ferroelectric memory device
Patent Number: 7,436,013 Issued on 10/14/2008 to Miyazawa,   et al.

Title: Solid state imaging apparatus and method for fabricating the same
Patent Number: 7,436,012 Issued on 10/14/2008 to Mori,   et al.

Title: CMOS image sensor
Patent Number: 7,436,011 Issued on 10/14/2008 to Chen,   et al.

Title: Solid state imaging apparatus, method for driving the same and camera using the same
Patent Number: 7,436,010 Issued on 10/14/2008 to Mori,   et al.

Title: Via structures and trench structures and dual damascene structures
Patent Number: 7,436,009 Issued on 10/14/2008 to Huang,   et al.

Title: Semiconductor device
Patent Number: 7,436,004 Issued on 10/14/2008 to Shimoida,   et al.

Title: Vertical thyristor for ESD protection and a method of fabricating a vertical thyristor for ESD protection
Patent Number: 7,436,003 Issued on 10/14/2008 to Jumpertz,   et al.

Title: Surface-mountable radiation-emitting component
Patent Number: 7,436,002 Issued on 10/14/2008 to Brunner,   et al.

PRO246 antibodies Number:7,417,126 from the United States Patent and Trademark Office (PTO) owispatent

Home    Author Login    Submit Article    Article Search    Add Your Link    Edit Your Link    Contact Us    Advertising    Disclaimer

   

 
Web LinkGrinder.com

Top Breaking News
     Greek, Cypriot Leaders Resume Unification Talks in Nicosia by Nathan Morley
     Indonesia Tobacco Sales Grow, Raising Health Fears
     South Korea Allows Top Defector to Travel Overseas by VOA News

Title: PRO246 antibodies

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Patent Number: 7,417,126 Issued on 08/26/2008 to Goddard,   et al.


Inventors: Goddard; Audrey (San Francisco, CA), Gurney; Austin L. (Belmont, CA), Godowski; Paul J. (Burlingame, CA), Wood; William I. (Hillsborough, CA)
Assignee: Genentech, Inc. (South San Francisco, CA)
Appl. No.: 11/353,554
Filed: February 13, 2006


Related U.S. Patent Documents

Application NumberFiling DatePatent NumberIssue Date
09907942Jul., 20017087738
09665350Sep., 2000
PCT/US00/04414Feb., 2000
PCT/US98/19330Sep., 1998
PCT/US98/18824Sep., 1998
60062285Oct., 1997

Current U.S. Class: 530/387.9 ; 530/388.1
Current International Class: C07K 16/18 (20060101)


References Cited [Referenced By]

U.S. Patent Documents
5942606 August 1999 Lal et al.
6406884 June 2002 Bossone
2002/0061567 May 2002 Tang et al.
2003/0027998 February 2003 Holtzman et al.
Foreign Patent Documents
1 067 182 Oct., 2001 EP
WO99/58660 Nov., 1999 WO
WO00/11015 Mar., 2000 WO
WO00/78808 Dec., 2000 WO
WO01/25427 Apr., 2001 WO
WO01/49728 Jul., 2001 WO

