Enhancing the circulating half-life of antibody-based fusion proteins Number:7,091,321 from the United States Patent and Trademark Office (PTO) owispatent Disclosed are compositions and methods for enhancing the circulating half-life of antibody-based fusion proteins. Disclosed methods and compositions rely on altering the amino acid sequence of the junction region between the antibody moiety and the fused protein moiety in an antibody-based fusion protein. An antibody-based fusion protein with an altered amino acid sequence in the junction region has a greater circulating half-life when administered to a mammal. Disclosed methods and compositions are particularly useful for reducing tumor size and metastasis in a mammal.<H circulating, Enhancing, Enhancing, the, c, 7091321.html, Patent, pto, 7091321

Title: Enhancing the circulating half-life of antibody-based fusion proteins

Abstract: Disclosed are compositions and methods for enhancing the circulating half-life of antibody-based fusion proteins. Disclosed methods and compositions rely on altering the amino acid sequence of the junction region between the antibody moiety and the fused protein moiety in an antibody-based fusion protein. An antibody-based fusion protein with an altered amino acid sequence in the junction region has a greater circulating half-life when administered to a mammal. Disclosed methods and compositions are particularly useful for reducing tumor size and metastasis in a mammal.

Patent Number: 7,091,321 Issued on 08/15/2006 to Gillies, et al.

Inventors: Gillies; Stephen D. (Carlisle, MA), Burger; Christa (Darmstadt, DE), Lo; Kin-Ming (Lexington, MA)
Assignee: EMD Lexigen Research Center Corp. (Billerica, MA)

Appl. No.: 09/780,668

Filed: February 9, 2001

Current U.S. Class: 530/387.3 ; 424/134.1

Current International Class: A61K 39/395 (20060101); C07K 16/00 (20060101)

Field of Search: 530/387.3 424/134.1

References Cited [Referenced By]

