Markush chemical structures

Markovnikov rule, 20 774 Markov property, 26 1022 Markush chemical structures, indexing and searching, 18 242. See also WPI entries... 

CAS = chemical abstracts service CDB = IFI/Plenem comprehensive code DWPI = Derwent world patents index INPI = Institut national de la propriete industrielle (the french patent office, producer of pharmsearch) MARPAT = chemical abstracts service database of Markush chemical structures from patents MDARC = Markush DARC MPHARM = pharmsearch Markush file, produced by INPI WPIM = world patents index Markush file. 

Chemical structures in patents fall broadly into two types specific compounds and Markush structures. The term Markush Structure refers to a generic structure that appears in patent claims, and typically encompasses a broad family of potential compounds well beyond any specific compounds named or exemplified in the patent. Thus, Markush structures in patents contain prophetic material, but this material can be used as prior art against others. Therefore, the indexing and searching of Markush chemical structures in patents is extremely important. The patent offices from all major countries and patent issuing authorities (e.g., the European Patent Office) recognize Markush claims as patentable material. 

A significant problem in the universe of Markush chemical structures is the matter of extreme complexity. Markush chemical representations leave room for ambiguity, and often extremely complex Markush structures are created that become very difficult for Markush database producers to code. Additionally, the scope of these Markush claims can be excessively broad, making establishment of the prior art essentially impossible to determine for purposes of a meaningful and defensible patent examination. Sibley has commented most eloquently on this subject, as have others. " ... 

Computational methods described in this work are tested using a tripeptoid combinatorial library described by Zuckermann et al. (35). These authors described chemical structures of 24 amines used as building blocks for the pep-toid synthesis. The common Markush structure of tripeptoids is shown in Fig. 3 where R1, R2, and R3 are the alkyl portions of primary amines used as building blocks. The structures of the building blocks are shown in Fig. 4 and we followed the abbreviations used in the original publication. 

In practice, where a chemical structure is claimed according to a Markush format, the variable descriptors at each position of the molecule will almost always (if not always) be read in a closed fashion unless the implication is clearly otherwise. To leave a molecule truly open at any single position might allow for an infinite set of molecules to be generated. Where the compound is an object of the claim, an infinite set of potential molecules is likely to draw a rejection for failure to satisfy the written description and enablement requirements of 112 1, to be discussed in Chapter 9. 

Figure 9.6. Chemical structure data for high-throughput chemistry. The generic structure representation is often referred to as a Markush structure.

Anon. Markush or Generic Structures. J. Chem. Inf. Comput. Sci. 1991 31(1) 1. A brief summary of the conceptual basis of generic chemical structures in patents and the terminology used in discussing it. Written as an introduction to a special issue of the journal devoted to the use of Markush structures in the patent literature and the databases that allow searching of Markush structures. 

Berks AH. Current State of the Art of Markush Topological Search Systems. World Patent Inf. 2001 23(19) 5-13. A review of the databases offering topological searching of chemical structures from patents, the indexing, coverage, and searchability of the Markush structures. 

Markush structures follow a similar approach. They were named after Eugene Markush, who used these structures to include them in a U.S. patent in the 1920s (U.S. Patent 1506316). In general, a Markush structure is a chemical structure with multiple functionally equivalent chemical entities (residues) allowed in one or more parts of the compound. Residues are structure fragments of not fully defined structures. The knowledge of these structure fragments is important to the analyst in evaluating a reaction path or a metabolic pathway. 

Markush Structure is a chemical structure with multiple functionally equivalent chemical entities (i.e., residues) allowed in one or more parts of the compound. Markush structures are a specific instance of generic structures. 

On this basis, the structure we have used for our example can be analyzed in the manner described to produce a series of three short codes, which describe not only this molecule, but also any nongeminal combination of the two substituents around the ring (see Figure 5). This is a really a similarity search in chemical structures, a capability which is complementary to a substructure search, and has some relevance for certain types of Markush representation- A brief inspection of the "chemical environment" of any randomly chosen region of ca. 30 pages of the Handbook will demonstrate the strengths and limitations of this approach. 

CAS will develop workstation software to build the Markush structures for a new Patent Service. The graphics software for building chemical structures could, ideally, also be used to build structure queries for STN International, connection tables for registration, and an image that is the appropriate quality for ACS publications ... 

Lynch, M.F. Generic Chemical Structures in Patents (Markush Structures) the Research Project at the University of Sheffield . World Patent Information 1986, 8, 85-91. 

CD/ChemSketch is a freeware for drawing chemical structures including organics, organometallics, polymers, and Markush stmctures [31]. It has options for structure cleaning, viewing and naming, inch conversion, stereo descriptors etc. For freeware, no technical support is provided and the functionalities are less compared to the commercial version which has structure search capabilities (Fig. 1.5). 

Several computational methods for generating large databases of chemically reasonable structures (virtual libraries) have been developed. They employ strategies such as the mutation of text strings representing chemical structures, the expansion of Markush structural representations, or virtual combinatorial libraries derived by exhaustive enumeration of all substituent variations at specific points on a core scaffold. An example of these large virtual libraries is the ChemSpace database, containing approx 10 trillion chemical structures for use in similarity and pharmacophore searches, approx 500,000 times more than all the compounds in Chemical Abstracts. 

Suhr, C von Harsdorf, E. Dethlefsen, W. Derwent s CPI and IDC s GREMAS Remarks on their Relative Retrieval Power with Regard to Markush Structures . In Proceedings of a Conference organised by the Chemic Structure Association at the University of Sheffield, England, 26-29 March 1984. 

Under Substances, search options include chemical structures, molecular formulas, and properties. Chemical structures may be searched as exact matches, substructures, and similarity matches. Exact matches will include enantiomers, stereoisomers, radicals, salts, and the like. These results can be filtered once the search is complete. Substructure matches allow substitution at any positions not specifically blocked. A similarity search is the broadest category. If an exact search doesn t result in sufficient matches, a substructure search may yield results. Markush searching is also available. Markush structures are found in the patent... 

W. Fisanick, Requirements for a System for Storage and Search of Markush Structures in Computer Handling of Generic Chemical Structures , eds. J. M. Barnard, Gower, Aldershot, UK, 1984, pp. 106-129. 

The IFI Comprehensive (CDB) code currently in use was created in 1972 by the merger of a DuPont coding system that commenced indexing of US patents in 1964, and an IFI code that began coding chemical structures in US patents in 1950. Most of the Markush codes in the present CDB are from the DuPont system, so the Markush backfile really only dates to 1964. Earlier coverage from the IFI system was limited to specific compounds and general terms. The IFI code is still... 

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