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1. 发明申请

WO2012097133A3 COMPOUNDS AND METHODS FOR INDUCING APOPTOSIS IN CANCER CELLS USING A BH3 ALPHA-HELICAL MIMETIC 审中-公开
标题翻译：使用BH3 ALPHA-HELICAL MIME技术诱导癌细胞凋亡的化合物和方法
公开(公告)号：WO2012097133A3
公开(公告)日：2012-11-01
申请号：PCT/US2012021049
申请日：2012-01-12
申请人： H LEE MOFFITT CANCER CT & RES , UNIV YALE , INTEZYNE TECHNOLOGIES INC , SEBTI SAID M , HAMILTON ANDREW D , SILL KEVIN , CARIE ADAM
发明人： SEBTI SAID M , HAMILTON ANDREW D , SILL KEVIN , CARIE ADAM
IPC分类号： C07C217/22 , A61K31/165 , A61P35/00 , C07C217/18
CPC分类号： A61K9/107 , A61K31/194 , A61K31/205 , A61K31/4035 , A61K31/407 , A61K31/69 , A61K45/06 , C07C59/70 , A61K2300/00
摘要： A novel BH3 a-helical mimetic, BH3-M6, which binds to Bcl-XL and prevents its binding to fluorescently-labeled Bak-BH3 peptide in vitro with an IC50 value of 734 nM is presented herein. BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-XL, Bcl-2 and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in a cell-free system and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6-induced apoptosis is caspase- and Bax- dependent. Furthermore, human cancer cells with high Bcl-2 or Bcl-XL levels are more sensitive to BH3-M6-induced cell death, suggesting that this compound can overcome drug resistance due to Bcl-2 or BCI-XL overexpression. The pan-Bcl-2 inhibitor BH3-M6 may be encapsulated in a micelle to provide a more bioavailable therapeutic agent. Specifically, the BH3-M6 compound may be encapsulated within a micelle comprising a multiblock copolymer according to the methods described herein.
摘要翻译：本文提供了一种新颖的BH3一螺旋模拟物BH3-M6，其结合Bcl-XL并且在体外阻止其与体外荧光标记的Bak-BH3肽结合，IC50值为734nM。 BH3-M6是Pan-Bcl-2拮抗剂，其抑制Bcl-XL，Bcl-2和Mcl-1与无细胞系统中多结构域Bax或Bak或仅BH3b或Bb结合完整的人类癌细胞，释放促凋亡蛋白以诱导细胞凋亡。 BH3-M6诱导的凋亡是caspase-和Bax依赖性的。此外，具有高Bcl-2或Bcl-XL水平的人类癌细胞对BH3-M6诱导的细胞死亡更敏感，这表明该化合物可以克服由于Bcl-2或BCI-XL过表达引起的耐药性。泛-Bcl-2抑制剂BH3-M6可以包封在胶束中以提供更具生物利用度的治疗剂。具体地，根据本文所述的方法，可以将BH3-M6化合物包封在包含多嵌段共聚物的胶束内。

2. 发明专利

AU2018263965A1 Manufacture of trans-(tetrachlorobis(1H-indazole)ruthenate (III)) and compositions thereof 未知
公开(公告)号：AU2018263965A1
公开(公告)日：2019-11-21
申请号：AU2018263965
申请日：2018-05-07
申请人： CARIE ADAM , INTEZYNE TECHNOLOGIES INC , SILL KEVIN , VOJKOVSKY TOMAS
发明人： VOJKOVSKY TOMAS , SILL KEVIN , CARIE ADAM
IPC分类号： A61K31/416 , A61K31/555 , A61K33/24
摘要： The present invention relates to the preparation of compositions comprising sodium

