A chemical structure or Markush structure is the basic backbone of almost all pharmaceutical and chemistry patent pools and is of utmost importance to inventions in achieving the greatest legal protection and scope. Markush structures are simplified versions of chemical compounds that list multiple chemical entities or species in a single structure.

The idea behind Markush Claims:

In general, the biological activity of a compound depends on the core structure aka Markush structure wherein most of the times such structures are complex. Often pharmaceutical patents disclose a few variations of a given structure, claiming a backbone that further lists groups of chemical moieties with similar function. Irrespective of numerous combinations encompassed by a Markush claim, the structure itself is considered to be generic. For instance, a drug based on slightly different structural variations from a Markush claim disclosing a chemical compound and displaying a similar activity as the claimed compound shall fall under the scope of the claim. An example of such structure is shown in a patent reference below:

Chemical Structures: Effective Patent Search and Analysis

Chemical Structures: Effective Patent Search and Analysis

Unique Search and Analysis:

In the case of Clearance Searches, unlike generic keywords based searches, structure-based searches are important to capture chemical backbones with variations in functional groups. For instance, before launching a chemical product such as an herbicide in the market, a clearance search identifying Markush structures is preferable than performing a typical keyword or class-based generic search. Markush search shall disclose numerous variations possible in a structure that can be refined to identify compounds with moieties possibly broad enough to weaken the clearance chances of specific yet an obvious structure of the herbicide.

Similarly, in the case of Validity/Invalidity searches, identifying a different functional group performing a similar activity in a compound is critical in affecting obviousness and thereby legal enforcement of the patent.

Such analysis is achieved by carefully designed comprehensive searches that identify relevant results. However, as much as it may appear simple, analysis and refinement of identified results is tricky and require high expertise.

Challenges:

  • Markush structures are complex in nature. While a simpler Markush structure may comprise more than a thousand compounds; a complex Markush structure may comprise more than 1×105
  • Databases (free and paid) which may provide wide coverage and details related to Markush structures are limited.
  • Searches are complex and may retrieve unlimited results if queries are not optimized.
  • Refining results based on structure similarity, identity and functionality is a task that requires high subject matter expertise and experience in analyzing Markush structures.
  • Databases for specific chemicals (Registry/DCR) or for common names are not comprehensive.
  • Similar structures may have applications in various industries, such as cosmetics, agricultural products, healthcare, homecare, textiles, etc.

Overcoming Challenges:

Simplifying structures/claims by identifying the active core and peripheral functional groups of the structure is the first step to avoid misinterpretation of structures during the course of analysis. The core is identified by understanding the property of the active agent and the overall activity of the compound. The next step involves designing a representation of the simplified core structure to formulate a query on search databases such as STN, SciFinder, etc. At this stage, a number of search hits may be retrieved. The search query can be optimized based on additional features such as relevant keywords and/or classes. Once the query search is comprehensively run and requisite search results have been identified, filtering or initial screening of relevant results is performed followed by analysis.

While generating a simplified core design and running a query require a clear understanding of the structure, it is usually the analysis aspect of the captured results that test the expertise of the researcher. Unlike keyword-based analysis, Markush structure analysis requires a correct interpretation of the compound with respect to the invention scope. For instance, in the case of a novelty search, a specific core structure with substituents similar to the subject invention shall be considered. In this case, there might be variations in the substituents that need to be noted. Alternatively, in a FTO/Clearance search, the analysis further requires considering broader versions of a structural backbone. In an exemplary scenario for a structure with the “R” group as propyl, a patent reference claiming R as C1-8 alkyl group is also relevant. This is because C1-8 alkyl group may comprise methyl, ethyl, propyl or octyl.

Therefore, in view of the above-identified challenges and requirements of effective IP searches, Sagacious IP recognizes and works towards value addition at each step of the innovation cycle and is, therefore, well-informed about global technology, market and IP footprints in the industry. With a dedicated team of highly experienced and extremely skillful researchers, we provide an array of services in Pharmaceuticals, Chemical, and Material Science industries. Let’s look at a case study of the service.

Case Study:

In one of the FTO projects involving a structure as the subject invention, Sagacious IP performed a search and subsequent analysis to determine if it is possible to claim benzoxazole derivatives or their target sites of action.

In order to establish a chemical basis, Markush compounds that contain benzoxazole core were studied. An initial search query on the specific structure retrieved thousands of results. Refining the query with one of the properties as an anti-cancer agent retrieved around 1300 results. Further, based on the client’s requirement, specific cancer pathways were determined that may be targeted by benzoxazole derivatives. At this stage, manual analysis and interpretation are of high importance so as to not miss any relevant result in the machine search algorithm and thereby refine results accordingly. Subsequently, biological targets were analyzed, starting off from a broad backbone to specific structure responsible for the inhibition of biological targets, such as MEK, EGFR, and DNA polymerase, etc. As requested, the client was provided all the relevant patent literature involving biological targets with analysis of various functional groups. Sagacious IP’s report was highly appreciated by the client and aided them in bagging a top spot for their product amongst highly competitive markets. The image below is a concise snapshot of the search query and retrieve

results, which were analyzed by our experts:

Chemical Structures: Effective Patent Search and Analysis

Chemical Structures: Effective Patent Search and Analysis

Figure 1: Overview of Benzoxazole containing Markush inhibitors (~9100 patents) with their biological activity. It also provides an in-depth analysis of benzoxazole containing anticancer (~1300 patents) agents with major anticancer targets e.g. CDKs, DNA polymerase, and EGFR.

Sagacious IP assists in conducting novelty, invalidity, clearance/FTO and infringement searches related to Markush structures and also assists clients in evaluating market trends, risks and overall complete techno-IP consulting. Download our sample Markush structure analysis report to know more.

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