Bortezomib – First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature

Author(s): Pratik A. Vora*, Rakesh Patel, Abhay Dharamsi

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 15 , Issue 2 , 2020


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Abstract:

Background: Bortezomib is a reversible inhibitor of proteasome proteins in mammalian cells. Bortezomib is proven to be cytotoxic to a number of tumor cells by disrupting their normal homeostatic mechanism and thereby, causing cell death. Currently, Bortezomib is prescribed for patients with multiple myeloma and mantle cell lymphoma.

Objective: This assessment highlights the overview of the recent patents of Bortezomib. This review includes patents grouped in sections like product patents, process patent, composition related patents as well as the treatment methodology. The objective of this article is to facilitate researchers with all existing patents at a single place.

Methods: Data were searched from various online databases. In which, paid databases include SciFinder® and Orbit®. Free databases include Patentscope® (WIPO), Worldwide Espacenet® (EPO), Google Patents and InPASS (Indian patent database).

Results: Several new processes and composition related patents of Bortezomib have been recently patented as its orange-book listed patents are going to soon expire during July 2022. Further, due to the problem of oxidation during development and long-term storage of Bortezomib formulation, a number of excipients are tried in these patents to stabilize the same. However, there is still a need for further development of an improved formulation of Bortezomib with better characteristics.

Conclusion: Extensive research has been carried out on various processes for preparing Bortezomib and the composition thereof. This type of dynamic research will clear the path for many generic players in the United States, which lead to the reduction of the price of the composition and thereby enhancing global health care at cheaper prices.

Keywords: Anticancer, bortezomib, cancer therapy, composition, oncology, patent, proteasome inhibitor, VELCADE.