3. 发明专利

SG11201910043PA MANUFACTURE OF TRANS-[TETRACHLOROBIS(1H-INDAZOLE)RUTHENATE (III)] AND COMPOSITIONS THEREOF 未知
公开(公告)号：SG11201910043PA
公开(公告)日：2019-11-28
申请号：SG11201910043P
申请日：2018-05-07
申请人： INTEZYNE TECHNOLOGIES INC , VOJKOVSKY TOMAS , SILL KEVIN , CARIE ADAM
发明人： VOJKOVSKY TOMAS , SILL KEVIN , CARIE ADAM
IPC分类号： A61K31/555 , A61K31/416 , A61K33/24
摘要： INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 08 November 2018 (08.11.2018) WIPO I PCT Iiiimmoimiolollmonolooloviimiflinomovom (10) International Publication Number WO 2018/204930 Al (51) International Patent Classification: A61K 31/416 (2006.01) A61K 33/24 (2006.01) A61K 31/555 (2006.01) (21) International Application Number: PCT/US2018/031436 (22) International Filing Date: 07 May 2018 (07.05.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/501,984 05 May 2017 (05.05.2017) US (71) Applicant: INTEZYNE TECHNOLOGIES, INC. [US/US]; 3720 Spectrum Blvd., Suite 104, Tampa, Florida 33612 (US). (72) Inventors; and (71) Applicants: VOJKOVSKY, Tomas [ /US]; 23 Shelby Lane, Palm Beach Gardens, Florida 33418 (US). SILL, Kevin [ /US]; 16308 Royal Park Ct., Tampa, Florida 33647 (US). CARIE, Adam [ /US]; 4206 Knob Lake Ct., Tampa, FL 33619 (US). (74) Agent: REID, Andrea L.C. et al.; One International Place, 100 Oliver Street, 40th Floor, Boston, Massachusetts 02110-2605 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (54) Title: MANUFACTURE OF TRANS-[TETRACHLOROBIS(1H-INDAZOLE)RUTHENATE (III)] AND COMPOSITIONS = THEREOF 120 100 IT- 139 Drug Su b O cr O 1 \ \ 80 1 \ 1 \ \ 60 7 1 \\ \ \ \ 40d \ , 1 20 1 \\ \ 1 01 1 0 10 20 IT-139 2-8°C - -0- - IT-13918-22°C 30 40 50 60 Time (h) Figure 1 1-1 (57) : The present invention relates to the preparation of compositions comprising sodium trans-[tetrachlorobis(1H- ei • mdazole)ruthenate (III)]. Synthesis and formulation preparation is detailed. Impurity profiles are also discussed. Compositions herein C are useful for anti-cancer applications. [Continued on next page] WO 2018/204930 Al MIDEDIMOMMIDIRE10100101011fifilIMIHMEMOIS TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3))

4. 发明专利

CA3062369A1 MANUFACTURE OF TRANS-[TETRACHLOROBIS(1H-INDAZOLE)RUTHENATE (III)] AND COMPOSITIONS THEREOF 未知
公开(公告)号：CA3062369A1
公开(公告)日：2018-11-08
申请号：CA3062369
申请日：2018-05-07
申请人： INTEZYNE TECH INC , VOJKOVSKY TOMAS , SILL KEVIN , CARIE ADAM
发明人： VOJKOVSKY TOMAS , SILL KEVIN , CARIE ADAM
IPC分类号： A61K31/416 , A61K31/555 , A61K33/24
摘要： The present invention relates to the preparation of compositions comprising sodium trans-[tetrachlorobis(1H-indazole)ruthenate (III)]. Synthesis and formulation preparation is detailed. Impurity profiles are also discussed. Compositions herein are useful for anti-cancer applications.

