US007935351B2 (12) United States Patent (10) Patent No.: US 7,935,351 B2 Klinman et al. (45) Date of Patent: *May 3, 2011 (54) USE OF CPG OLIGODEOXYNUCLEOTIDES 35. A 3. 2. RS:udolph s et alal. TO INDUCE ANGOGENESIS 5,288,509 A 2f1994 Potman et al. 5.488,039 A 1, 1996 M tal. (75) Inventors: Dennis M. Klinman, Potomac, MD 5.492.899 A 2, 1996 NE al. (US); Mei Zheng, Augusta, GA (US); 5,585,479 A 12/1996 Hoke et al. Barry T. Rouse, Knoxville, TN (US) 5,602,1095,591,721 A 2/19971/1997 MasorAgrawal et etal. al. 5,612,060 A 3, 1997 A1 d (73) Assignees: The United States of America as 5,614,191 A 3, 1997 al represented by the Department of 5,650,156 A 7/1997 Grinstaffet al. Health and Human Services, 5,663,153 A 9, 1997 Hutcerson et al. Washington, DC (US); University of 3. A RE SEE, Tennessee Research Foundation, 5,700,590 A 12/1997 Masoretal Knoxville, TN (US) 5,712.256 A 1/1998 Kulkarni et al. 5,723,335 A 3, 1998 Hutcerson et al. (*) Notice: Subject to any disclaimer, the term of this 3. 2. A 38. El cal patent is extended or adjusted under 35 5.840,705 A 11/1998 Tsukuda U.S.C. 154(b) by 761 days. 5,849,719 A 12, 1998 Carson et al. This patent is Subject to a terminal dis- 33: A 23: SEE claimer. 5,922,766 A 7/1999 Acosta et al. 5,976,580 A 1 1/1999 Ivey et al. (21) Appl. No.: 11/839,217 5,980,958 A 1 1/1999 Naylor et al. 5,994,126 A 11/1999 Stienman et al. (22) Filed: Aug. 15, 2007 6,022,853. A 2/2000 Kuberasampath et al. e - a 9 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2008/OO27021 A1 Jan. 31, 2008 EP O 286 224 10, 1988 Related U.S. Application Data (Continued) (63) Continuation of application No. 10/499.597, filed as application No. PCT/US02/40955 on Dec. 19, 2002, OTHER PUBLICATIONS now Pat. No. 7,615,227. Zheng et al. Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic (60) gyal application No. 60/343,457, filed on Dec. stromal keratitis. Journal of Virology, Oct. 2001, vol. 75, No. 20, pp. s 9828-9835. (51) Int. Cl McGeoch et al. The complete DNA sequence of the long unique Asik 3900 2006.O1 region in the genome of herpes simplex virus type 1. J. Gen. Virol. ( .01) 1988, vol. 69, 1531-1574.* A6 IK39/38 (2006.01) US 6,008,200, Dec. 28, 1999 (withdrawn). A6 IK 45/00 (2006.01) Adya, et al., “Expansion of CREB's DNA recognition specificity by A6 IK 47/00 (2006.01) Tax results from interaction with Ala-Ala-Arg at positions 282-284 AOIN 43/04 (2006.01) near the conserved DNA-binding domain of CREB'. Proc. Natl. (52) U.S. Cl. ............... 424/198.1; 424/1841; 424/278.1; Acad. Sci. USA 91(12):5642-5646 (1994). 514744 R (Continued) (58) Field of Classification Search ........................ None See application file for complete search history. Primary Examiner – N. M. Minnifield (56) References Cited (74) Attorney, Agent, or Firm — Klarduist Sparkman, LLP U.S. PATENT DOCUMENTS (57) ABSTRACT 2,215,233 A 9, 1940 Ruskin 3,906,092 A 9, 1975 Hilleman et al. This disclosure provides a method of inducing production of 3,911,117 A 10, 1975 Ender vascular endothelial growth factor by a cell. The method 3,914.450 A 10, 1975 Robbins et al. 4,469,863. A 9, 1984 Ts'o et al. includes contacting the cell with a CpG oligonucleotide, 4,544.559 A 10, 1985 Gilet al. thereby inducing the production of vascular endothelial 4,741,914 A 5, 1988 Kimizuka et al. growth factor by the cell. The disclosure further provides a 4,758,553 A 7/1988 Ogoshi method inducing neovascularization in a tissue. This method 4,806,376 A 2f1989 Saeki et al. includes comprising introducing a CpG oligodeoxynucle 4.956,296 A 9, 1990 Fahnestock 4,963,387 A 10/1990 Nakagawa et al. otide into an area of the tissue wherein the formation of new 4,994,442 A 2f1991 Gil et al. blood vessels is desired, thereby inducing neovascularization 5,023,243 A 6, 1991 Tullis in the area of the tissue. 