Other References

Robert L. Harmon, "Patents and the Federal Circuit", Fifth Edition, (BNA Books Washington D.C.), p. 85, 2001. cited by other .
RP Tomko, et al., "HCAR and MCAR: The Human and Mouse Cellular Receptors for Subgroup C Adenoviruses and Group B Coxsackieviruses", Proceedings of the National Academy of Science USA, vol. 94, Apr. 1, 1997, pp. 3352-3356. cited by other .
JM McNicholl, et al. "Host genes and HIV: the role of the chemokine receptor gene CCR5 and its allele" Emerg Infect Dis., vol. 3, No. 3, pp. 261-271; Jul.-Sep. 1997. cited by other .
F. Struyf, et al., "Mutations in the N-terminal domains of nectin-1 and nectin-2 reveal differences in requirements for entry of various alphaherpesviruses and for nectin-nectin interactions", J Virol., vol. 76, No. 24, pp. 12940-12950; Dec. 2002. cited by other .
SD Carson, "Receptor for the group B coxsackieviruses and adenoviruses: CAR" Rev Med Virol., vol. 11, No. 4, pp. 219-226, Jul.-Aug. 2001. cited by other .
CJ Cohen, et al., "Multiple regions within the coxsackievirus and adenovirus receptor cytoplasmic domain are required for basolateral sorting", J Biol Chem., vol. 276, No. 27, pp. 25392-25398, Jul. 6, 2001; Epub Apr. 20, 2001. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB53082; Publication: WO2000/53753-A2; Publication Date: Sep. 14, 2000; Inventor: AJ Ashkenazi, et al.; Priority Date: Mar. 8, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB80219; Publication: WO2001/04311-A1; Publication Date: Jan. 18, 2001; Inventor: AJ Ashkenazi, et al.; Priority Date: Jul. 7, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB31207; Publication: WO2000/77037-A2; Publication Date: Dec. 21, 2000; Inventor: AJ Ashkenazi, et al.; Priority Date: Jun. 15, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB68599; Publication: WO2001/05836-A1; Publication Date: Jan. 25, 2001; Inventor: D. Botstein, et al.; Priority Date: Jul. 20, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB88358; Publication: EP1067182-A2; Publication Date: Jan. 10, 2001; Inventor: T. Ota, et al.; Priority Date: Jul. 8, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY94999; Publication: WO2000/11015-A1; Publication Date: Mar. 2, 2000; Inventor: D. Valenzuela, et al.; Priority Date: Aug. 24, 1998. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY88574; Publication: WO2000/15666-A2; Publication Date: Mar. 23, 2000; Inventor: A. Goddard, et al.; Priority Date: Sep. 10, 1998. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY05286; Publication: WO1999/14327-A2; Publication Date: Mar. 25, 1999; Inventor: D. Botstein, et al.; Priority Date: Sep. 17, 1997. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY13351; Publication: WO1999/14328-A2; Publication Date: Mar. 25, 1999; Inventor: WI Wood, et al.; Priority Date: Sep. 17, 1997. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY27096; Publication: US 5,942,606; Issue Date: Aug. 24, 1999; Inventor: P. Lal, et al.; Priority Date: Nov. 24, 1997. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB90818; Publication: WO2001/25427-A1; Publication Date: Apr. 12, 2001; Inventor: H. Nojima, et al.; Priority Date: Oct. 1, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAY76303; Publication: WO1999/58660-A1; Publication Date: Nov. 18, 1999; Inventor: SM Ruben, et al.; Priority Date: May 12, 1998. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB65832; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB65906; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB65907; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor; KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB65905; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
Dayhoff Protein Database Accesion No. P.sub.--AAB65904; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
GenBank Accession No. P.sub.--AAC97441; Publication: WO2000/53753-A2; Publication Date: Sep. 14, 2000; Inventor: AJ Ashkeriazi, et al.; Priority Date: Mar. 8, 1999. cited by other .
GenBank Accession No. P.sub.--AAF72379; Publication: WO2001/04311-A1; Publication Date: Jan. 18, 2001; Inventor: AJ Ashkenazi, et al.; Priority Date: Jul. 7, 1999. cited by other .
GenBank Accession No. P.sub.--AAC87040; Publication: WO2000/77037-A2; Publication Date: Dec. 21, 2000; Inventor: AJ Ashkenazi, et al.; Priority Date: Jun. 15, 1999. cited by other .
GenBank Accession No. P.sub.--AAF60372; Publication: WO2001/05836-A1; Publication Date: Jan. 25, 2001; Inventor: D. Botstein, et al.; Priority Date: Jul. 20, 1999. cited by other .
GenBank Accession No. P.sub.--AAA30052; Publication: WO2000/15666-A2; Publication Date: Mar. 23, 2000; Inventor: A. Goddard, et al.; Priority Date: Sep. 10, 1998. cited by other .
GenBank Accession No. P.sub.--AAX28436; Publication: WO1999/14327-A2; Publication Date: Mar. 25, 1999, Inventor: D. Botstein, et al.; Priority Date: Sep. 17, 1997. cited by other .
GenBank Accession No. P.sub.--AAX52221; Publication: WO1999/14328-A2; Publication Date: Mar. 25, 1999; Inventor: WI Wood, et al.; Priority Date: Sep. 17, 1997. cited by other .
GenBank Accession No. AX076924; Publication: WO2001/05836-A1; Publication Date: Jan. 25, 2001; Inventor: D. Botstein, et al.; Priority Date: Jul. 20, 1999. cited by other .
GenBank Accession No. P.sub.--AAF93785; Publication: EP1067182-A2; Publication Date: Jan. 10, 2001; Inventor: T. Ota, et al.; Priority Date: Jul. 8, 1999. cited by other .
GenBank Accession No. AX136161; Publication: EP1067182-A2; Publication Date: Jan. 10, 2001; Inventor: T. Ota, et al.; Priority Date: Jul. 8, 1999. cited by other .
GenBank Accession No. P.sub.--AAA23441; Publication: WO2000/11015-A1; Publication Date: Mar. 2, 2000; Inventor: D. Valenzuela, et al.; Priority Date: Aug. 24, 1998. cited by other .
GenBank Accession No. AF361746; Publication: "Cloning of an Immunoglobulin Family Adhesion Molecule Selectively Expressed by Endothelial Cells" Journal of Biological Chemistry 276(19) pp. 16223-16231; Inventor: KI Hirata, et al.; Publication Date: May 11, 2001. cited by other .
GenBank Accession No. P.sub.--AAH02949; Publication: WO2001/25427-A1; Publication Date: Apr. 12, 2001; Inventors: H. Nojima, et al.; Priority Date: Oct. 1, 1999. cited by other .
GenBank Accession No. P.sub.--AAZ65278 ; Publication: WO1999/58660-A1; Publication Date: Nov. 18, 1999; Inventors: SM Ruben, et al.; Priority Date: May 12, 1998. cited by other .
GenBank Accession No. P.sub.--AAF45017; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
GenBank Accession No. P.sub.--AAF45016; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other .
GenBank Accession No. P.sub.--AAF45014; Publication: WO2000/78808-A1; Publication Date: Dec. 28, 2000; Inventor: KR Leiby, et al.; Priority Date: Jun. 18, 1999. cited by other.