5. 发明专利

AU2013201541A1 BLOCK COPOLYMERS FOR STABLE MICELLES 未知
公开(公告)号：AU2013201541A1
公开(公告)日：2013-10-31
申请号：AU2013201541
申请日：2013-03-15
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , VOJKOVSKY TOMAS , SEMPLE JOSEPH EDWARD
IPC分类号： C08G81/00 , A61K9/00 , A61K47/32 , A61K47/34 , A61K47/48
摘要： 1l: rxs [lntrwven- NRPrIbl DCC RXS\4994935 I.DOCX-3 15/2013 The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

6. 发明专利

AU2016250403B2 Block copolymers for stable micelles 未知
公开(公告)号：AU2016250403B2
公开(公告)日：2018-12-06
申请号：AU2016250403
申请日：2016-10-27
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , VOJKOVSKY TOMAS , SEMPLE JOSEPH EDWARD
IPC分类号： C08G81/00 , A61K9/00 , A61K47/32 , A61K47/34
摘要： The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications. - 1 / 25 Fare Ia- Tribkck Copolymer Hydrophobic D,L Mixed Polymeric Hydrophilic Block Crosslnkable Poly(amo acid) Block Figure 1 b Polymer M ce Crosslinkable Outer Core Hydrophilic Shell Hydrophobic Inner Core

7. 发明专利

AU2016250403A1 Block copolymers for stable micelles 未知
公开(公告)号：AU2016250403A1
公开(公告)日：2016-11-17
申请号：AU2016250403
申请日：2016-10-27
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , VOJKOVSKY TOMAS , SEMPLE JOSEPH EDWARD
IPC分类号： C08G81/00 , A61K9/00 , A61K47/32 , A61K47/34 , A61K47/48
摘要： The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications. - 1 / 25 Fare Ia- Tribkck Copolymer Hydrophobic D,L Mixed Polymeric Hydrophilic Block Crosslnkable Poly(amo acid) Block Figure 1 b Polymer M ce Crosslinkable Outer Core Hydrophilic Shell Hydrophobic Inner Core

8. 发明专利

CA2868274A1 BLOCK COPOLYMERS FOR STABLE MICELLES 未知
公开(公告)号：CA2868274A1
公开(公告)日：2013-10-17
申请号：CA2868274
申请日：2013-03-15
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , SEMPLE JOSEPH EDWARD , VOJKOVSKY TOMAS
IPC分类号： C08G63/48
摘要： The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

9. 发明专利

NZ709953A Block copolymers for stable micelles 未知
公开(公告)号：NZ709953A
公开(公告)日：2016-09-30
申请号：NZ70995313
申请日：2013-03-15
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , SEMPLE JOSEPH EDWARD , VOJKOVSKY TOMAS
IPC分类号： C08G69/10 , A61K47/42 , C08G81/00
摘要： The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. In particular, the invention relates to a micelle comprising at least one multiblock copolymer, said multiblock copolymer comprising a polymeric block, wherein the polymeric block is hydrophilic, a crosslinkable or crosslinked poly(amino acid) block, a D,L-mixed poly(amino acid) block, wherein said micelle has an inner core, a crosslinkable or crosslinked outer core, and a shell, wherein the polymeric block corresponds to the shell, the crosslinkable or crosslinked poly(amino acid block) corresponds to the outer core, and the D,L-mixed poly(amino acid) block corresponds to the inner core, of the micelle, respectively; characterized in that said crosslinkable or crosslinked poly(amino acid) block comprises a chemical functionality that strongly binds or coordinates with metal ions, wherein said chemical functionality is or comprises hydroxamic acid, a hydroxamate, or a derivative thereof, or is or comprises an ortho-substituted dihydroxy benzene group or a derivative thereof. Compositions herein are useful for drug-delivery applications.

10. 发明专利

AU2013201541B2 BLOCK COPOLYMERS FOR STABLE MICELLES 未知
公开(公告)号：AU2013201541B2
公开(公告)日：2014-08-14
申请号：AU2013201541
申请日：2013-03-15
申请人： INTEZYNE TECHNOLOGIES INC
发明人： SILL KEVIN , CARIE ADAM , VOJKOVSKY TOMAS , SEMPLE JOSEPH EDWARD
IPC分类号： C08G81/00 , A61K9/00 , A61K47/32 , A61K47/34 , A61K47/48
摘要： 1l: rxs [lntrwven- NRPrIbl DCC RXS\4994935 I.DOCX-3 15/2013 The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

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