(12) United States Patent (10) Patent No.: US 7,846.445 B2 Schellenberger Et Al

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(12) United States Patent (10) Patent No.: US 7,846.445 B2 Schellenberger Et Al USOO7846445B2 (12) United States Patent (10) Patent No.: US 7,846.445 B2 Schellenberger et al. (45) Date of Patent: Dec. 7, 2010 (54) METHODS FOR PRODUCTION OF 5,176,502 A 1/1993 Sanderson et al. UNSTRUCTURED RECOMBINANT 5, 186,938 A 2/1993 Sablotsky et al. POLYMERS AND USES THEREOF 5,215,680 A 6/1993 D'arrigo 5,223,409 A 6/1993 Ladner et al. (75) Inventors: Volker Schellenberger, Palo Alto, CA 5,270,176 A * 12/1993 Dorschug et al. .......... 435/69.7 (US); Willem P. Stemmer, Los Gatos, 5,298,022 A 3, 1994 Bernardi CA (US); Chia-wei Wang, Santa Clara, 5,318.540 A 6, 1994 Athayde et al. CA (US); Michael D. Schole, Mountain 5,407,609 A 4/1995 Tice et al. View, CA (US); Mikhail Popkov, San 2. 3. E. 1 Diego, CA (US); Nathaniel C. Gordon, - - I oiszwillo et al. Campbell, CA (US); Andreas Crameri, 5,573,776 A 11, 1996 Harrison et al. 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(22) Filed: Mar 6, 2007 6,056,973 A 5, 2000 Allen et al. a vs. (65) Prior Publication Data (Continued) US 2008/O2868O8A1 Nov. 20, 2008 FOREIGN PATENT DOCUMENTS Related U.S. Application Data WO WO 89,09051 A1 10, 1989 (63) Continuation-in-part of application No. 1 1/528,927, filed on Sep. 27, 2006, and a continuation-in-part of (Continued) application No. 1 1/528,950, filed on Sep. 27, 2006. (60) Provisional application No. 60/721,270, filed on Sep. OTHER PUBLICATIONS 27, 2005, provisional application No. 60/721,188, Ackerman et al. Ion Channels—Basic Science and Clinical Disease. filed on Sep. 27, 2005, provisional application No. New Engl. J. Med. 1997; 336:1575-1595. 60/743,622, filed on Mar. 21, 2006, provisional appli- Alvarez, et al. Improving Protein Pharmacokinetics by Genetic cation No. 60/743,410, filed on Mar. 6, 2006. Fusion to Simple Amino Acid Sequences. J Biol Chem. 2004; 279: 3375-81. (51) Int. Cl. Amin, et al. 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Wessendorf (74) Attorney, Agent, or Firm Wilson Sonsini Goodrich & (56) References Cited Rosati U.S. PATENT DOCUMENTS (57) ABSTRACT 3,992,518 A 11, 1976 Chien et al. 4,088,864 A 5, 1978 Theeuwes et al. 4,200,984 A 5, 1980 Fink The present invention provides methods of using unstruc 4,284.444 A 8, 1981 Bernstein et al. tured recombinant polymers (URPs) and proteins containing 4,398,908 A 8/1983 Siposs one or more of the URPs. The present invention also provides 4,435,173 A 3/1984 Siposs et al. microproteins, toxins and other related proteinaceous enti 4,542,025 A 9, 1985 Tice et al. ties, as well as genetic packages displaying these entities, and 4,684,479 A 8/1987 Darrigo the uses thereof. The present invention also provides recom 4,861,800 A 8/1989 Buyske binant polypeptides including vectors encoding the Subject 4,897.268 A 1/1990 Tice et al. 4,933,185 A 6/1990 Wheatley et al. proteinaceous entities, as well as host cells comprising the 4,976,696 A 12/1990 Sanderson et al. vectors. 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