Multiple CPG oligodeoxynucleotides and their use to induce an immune response Number:7,521,063 from the United States Patent and Trademark Office (PTO) owispatent Compositions including multiple oligodeoxynucleotides with a CpG motif are disclosed herein. The compositions can include either D or K type oligodeoxynucleotides. These compositions are of use in inducing an immune response in a large percentage of the individuals in a population.<H oligodeoxynucleotides, response, Multiple, CPG, ol, 7521063.html, Patent, pto, 7521063

Title: Multiple CPG oligodeoxynucleotides and their use to induce an immune response

Abstract: Compositions including multiple oligodeoxynucleotides with a CpG motif are disclosed herein. The compositions can include either D or K type oligodeoxynucleotides. These compositions are of use in inducing an immune response in a large percentage of the individuals in a population.

Patent Number: 7,521,063 Issued on 04/21/2009 to Klinman, et al.

Inventors: Klinman; Dennis (Potomac, MD), Ishii; Ken (Columbia, MD), Verthelyi; Daniela (Potomac, MD)
Assignee: The United States of America as represented by the Department of Health and Human Services (Washington, DC)
N/A (

Appl. No.: 10/194,035

Filed: July 12, 2002

Related U.S. Patent Documents


Application Number	Filing Date	Patent Number	Issue Date
PCT/US01/01122	Jan., 2001
60176115	Jan., 2000

Current U.S. Class: 424/282.1 ; 424/278.1; 424/280.1; 514/44R

Current International Class: A61K 45/00 (20060101)

Field of Search: 424/130.1,133.1,1.11,1.53,1.57,1.65 435/6,91.1,91.7,458,455,328 536/23.1 530/300

References Cited [Referenced By]

