Introducing Negative Limitations in Pharmaceutical Patents

Pharmaceutical patents fall under the following International Patent Classification (IPC) codes A61K, A61P, C07C, and C07D. The claim drafting involves carefully capturing and wording the unique features of the invention without encroaching others IP space. The negative limitations are used to elicit an invention to bypass an already existing one. The commonly used negative limitations in the claim languages are “without”, “excepting”, “excluding”, etc. The US patent law permits the use of negative limitations in a claim provided their usage won’t make the claim language too broad or indefinite or unclear. In pharmaceutical patents to override a prior art compound, it is easier to capture a single structure showing a derivative than a Markush structure, which is a representation of a group of related chemical structures. So, how to represent these structures using Markush but still eliminate a subset of structures from the parent backbone to define negative limitations? In order to understand this, let us first look at a Markush structure from the following example, US 10,214,498 B2. For the compound disclosed, ring A, X, and R are the variables that can carry any substituents and the variables are listed in the claim and most importantly anything that is not listed here are not claimed for this backbone structure or it has been previously claimed. Any restrictions on the limit to which one can claim?

Let us analyse few examples by taking a closer look. In the application, 3924/DELNP/2010, Markush structure was claimed for Somatostatin analogue and interestingly, “excluding indole” was also included in the claim language. In the First Examination Report (FER), the Examiner had raised objections by citing the prior art, WO 97/01579, of Somatostatin. The applicant argument was by excluding Indole , which was considered as one of the key determinants for the activity of Somatostatin, a novel analogue with interesting property and therapeutically more effective compound was discovered. This application was eventually granted, but what was striking is that the applicant could have listed only aromatic groups for R1 instead of including a negative limitation (“excluding indole”), but by doing so they have overcome the prior art and explicitly showcased the unique feature of the invention.

In another interesting case, IN201837029189 involving Dolastatin 10, by excluding two sets of cases, (X=NH; Y=NH2, and X=NH; Y=N(Me)H), the other possibilities were captured as shown in Claim 1 below. Here use of excluding is justifiable as it is easier to exclude specific smaller set of compounds than broader set of compounds, which would otherwise make the claim language broader . Similarly, application IN201747009599, involves claiming broader set of compounds but excluding specific structures listed in the application (space constraint, please see application).

In essence, negative limitations can be used as a two way switch either by claiming through appropriately placed Markush elements or by explicitly using the word “exclude” to eliminate compounds and thereby override prior art citations.