5,066,500 A 11, 1991 Gilet al. 5,231,085 A 7, 1993 Alexander et al. 5,234,811 A 8, 1993 Beutler et al. 24 Claims, 6 Drawing Sheets US 7,935,351 B2 Page 2 U.S. PATENT DOCUMENTS 2003/010.0527 A1 5/2003 Krieg et al. 2003/0104044 A1 6/2003 Semple et al. 6, 194,388 B1 2/2001 Krieg et al. 2003. O104523 A1 6, 2003 E. 6,207,646 B1 3/2001 Krieg et al. 2003/0109469 A1 6/2003 Carson et al. 6.214.806 B1 4/2001 Krieg et al. 2003/01 19773 A1 6, 2003 Raz et al. 6.218.371 B1 4/2001 Krieg et al. 2003/01 19774 A1 6, 2003 Foldvariet al. 3. R 299; E. et al 2003/01 19776 A1 6/2003 Phillips et al. 6,406.705 Bi 6/2002 SE A. 2003/O125284 A1 7, 2003 Raz et al. w s 2003/0129251 A1 7, 2003 Van Nest et al. 6.423,539 B2 7/2002 Fong et al. 2003. O130217 A1 7, 2003 Raz et al. 6.428,788 B1 8/2002 Debinski et al. 2003/0.133988 A1 7/2003 Fearon et al. 6,429,199 B1 8/2002 Krieg et al. 2003. O135875 A1 7, 2003 Ehrhardt et al. 6,498,148 B1 12/2002 Raz 2003. O1384.13 A1 7, 2003 Vicari et al. 6,514,948 B1 2/2003 Raz et al. 2003/0138453 A1 7/2003 O'Hagan et al. 6,534,062 B2 3/2003 Raz et al. 2003/0139364 A1 7/2003 Krieg et al. 6,552,006 B2 4/2003 Raz et al. 2003.0143213 A1 7, 2003 Raz et al. 6,562,798 B1 5/2003 Schwartz 2003.0143743 A1 7, 2003 Schuler et al. 6,589,940 B1 7/2003 Raz et al. 2003/0144229 A1 7/2003 Klinman et al. 6,610,661 B1 8/2003 Carson et al. 2003. O14787.0 A1 8, 2003 Raz et al. 6,613,751 B2 9/2003 Raz et al. 2003/0148316 A1 8/2003 Lipford et al. 6,653,292 B 11/2003 Krieg et al. 2003/0148976 A1 8/2003 Krieg et al. 7.354,909 B2 * 4/2008 Klinman et al. 514.44 R 2003/0148983 A1 8/2003 Fontoura etal 7,521,063 B2 * 4/2009 Klinman et al. 424,282.1 2003/015777 Ai 8/2003 Draghia Aki 7,560,436 B2 * 7/2009 Raz et al. ........................ 514,43 2003. O158136 A1 8, 2003 Rice et all 7,615,227 B2 * 1 1/2009 Klinman et al. ........... 424,198.1 2003/065478 A 9/2003 Sokoli 7,666,674 B2 * 2/2010 Klinman et al. .............. 435/375 2003/0166001 A1 9/2003 Lipford 7,758,876 B2 * T/2010 Klinman et al. ........... 424,278.1 2003/0170273 A1 9, 2003 O'Hagan et al. 58-83.3 A. 299; al 2003/0171321 A1 9, 2003 Schmidt et al. get al. 2003/0175731 A1 9, 2003 Fearon et al. 2001/0044416 A1 11/2001 McCluskie et al. 2003/0176373 A1 9, 2003 Raz et al. 2001, 0046967 A1 11, 2001 Van Nest 2003/0176389 A1 9, 2003 Raz et al. 2002fOOO6403 A1 1/2002 Yu et al. 2003/0180320 A1 9/2003 Darju et al. 2002/0028784 A1 3, 2002 Van Nest 2003/0181406 A1 9, 2003 Schetter et al. 2002fOO42383 A1 4, 2002 Yew et al. 2003/0185848 A1 10, 2003 Johnston et al. 2002fOO42387 A1 4, 2002 Raz et al. 2003.0185900 A1 10, 2003 Choi et al. 2002/0055477 A1 5, 2002 Van Nest et al. 2003/0186921 A1 10, 2003 Carson et al. 2002/0064515 A1 5/2002 Krieg et al. 2003/019 1079 A1 10/2003 Krieg et al. 2002/0065236 A1 5, 2002 Yew et al. 2003. O1994.66 A1 10, 2003 F tal 2002fOO86295 A1 7, 2002 Raz et al. eaC ca. 2003/0203861 A1 10, 2003 Carson et al. 2002fOO86839 A1 7, 2002 Raz et al. 2003/0206967 A1 11/2003 Choi et al. 2002/0090724 A1 7/2002 Taylor et al. 2002/009 1095 A1 7/2002 Phillips et al. 2003/02O7287 A1 11/2003 Short 2002/009 1097 A1 7, 2002 Bratzler et al. 2003/0212026 A1 1 1/2003 Krieg et al. 2002/0098199 A1 7, 2002 Van N 1 2003/0212028 A1 11/2003 Raz et al. an Nest et al. 2003/021634.0 A1 11/2003 Van Nest et al. 2002/0098.205 A1 7/2002 Choi et al. 2003/0219752 A1 11/2003 Short 2002fOO98980 A1 7, 2002 Choi et al. 2003,022O277 A1 11/2003 Yew et al. 2002/010.7212 A1 8/2002 Van Nest et al. 2002fO110569 A1 8, 2002 Granoffetal 2003/022401.0 A1 12/2003 Davis et al. ranOffetal. 2003/022501.6 A1 12/2003 Fearon et al. 2002/011 1323 A1 8/2002 Martin et al. 2003/0232780 A1 12/2003 Carson et al. 2002/013.6776 A1 9/2002 Fang et al.