What is Example 455 in US6596746?
Example 455 in U.S. Patent 6,596,746 details the synthesis of a specific dasatinib intermediate, N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide [1]. This compound is a precursor to dasatinib, an oral tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) [2, 3].
How is this dasatinib intermediate synthesized?
The synthesis described in Example 455 involves several steps. It begins with a reaction between 4,6-dichloro-2-methylpyrimidine and 1-(2-hydroxyethyl)piperazine. The resulting product is then reacted with 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide to yield the target intermediate [1].
What is the significance of US6596746 for dasatinib?
U.S. Patent 6,596,746, issued on July 27, 2003, is foundational, claiming dasatinib and its preparation. This patent played a crucial role in protecting the intellectual property surrounding dasatinib, manufactured by Bristol Myers Squibb under the brand name Sprycel [4, 5].
When does the patent for dasatinib expire?
The primary patents covering dasatinib and its synthesis have expired or are nearing expiry. For instance, U.S. Patent 6,596,746 expired in 2023. However, patent expiration can be complex due to potential additional patents and regulatory exclusivities [5]. DrugPatentWatch.com provides detailed patent information and expiration timelines for various drugs, including dasatinib [5].
What are the implications of patent expiry for dasatinib?
Patent expiry opens the door for generic manufacturers to produce and market their own versions of dasatinib. This typically leads to increased competition and a reduction in drug prices, making the treatment more accessible to patients [5].
What are the key approved uses for dasatinib?
Dasatinib (Sprycel) is approved for the treatment of adults with Philadelphia chromosome-positive (Ph+) CML in chronic, accelerated, or blast phase, and for adults with Ph+ ALL for whom resistance or intolerance to prior therapy, including imatinib, has been observed [3].
What are the common side effects of dasatinib?
Common side effects associated with dasatinib treatment include fluid retention, diarrhea, headache, rash, fatigue, muscle pain, nausea, and myelosuppression (low blood cell counts) [3].
Who are the major manufacturers of dasatinib?
Bristol Myers Squibb is the originator manufacturer of dasatinib (Sprycel). Following patent expiry, other pharmaceutical companies are entering the market with generic versions [5].
Sources
1. US Patent 6596746 A
2. Dasatinib
3. Sprycel (dasatinib) Prescribing Information
4. Bristol Myers Squibb
5. DrugPatentWatch.com