US 20060O84799A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0084799 A1 Williams et al. (43) Pub. Date: Apr. 20, 2006 (54) HUMAN CDNA CLONES COMPRISING filed on Mar. 1, 2004. Provisional application No. POLYNUCLEOTDES ENCODING 60/589,826, filed on Jul. 22, 2004. Provisional appli POLYPEPTIDES AND METHODS OF THEIR cation No. 60/589,788, filed on Jul. 22, 2004. USE Publication Classification (76) Inventors: Lewis T. Williams, Mill Valley, CA (US); Keting Chu, Woodside, CA (US); (51) Int. Cl. Ernestine Lee, Kensington, CA (US); C07K I4/705 (2006.01) Kevin Hestir, Kensington, CA (US); AOIK 67/00 (2006.01) Justin Wong, Oakland, CA (US); C7H 2L/04 (2006.01) Stephen K. Doberstein, San Francisco, CI2P 2/06 (2006.01) CA (US) CI2N 5/06 (2006.01) (52) U.S. Cl. .................... 536/23.5; 435/69.1; 435/320.1; Correspondence Address: 435/325; 530/350; 800/8 FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER (57) ABSTRACT LLP The invention provides novel human full-length cDNA 901 NEW YORK AVENUE, NW clones, novel polynucleotides, related polypeptides, related WASHINGTON, DC 20001-4413 (US) nucleic acid and polypeptide compositions, and related (21) Appl. No.: 10/948,571 modulators, such as antibodies and Small molecule modu lators. The invention also provides methods to make and use (22) Filed: Sep. 24, 2004 these cDNA clones, polynucleotides, polypeptides, related compositions, and modulators. These methods include diag Related U.S. Application Data nostic, prophylactic and therapeutic applications. The com positions and methods of the invention are useful in treating (60) Provisional application No. 60/505,144, filed on Sep. proliferative disorders, e.g., cancers, and inflammatory, 24, 2003. Provisional application No. 60/548,191, immune, bacterial, and viral disorders. US 2006/0O84799 A1 Apr. 20, 2006 HUMAN CONACILONES COMPRISING tors responsive to secreted proteins are many and various, POLYNUCLEOTIDES ENCODING POLYPEPTIDES including, any cell type of any tissue origin or developmen AND METHODS OF THEIR USE tal state, and including normal cells and cells implicated in pathological conditions or other disorders. CROSS REFERENCE TO RELATED 0008 Transmembrane proteins extend into or through the APPLICATIONS cell membrane's lipid bilayer, they can span the membrane 0001) This application claims the benefit of U.S. Provi once, or more than once. Transmembrane proteins that span sional Application No. 60/505,144, filed Sep. 24, 2003, and the membrane once are designated “single transmembrane U.S. Provisional Application No. 60/548,191, filed Mar. 1, proteins’ (STM), and transmembrane proteins that span the 2004, the disclosures of which are incorporated in their membrane more than once are designated “multiple trans entireties. This application also incorporates U.S. Provi membrane proteins’ (MTM). A single transmembrane pro sional No. 60/589,826, filed Apr. 28, 2004; U.S. Provisional tein typically has one transmembrane (TM) domain, Span (application number pending) “Inhibitory RNA Library.” ning a series of consecutive amino acid residues, numbered filed Jul 22, 2004; and U.S. Provisional No. 60/589,788, on the basis of distance from the N-terminus, with the first filed Jul. 22, 2004; in their entireties. amino acid residue at the N-terminus as number 1. A multi-transmembrane protein typically has more than one SEQUENCE LISTING TM domain, each spanning a series of consecutive amino acid residues, numbered in the same way as the STM 0002 This application contains a Sequence Listing which protein. has been Submitted via a printed paper copy, and is hereby incorporated by reference in its entirety. A computer read 0009 Transmembrane proteins, having part of their mol able version with content identical to the printed paper copy ecules on either side of the bilayers, also have many and is also submitted herein. widely variant biological functions. They transport mol ecules, e.g., ions or proteins, across membranes, transduce BACKGROUND OF THE INVENTION signals across membranes, act as receptors, and function as antigens. Transmembrane proteins are often involved in cell 0003) 1. Field of the Invention signaling events; they can comprise signaling molecules, 0004 The invention relates to cDNA clones which and/or can interact with signaling molecules. encode one or more polypeptide gene products. These cDNA 0010 Transmembrane proteins with extracellular frag clones encode secreted and/or transmembrane proteins. The ments that can be cleaved may act as secreted proteins and invention provides the nucleotide and amino acid sequences bind to receptors as ligands. Transmembrane proteins of these cDNA clones as well as their tissue sources, embedded in the membrane may act as receptors, and may expression patterns, an annotative description, and their possess both a ligand-binding extracellular portion exposed predicted function. The cDNA clones of the invention are on a cell Surface and an intracellular portion that interacts useful for investigative, diagnostic, and therapeutic pur with other cellular components upon activation. Both poses, as described in detail herein. secreted and embedded transmembrane proteins can mediate intracellular responses and extracellular responses. 