Patent

Patent office rejects Tofacitinib patent application: An analysis [Part I]


On September 3, 2015, the Indian patent office rejected Pfizer’s Tofacitinib patent application 991/MUMNP/2003 second time around. The patent was rejected based on grounds of anticipation by prior claiming  and Section 3(d). I have divided this post into two parts to analyze the Controller’s decision. In part I, I analyze the anticipation ground and patentability of an enantiomer. Part II of the post examines the Section 3(d) rejection.[ 991/MUMNP/2003 DECISION]

Image from here

Image from here

Background:

Pfizer had filed a national phase patent application 991/MUMNP/2003 for its rheumatoid arthritis drug Tofacitinib (marketed as Xeljanz) on October 27, 2003. After examination, a first examination report(FER) was issued and the examiner rejected claims based on novelty over prior art D1(WO/0142246). In response to the FER, Pfizer submitted a response and amended claims. Since certain objections pertaining to Section 8 were still outstanding, the Controller offered the applicants a hearing. During hearing, the Controller raised a new ground of objection, Section 3(d) and the patent was rejected. Pfizer appealed the Controller’s decision and contended that the Controller had not raised the Section 3(d) objection in the FER or in the hearing notice and stated that the new ground was raised first time during the hearing, which was prejudicial to the applicant. The IPAB opined that the patent office had violated the principles of natural justice and set aside the order. The IPAB directed the patent office to reconsider the patent application.Pursuant to the IPAB Order, the Controller started examination of the ‘991 application.

What does prior art D1 exactly disclose?

Prior art D1 IN 241773 or WO/0142246: discloses 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d] pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile.

991/MUMNP/2003 or WO/02/096909: claims the enantiomer 3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d] pyrimidin-4-yl) amino] piperidin-1-yl]-3-oxopropanenitrile.

Prior art D1 DOES NOT disclose any specific enantiomers, it generically teaches that compounds have asymmetric centers and exist in different enantiomeric and diastereomeric forms. Relevant excerpt from specification states, “This invention relates to the use of all optical isomers and stereoisomers of the compounds of the present invention, and mixtures thereof, and to all pharmaceutical compositions and methods of treatment that may employ or contain them. In this regard, the invention includes both the E and Z configurations. The compounds of formula I may also exist as tautomers.

The present application 991/MUMNP/2003 claims an enantiomeric form of a compound disclosed in D1 WO/0142246 which was cited as prior art D1

Is the invention anticipated due to prior claiming :Section 13(1)(b)?

Present application 991/MUMNP/2003 or WO/02/096909 has a filing date of May 29,2002, claims a priority of May 31, 2001.

Prior art D1 IN 241773 or WO/0142246 was filed on November 23, 2000, claims a priority date of December 10,1999 and was published on June 14, 2001.

Although prior art D1 has an earlier priority and filing date than 991/MUMNP/2003, D1 was published after the priority date of present application 991/MUMNP/2003.

The applicants argued that because D1 was published after the priority date, it cannot qualify as prior art. See Section 11(8) (a).  However, the Controller rejected the applicant’s contention and instead cited Section 13(1)(b) i.e. anticipation by prior claiming. Section 13(1)(b) reads “the invention is claimed in any claim of any other complete specification published on or after the date of filing of the applicant’s complete specification, being a specification filed in pursuance of an application for a patent made in India and dated before or claiming the priority date earlier than that date”.

Further, the Controller opined that he did not find any “distinctive difference” between the present application 991/MUMNP/2003 claim and prior art D1 claim except for the fact that former is the enantiomer of the latter.

I believe that the Controller’s decision to reject claims based on anticipation by prior claiming is inaccurate, because in order for prior claiming to be applicable the prior art should exactly claim the same substance. It is appalling that the Controller believes that the enantiomer (Tofacitinib) is same as the compound in prior art D1 and there is no distinctive difference between them!

In order to understand the examiner’s objection, it is important to understand chirality and enantiomers. For the uninitiated, an object is chiral if it is distinguishable from its mirror image;i.e.it cannot be superposed onto it. Mirror image of an achiral object is indistinguishable from the object itself . A chiral object and its mirror image are called enantiomers.

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To draw a simple analogy , let us consider our hands. Our right and left hands are perfect examples of chiral objects.Since your left and right hands are non-superimposable mirror images, they can be called a pair of enantiomers. In the hand example, the right hand can be considered as the R-enantiomer and the left hand can be called the S-enantiomer and a mixture of equal amounts of left hand and right hands can be called a racemic mixture. Enantiomers differ from each and also differ from the racemate with respect to biological activity and in some cases the difference is vast.

For example, in case of a sleep aid drug called zopiclone which is a racemic mixture, enatiomers and racemates differ vastly in their activity.Eszopiclone the S- enantiomer is responsible for all the desired effects and the other R-enantiomer is virtually inactive; while an individual must take twice the dose of zopiclone(racemate) to achieve the same effect as they would receive from single dose of eszopiclone. Similarly, in case of Thalidomide, (R)-thalidomide is a sedative, whereas the (-) (S)-thalidomide is a teratogen.

So the Controller’s statements that he does not find any “distinctive difference” between the ‘991 application claim and prior art D1 claim is bizarre!  Prior art D1 is a racemic mixture whereas the ‘991 application claims the 3R,4R enantiomer. The controller further cited section 46(2) “a patent can be granted for a single invention only” and reasons that two patents cannot be granted for the same invention since the compound has been granted earlier. The Controller’s reasoning is flawed in this case  and prior claiming is not applicable because prior art D1 and the 991 application claim different things!

An enantiomer has novelty over its racemic mixture. For example, in re Williams a lack of novelty rejection was based on a prior art reference that disclosed the production of a compound having a formula identical to the claimed compound and the US court ruled that “the existence of a compound as an ingredient of another substance does not negative novelty in a claim to the pure compound

In part II of my post, I examine the Section 3(d) rejection.Click here to read Part II of this post.

Madhulika Vishwanathan

Madhulika Vishwanathan

Madhulika is a registered Indian patent agent and has completed her Master’s in Pharmacology from the Institute of Chemical Technology (ICT), Mumbai. Her interests include issues involving pharmaceutical and biotechnology patent law, regulatory aspects like Hatch Waxman litigation and antitrust law.She is currently working at law firm based out of Memphis, TN.

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