Intrathecal dose not obvious

Ex Parte Thakker, 2019 Pat. App. Lexis 9512 (PTAB 2019) shows how a teaching away in the prior art can overcome an examiner’s routine optimization rejection of a dosing claim.  The inventors in Ex Parte Thakker had discovered that low molecular weight molecules such as morphine can be transported to the brain in therapeutically effective concentrations via intrathecal administration at flow rates of less than 500 microliters (0.5 ml) per hour.  Claim 1 of the application recited:

1. A method comprising:

selecting a subject for which delivery of a therapeutic or diagnostic molecule to cerebrospinal fluid (CSF) of a brain is desired; and

administering a liquid formulation comprising the molecule to an CSF-containing intrathecal space of the subject at a flow rate of less than 500 microliters per hour, wherein the liquid formulation is administered for a period of time sufficient to reach a steady state concentration in CSF of the brain, and wherein the molecular weight of the molecule is less than 5 kDa, … and wherein the molecule is generally distributed throughout at least most of the CSF of the brain at therapeutically or diagnostically effective concentrations.

The Examiner rejected the claim because a prior art patent (“Heruth”) taught that morphine, which had a molecular weight less than 5 kDa, could be administered intrathecally.  Heruth did not teach the rate at which morphine should be administered to achieve distribution of the drug throughout the brain but, according to the Examiner, this rate could have been determined through routine optimization.   

However, the dosage rates disclosed by Heruth generally were much greater than the dosage rate recited in the claims. Heruth stated:

In variations on this method, the maximum infusion rate may be, e.g., no more than 25 ml per hour, no more than 10 ml per hour, no more than 5 ml per hour, or even potentially no more than 2 ml per hour

In addition, Heruth suggested that lower rates of administration would cause the drug to localize in the spinal column and not reach the brain.  Heruth stated:

if it is desirable to reach a variety of levels of a spinal column with drug, the flow rate with which the drug is delivered may be increased. . . . If it is desired to have a drug localized to a region around a particular level of the spinal column, the flow rate with which the drug is delivered may be decreased.

Based on this disclosure, the PTAB concluded:

Heruth therefore teaches that reduction of the flow rate results in localization of drug delivery, not a broad distribution in the CSF as taught by Appellant. This is a teaching away because it leads "in a direction divergent from the path that was taken by the applicant." (Citing and quoting In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994)).

The PTAB did not even discuss the Examiner’s routine optimization argument, relying entirely on this “teaching away” to support its decision.