U.S. Patent Documents


4196265	April 1980	Koprowski et al.
4469797	September 1984	Albarella
4522811	June 1985	Eppstein et al.
4667016	May 1987	Lai et al.
4676980	June 1987	Segal et al.
4703008	October 1987	Lin
4732683	March 1988	Georgiades et al.
4737462	April 1988	Mark et al.
4816567	March 1989	Cabilly et al.
4946778	August 1990	Ladner et al.
4975369	December 1990	Beavers et al.
5019368	May 1991	Epstein et al.
5073627	December 1991	Curtis et al.
5082658	January 1992	Palladino
5091513	February 1992	Huston et al.
5114711	May 1992	Bell et al.
5116964	May 1992	Capon et al.
5199942	April 1993	Gillis
5225538	July 1993	Capon et al.
5225539	July 1993	Winter
5258498	November 1993	Huston et al.
5314995	May 1994	Fell, Jr. et al.
5349053	September 1994	Landolfi
5359035	October 1994	Habermann
5399346	March 1995	Anderson et al.
5428130	June 1995	Capon et al.
5441868	August 1995	Lin
5457038	October 1995	Trinchieri et al.
5480981	January 1996	Goodwin et al.
5514582	May 1996	Capon et al.
5538866	July 1996	Israeli et al.
5541087	July 1996	Lo et al.
5543297	August 1996	Cromlish et al.
5547933	August 1996	Lin
5552524	September 1996	Basinski et al.
5585089	December 1996	Queen et al.
5589466	December 1996	Felgner et al.
5601819	February 1997	Wong et al.
5609846	March 1997	Goldenberg
5614184	March 1997	Sytkowski et al.
5618698	April 1997	Lin
5624821	April 1997	Winter et al.
5639725	June 1997	O'Reilly et al.
5645835	July 1997	Fell, Jr. et al.
5650150	July 1997	Gillies
5650492	July 1997	Gately et al.
5667776	September 1997	Zimmerman et al.
5679543	October 1997	Lawlis
5688679	November 1997	Powell
5691309	November 1997	Basinski et al.
5709859	January 1998	Aruffo et al.
5712120	January 1998	Rodriguez et al.
5719266	February 1998	DiMarchi et al.
5723125	March 1998	Chang et al.
5726044	March 1998	Lo et al.
5728552	March 1998	Fujisawa et al.
5733876	March 1998	O'Reilly et al.
5738852	April 1998	Robinson et al.
5756349	May 1998	Lin
5756461	May 1998	Stephens
5759551	June 1998	Ladd et al.
5770195	June 1998	Hudziak et al.
5795779	August 1998	McCormick et al.
5800810	September 1998	Doyle et al.
5807715	September 1998	Morrison et al.
5827516	October 1998	Urban et al.
5827703	October 1998	Debs et al.
5837682	November 1998	Folkman et al.
5837821	November 1998	Wu et al.
5843423	December 1998	Lyman et al.
5854205	December 1998	O'Reilly et al.
5856298	January 1999	Strickland
5858347	January 1999	Bauer et al.
5885795	March 1999	O'Reilly et al.
5886178	March 1999	Allen et al.
5888772	March 1999	Okasinski et al.
5888773	March 1999	Jost et al.
5891680	April 1999	Lieschke et al.
5908626	June 1999	Chang et al.
5922685	July 1999	Rakhmilevich et al.
5955422	September 1999	Lin
5994104	November 1999	Anderson et al.
5994126	November 1999	Steinman et al.
6080409	June 2000	Laus et al.
6086875	July 2000	Blumberg et al.
6100387	August 2000	Herrmann et al.
6169070	January 2001	Chen et al.
6171588	January 2001	Carron et al.
6231536	May 2001	Lentz
6277375	August 2001	Ward
6281010	August 2001	Gao et al.
6284536	September 2001	Morrison et al.
6291158	September 2001	Winter et al.
6335176	January 2002	Inglese et al.
6340742	January 2002	Burg et al.
6348192	February 2002	Chan et al.
6406689	June 2002	Falkenberg et al.
6429199	August 2002	Krieg et al.
6444792	September 2002	Gray et al.
6475717	November 2002	Enssle et al.
6485726	November 2002	Blumberg et al.
6500641	December 2002	Chen et al.
6506405	January 2003	Desai et al.
6551592	April 2003	Lindhofer et al.
6583272	June 2003	Bailon
6586398	July 2003	Kinstler et al.
6617135	September 2003	Gillies et al.
6627615	September 2003	Debs et al.
6646113	November 2003	Dretfuss et al.
2001/0053539	December 2001	Lauffer et al.
2002/0037558	March 2002	Lo et al.
2002/0081664	June 2002	Lo et al.
2002/0142374	October 2002	Gallo et al.
2002/0146388	October 2002	Gilles
2002/0147311	October 2002	Gillies et al.
2002/0192222	December 2002	Blumberg et al.
2002/0193570	December 2002	Gillies et al.
2003/0003529	January 2003	Bayer
2003/0012789	January 2003	Blumberg et al.
2003/0044423	March 2003	Gillies et al.
2003/0049227	March 2003	Gillies et al.
2003/0105294	June 2003	Gillies et al.
2003/0139365	July 2003	Lo et al.
2003/0139575	July 2003	Gillies
2003/0157054	August 2003	Gillies et al.
2003/0166163	September 2003	Gillies
2003/0166877	September 2003	Gillies et al.
2004/0013640	January 2004	Zardi et al.
2004/0033210	February 2004	Gillies
2004/0043457	March 2004	Schumacher et al.
2004/0053366	March 2004	Lo et al.
2004/0072299	April 2004	Gillies et al.
2004/0082039	April 2004	Gillies et al.
2004/0180035	September 2004	Gillies et al.