U.S. Patent Documents


2215233	September 1940	Ruskin
3906092	September 1975	Hilleman et al.
3911117	October 1975	Ender
3914450	October 1975	Robbins et al.
4469863	September 1984	Ts'o et al.
4544559	October 1985	Gil et al.
4741914	May 1988	Kimizuka et al.
4758553	July 1988	Ogoshi
4806376	February 1989	Saeki et al.
4956296	September 1990	Fahnestock
4963387	October 1990	Nakagawa et al.
4994442	February 1991	Gil et al.
5023243	June 1991	Tullis
5066500	November 1991	Gil et al.
5231085	July 1993	Alexander et al.
5234811	August 1993	Beutler et al.
5248670	September 1993	Draper et al.
5268365	December 1993	Rudolph et al.
5288509	February 1994	Potman et al.
5488039	January 1996	Masor et al.
5492899	February 1996	Masor et al.
5585479	December 1996	Hoke et al.
5591721	January 1997	Agrawal et al.
5602109	February 1997	Masor et al.
5612060	March 1997	Alexander
5614191	March 1997	Puri et al.
5650156	July 1997	Grinstaff et al.
5663153	September 1997	Hutcherson et al.
5679397	October 1997	Kuroda et al.
5684147	November 1997	Agrawal et al.
5700590	December 1997	Masor et al.
5712256	January 1998	Kulkarni et al.
5723335	March 1998	Hutcherson et al.
5786189	July 1998	Loct et al.
5804566	September 1998	Carson et al.
5840705	November 1998	Tsukuda
5849719	December 1998	Carson et al.
5895652	April 1999	Giampapa
5919456	July 1999	Puri et al.
5922766	July 1999	Acosta et al.
5976580	November 1999	Ivey et al.
5980958	November 1999	Naylor et al.
5994126	November 1999	Steinman et al.
6022853	February 2000	Kuberasampath et al.
6194388	February 2001	Krieg et al.
6207646	March 2001	Krieg et al.
6214806	April 2001	Krieg et al.
6218371	April 2001	Krieg et al.
6239116	May 2001	Krieg et al.
6339068	January 2002	Krieg et al.
6406705	June 2002	Davis et al.
6423539	July 2002	Fong et al.
6428788	August 2002	Debinski et al.
6429199	August 2002	Krieg et al.
6498148	December 2002	Raz
6514948	February 2003	Raz et al.
6534062	March 2003	Krieg et al.
6552006	April 2003	Raz et al.
6562798	May 2003	Schwartz
6589940	July 2003	Raz et al.
6610661	August 2003	Carson et al.
6613751	September 2003	Raz et al.
6653292	November 2003	Krieg et al.
2001/0034330	October 2001	Kensil
2001/0036462	November 2001	Fong et al.
2001/0044416	November 2001	McCluskie et al.
2001/0046967	November 2001	Van Nest
2002/0006403	January 2002	Yu et al.
2002/0028784	March 2002	Van Nest
2002/0042383	April 2002	Yew et al.
2002/0042387	April 2002	Raz et al.
2002/0055477	May 2002	Van Nest et al.
2002/0064515	May 2002	Krieg et al.
2002/0065236	May 2002	Yew et al.
2002/0086295	July 2002	Raz et al.
2002/0086839	July 2002	Raz et al.
2002/0090724	July 2002	Taylor et al.
2002/0091095	July 2002	Phillips et al.
2002/0091097	July 2002	Bratzler et al.
2002/0098199	July 2002	Van Nest et al.
2002/0098205	July 2002	Choi et al.
2002/0098980	July 2002	Choi et al.
2002/0107212	August 2002	Van Nest et al.
2002/0110569	August 2002	Granoff et al.
2002/0111323	August 2002	Martin et al.
2002/0136776	September 2002	Fang et al.
2002/0137714	September 2002	Kandimalla et al.
2002/0142974	October 2002	Kohn et al.
2002/0142977	October 2002	Raz et al.
2002/0142978	October 2002	Raz et al.
2002/0156033	October 2002	Bratzler et al.
2002/0164341	November 2002	Davis et al.
2002/0165178	November 2002	Schetter et al.
2002/0183272	December 2002	Johnston et al.
2002/0197269	December 2002	Lingnau et al.
2002/0198165	December 2002	Bratzler et al.
2003/0003579	January 2003	Kadowaki et al.
2003/0022849	January 2003	Chang
2003/0022852	January 2003	Van Nest et al.
2003/0026782	February 2003	Krieg
2003/0026801	February 2003	Weiner et al.
2003/0049266	March 2003	Fearon et al.
2003/0050261	March 2003	Krieg et al.
2003/0050263	March 2003	Krieg et al.
2003/0050268	March 2003	Krieg et al.
2003/0052839	March 2003	Binley et al.
2003/0055014	March 2003	Bratzler
2003/0059773	March 2003	Van Nest et al.
2003/0060440	March 2003	Klinman et al.
2003/0064064	April 2003	Dina
2003/0072762	April 2003	Van de Winkel et al.
2003/0073142	April 2003	Chen et al.
2003/0078223	April 2003	Raz et al.
2003/0091599	May 2003	Davis et al.
2003/0092663	May 2003	Raz
2003/0096417	May 2003	Fischer
2003/0100527	May 2003	Krieg et al.
2003/0104044	June 2003	Semple et al.
2003/0104523	June 2003	Lipford et al.
2003/0109469	June 2003	Carson et al.
2003/0119773	June 2003	Raz et al.
2003/0119774	June 2003	Foldvari et al.
2003/0119776	June 2003	Phillips et al.
2003/0125284	July 2003	Raz et al.
2003/0129251	July 2003	Van Nest et al.
2003/0130217	July 2003	Raz et al.
2003/0133988	July 2003	Fearon et al.
2003/0135875	July 2003	Ehrhardt et al.
2003/0138413	July 2003	Vicari et al.
2003/0138453	July 2003	O'Hagan et al.
2003/0139364	July 2003	Krieg et al.
2003/0143213	July 2003	Raz et al.
2003/0143743	July 2003	Schuler et al.
2003/0144229	July 2003	Klinman et al.
2003/0147870	August 2003	Raz et al.
2003/0148316	August 2003	Lipford et al.
2003/0148976	August 2003	Krieg et al.
2003/0148983	August 2003	Fontoura et al.
2003/0157717	August 2003	Draghia-Akli
2003/0158136	August 2003	Rice et al.
2003/0165478	September 2003	Sokoll
2003/0166001	September 2003	Lipford
2003/0170273	September 2003	O'Hagan et al.
2003/0171321	September 2003	Schmidt et al.
2003/0175731	September 2003	Fearon et al.
2003/0176373	September 2003	Raz et al.
2003/0176389	September 2003	Raz et al.
2003/0180320	September 2003	Darju et al.
2003/0181406	September 2003	Schetter et al.
2003/0185848	October 2003	Johnston et al.
2003/0185900	October 2003	Choi et al.
2003/0186921	October 2003	Carson et al.
2003/0191079	October 2003	Krieg et al.
2003/0199466	October 2003	Fearon et al.
2003/0203861	October 2003	Carson et al.
2003/0206967	November 2003	Choi et al.
2003/0207287	November 2003	Short
2003/0212026	November 2003	Krieg et al.
2003/0212028	November 2003	Raz et al.
2003/0216340	November 2003	Van Nest et al.
2003/0219752	November 2003	Short
2003/0220277	November 2003	Yew et al.
2003/0224010	December 2003	Davis et al.
2003/0225016	December 2003	Fearon et al.
2003/0232780	December 2003	Carson et al.
2004/0005588	January 2004	Cohen et al.
2004/0006010	January 2004	Carson et al.
2004/0006032	January 2004	Lopez
2004/0006034	January 2004	Raz et al.
2004/0009897	January 2004	Sokoll
2004/0009942	January 2004	Van Nest
2004/0009949	January 2004	Krieg
2004/0013686	January 2004	Granoff et al.
2004/0013688	January 2004	Wise et al.
2004/0028693	February 2004	Wu et al.