Primary Examiner: Mosher; Mary E
Attorney, Agent or Firm: Barnes; Elizabeth M. De Vry; Christopher Dreger; Ginger R.

Parent Case Text



RELATED APPLICATIONS

This application is a continuation of, and claims priority under 35 USC .sctn.120 to, U.S. application Ser. No. 09/907,942 filed Jul. 17, 2001, which is a continuation of, and claims priority under 35 USC .sctn.120 to, U.S. application Ser. No. 09/665,350 filed Sep. 18, 2000, which is a continuation of, and claims priority under 35 USC .sctn.120 to, PCT Application PCT/US00/04414 filed Feb. 22, 2000, which is a continuation-in-part of, and claims priority under 35 USC .sctn.120 to, PCT Application PCT/US98/19330 filed Sep. 16, 1998, which is a continuation-in-part of, and claims priority under 35 USC .sctn.120 to, PCT Application PCT/US98/18824 filed Sep. 10, 1998, which claims priority under 35 USC .sctn.119 to U.S. Provisional Application 60/062,285 filed Oct. 17, 1997, the entire disclosures of which are hereby expressly incorporated by reference.
Claims



What is claimed is:

1. An isolated antibody that specifically binds to the polypeptide shown in FIG. 2 (SEQ ID NO:2).

2. The antibody of claim 1, which is a monoclonal antibody.

3. The antibody of claim 1, which is a humanized antibody.

4. The antibody of claim 1, which is an antibody fragment.

5. The antibody of claim 1, which is labeled.
Description



FIELD OF THE INVENTION

The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.

BACKGROUND OF THE INVENTION

Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. These secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment.

Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors. Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins. Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents. Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Pat. No. 5,536,637)].

Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.

Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.

Efforts are being undertaken by both industry and academia to identify new, native receptor or membrane-bound proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor or membrane-bound proteins.

PRO246

The cell surface protein HCAR is a membrane-bound protein that acts as a receptor for subgroup C of the adenoviruses and subgroup B of the coxsackieviruses. Thus, HCAR may provide a means for mediating viral infection of cells in that the presence of the HCAR receptor on the cellular surface provides a binding site for viral particles, thereby facilitating viral infection.

In light of the physiological importance of membrane-bound proteins and specficially those which serve a cell surface receptor for viruses, efforts are currently being undertaken by both industry and academia to identify new, native membrane-bound receptor proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. We herein describe a novel membrane-bound polypeptide (designated herein as PRO246) having homology to the cell surface protein HCAR and to various tumor antigens including A33 and carcinoembryonic antigen, wherein this polypeptide may be a novel cell surface virus receptor or tumor antigen.