Foreign Patent Documents


21725/88	Mar., 1989	AU
931001153	Jul., 1993	CN
37 12985	Nov., 1988	DE
0 158 198	Oct., 1985	EP
0 211 769	Feb., 1987	EP
0 237 019	Sep., 1987	EP
0 256 714	Feb., 1988	EP
0 294 703	Dec., 1988	EP
0 308 936	Mar., 1989	EP
0 314 317	May., 1989	EP
0 318 554	Jun., 1989	EP
0 319 012	Jun., 1989	EP
0 326 120	Aug., 1989	EP
0 350 230	Jan., 1990	EP
0 375 562	Jun., 1990	EP
0 396 387	Nov., 1990	EP
0 439 095	Jul., 1991	EP
0 511 747	Nov., 1992	EP
0 519 596	Dec., 1992	EP
0 334 134	Jan., 1994	EP
0 601 043	Jun., 1994	EP
0 640 619	Mar., 1995	EP
0 668 353	Aug., 1995	EP
0 428 596	Apr., 1996	EP
0 706 799	Apr., 1996	EP
0 428 267	Dec., 1996	EP
0 790 309	Aug., 1997	EP
0 433 827	Mar., 1998	EP
0 668 351	Sep., 1999	EP
1 088 888	Apr., 2001	EP
0 699 755	Apr., 2004	EP
2 188 638	Oct., 1987	GB
2 292 382	Feb., 1996	GB
63-267278	Nov., 1988	JP
63-267296	Nov., 1988	JP
WO 86/01533	Mar., 1986	WO
WO 88/00052	Jan., 1988	WO
WO 88/09344	Dec., 1988	WO
WO 89/02922	Apr., 1989	WO
WO 89/09620	Oct., 1989	WO
WO 90/03801	Apr., 1990	WO
WO 91/00360	Jan., 1991	WO
WO 91/04329	Apr., 1991	WO
WO 91/08298	Jun., 1991	WO
WO 91/13166	Sep., 1991	WO
WO 91/14438	Oct., 1991	WO
WO 92/02240	Feb., 1992	WO
WO 92/08495	May., 1992	WO
WO 92/08801	May., 1992	WO
WO 92/10755	Jun., 1992	WO
WO 92/16562	Oct., 1992	WO
WO 93/03157	Feb., 1993	WO
WO 93/10229	May., 1993	WO
WO 93/20185	Oct., 1993	WO
WO 94/24160	Oct., 1994	WO
WO 94/25055	Nov., 1994	WO
WO 94/25609	Nov., 1994	WO
WO 95/05468	Feb., 1995	WO
WO 95/21258	Aug., 1995	WO
WO 95/28427	Oct., 1995	WO
WO 95/31483	Nov., 1995	WO
WO 96/04388	Feb., 1996	WO
WO 96/05309	Feb., 1996	WO
WO 96/08570	Mar., 1996	WO
96/18412	Jun., 1996	WO
WO 96/18412	Jun., 1996	WO
WO 96/31526	Oct., 1996	WO
WO 96/40792	Dec., 1996	WO
97/00319	Jan., 1997	WO
WO 97/00317	Jan., 1997	WO
WO 97/15666	May., 1997	WO
WO 97/20062	Jun., 1997	WO
WO 97/24137	Jul., 1997	WO
WO 97/24440	Jul., 1997	WO
WO 97/26335	Jul., 1997	WO
WO 97/30089	Aug., 1997	WO
WO 97/33617	Sep., 1997	WO
WO 97/33619	Sep., 1997	WO
WO 97/34631	Sep., 1997	WO
WO 97/43316	Nov., 1997	WO
WO 98/00127	Jan., 1998	WO
WO 98/06752	Feb., 1998	WO
WO 98/28427	Jul., 1998	WO
WO 98/30706	Jul., 1998	WO
WO 98/46257	Oct., 1998	WO
WO 98/52976	Nov., 1998	WO
WO 98/59244	Dec., 1998	WO
WO 99/02709	Jan., 1999	WO
WO 99/03887	Jan., 1999	WO
WO 99/29732	Jun., 1999	WO
WO 99/43713	Sep., 1999	WO
WO 99/52562	Oct., 1999	WO
WO 99/53958	Oct., 1999	WO
WO 99/60128	Nov., 1999	WO
WO 99/62944	Dec., 1999	WO
WO 99/66054	Dec., 1999	WO
WO 00/01822	Jan., 2000	WO
WO 00/11033	Mar., 2000	WO
WO 00/24893	May., 2000	WO
WO 00/34317	Jul., 2000	WO
WO 00/40615	Jul., 2000	WO
WO 00/68376	Nov., 2000	WO
WO 00/69913	Nov., 2000	WO
WO 00/78334	Dec., 2000	WO
WO 01/07081	Feb., 2001	WO
WO 01/10912	Feb., 2001	WO
WO 01/36489	May., 2001	WO
WO 01/58957	Aug., 2001	WO
WO 02/02143	Jan., 2002	WO
WO 02/066514	Aug., 2002	WO
WO 02/072605	Sep., 2002	WO
WO 02/079232	Oct., 2002	WO
WO 02/079415	Oct., 2002	WO
WO 02/090566	Nov., 2002	WO
WO 03/015697	Feb., 2003	WO
WO 03/048334	Jun., 2003	WO
WO 03/077834	Sep., 2003	WO