0005 2. Background Information SUMMARY OF THE INVENTION 0006 Secreted proteins, also referred to as secreted fac 0011. The present invention relates generally to novel tors or secreted polypeptides, include polypeptides and nucleic acids embodied in cDNA clones and the polypep active fragments of polypeptides that are produced by cells tides they encode. Sequences encompassed by the invention and exported extracellularly. Secreted proteins also include include, but are not limited to, the polypeptide and poly extracellular fragments of transmembrane proteins that are nucleotide sequences of the molecules shown in the proteolytically cleaved, and extracellular fragments of cell Sequence Listing and corresponding molecular sequences Surface receptors; these fragments may be soluble. Many found at all developmental stages of an organism, genes or and widely variant biological functions are mediated by a gene segments designated by the Sequence Listing, and their wide variety of different types of secreted proteins. Yet, corresponding gene products, i.e., RNA and polypeptides. despite the sequencing of the human genome, relatively few Sequences encompassed by the invention also include vari pharmaceutically useful secreted proteins have been identi ants of those presented in the Sequence Listing which are fied and brought to the clinic or to the market. It would be present in the normal physiological state, e.g., variant alleles advantageous to discover novel secreted proteins or such as SNPs, splice variants, as well as variants that are polypeptides, and their corresponding polynucleotides, present in pathological states, such as disease-related muta which have medical utility. tions or sequences with alterations that lead to pathology. 0007 Pharmaceutically useful secreted proteins of the Variants of the invention include polypeptides with conser present invention will have in common the ability to act as Vative amino acid changes; as well as complements and ligands for binding to receptors on cell Surfaces in ligand/ fragments, for example, signal peptides, mature polypep receptor interactions; to bind to ligands, soluble or other tides, biologically active fragments, Pfam domains, and wise; to inhibit ligand/receptor interactions; to trigger cer structural motifs. The invention also includes vectors and tain intracellular responses, such as inducing signal host cells that can be used to produce the polypeptides of the transduction to activate cells or inhibit cellular activity; to invention and gene products of the polynucleotides of the induce cellular growth, proliferation, or differentiation; to invention, as well as methods of using these vectors and host induce the production of other factors that, in turn, mediate cells to produce gene products. The invention includes such activities; and/or to inhibit cell activation or other cell antibodies that specifically bind to the molecules of the signaling activities. The cell types having cell Surface recep invention. US 2006/0O84799 A1 Apr. 20, 2006 0012. The novel amino acid molecules of the invention 0016. A "polymerase chain reaction' is a chemical reac are secreted and/or transmembrane proteins. They can func tion capable of amplifying DNA in vitro. It is performed tion as agonists, antagonists, ligands, and/or receptors, and using two oligonucleotide primers, which are complemen they can have diagnostic, prophylactic, and therapeutic tary to two regions of the target DNA to be amplified, one effects. The invention provides methods of making the for each strand. The primers are added to the target DNA in polynucleotides and polypeptides of the invention, as well as the presence of excess deoxynucleotides and a heat stable methods of determining their presence. The invention pro DNA polymerase. The target DNA can be provided to the vides diagnostic kits and methods of using the novel nucleic reaction mixture in pure or relatively pure form, or it may be acids and amino acids to diagnose disease. It also provides present as a minor component, as is typically the case when methods of using the polynucleotides and polypeptides of it is provided as a component of a biological sample. In a the invention to modulate biological activity; this modula series of temperature cycles, the target