SUMMARY OF THE INVENTION

PR246

Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PRO246".

In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO246 polypeptide. In one aspect, the isolated nucleic acid comprises DNA encoding the PRO246 polypeptide having amino acid residues 1 to 390 of FIG. 2 (SEQ ID NO:2), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.

In another embodiment, the invention provides isolated PRO246 polypeptide. In particular, the invention provides isolated native sequence PRO246 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 390 of FIG. 2 (SEQ ID NO:2). An additional embodiment of the present invention is directed to an isolated extracellular domain of a PRO246 polypeptide.

Additional Embodiments

In other embodiments of the present invention, the invention provides vectors comprising DNA encoding any of the herein described polypeptides. Host cell comprising any such vector are also provided. By way of example, the host cells may be CHO cells, E. coli, or yeast. A process for producing any of the herein described polypeptides is further provided and comprises culturing host cells under conditions suitable for expression of the desired polypeptide and recovering the desired polypeptide from the cell culture.

In other embodiments, the invention provides chimeric molecules comprising any of the herein described polypeptides fused to a heterologous polypeptide or amino acid sequence. Example of such chimeric molecules comprise any of the herein described polypeptides fused to an epitope tag sequence or a Fc region of an immunoglobulin.

In another embodiment, the invention provides an antibody which specifically binds to any of the above or below described polypeptides. Optionally, the antibody is a monoclonal antibody, humanized antibody, antibody fragment or single-chain antibody.

In yet other embodiments, the invention provides oligonucleotide probes useful for isolating genomic and cDNA nucleotide sequences, wherein those probes may be derived from any of the above or below described nucleotide sequences.

In other embodiments, the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a PRO polypeptide.

In one aspect, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule encoding a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein, or (b) the complement of the DNA molecule of (a).

In other aspects, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule comprising the coding sequence of a full-length PRO polypeptide cDNA as disclosed herein, the coding sequence of a PRO polypeptide lacking the signal peptide as disclosed herein or the coding sequence of an extracellular domain of a transmembrane PRO polypeptide, with or without the signal peptide, as disclosed herein, or (b) the complement of the DNA molecule of (a).

In a further aspect, the invention concerns an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule that encodes the same mature polypeptide encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein, or (b) the complement of the DNA molecule of (a).

Another aspect the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding a PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated, or is complementary to such encoding nucleotide sequence, wherein the transmembrane domain(s) of such polypeptide are disclosed herein. Therefore, soluble extracellular domains of the herein described PRO polypeptides are contemplated.

Another embodiment is directed to fragments of a PRO polypeptide coding sequence, or the complement thereof, that may find use as, for example, hybridization probes or for encoding fragments of a PRO polypeptide that may optionally encode a polypeptide comprising a binding site for an anti-PRO antibody. Such nucleic acid fragments are usually at least about 20 nucleotides in length, preferably at least about 30 nucleotides in length, more preferably at least about 40 nucleotides in length, yet more preferably at least about 50 nucleotides in length, yet more preferably at least about 60 nucleotides in length, yet more preferably at least about 70 nucleotides in length, yet more preferably at least about 80 nucleotides in length, yet more preferably at least about 90 nucleotides in length, yet more preferably at least about 100 nucleotides in length, yet more preferably at least about 110 nucleotides in length, yet more preferably at least about 120 nucleotides in length, yet more preferably at least about 130 nucleotides in length, yet more preferably at least about 140 nucleotides in length, yet more preferably at least about 150 nucleotides in length, yet more preferably at least about 160 nucleotides in length, yet more preferably at least about 170 nucleotides in length, yet more preferably at least about 180 nucleotides in length, yet more preferably at least about 190 nucleotides in length, yet more preferably at least about 200 nucleotides in length, yet more preferably at least about 250 nucleotides in length, yet more preferably at least about 300 nucleotides in length, yet more preferably at least about 350 nucleotides in length, yet more preferably at least about 400 nucleotides in length, yet more preferably at least about 450 nucleotides in length, yet more preferably at least about 500 nucleotides in length, yet more preferably at least about 600 nucleotides in length, yet more preferably at least about 700 nucleotides in length, yet more preferably at least about 800 nucleotides in length, yet more preferably at least about 900 nucleotides in length and yet more preferably at least about 1000 nucleotides in length, wherein in this context the term "about" means the referenced nucleotide sequence length plus or minus 10% of that referenced length. It is noted that novel fragments of a PRO polypeptide-encoding nucleotide sequence may be determined in a routine manner by aligning the PRO polypeptide-encoding nucleotide sequence with other known nucleotide sequences using any of a number of well known sequence alignment programs and determining which PRO polypeptide-encoding nucleotide sequence fragment(s) are novel. All of such PRO polypeptide-encoding nucleotide sequences are contemplated herein. Also contemplated are the PRO polypeptide fragments encoded by these nucleotide molecule fragments, preferably those PRO polypeptide fragments that comprise a binding site for an anti-PRO antibody.