Other References

Batova et al., "The Ch 14.18-GM-CSF Fusion Protein Is Effective at Mediating Antibody-dependent Cellular Cytotoxicity and Complement-dependent Cytotoxicity in Vitro," Clinical Cancer Research, 5: 4259-4263 (1999). cited by other .
Gillies et al., "Improving the Efficacy of Antibody-Interleukin 2 Fusion Proteins by Reducing Their Interaction with Fe Receptors," Cancer Research, 59: 2159-2166 (1999). cited by other .
Kendra et al., "Pharmacokinetics and stability of the ch 14.18-interleukin-2 fusion protein in mice," Cancer Immunol Immunother, 48: 219-229 (1999). cited by other .
Abaza et al., (1992), "Effects of Amino Acid Substitutions Outside an Antigenic Site on Protein Binding to Monoclonal Antibodies of Predetermined Specificity Obtained by Peptide Immunization," Journal of Protein Chemistry, 11:5:433-444. cited by other .
Abstract XP-002116766, (1996), "Prostaglandins, their inhibitors and cancer," Prostaglandins, Leukotrienes and Essential Fatty Acids, 54:2:83-94. cited by other .
Afonso et al., (1994), "The Adjuvant Effect of Interleukin-12 in a Vaccine Against Leishmania Major," Science, 263:235-237. cited by other .
Arenberg et al. (1996), "Interferon-.gamma.-inducible Protein 10 (IP-10) Is an Angiostatic Factor That Inhibits Human Non-small Cell Lung Cancer (NSCLC) Tumorigenesis and Spontaneous Metastases," J. Exp. Med. 184:981-992. cited by other .
Bacha et al., (1988), "Interleukin 2 Receptor-Targeted Cytotoxicity Interleukin 2 Receptor-mediated Action of a Diphtheria Toxin-related Interleukin 2 Fusion Protein," J. Experimental Medicine, 167:612-622. cit- ed by other .
Bachelot et al., (Mar. 1998), "Retrovirus-Mediated Gene Transfer of an Angiostatin-Endostatin Fusion protein with Enhanced Anti-Tumor Properties In Vivo," Proceedings of the Annual Meeting of the American Association for Cancer Research, 39:271, Abstract # 1856. cited by other .
Barnett et al., (1994), "Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system," Biochimica et Biophysica Acta, 1209:130-139. cited by other .
Baselga, et al., (1998), "Recombinant Humanized Anti-HER2 Antibody (Herceptin .TM.) Enhances the Antitumor activity of Paclitazel and Doxorubicin against HER3/neu Overexpressing Human Breast Cancer Xenografts," Cancer Research, 58:2825-2831. cited by other .
Batra et al., (1993), "Insertion of Constant Region Domains of Human IgG1 into CD4-PE40 Increases Its Plasma Half-Life," Mol. Immunol., 30:379-386. cited by other .
Becker et al., (1996), "An Antibody-Interleukin 2 Fusion Protein Overcomes Tumor Heterogeneity by Induction of a Cellular Immune Response," Proc. Natl. Acad. Sci., 93:7826-7831. cited by other .
Becker et al., (1996), "Eradication of human hepatic and pulmonary melanoma metastases in SCID mice by antibody-interleukin 2 fusion proteins," Proc. Natl. Acad. Sci. USA, 93:2702-2707. cited by other .
Beutler et al., (1988), "Tumor Necrosis, Cachexia, Shock, and Inflammation: A Common Mediator," Ann. Rev. Biochem., 57:505-518. cited by other .
Bissery et al., (1997), "The Taxoids," in Cancer Therapeutics: Experimental and Clinical Agents, Teichen, ed., 175-193. cited by other .