[1]
Brazier Y. What are the different types of tumor? Available from: https://www.medicalnewstoday.com/articles/249141.php (Access on: September 30, 2019).
[2]
Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood 2012; 120(5): 947-59.
[http://dx.doi.org/10.1182/blood-2012-04-403733] [PMID: 22645181]
[3]
Velcade FDA Label, Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf (Access on: October 1, 2019).
[4]
Reid EG, Suazo A, Lensing SY, et al. Pilot trial AMC-063: Safety and efficacy of bortezomib in AIDS-associated Kaposi sarcoma. Clin Cancer Res 2020; 26(3): 558-65.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-1044] [PMID: 31624104]
[5]
Bassiony E, Barakat A, Ghannam A, Abozena E. Bortezomib in multiple myeloma: Treatment response and survival outcome. Tanta Med J 2017; 45(3): 129-34.
[http://dx.doi.org/10.4103/tmj.tmj_21_17]
[7]
Adams J, Ma Y-T, Stein R, Baevsky M, Grenier L, Plamondon L. Boronic ester and acid compounds, synthesis and uses. WO9613266, 1996.
[8]
Pickersgill IF, Bishop J, Koellner C, et al. Synthesis of peptidyl boronic acids and esters. WO2005097809, 2005.
[9]
Palle RV, Kadaboina R, Murki V, et al. Preparation of bortezomib in crystalline form. WO2009036281, 2009.
[10]
Zhao J, Du Y, Zhao Y, Cai K, Wu C, Yang J. Manufacture method of high optical purity bortezomib and its intermediate. CN103304629, 2013.
[11]
Rao DR, Kankan RN, Pathi SL, Puppala R. Lawrence Louis Process for preparing of bortezamib. WO2014041324, 2014.
[12]
Dhar DS, Kamlesh SK, Dnyaneshwar NS. An improved process for preparation of bortezomib. IN972/MUM/2013 2015.
[13]
Zhao X, Li X, Zhao Y. Synthesis method of high-purity bortezomib and its intermediates. CN103012551, 2013.
[14]
Zou Y, Huang Q, Jiang X, Tang Y, Zou C, Yuan Q. Impurity of bortezomib and preparation method thereof. CN109134601, 2019.
[15]
Ravi JRR, Pulla Reddy M, Adibatla Kali Satya BR, Benkaiah Chowdary N. Polymorphic forms of bortezomib and process for their preparation. WO2008075376, 2008.
[16]
Reddy BP, Reddy KR, Reddy DM, Reddy RR, Ramachandra P, Krishna BV. Polymorphs of bortezomib. WO2011099018, 2011.
[17]
Jamjanam SR, Moturu VRM, Dammalapati VLNR, Gorantla SR. Preparation of a novel crystalline form of bortezomib and pharmaceutical composition thereof. WO2012131707, 2012.
[18]
Xie T, Xu Z, Zhou H, Chen F. One kind of bortezomib crystal form, and its preparation method, pharmaceutical compositions and application in antitumor drugs. CN104693271, 2015.
[19]
Son HJ, Park YK, Kim Y-M, Hwang J-M, Kim JH. Novel crystalline form of bortezomib and preparation method thereof. WO2015122702, 2015.
[20]
Ding J, Xu W, Zhuang X, Chen X. Dextran-bortezomib conjugate medicine and its preparation method. CN104958768, 2015.
[21]
Shrawat VK. A process for the preparation of crystalline bortezomib. WO201407613, 2014.
[22]
Ravi JRR, Kondaveeti S, Adibhatla KSBR, Muddasani PR, Nannapaneni VC. Stable and pure polymorphic form of bortezomib. WO2014097306, 2014.
[23]
Shivakumar P, Ramakrishnaiah S, Alampalli B, Chaturvedi A. Bortezomib injection formulations. WO2014102755, 2014.
[24]
Joo SH. Stable crystalline form bortezomib. KR101741403, 2016.
[25]
Furuya T, Abe M. Manufacturing method for bortezomib crystals. WO2019151133, 2019.
[26]
Farag SS. Combined use of bendamustine, doxorubicin and bortezomib for the treatment of multiple myeloma. WO2010056733, 2010.
[27]
Shaughnessy JD Jr, Barlogie B, Qu P. Uses of bortezomib in predicting survival in multiple myeloma patients. WO2010078531, 2010.
[28]
Liu X, Li X, Qin Q, Gao C, Yu X. Pharmaceutical use of a dicycloplatin (DCP) for the prophylaxis or treatment of proliferative diseases. WO2016172393, 2016.
[29]
Won PJ, Park WJ. Composition for relief and treatment of liver injury comprising bortezomib as a active ingredient. KR101695237, 2017.
[30]
Kim NS, Park J-S, Yi J-M, et al. Composition, containing Lithospermum erythrorhizon extract as active ingredient, for preventing, alleviating, or treating peripheral neuropathy. WO2016182139, 2016.
[31]
Chen T, Shachar Y. Intratumoral delivery of bortezomib into brain tumor by pump implanted in brain. WO2019148181, 2019.
[32]
Xie H, Cakana A. Methods of treating multiple myeloma. US20190298827, 2019.
[33]
Gupta S. Lyophilized formulation of sugar-containing boronic acid compounds. WO2002059130, 2002.
[34]
Plamondon L, Grenier L, Adams J, Gupta SL. Lyophilized formulation of boronic acid compounds. WO2002059131, 2002.
[35]
Zalipsky S, Martin F. Liposomal formulation of bortezomib (PS-341). WO2006052733, 2006.
[36]
Sun L, Sun Z, Zhang W. Antitumor sustained-release injection containing taxol and bortezomib. CN101301472, 2008.
[37]
Hou H, Sun Q, Sun Z. Bortezomib and alkylating agent composite sustained-release injection with drug delivery delayed greatly and preparation method thereof. CN101336926, 2009.
[38]
Mao H, Wang M, Chen Y. Antitumor sustained-release injection containing bortezomib and topoisomerase inhibitors. CN101336893, 2009.
[39]
Soppimath K, Pejaver S, Patel KR, et al. Stable bortezomib formulations. WO2011116286, 2011.
[40]
Usayapant A, Bowman D. Bortezomib formulations stabilized with boric. WO2012047845, 2012.
[41]
Xia F. Pharmaceutical composition containing bortezomib for treating T cell lymphoma. CN103191405, 2013.
[42]
Zhao J, Cai J, Zong Z, Ji T, Jia Y. Bortezomib lyophilized composition and preparation method thereof. CN103446068, 2013.
[43]
Yeon WK, Wook KD, Pyo HE. Oral pharmaceutical composition comprising bortezomib. KR20140057048, 2014.
[44]
Puppala R, Pathi SL, Rao DR, Kankan RN. Process for the preparation of bortezomib mannitol ester substantially free of the degradation impurity. WO2014170628, 2014.
[45]
