Polyglutamic acid-camptothecin conjugates and methods of preparation
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-043/42
A01N-043/34
A61K-031/44
A01N-043/40
출원번호
US-0407218
(2003-04-07)
발명자
/ 주소
Bhatt,Rama
Vries,Peter de
Klein,J. Peter
Tulinsky,John
Lewis,Robert A.
Singer,Jack W.
출원인 / 주소
Cell Therapeutics Inc.
대리인 / 주소
Foley &
인용정보
피인용 횟수 :
3인용 특허 :
51
초록
The invention provides polyglutamic acid-therapeutic agent conjugates and methods for their preparation and use.
대표청구항▼
What is claimed is: 1. A composition comprising a polyglutamic acid-camptothecin conjugate having the formula: wherein: PG is polyglutamic acid polymer; Camptothecin is 20(S)-camptothecin or a biologically active 20(S)-camptothecin analog linked via the oxygen at position 20 of Camptothecin; wher
What is claimed is: 1. A composition comprising a polyglutamic acid-camptothecin conjugate having the formula: wherein: PG is polyglutamic acid polymer; Camptothecin is 20(S)-camptothecin or a biologically active 20(S)-camptothecin analog linked via the oxygen at position 20 of Camptothecin; wherein the 20(S)-camptothecin analog is of the formula wherein one or more of R1 -R5 is other than H and n is an integer between 1 and 10; PG is attached to the moiety--O--(CH2)n--C(O)-[Camptothecin] through the γ-carbonyl group of a monomeric unit of said polyglutamic acid polymer. 2. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is about 1-60%. 3. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 1-45%. 4. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 25-50%. 5. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 27-40%. 6. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-50%. 7. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-47%. 8. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-45%. 9. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-40%. 10. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-37%. 11. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 30-35%. 12. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 35-47%. 13. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 35-45%. 14. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 35-40%. 15. The composition of claim 1, wherein the weight % ratio of said camptothecin to said PG is 35-39%. 16. The composition of claim 1, wherein said camptothecin analog is selected from the group consisting of 20(S)-camptothecin, 20(S)-topotecan; 20(S)-9-aminocamptothecin; 20(S)-9-nitrocamptothecin; 20(S)-i 10-hydroxycamptothecin; SN-38; 20(S)-10,11-methylenedioxycamptothecin; lurtotecan; irinotecan; DX-8951 F or DB 67. 17. The composition of claim 1, wherein said camptothecin analog is selected from 20(S)-camptothecin, 20(S)-9-aminocamptothecin, 20(S)-9-nitrocamptothecin, 20(S)-7-ethyl-10-hydroxycamptothecin, 20(S)-i 10-hydroxycamptothecin and 20(S)-10-acetoxycamptothecin. 18. The composition of claim 17, wherein said camptothecin analog is 20(S)-camptothecin. 19. A method of preparing a composition comprising a polyglutamic acid-camptothecin conjugate of claim 1 wherein said method comprises: (a) providing a polyglutamic acid polymer having a MW of about 25,000 to about 60,000 daltons, as determined by viscosity, and HO--(CH2)n--C(O)-[Camptothecin], or a protected form thereof, for conjugation thereto; and (b) covalently linking said HO--(CH2)n--C(O) [Camptothecin] to said polyglutamic acid polymer under conditions sufficient to attach at least 5 moles of 20(S)-camptothecin per mole of polymer, thereby forming said polyglutamic acid-camptothecin conjugate. 20. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 15-50%. 21. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 1-45%. 22. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 25-50%. 23. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 27-40%. 24. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-50%. 25. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-47%. 26. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-45%. 27. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-40%. 28. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-37%. 29. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 30-35%. 30. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 35-47%. 31. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 35-45%. 32. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 35-40%. 33. The composition of claim 19, wherein the weight % ratio of said camptothecin to said PG is 35-39%. 34. A pharmaceutical composition for the treatment of cancer, comprising an effective amount of the polyglutamic acid-camptothecin conjugate of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier and/or diluent. 35. The pharmaceutical composition of claim 34, wherein said camptothecin is 20(S)-camptothecin. 36. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 15-50%. 37. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 1-45%. 38. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 25-50%. 39. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 27-40%. 40. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-50%. 41. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-47%. 42. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-45%. 43. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-40%. 44. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-37%. 45. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 30-35%. 46. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 35-47%. 47. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 35-45%. 48. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 35-40%. 49. The composition of claim 34, wherein the weight % ratio of said camptothecin to said PG is 35-39%. 50. A method of treating cancer, comprising administering to a patient in need of such treatment a pharmaceutical composition according to claim 34, thereby effecting treatment of said cancer. 51. The pharmaceutical composition of claim 50, wherein said camptothecin is 20(S)-camptothecin. 52. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 15-50%. 53. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 20-45%. 54. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 25-50%. 55. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 27-40%. 56. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 30-50%. 57. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 30-47%. 58. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 30-45%. 59. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 30-40%. 60. The composition of claim 50, wherein the weight% ratio of said camptothecin to said PG is 30-37%. 61. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 30-35%. 62. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 35-47%. 63. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 35-45%. 64. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 35-40%. 65. The composition of claim 50, wherein the weight % ratio of said camptothecin to said PG is 35-39%. 66. The composition of claim 1, wherein the 20(S)-camptothecin analog is selected from the group consisting of topotecan, 20(S)-9-amino camptothecin, 20(S)-9-nitro camptothecin, 10-hydroxy-camptothecin, SN-38, 20(S)-10,11-methylenedioxycampto-thecin, Lurtotecan, Irinotecan, DX-8951F, DB 67. 67. The composition of claim 1, wherein R4 is H and (a) R1 is CH2N(CH3)2, R2 is OH, R3 is H, and R5 is H; or (b) R1 is NH2 and R2, R3, and R5 are H; or (c) R1 is NO2 and R2, R3, and R5 are each H; or (d) R2 is OH and R1 , R3, and R 5 are each H; or (e) R1 is H, R2 is OH, R3 is H, and R5 is CH2CH3; or (f) R1 and R5 are each H and R2 and R3 are each--CH2--O--CH2-; or (g) R1 is H, R2 and R3 are each--O--CH2--CH2--O--, and R5 is--CH2--(N-methyl piperazine); or (h) R1 and R3 are each H, R2 is OCO-[1,4'-bipiperidinyl], and R5 is CH2CH3; or (i) R1 and R5 are each--CH2--CH2--CH(NH2)--, R2 is CH3, and R3 is F; or (j) R1 and R3 are each H, R2 is--OH, and R5 is--SiMe2t-Bu.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (51)
Chen Shu-Hui (Hamden CT) Farina Vittorio (West Hartford CT) Roth Gregory (Cheshire CT) Kadow John (Wallingford CT), 6,7-modified paclitaxels.
Brem Henry (Lutherville MD) Langer Robert S. (Newton MA) Domb Abraham J. (Efrat ILX), Controlled local delivery of chemotherapeutic agents for treating solid tumors.
Anderson David C. (Seattle WA) Morgan ; Jr. A. Charles (Edmonds WA) Abrams Paul G. (Seattle WA) Fritzberg Alan R. (Edmonds WA) Nichols Everett J. (Seattle WA), Covalently-linked complexes and methods for enhanced cytotoxicity and imaging.
Stella Valentino J. (Lawrence KS) Mathew Abraham E. (Lenexa KS), Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof.
Hanigan Marie ; MacDonald Timothy, Gamma-glutamyl transpeptidase-specific antibody, prodrugs for the treatment of gamma-glutamyl transpeptidase-expressing.
Wall Monroe E. (Chapel Hill NC) Wani Mansukh C. (Durham NC) Nicholas Allan W. (Raleigh NC) Manikumar Govindarajan (Raleigh NC), Method of treating tumors with anti-tumor effective camptothecin compounds.
Zalipsky Samuel (Princeton NJ) Bolikal Durgadas (Edison NJ) Nathan Aruna (Piscataway NJ) Kohn Joachim B. (Highland Park NJ), Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon.
Butterfield Dennis E. ; Fujii Dennis K. ; Ladd David L. ; Snow Robert A. ; Tan Julia S. ; Toner John L., Segmented chelating polymers as imaging and therapeutic agents.
Zheng Qun Y. (Superior CO) Darbie Lynn G. (Boulder CO) Murray Christopher K. (Boulder CO), Selective process for the deacylation and deacetylation of taxol and taxanes.
Ragheb Anthony O. ; Bates Brian L. ; Fearnot Neal E. ; Osborne Thomas A. ; Kozma Thomas G. ; Roberts Joseph W. ; Voorhees ; III William D., Silver implantable medical device.
Kunz Lawrence L. ; Klein Richard A. ; Reno John M. ; Grainger David J.,GB2 ; Metcalfe James C.,GB2 ; Weissberg Peter L.,GB2 ; Anderson Peter G., Therapeutic inhibitor of vascular smooth muscle cells.
Kunz Lawrence L. ; Klein Richard A. ; Reno John M. ; Grainger David J.,GBX ; Metcalfe James C.,GBX ; Weissberg Peter L.,GBX ; Anderson Peter G., Therapeutic inhibitor of vascular smooth muscle cells.
Peterson Robert V. (Murray UT) Anderson James M. (Cleveland Heights OH) Gregonis Donald E. (Salt Lake City UT) Kim Sunj-Wan (Salt Lake City UT) Feijen Jan (Hengelo NLX), Time-release chemical delivery system.
Haugwitz Rudiger D. (Bethesda MD) Zalkow Leon (Atlanta GA) Glinski Jan (Ridgefield CT) Suffness Mathew (Silver Spring MD) Deutsch Howard M. (Atlanta GA) Narayanan Venkatachala (Gaithersburg MD), Water soluble, antineoplastic derivatives of taxol.
Van, Sang; Song, Yucheng; Wang, Xinghe; Hou, Zheng; Feng, Zhongling; Zhao, Gang; Yu, Lei, Compositions that include a hydrophobic compound and a polyamino acid conjugate.
Van, Sang; Song, Yucheng; Wang, Xinghe; Hou, Zheng; Feng, Zhongling; Zhao, Gang; Yu, Lei, Compositions that include a hydrophobic compound and a polyamino acid conjugate.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.