Foreign Patent Documents


0 286 224	Oct., 1988	EP
0 302 758	Nov., 1989	EP
0 468 520	Jan., 1991	EP
0 092 574	Apr., 1992	EP
0 572 735	Dec., 1993	EP
0 855 184	Jul., 1998	EP
1 198 249	Apr., 2002	EP
WO 91/12811	Sep., 1991	WO
WO 92/03458	Apr., 1992	WO
WO 92/18522	Oct., 1992	WO
WO 92/21353	Dec., 1992	WO
WO 93/17115	Sep., 1993	WO
WO 94/19945	Sep., 1994	WO
WO 95/05853	Mar., 1995	WO
WO 95/18231	Jul., 1995	WO
WO 95/26204	Oct., 1995	WO
WO 96/02555	Feb., 1996	WO
WO 96/24380	Feb., 1996	WO
WO 96/35782	Nov., 1996	WO
WO 97/28259	Jan., 1997	WO
WO 97/28259	Aug., 1997	WO
WO 98/29430	Dec., 1997	WO
WO 98/11211	Mar., 1998	WO
WO 98/14210	Apr., 1998	WO
WO 98/16247	Apr., 1998	WO
WO 98/18810	May., 1998	WO
WO 98/32462	Jul., 1998	WO
WO 98/37919	Sep., 1998	WO
WO 98/40100	Sep., 1998	WO
WO 98/49288	Nov., 1998	WO
WO 98/49348	Nov., 1998	WO
WO 98/52581	Nov., 1998	WO
WO 98/55495	Dec., 1998	WO
WO 99/11275	Mar., 1999	WO
WO 99/37151	Jul., 1999	WO
WO 99/51259	Oct., 1999	WO
WO 99/56755	Nov., 1999	WO
WO 99/58118	Nov., 1999	WO
WO 99/61056	Dec., 1999	WO
WO 99/62923	Dec., 1999	WO
WO 00/06588	Feb., 2000	WO
WO 00/14217	Mar., 2000	WO
WO 00/20039	Apr., 2000	WO
WO 00/21556	Apr., 2000	WO
WO 00/06588	Oct., 2000	WO
WO 00/61151	Oct., 2000	WO
WO 00/62787	Oct., 2000	WO
WP 00/62787	Oct., 2000	WO
WO 0/67023	Nov., 2000	WO
WO 00/67023	Nov., 2000	WO
WO 00/67787	Nov., 2000	WO
WO 00/00232	Jan., 2001	WO
WO 01/00232	Jan., 2001	WO
WO 01/02007	Jan., 2001	WO
WO 01/12223	Feb., 2001	WO
WO 01/12804	Feb., 2001	WO
WO 01/22990	Apr., 2001	WO
WO 01/51500	Jul., 2001	WO
WO 0151500	Jul., 2001	WO
WO 01/55341	Aug., 2001	WO
WO 01/68077	Sep., 2001	WO
WO 01/68103	Sep., 2001	WO
WO 01/68116	Sep., 2001	WO
WO 01/68117	Sep., 2001	WO
WO 02/69369	Sep., 2002	WO