In another embodiment, the invention provides isolated PRO polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.

In a certain aspect, the invention concerns an isolated PRO polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptide comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91% sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to an amino acid sequence encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptide comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 81% positives, more preferably at least about 82% positives, yet more preferably at least about 83% positives, yet more preferably at least about 84% positives, yet more preferably at least about 85% positives, yet more preferably at least about 86% positives, yet more preferably at least about 87% positives, yet more preferably at least about 88% positives, yet more preferably at least about 89% positives, yet more preferably at least about 90% positives, yet more preferably at least about 91% positives, yet more preferably at least about 92% positives, yet more preferably at least about 93% positives, yet more preferably at least about 94% positives, yet more preferably at least about 95% positives, yet more preferably at least about 96% positives, yet more preferably at least about 97% positives, yet more preferably at least about 98% positives and yet more preferably at least about 99% positives when compared with the amino acid sequence of a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein.

In a specific aspect, the invention provides an isolated PRO polypeptide without the N-terminal signal sequence and/or the initiating methionine and is encoded by a nucleotide sequence that encodes such an amino acid sequence as hereinbefore described. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.

Another aspect the invention provides an isolated PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists and antagonists of a native PRO polypeptide as defined herein. In a particular embodiment, the agonist or antagonist is an anti-PRO antibody or a small molecule.

In a further embodiment, the invention concerns a method of identifying agonists or antagonists to a PRO polypeptide which comprise contacting the PRO polypeptide with a candidate molecule and monitoring a biological activity mediated by said PRO polypeptide. Preferably, the PRO polypeptide is a native PRO polypeptide.

In a still further embodiment, the invention concerns a composition of matter comprising a PRO polypeptide, or an agonist or antagonist of a PRO polypeptide as herein described, or an anti-PRO antibody, in combination with a carrier. Optionally, the carrier is a pharmaceutically acceptable carrier.

Another embodiment of the present invention is directed to the use of a PRO polypeptide, or an agonist or antagonist thereof as hereinbefore described, or an anti-PRO antibody, for the preparation of a medicament useful in the treatment of a condition which is responsive to the PRO polypeptide, an agonist or antagonist thereof or an anti-PRO antibody.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a nucleotide sequence (SEQ ID NO:1) of a native sequence PRO246 cDNA, wherein SEQ ID NO:1 is a clone designated herein as "DNA35639-1172".

FIG. 2 shows the amino acid sequence (SEQ ID NO:2) derived from the coding sequence of SEQ ID NO:1 shown in FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

I. Definitions

The terms "PRO polypeptide" and "PRO" as used herein and when immediately followed by a numerical designation refer to various polypeptides, wherein the complete designation (i.e., PRO/number) refers to specific polypeptide sequences as described herein. The terms "PRO/number polypeptide" and "PRO/number" wherein the term "number" is provided as an actual numerical designation as used herein encompass native sequence polypeptides and polypeptide variants (which are further defined herein). The PRO polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods.

A "native sequence PRO polypeptide" comprises a polypeptide having the same amino acid sequence as the corresponding PRO polypeptide derived from nature. Such native sequence PRO polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. The term "native sequence PRO polypeptide" specifically encompasses naturally-occurring truncated or secreted forms of the specific PRO polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide. In various embodiments of the invention, the native sequence PRO polypeptides disclosed herein are mature or full-length native sequence polypeptides comprising the full-length amino acids sequences shown in the accompanying figures. Start and stop codons are shown in bold font and underlined in the figures. However, while the PRO polypeptide disclosed in the accompanying figures are shown to begin with methionine residues designated herein as amino acid position 1 in the figures, it is conceivable and possible that other methionine residues located either upstream or downstream from the amino acid position 1 in the figures may be employed as the starting amino acid residue for the PRO polypeptides.

