US007585493B2 (12) United States Patent (10) Patent No.: US 7,585,493 B2 Hale et al. (45) Date of Patent: *Sep. 8, 2009 (54) THIN-FILM DRUG DELIVERY ARTICLE AND tion No. 60/336,218, filed on Oct. 30, 2001, provi METHOD OF USE sional application No. 60/335,049, filed on Oct. 30, 2001, provisional application No. 60/345,882, filed on (75) Inventors: Ron L. Hale, Woodside, CA (US); Amy Nov. 9, 2001, provisional application No. 60/345,145, Lu, Los Altos, CA (US); Daniel J. filed on Nov. 9, 2001, provisional application No. Myers, Mountain View, CA (US); 60/345,876, filed on Nov. 9, 2001, provisional appli Joshua D. Rabinowitz, Mountain View, cation No. 60/332,280, filed on Nov. 21, 2001, provi CA (US); Martin J. Wensley, San sional application No. 60/332.279, filed on Nov. 21, Francisco, CA (US) 2001, provisional application No. 60/332,165, filed on Nov. 21, 2001, provisional application No. 60/342, (73) Assignee: Alexza Pharmaceuticals, Inc., 066, filed on Dec. 18, 2001, provisional application Mountain View, CA (US) No. 60/371,457, filed on Apr. 9, 2002, provisional - application No. 60/412,068, filed on Sep. 18, 2002. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (51) Int. Cl. U.S.C. 154(b) by 995 days. A6IR 9/12 (2006.01) A6IR 9/14 (2006.01) This patent is Subject to a terminal dis- A6M I5/00 (2006.01) claimer. (52) U.S. Cl. ........................... 424/45; 424/46; 424/434; 424/489: 424/499; 514/958: 128/200.14: (21) Appl. No.: 10/633,877 128/200.15; 128/200.24 (22) Filed: Aug. 4, 2003 (58) Field of Classification Search ................... 424/45, 424/46, 489, 499, 434; 514/958: 128/200.14, (65) Prior Publication Data 128/200.24, 203.15 See application file for complete search history. US 2007/OO31340 A1 Feb. 8, 2007 (56) References Cited Related U.S. Application Data U.S. PATENT DOCUMENTS (63) Continuation-in-part of application No. 10/322.227, filed on Dec. 17, 2002, now abandoned, application 1,239,634 A 9, 1917 Stuart No. 10/633,877, which is a continuation-in-part of Continued application No. 10/280,315, filed on Oct. 25, 2002, (Continued) now abandoned, application No. 10/633,877, which is FOREIGN PATENT DOCUMENTS a continuation-in-part of application No. 10/302.614, filed on Nov. 21, 2002, application No. 10/633,877, CA 2152684 1, 1996 which is a continuation-in-part of application No. 10/302,010, filed on Nov. 21, 2002, now Pat. No. (Continued) 7,078,016, application No. 10/633,877, which is a con- OTHER PUBLICATIONS tinuation-in-part of application No. 10/154,594, filed on May 23, 2002, now Pat. No. 6,740,309, application U.S. Appl. No. 10/633,876, filed Aug. 4, 2003, Hale et al. No. 10/633,877, which is a continuation-in-part of (Continued) application No. 10/154,765, filed on May 23, 2002, now Pat. No. 6,814,955, application No. 10/633,877, Primary Examiner Mina Haghighatian which is a continuation-in-part of application No. (74) Attorney, Agent, or Firm—Swanson & Bratschun, 10/155,097, filed on May 23, 2002, now Pat. No. L.L.C. 6,716,417, application No. 10/633,877, which is a con tinuation-in-part of application No. 10/155,373, filed (57) ABSTRACT on May 22, 2002, now Pat. No. 6,737,043, application No. 10/633,877, which is a continuation-in-part of An article for use in an aerosol device, for producing an application No. 10/155,621, filed on May 22, 2002, aerosol of a drug composition is disclosed. The article now Pat. No. 6,759,029, application No. 10/633,877, includes a heat-conductive Substrate having a Surface with a which is a continuation-in-part of application No. selected Surface area, and a drug composition film on the 10/155,703, filed on May 22, 2002, now Pat. No. substrate surface having a selected film thickness of between 6,803,031, application No. 10/633,877, which is a con- 0.05 and 20 um. The film thickness is such that an aerosol tinuation-in-part of application No. 10/155,705, filed formed by vaporizing the drug composition by heating the on May 22, 2002, now Pat. No. 6,805,854, application Substrate and condensing the vaporized