Other References

US 6,008,200, 12/1999, Krieg (withdrawn) cited by other .
U.S. Appl. No. 60/156,135. cited by examiner .
Krieg et al., CpG motif in bacterial DNA and their immune effects. Annu. Rev. Immunol., 2002, vol. 20, 709-760. cited by examiner .
Mutwiri et al. Biological activity of immunostimulatory CpG DNA motifs in domestic animals. Veterinary Immunology and Immunopathology, 2003, vol. 91, 89-103. cited by examiner .
Alama et al., "Antisense Oligonucleotides as Therapeutic Agents," Pharmacol. Res. 36: 171-178 (1997). cited by other .
Ballas et al., "Induction of NK Activity in Murine and Human Cells by CpG Motifs in Oligodeoxynucleotides and Bacterial DNA," J. Immun. 157: 1840-1845 (1996). cited by other .
Klinman et al., "CpG Motifs Present in Bacterial DNA Rapidly Induce Lymphocytes to Secrete Interleukin 6, Interleukin 12 and Interferon .gamma.," Proc. Natl. Acad. Sci. USA 93: 2879-2883 (1996). cited by other .
Klinman et al., "CpG Motifs as Immune Adjuvants," Vaccine 17: 19-25 (1999). cited by other .
Krieg et al., "CpG Motifs in Bacterial DNA Trigger Direct B-Cell Activation," Nature 374: 546-549 (1995). cited by other .
Liang et al., "Activation of Human B Cells by Phosphorothioate Oligodeoxynucleotides," J. Clin. Invest. 98: 1119-1129 (1996). cited by other .
Lonnberg et al., "Towards Genomic Drug Therapy with Antisense Oligonucleotides," Ann. Med. 28: 511-522 (1996). cited by other .
McCluskie et al., "CpG DNA is a Potent Enhancer of Systemic & Mucosal Immune Response Against Hepatitis B Surface Antigen with Intra-Nasal Administration to Mice," J. Immun. 161: 4463-4465 (1998). cited by other .
Oberbauer, "Not Non-Sense but Antisense-Applications of Antisense Oligonucleotides in Different Fields of Medicine," Wein Klin Wochenschr 109: 40-46 (1997). cited by other .
Scanlon et al., "Oligonucleotide-Mediated Modulation of Mammalian Gene Expression," FASEB J. 9: 1288-1295 (1995).. cited by other .
Yi et al., "Rapid Immune Activation by CpG Motifs in Bacterial DNA," J. Immun. 157: 5394-5402 (1996). cited by other .
Adya, et al., "Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA-binding domain of CREB". Proc. Natl. Acad. Sci. USA 91(12):5642-5646 (1994). cited by other .
Agrawal, et al., "Pharmacokinetics of Oligonucleotides". Ciba. Found. Symp. 209:60-78 (1997), abstract. cited by other .
Agrawal, et al., "Pharmacokinetics and Bioavailability of Antisense Oligonucleotides Following Oral and Colorectal Adminstration of Experimental Animals". Handb. Exp. Pharmacol.: Antisense Research and Application 131:525-543 (1998). cited by other .
Agrawal, "Antisense Oligonucleotides: Toward Clinical Trials". Tibtech 14:376-387 (1996). cited by other .
Agrawal, et al., "In Vivo Pharmacokinetics of Phosphorothioate Oligonucleotides Containing Contiguous Guanosines". Antisense & Nucleic Acid Drug Development 7:245-249 (1997). cited by other .
Agrawal, et al., "Absorption, Tissue Distribution and In Vivo Stability in Rats of a Hybrid Antisense Oligonucleotide Following Oral Administration". Biochemical Pharmacology 50(4):571-576 (1995). cited by other .
Agrawal, et al., "Pharmacokinetics of Antisense Oligonucleotides". Clin. Pharmacokinet 28(1):7 (1995). cited by other .
Agrawal, et al., "Antisense therapeutics: is it as simple as complementary base recognition?". Molecular Med. Today 6(2):72-81 (2000), abstract. cited by other .
Agrawal, et al., "Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice". Proc. Natl. Acad. Sci. USA 88:7595-7599 (1991). cited by other .
Agrawal, "Medicinal Chemistry and Therapeutic Potential of CpG DNA". Trends in Molecular Medicine 8(3):114-121 (2002). cited by other .
Amaral, et al., "Leishmania amazonensis: The asian rhesus macaques (Macaca mulatta) as an experimental model for study of Cutaneous leishmaniasis". Exp. Parasitol. 82(1):34-44 (1996). cited by other .
Anderson, "Human Gene Therapy". Nature 392:25-30 (Apr. 1998). cited by other .
Anderson, et al., "TH2 and `TH2-like` cells in allergy and asthma; pharmacological perspectives". TiPS 15:324-332 (1994). cited by other .
Anfossi, et al., "An oligomer complementary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines". Proc. Natl. Acad. Sci. USA 86:3379-3383 (May 1989). cited by other .
Angier, "Microbe DNA seen as alien by immune system". New York Times p. C1, 2 pages (1995). cited by other .
Azad, et al., "Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region". Amtimicrobial Agents and Chemotherapy 37:1945-1954 (1993). cited by other .
Azuma, "Biochemical and immunological studies on cellular components of tubercle bacilli". Kekkaku 69(9):

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