The PRO polypeptide "extracellular domain" or "ECD" refers to a form of the PRO polypeptide which is essentially free of the transmembrane and cytoplasmic domains. Ordinarily, a PRO polypeptide ECD will have less than 1% of such transmembrane and/or cytoplasmic domains and preferably, will have less than 0.5% of such domains. It will be understood that any transmembrane domains identified for the PRO polypeptides of the present invention are identified pursuant to criteria routinely employed in the art for identifying that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain as initially identified herein. Optionally, therefore, an extracellular domain of a PRO polypeptide may contain from about 5 or fewer amino acids on either side of the transmembrane domain/extracellular domain boundary as identified in the Examples or specification and such polypeptides, with or without the associated signal peptide, and nucleic acid encoding them, are comtemplated by the present invention.

The approximate location of the "signal peptides" of the various PRO polypeptides disclosed herein are shown in the present specification and/or the accompanying figures. It is noted, however, that the C-terminal boundary of a signal peptide may vary, but most likely by no more than about 5 amino acids on either side of the signal peptide C-terminal boundary as initially identified herein, wherein the C-terminal boundary of the signal peptide may be identified pursuant to criteria routinely employed in the art for identifying that type of amino acid sequence element (e.g., Nielsen et al., Prot. Eng. 10:1-6 (1997) and von Heinje et al., Nucl. Acids. Res. 14:4683-4690 (1986)). Moreover, it is also recognized that, in some cases, cleavage of a signal sequence from a secreted polypeptide is not entirely uniform, resulting in more than one secreted species. These mature polypeptides, where the signal peptide is cleaved within no more than about 5 amino acids on either side of the C-terminal boundary of the signal peptide as identified herein, and the polynucleotides encoding them, are contemplated by the present invention.

"PRO polypeptide variant" means an active PRO polypeptide as defined above or below having at least about 80% amino acid sequence identity with a full-length native sequence PRO polypeptide sequence as disclosed herein, a PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Such PRO polypeptide variants include, for instance, PRO polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C-terminus of the full-length native amino acid sequence. Ordinarily, a PRO polypeptide variant will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, more preferably at least about 83% amino acid sequence identity, more preferably at least about 84% amino acid sequence identity, more preferably at least about 85% amino acid sequence identity, more preferably at least about 86% amino acid sequence identity, more preferably at least about 87% amino acid sequence identity, more preferably at least about 88% amino acid sequence identity, more preferably at least about 89% amino acid sequence identity, more preferably at least about 90% amino acid sequence identity, more preferably at least about 91% amino acid sequence identity, more preferably at least about 92% amino acid sequence identity, more preferably at least about 93% amino acid sequence identity, more preferably at least about 94% amino acid sequence identity, more preferably at least about 95% amino acid sequence identity, more preferably at least about 96% amino acid sequence identity, more preferably at least about 97% amino acid sequence identity, more preferably at least about 98% amino acid sequence identity and most preferably at least about 99% amino acid sequence identity with a full-length native sequence PRO polypeptide sequence as disclosed herein, a PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of a full-length PRO polypeptide sequence as disclosed herein. Ordinarily, PRO variant polypeptides are at least about 10 amino acids in length, often at least about 20 amino acids in length, more often at least about 30 amino acids in length, more often at least about 40 amino acids in length, more often at least about 50 amino acids in length, more often at least about 60 amino acids in length, more often at least about 70 amino acids in length, more often at least about 80 amino acids in length, more often at least about 90 amino acids in length, more often at least about 100 amino acids in length, more often at least about 150 amino acids in length, more often at least about 200 amino acids in length, more often at least about 300 amino acids in length, or more.

"Percent (%) amino acid sequence identity" with respect to the PRO polypeptide sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific PRO polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, Calif. or may be compiled from the source code provided in Table 1 below. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. As examples of % amino acid sequence identity calculations using this method, Tables 2 and 3 demonstrate how to calculate the % amino acid sequence identity of the amino acid sequence designated "Comparison Protein" to the amino acid sequence designated "PRO", wherein "PRO" represents the amino acid sequence of a hypothetical PRO polypeptide of interest, "Comparison Protein" represents the amino acid sequence of a polypeptide against which the "PRO" polypeptide of interest is being compared, and "X, "Y" and "Z" each represent different hypothetical amino acid residues.

Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. However, % amino acid sequence identity values may also be obtained as described below by using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzymology 266:460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to the default values. Those not set to default values, i.e., the adjustable parameters, are set with the following values: overlap span=1, overlap fraction=0.125, word threshold (T)=11, and scoring matrix=BLOSUM62. When WU-BLAST-2 is employed, a % amino acid sequence identity value is determined by dividing (a) the number of matching identical amino acid residues between the amino acid sequence of the PRO polypeptide of interest having a sequence derived from the native PRO polypeptide and the comparison amino acid sequence of interest (i.e., the sequence against which the PRO polypeptide of interest is being compared which may be a PRO variant polypeptide) as determined by WU-BLAST-2 by (b) the total number of amino acid residues of the PRO polypeptide of interest. For example, in the statement "a polypeptide comprising an the amino acid sequence A which has or having at least 80% amino acid sequence identity to the amino acid sequence B", the amino acid sequence A is the comparison amino acid sequence of interest and the amino acid sequence B is the amino acid sequence of the PRO polypeptide of interest.

Percent amino acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov. NCBI-BLAST2 uses several search parameters, wherein all of those search parameters are set to default values including, for example, unmask=yes, strand=all, expected occurrences=10, minimum low complexity length=15/5, multi-pass e-value=0.01, constant for multi-pass=25, dropoff for final gapped alignment=25 and scoring matrix=BLOSUM62.

In situations where NCBI-BLAST2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program NCBI-BLAST2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A.

"PRO variant polynucleotide" or "PRO variant nucleic acid sequence" means a nucleic acid molecule which encodes an active PRO polypeptide as defined below and which has at least about 80% nucleic acid sequence identity with a nucleotide acid sequence encoding a full-length native sequence PRO polypeptide sequence as disclosed herein, a full-length native sequence PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Ordinarily, a PRO variant polynucleotide will have at least about 80% nucleic acid sequence identity, more preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity and yet more preferably at least about 99% nucleic acid sequence identity with a nucleic acid sequence encoding a full-length native sequence PRO polypeptide sequence as disclosed herein, a full-length native sequence PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal sequence, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein. Variants do not encompass the native nucleotide sequence.

Ordinarily, PRO variant polynucleotides are at least about 30 nucleotides in length, often at least about 60 nucleotides in length, more often at least about 90 nucleotides in length, more often at least about 120 nucleotides in length, more often at least about 150 nucleotides in length, more often at least about 180 nucleotides in length, more often at least about 210 nucleotides in length, more often at least about 240 nucleotides in length, more often at least about 270 nucleotides in length, more often at least about 300 nucleotides in length, more often at least about 450 nucleotides in length, more often at least about 600 nucleotides in length, more often at least about 900 nucleotides in length, or more.

"Percent (%) nucleic acid sequence identity" with respect to PRO-encoding nucleic acid sequences identified herein is defined as the percentage of nucleotides in a candidate sequence that are identical with the nucleotides in the PRO nucleic acid sequence of interest, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. For purposes herein, however, % nucleic acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, Calif. or may be compiled from the source code provided in Table 1 below. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for nucleic acid sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C. As examples of % nucleic acid sequence identity calculations, Tables 4 and 5, demonstrate how to calculate the % nucleic acid sequence identity of the nucleic acid sequence designated "Comparison DNA" to the nucleic acid sequence designated "PRO-DNA", wherein "PRO-DNA" represents a hypothetical PRO-encoding nucleic acid sequence of interest, "Comparison DNA" represents the nucleotide sequence of a nucleic acid molecule against which the "PRO-DNA" nucleic acid molecule of interest is being compared, and "N", "L" and "V" each represent different hypothetical nucleotides.