Zhong Z, Chen Y, Wang X, Ma Y. Bortezomib medicinal composition and preparation method thereof. CN103212055, 2013.
[46]
Chen Q, Zong Z, Jia Y. Bortezomib lyophilized composition and its preparation method. CN103070835, 2013.
[47]
Zaludek B. Pharmaceutical compositions comprising bortezomib. WO2015025000, 2015.
[48]
Yuan S, Yang X, Wang L, et al. Method for preparing bortezomib powder for injection. CN103505424, 2014.
[49]
Shivakumar P, Ramakrishnaiah S, Alampalli B, Chaturvedi AK. Bortezomib formulations. WO2016059515, 2016.
[50]
Yao Z, Luo Y, Yan F, Zhang H, Che B. Pharmaceutical composition containing bortezomib and preparation method thereof. CN105056205, 2015.
[51]
Shaik RA, Chaurasiya A, Saha A, Patel BV, Bhagwatwar H, Pillai SA. Stable liquid ready-to-use injectable formulation of bortezomib. WO2016001905, 2016.
[52]
Pasqua L, Leggio A, Liguori A, Morelli C, Ando S. Bortezomib-based delivery system. WO2016174693, 2016.
[53]
Chen Z, Zheng Q, Wang S, Zhao X. Bortezomib injection agent and preparation method thereof. CN105496960, 2016.
[54]
Shivakumar P, Dasari N, Kulkarni R, Chaturvedi AK. Bortezomib pharmaceutical formulations comprising orthophosphoric acid for treating cancer. WO2016059515, 2016.
[55]
Mudri D, Vince N. Malic acid esters of bortezomib. EP3031811, 2016.
[56]
Gondaliya DP, Gurjar MK, Mehta SS, Patel HP, Patel HI, Patel NM. Pharmaceutical composition of bortezomib. WO2016110870, 2016.
[57]
Sun J, Wang Y, Wu Z. Bortezomib sustained-release preparation and its preparation method. CN103656668, 2014.
[58]
Jae PW, Won PJ. Composition for preventing or treating obesity or non-alcoholic fatty liver, containing bortezomib. KR20160117839 2016.
[59]
Chandrashekhar K, Nagaraju B. Stable liquid pharmaceutical compositions of bortezomib. WO2016166653, 2016.
[60]
Zhang G, Zhao Z, Cheng Z. A kind of bortezomib lyophilized powder injection and the production method thereof. CN104546744, 2015.
[61]
Yuan H, Wang Y, Dong L, Sun Y, Sun C. Lyophilized preparation of bortezomib and preparation method thereof. CN106176637, 2016.
[62]
Sun Y, Wang Y, Dong L, Huang Y, Yuan H. Bortezomib freeze-dried powder injection and its making process. CN106309385, 2017.
[63]
Schridde E. Ready-to-use bortezomib solution. WO2017013208, 2017.
[64]
Kanteepan P, Vekariya SL, Mandal JK, Mehta SP. Composition comprising bortezomib. US10314880, 2017.
[65]
Katori K, Kinoshita M, Isane M, Inoue H. Freeze-dried compositions containing bortezomib and tartaric acid prepared for reconstitution of pH-controlled pharmaceutical infection solution. JP2017057202, 2017.
[66]
Ebetino F, Boeckman R, Xing L, Xiao L, Boyce B. Bortezomib conjugates and methods using same. WO2017079262, 2017.
[67]
Lu W, Wang X, Xie C, Wei G, Hu X. Bortezomib water-soluble medicinal composition and preparation method and application method thereof to antitumor agents. CN107224569, 2017.
[68]
Liu C, Zhuang H, Wang Y, et al. Bortezomib pharmaceutical composition for injection. CN103142509, 2013.
[69]
Aydinlar T. Pharmaceutical formulations comprising a bortezomib-cyclodextrin complex for use in treatment of cancers such as multiple myeloma and mantle cell lymphoma. WO2018038687, 2018.
[70]
Lee JH, Cho TK, Ryu CY, Cho YD. Stable preparation containing bortezomib and preparation method therefor. WO2018164513, 2018.
[71]
Kharbanda S, Shukla V, Kufe D, Singh H. Polymeric nanoparticles and antitumor uses thereof. WO2018085407, 2018.
[72]
Gan Y, Zhu Q, Zhu C, Ji L, Jin Y, Guo S. Bortezomib pharmaceutical composition and applications thereof. WO2018108164, 2018.
[73]
Zhao Z, Hao G, Shao J, Fan F, Wu S. Bortezomib freeze-dried powder injection and preparation method thereof. CN104414982, 2015.
[74]
Nazarenko AB, Kinasov DG, Ladygin VV, Kornev KO, Zakoryukin NV. Bortezomib lyophilizate production method and a bortezomib-containing pharmaceutical composition in the form of stable lyophilizated product produced by said method. RU2659160, 2018.
[75]
Yoshioka Y, Fujiki D. Bortezomib liquid preparation comprising propylene glycol and ascorbic acid compound. JP2018168088, 2018.
[76]
Hidaka A, Motoyama J. Preparation of pharmaceutical composition containing bortezomib. JP2018177649A, 2018.
[77]
Hou L. Bortezomib phosphatide complex and preparation method and application thereof. CN109045272, 2018.
[78]
Sun C, Wang X, Yuan H, Sun Y, Meng W. Bortezomib pharmaceutical composition and preparation method thereof. CN106265536, 2017.
[79]
Li N, Wang J, Li F. Bortezomib lyophilized powder for injection and its preparation method. CN109364030, 2019.
[80]
Kwang KK, Eun KY. Composition for preventing, improving or treating atopic skin diseases containing proteasome inhibitor as active ingredient. KR101953671, 2019.
[81]
Li N, Gui J, Shi X. Freeze-drying process of bortezomib freeze-dried powder for injection. CN109453125, 2019.
[82]
Jae PW, Keun PI. Composition comprising bortezomib or its pharmaceutically acceptable salt as active ingredient for inhibiting multidrug resistance. KR20190027148, 2019.
[83]
Kharbanda S, Singh H. Polymeric nanoparticles comprising bortezomib. WO2019104001, 2019.
[84]
Hattori H. Lyophilized pharmaceutical composition comprising bortezomib. JP2019085338, 2019.
[85]
Serda RE, Noureddine A. A high capacity platform for immunogenic cancer cell death using siliceous nanoparticles comprising TLR ligand or other immunostimulant. WO2019173391, 2019.
[86]
Mandal JK, Mehta SP. Composition comprising bortezomib. US20190290718, 2019.


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Article Details

VOLUME: 15
ISSUE: 2
Year: 2020
Page: [113 - 131]
Pages: 19
DOI: 10.2174/1574892815666200401113805
Price: $65

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