Bjorn et al., (1985), "Evaluation of Monoclonal Antibodies for the Development of Breast Cancer Immunotoxins," Cancer Research, 45:1214-1221. cited by other .
Boehm et al., (1997), "Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance," Nature, 390:404-407. cited by other .
Boehm et al., (1998), "Zinc-Binding of Endostatin Is Essential for Its Antiangiogenic Activity" Biochemical and Biophysical Research Communications, 252:190-194. cited by other .
Boissel et al., (1993), "Erythropoietin Structure-Function Relationships," The Journal of Biological Chemistry, 268:15983-15993. cited by other .
Brooks et al., (1994), "Integrin a.alpha.,.beta..sub.3 Antagonists Promote Tumor Regression by Inducing Apoptosis of Angiogenic Blood Vessels," Cells, 79:1157-1164. cited by other .
Buchli et al., (1993), "Structural and Biologic Properties of a Human Aspartic Acid-126 Interleukin-2 Analog," Archives of Biochemistry and Biophysics, 307:2:411-415. cited by other .
Burgess et al., (1990), "Possible Dissociation of the Heparin-binding and Mitogenic Activities of Heparin-binding (Acidic Fibroblast) Growth Factor-1 from Its Receptor-binding Activities by Site-directed Mutagenesis of a Single Lysine Residue," Journal of Cell Biology, 111:2129-2138. cited by other .
Canfield et al., (1991), "The Binding Affinity of Human IgG for its High Affinity Fc Receptor is Determined by Multiple Amino Acids in the CH2 Domain and Is Modulated by the Hinge Region," Journal of Experimental Medicine, 173:6:1483-1491. cited by other .
Cao et al., (1996), "Kringle Domains of Human Angiostatin," The Journal of Biological Chemistry, 271:46:29461-29467. cited by other .
Cao et al., (1997), "Kringle 5 of Plasminogen is a Novel Inhibitor of Endothelial Cell Growth," The Journal of Biological Chemistry, 272:36:22924-22928. cited by other .
Capon et al., (1989), "Designing CD4 immunoadhesins for AIDS therapy," Nature, 337:525-531. cited by other .
Caton et al., (1986), "Structural and functional implications of a restricted antibody response to a defined antigenic region on the influenza virus hemagglutinin," The EMBO Journal, 5:7:1577-1587. cited by other .
Chan et al., (1991), "Induction of Interferon .gamma. Production by Natural Killer Cell Stimulatory Factor: Characterization of the Responder Cells and Synergy with Other Inducers," J. Exp. Med., pp. 869-879. cited by other .
Chang et al., (1989), "Overview of Interleukin-2 as an Immunotherapeutic Agent," Seminars in Surgical Oncology, 5:385-390. cited by other .
Chang et al., (1996), "A Point Mutation in Interleukin-2 that Alters Ligand Internalization," Journal of Biological Chemistry, 271:23:13349-13355. cited by other .
Chaudhary et al., (1988), "Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein," Nature, 335:370-372. cited by other .
Chaudhary et al., (1989), "A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin," Nature, 339:394-397. cited by other .
Chen et al., (1997), "Eradication of Murine Bladder Carc

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