Unless specifically stated otherwise, all % nucleic acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. However, % nucleic acid sequence identity values may also be obtained as described below by using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzymology 266:460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to the default values. Those not set to default values, i.e., the adjustable parameters, are set with the following values: overlap span=1, overlap fraction=0.125, word threshold (T)=11, and scoring matrix=BLOSUM62. When WU-BLAST-2 is employed, a % nucleic acid sequence identity value is determined by dividing (a) the number of matching identical nucleotides between the nucleic acid sequence of the PRO polypeptide-encoding nucleic acid molecule of interest having a sequence derived from the native sequence PRO polypeptide-encoding nucleic acid and the comparison nucleic acid molecule of interest (i.e., the sequence against which the PRO polypeptide-encoding nucleic acid molecule of interest is being compared which may be a variant PRO polynucleotide) as determined by WU-BLAST-2 by (b) the total number of nucleotides of the PRO polypeptide-encoding nucleic acid molecule of interest. For example, in the statement "an isolated nucleic acid molecule comprising a nucleic acid sequence A which has or having at least 80% nucleic acid sequence identity to the nucleic acid sequence B", the nucleic acid sequence A is the comparison nucleic acid molecule of interest and the nucleic acid sequence B is the nucleic acid sequence of the PRO polypeptide-encoding nucleic acid molecule of interest.

Percent nucleic acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov. NCBI-BLAST2 uses several search parameters, wherein all of those search parameters are set to default values including, for example, unmask=yes, strand=all, expected occurrences=10, minimum low complexity length=15/5, multi-pass e-value=0.01, constant for multi-pass=25, dropoff for final gapped alignment=25 and scoring matrix=BLOSUM62.

In situations where NCBI-BLAST2 is employed for sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program NCBI-BLAST2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C.

In other embodiments, PRO variant polynucleotides are nucleic acid molecules that encode an active PRO polypeptide and which are capable of hybridizing, preferably under stringent hybridization and wash conditions, to nucleotide sequences encoding a full-length PRO polypeptide as disclosed herein. PRO variant polypeptides may be those that are encoded by a PRO variant polynucleotide.

The term "positives", in the context of sequence comparison performed as described above, includes residues in the sequences compared that are not identical but have similar properties (e.g. as a result of conservative substitutions, see Table 6 below). For purposes herein, the % value of positives is determined by dividing (a) the number of amino acid residues scoring a positive value between the PRO polypeptide amino acid sequence of interest having a sequence derived from the native PRO polypeptide sequence and the comparison amino acid sequence of interest (i.e., the amino acid sequence against which the PRO polypeptide sequence is being compared) as determined in the BLOSUM62 matrix of WU-BLAST-2 by (b) the total number of amino acid residues of the PRO polypeptide of interest.

Unless specifically stated otherwise, the % value of positives is calculated as described in the immediately preceding paragraph. However, in the context of the amino acid sequence identity comparisons performed as described for ALIGN-2 and NCBI-BLAST-2 above, includes amino acid residues in the sequences compared that are not only identical, but also those that have similar properties. Amino acid residues that score a positive value to an amino acid residue of interest are those that are either identical to the amino acid residue of interest or are a preferred substitution (as defined in Table 6 below) of the amino acid residue of interest.

For amino acid sequence comparisons using ALIGN-2 or NCBI-BLAST2, the % value of positives of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % positives to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scoring a positive value as defined above by the sequence alignment program ALIGN-2 or NCBI-BLAST2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % positives of A to B will not equal the % positives of B to A.

"Isolated," when used to describe the various polypeptides disclosed herein, means polypeptide that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the polypeptide will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Isolated polypeptide includes polypeptide in situ within r


Free Web Sudoku Puzzles.
Solve with your browser.
2 9       7     1
  5       3     7
          1   6 5
        4   2    
  6 7       8 5  
    3   7        
3 7   9          
1     8       9  
5     7       3 2
What is it?



Add Your Site · Terms Of Service · Privacy Policy


DISCLAIMER
Linkgrinder is a free service that searches the Internet and indexes all files found so that you may search quickly and easily for shared files. These files are created and made available individually by users whose identity we are not aware of and who we have no control over. In essence we function like a search engine tool; these files ARE NOT STORED OR SERVED BY OUR NETWORK. We are not responsible for any materials obtained by using our service. We do not monitor any of the contents of these files. These files may contain viruses, illegal materials, materials inappropriate for minors, offensive files and the like. BY USING OUR SERVICE, YOU ASSUME FULL RESPONSIBILITY FOR DOWNLOADING THESE MATERIALS AND WILL INDEMNIFY US FOR ANY DAMAGES THAT MAY BE INCURRED.

For More Specific Information VIEW OUR TERMS OF SERVICE.

Thank you and Enjoy!