USOO8603824B2 (12) United States Patent (10) Patent No.: US 8,603,824 B2 Ramseier et al. (45) Date of Patent: Dec. 10, 2013 (54) PROCESS FOR IMPROVED PROTEIN 5,399,684 A 3, 1995 Davie et al. EXPRESSION BY STRAIN ENGINEERING 5,418, 155 A 5/1995 Cormier et al. 5,441,934 A 8/1995 Krapcho et al. (75) Inventors: Thomas M. Ramseier, Poway, CA 5,508,192 A * 4/1996 Georgiou et al. .......... 435/252.3 (US); Hongfan Jin, San Diego, CA 5,527,883 A 6/1996 Thompson et al. (US); Charles H. Squires, Poway, CA 5,558,862 A 9, 1996 Corbinet al. 5,559,015 A 9/1996 Capage et al. (US) 5,571,694 A 11/1996 Makoff et al. (73) Assignee: Pfenex, Inc., San Diego, CA (US) 5,595,898 A 1/1997 Robinson et al. 5,610,044 A 3, 1997 Lam et al. (*) Notice: Subject to any disclaimer, the term of this 5,621,074 A 4/1997 Bjorn et al. patent is extended or adjusted under 35 5,622,846 A 4/1997 Kiener et al. 5,641,671 A 6/1997 Bos et al. 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The invention is a process of comparing two 5,169,772 A 12, 1992 Zimmerman et al. genetic profiles of a cell that expresses a recombinant protein 5,173,616 A 12/1992 Hinooka and modifying the cell to change the expression of a gene 5,232,840 A 8, 1993 Olins product that is upregulated in response to the recombinant 5,264,365 A 11/1993 Georgiou et al. protein expression. The process can improve protein produc 5,281,532 A 1/1994 Rammler et al. 5,292,507 A 3/1994 Charley tion or can improve protein quality, for example, by increas 5,292,658 A 3, 1994 Cormier et al. ing solubility of a recombinant protein. 5,348,867 A 9/1994 Georgiou et al. 35 Claims, 15 Drawing Sheets US 8,603,824 B2 Page 2 (56) References Cited 6,180.343 B1 1/2001 Anderson et al. 6,184,440 B1 2/2001 Shoseyov et al. 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