compound contains No. 10/633,877, which is a continuation-in-part of 10% or less drug-degradation product and at least 50% of the total amount of drug composition contained in the film. The (Continued) selected substrate surface area is such as to yield an effective (60) Provisional application No. 60/294.203, filed on May human therapeutic dose of the drug aerosol. Also disclosed 24, 2001, provisional application No. 60/296,225, are methods of making and using the article. filed on Jun. 5, 2001, provisional application No. 60/317,479, filed on Sep. 5, 2001, provisional applica 12 Claims, 18 Drawing Sheets US 7,585,493 B2 Page 2 Related U.S. Application Data 2,309,846 2, 1943 Einar 2.469,656 5, 1949 Lienert application No. 10/153,839, filed on May 21, 2002, 2,714,649 8, 1955 Critzer now Pat. No. 6,776,978, application No. 10/633,877, 2,741,812 4, 1956 Andre which is a continuation-in-part of application No. 2,761,055 8, 1956 Ike 10/153.311, filed on May 21, 2002, now Pat. No. 2,887, 106 5, 1959 Robinson 6,884,408, application No. 10/633,877, which is a con 2,898,649 8, 1959 Murray tinuation-in-part of application No. 10/153,831, filed 2.902,484 9, 1959 Horclois 3,043,977 T. 1962 Morowitz on May 21, 2002, now Pat. No. 6,740,308, application 3,080,624 3, 1963 Webber, III No. 10/633,877, which is a continuation-in-part of 3,164,600 1, 1965 Janssen et al. application No. 10/153.313, filed on May 20, 2002, 3,169,095 2, 1965 Thiel et al. now abandoned, application No. 10/633,877, which is 3,200,819 8, 1965 Gilbert a continuation-in-part of application No. 10/153,139, 3,219,533 11, 1965 Mullins filed on May 20, 2002, now Pat. No. 6,814,954, appli 3,282,729 11, 1966 Richardson et al. cation No. 10/633,877, which is a continuation-in-part 3,296,249 1, 1967 Bell of application No. 10/152,652, filed on May 20, 2002, 3,299,185 1, 1967 Oda et al. now Pat. No. 6,740,307, application No. 10/633,877, 3,371,085 2, 1968 Reeder et al. which is a continuation-in-part of application No. 3,393, 197 T. 1968 Pachter 3.433,791 3, 1969 Bentley et al. 10/152,640, filed on May 20, 2002, now Pat. No. 3,560,607 2, 1971 Hartley et al. 6,743,415, application No. 10/633,877, which is a con 3,701,782 10, 1972 Hester tinuation-in-part of application No. 10/152,639, filed 3,749,547 7, 1973 Gregory et al. on May 20, 2002, now Pat. No. 6,716,416, application 3,763,347 10, 1973 Whitaker et al. No. 10/633,877, which is a continuation-in-part of 3,773.995 11, 1973 Pachter et al. application No. 10/150,857, filed on May 17, 2002, 3,831,606 8, 1974 Damani now Pat. No. 6,716,415, application No. 10/633,877, 3,847,650 11, 1974 Gregory et al. which is a continuation-in-part of application No. 10/ 3,864,326 2, 1975 Babington 3,894,040 7, 1975 Buzby, Jr. 150,591, filed on May 17, 2002, now Pat. No. 6,780, 3,909,463 9, 1975 Hartman 400, application No. 10/633,877, which is a continua 3,930,796 1, 1976 Haensel tion-in-part of application No. 10/151,596, filed on 3,943,941 3, 1976 Boyd et al. May 16, 2002, now Pat. No. 6,855,310, application 3,949,743 4, 1976 Shanbrom No. 10/633,877, which is a continuation-in-part of 3,971,377 7, 1976 Damani application No. 10/151,626, filed on May 16, 2002, 3,982,095 9, 1976 Robinson now Pat. No. 6,783,753, application No. 10/633,877, 3,987,052 10, 1976 Hester, Jr. which is a continuation-in-part of application No. 4,008,723 2, 1977 Borthwicket al. 10/150,267, filed on May 16, 2002, now Pat. No. 4,020,379 4, 1977 Manning 4,045,156 8, 1977 Chu et al. 6,797.259, application No. 10/633,877, which is a con 4,079,742 3, 1978 Rainer et al. tinuation-in-part of application No. 10/150.268, filed 4,104,210 8, 1978 Coran et al. on May 15, 2002, now Pat. No. 6,780,399, application 4,121,583 10, 1978 Chen No. 10/633,877, which is a continuation-in-part of 4,141,369 2, 1979 Burruss application No. 10/150,056, filed on May 15, 2002, 4, 160,765 7, 1979 Weinstock now Pat. No. 6,805,853, application No. 10/633,877, 4,166,087 8, 1979 Cline et al. which is a continuation-in-part of application No.