Polymer drug conjugates with tether groups for controlled drug delivery
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/14
A61K-047/48
B82Y-005/00
출원번호
US-0922739
(2013-06-20)
등록번호
US-9610360
(2017-04-04)
발명자
/ 주소
Davis, Mark E.
Hwang, Jungyeon
Ke, Tianyi
Lim, Ching-jou
Schluep, Thomas
출원인 / 주소
CERULIEAN PHARMA INC.
대리인 / 주소
Lando & Anastasi, LLP
인용정보
피인용 횟수 :
0인용 특허 :
134
초록
Described herein is a cyclodextrin containing polymer conjugate.
대표청구항▼
1. A linear, cyclodextrin containing polymer conjugate, comprising a therapeutic agent covalently attached to a polymer through a tether, wherein the tether comprises an aminoalkylcarbonyloxyalkyl moiety whereupon being subjected to biological conditions the tether undergoes self-cyclization to form
1. A linear, cyclodextrin containing polymer conjugate, comprising a therapeutic agent covalently attached to a polymer through a tether, wherein the tether comprises an aminoalkylcarbonyloxyalkyl moiety whereupon being subjected to biological conditions the tether undergoes self-cyclization to form a five- or six-membered heterocyclic ring that comprises at least one heteroatom selected from nitrogen, oxygen and sulfur, thereby releasing the therapeutic agent. 2. The polymer conjugate of claim 1, wherein the cyclization forms a five-membered heterocyclic ring. 3. The polymer conjugate of claim 2, wherein the five-membered heterocyclic ring comprises two oxygen atoms. 4. The polymer conjugate of claim 1, wherein the cyclodextrin containing polymer comprises a copolymer comprising cyclodextrin moieties and linker groups that do not comprise cyclodextrin moieties. 5. The polymer conjugate of claim 4, wherein the cyclodextrin moieties and the linker groups alternate in the copolymer. 6. The polymer conjugate of claim 4, wherein each linker group independently comprises an alkyl chain, a polyethylene glycol (PEG) chain, polysuccinic anhydride, poly-L-glutamic acid, poly(ethyleneimine), an oligosaccharide, or an amino acid chain. 7. The polymer conjugate of claim 4, wherein each linker group comprises PEG. 8. The polymer conjugate of claim 1, wherein the cyclodextrin is alpha-, beta-, or gamma-cyclodextrin. 9. The polymer conjugate of claim 1, wherein the therapeutic agent is a small molecule, a peptide, a protein, a nucleotide, a polynucleotide, or a polymer that has therapeutic function. 10. The polymer conjugate of claim 1, wherein the therapeutic agent is an anti-cancer, anti-fungal, anti-bacterial, anti-mycotic, or anti-viral therapeutic. 11. The polymer conjugate of claim 1, wherein the therapeutic agent is a protease inhibitor. 12. The polymer conjugate of claim 1, wherein the therapeutic agent comprises an amino, hydroxyl, or thiol group. 13. The polymer conjugate of claim 12, wherein the therapeutic agent is attached to the tether through the amino, hydroxyl, or thiol group of the therapeutic agent. 14. The polymer conjugate of claim 1, wherein the therapeutic agent is attached to the tether through the amino group of the therapeutic agent. 15. The polymer conjugate of claim 1, wherein the tether comprises an amino acid or peptide, or derivative thereof. 16. The polymer conjugate of claim 1, wherein the therapeutic agent makes up at least 5% by weight of the polymer conjugate. 17. The polymer conjugate of claim 1, wherein the therapeutic agent makes up at least 10% by weight of the polymer conjugate. 18. The polymer conjugate of claim 1, wherein the therapeutic agent makes up at least 15% by weight of the polymer conjugate. 19. The polymer conjugate of claim 1, wherein the polymer conjugate has a molecular weight of 10,000-500,000 amu. 20. A pharmaceutical composition comprising a polymer conjugate of claim 1, and a pharmaceutically acceptable excipient, or a pharmaceutically acceptable salt thereof. 21. The pharmaceutical composition of claim 20, wherein upon administration to a subject, the therapeutic agent is delivered to the subject for a period of from about 1 to about 2,000 hours. 22. The polymer conjugate of claim 1, wherein the polymer comprises a copolymer comprising beta-cyclodextrin moieties and PEG groups that alternate in the copolymer, the therapeutic agent is an anti-cancer agent. 23. A pharmaceutical composition comprising the polymer conjugate of claim 22, and a pharmaceutically acceptable excipient, or a pharmaceutically acceptable salt thereof.
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