Markush Structures

When you're sitting there with your chemistry book open and are staring at the examples of reactions, ever wonder why they use that generic form for the molecule? You know, the one that gives you an R-group instead of something specific. Well, those are called Markush structures; they have quite a history, dating back to the 1920s.

First, a definition for reference: A Markush structure is a structure that denotes a substance or substituent, agent, reactant, or other material that is described as being from a group consisting of certain specified materials. Specified structures can be an element, a chemical structure, a functional group, a class of chemical structures (e.g., alkyls, aryls, etc), or a class of functional groups (e.g., esters, alcohols, carboxylic acids, etc).

In 1924, Eugene A. Markush filed a patent for the preparation of a powder dye with its base compound pyrazolone, which could be used to dye wool and silk in an acid bath. The structure groups he specified in his now famous patent claim, however, were generalized and used to make claim to many variations of the pyralozone structure. He designed his patent claim in such a way so he could avoid having to file an individual patent for every variation he made.

As a result for filing such a patent the United States Patent and Trademark Office challenged it for not being specific enough. For being too vague of a structure. After much appeals and court cases by different parties, the issue had gone to court in 1935, 1938, 1947, 1970. Finally, in 1978, in the case of Horst Hornisch vs. the United States Patent and Trademark Office in the U.S. Court of Customs and Patent Appeals, the original rejection was reversed and Markush structures became patentable.

Markush claims are now legal and patentable.

A Markush Claim is a form of claim that allows claiming of members of a finite group by means of a phrase like “...a member of the class consisting of...” followed by a list of members of the group linked by the word “and”. The members of a Markush group must have at least one property that is mainly responsible for their membership in the group.

The claiming of a Markush Group means reciting “selected from the group consisting of...” This statement creates a limited type of generic claim. To be permitted, the members of the designated group must have at least one property in common which is primarily responsible for their function in the claimed relationsihp.

An example is if we have:

The values of filing Markush structures in patents is that a number of different compounds can be desribed in a single claim. There is no need to file a patent for every compound that you want to lay claim to. Similar compounds are covered under a single patent claim.

An example of how to determine the number of possible structures you can lay claim to is as follows:

Suppose we have 4 compounds:

We want to make the same structure from the Markush structure, so we lay claim to ___ where, based on the 4 above structures, Rn represent:

R-Group	Group	# of Groups
R1	H, F, Cl	3
R2	H, Cl	2
R3	H, Cl, F	3
R4	H	1
R5	H	1
R6	H, F	2

We multiply all the types of compounds: 3x2x3x1x1x2 = 36.

We therefore have 36 different compounds we have laid claim to. The 4 original compounds, and 32 different combinations consisting of the listed groups. All can be filed as patents (assuming all laid claim to are neither naturally occuring or already patented).

So the next time you see a molecule with an R-group attached, you will know that that compound is a Markush structure, and that a lot of patent claims, and legal court battles have occurred to make that little group important contributor to chemical and pharmaceutical discovery.