Bristol-Myers Squibb Holdings Ireland Unlimited Company v BDR Pharmaceuticals International Pvt Ltd (2020)

Summary

“Plaintiff No.1 is the owner of the suit patent titled as ‘Lactam-Containing Compounds and Derivatives Thereof as Factor Xa Inhibitors’ and has been granted the Indian Patent No.247381” ... “The suit patent would expire on 17th September, 2022.” (para 3) “The suit patent specifically describes and covers a molecule having an International Non-Proprietary Name (INN) APIXABAN” ... “It is used for the prevention and treatment of thromboembolic diseases.” (para 5) “On 18th January, 2020 the plaintiffs through their credible sources received information that the defendants participated in a tender floated by Diesel Locomotive Works (DLW) regarding APIXABAN 2.5 mg.” (para 8) The defendant handed over “nine documents including a revocation petition filed in December, 2019” (para 2), and “the challenge to the suit patent in the course of arguments is based not on anticipation but on obviousness.” (para 29)

Noting that “no such expert evidence has been placed on record much less on an affidavit”, the Court proceeded “to examine the contentions urged by learned counsel for the defendants to ascertain whether defendants have made out a case for revocation of the suit patent” (para 27). It held that “in case prior art document show a concept of teaching away from the inventive step, the said prior art document cannot be used to demonstrate that the invention is obvious” (para 38), that “in most of the documents there are teachings away from lactam ring much less a terminal lactam” (para 37), and that “no drug came out of IN-917” (“IN 243917”) “and the first marketable drug came pursuant to the suit patent IN-381” (“Indian Patent No.247381”) “which itself is sufficient to show enhanced efficacy.” (paras 3, 7, 45) “Consequently, an ad-interim injunction is granted in favour of the plaintiffs and against the defendants in terms of prayer ‘A’ of Para 17 of the application.” (para 47)

What the court decided

1. Procedure. Invalidity at the interlocutory stage. “Since extensive arguments were addressed and number of documents were relied upon by learned counsel for the defendants despite the fact that this Court in Strix Limited (supra) held that even at an interlocutory stage the defendant will have to place on record some acceptable scientific material, supported and explained by evidence of an expert that the plaintiff’s patent is prima facie vulnerable to revocation and no such expert evidence has been placed on record much less on an affidavit, this Court is proceeding to examine the contentions urged by learned counsel for the defendants to ascertain whether defendants have made out a case for revocation of the suit patent and in the light thereof whether the triple test laid down for grant of injunction i.e. a prima facie case, irreparable loss and balance of convenience is satisfied or not.” (para 27)
2. Principles on obviousness. After reviewing Cipla v F Hoffmann-La Roche (2015) and foreign decisions, the Court held: “From the judgments as noted above, some of the principles which govern the field to find out whether an invention is obvious or not can be summed up as under:-” “(i) A hindsight reconstruction by using the patent in question as a guide through the maze of prior art references in the right way so as to achieve the result of the claim in the suit, is required to be avoided.” “(ii) The patent challenger must demonstrate the selection of a lead compound based on its promising useful properties and not a hindsight driven search for structurally similar compounds.” “(iii) There should be no teachings away from the patent in question in the prior art.” “(iv) Mere structural similarity cannot form the basis of selection of lead compound in a prior art and the structural similarity in the prior art document must give reason or motivation to make the claim composition.” “(v) Though mosaic of prior art documents may be done in order to claim obviousness, however, in doing so, the party claiming obviousness must be able to demonstrate not only the prior art exists but how the person of ordinary skill in the art would have been led to combine the relevant components from the mosaic of prior art.” “(vi) It has to be borne in mind, small changes in structures can have unpredictable pharmacological effects and thus, structural similarity alone is not sufficient to motivate to selection of the lead compound.” “(vii) Though it would be tempting to put together a combination of prior arts but this requires a significant degree of hindsight, both in selection of relevant disclosures from these documents and also in disregarding the irrelevant or unhelpful teachings in them.” (para 36)
3. The mosaic applied. “Even accepting the fact that for a person ordinarily skilled in the art of average intelligence, publications prior to the prior art were known to him, in most of the documents there are teachings away from lactam ring much less a terminal lactam and even by mosaicing the relevant documents by an unimaginative man with no inventive capacity they do not lead to the suit patent being obvious.” (para 37)
4. Teaching away. “As noted above, it is thus well settled that in case prior art document show a concept of teaching away from the inventive step, the said prior art document cannot be used to demonstrate that the invention is obvious and thus not liable to be patented.” Of the Tamura publication: “this publication would give motivation to work on compound 5 with least IC value, hence most favourable, however the said compound clearly has teachings away from APIXABAN which has hydrogen therein.” (para 38)
5. Thrombin inhibitor publications. “Even the publications by Philip E. Sanderson and L. Leblond, et al, do not show prior teachings for the reason the same are not based on factor Xa inhibitors but on thrombin inhibitors. None of the compounds stated in the publication by Philip E.J. Sanderson use a lactam ring much less a terminal lactam.” (para 38) “Contention of learned counsel for the defendants that the suit patent specifications also notes thrombin inhibitors ignores the fact that the claim of the plaintiffs in IN ‘381” (“Indian Patent No.247381”) “is based on factor Xa inhibitor even though in the document thrombin inhibitors may be noted.” (paras 3, 38, 42)
6. The Bayer patent. “Hence, this compound made from Example 17 of CA 2396561 does not give a motivation for making a compound with the lactam ring and the best Example being 127 which has the least IC value being 0.0007 does not have a lactam ring on the left side but a morphalenone moiety. The claim in this patent of Bayer Healthcare AG, DE uses an oxygen atom in the ring which is thus not a lactam ring. Further, none of the 254 examples in the said claim has a lactam ring much less a terminal lactam ring” (para 39)
7. The COR Therapeutics application. “In the PCT application No. WO 98/16523 relied upon by learned counsel for the defendant, the invention relates to selective factor Xa inhibitors from peptide and peptide mimetic analogs, their isomers, salts, hydrates, solvates, etc. and has no teachings qua APIXABAN. This application by COR THERAPEUTICS. INC. US was for factor Xa inhibitors, wherein the lactam ring is a central lactam ring and not a terminal lactam ring” (para 40)
8. Example 99 of the earlier patent. Of IN-917 (“IN 243917”), the Court held: “The defendant’s argument is also based on the revocation petition filed in December, 2019 wherein it is claimed that Example 99 of IN ‘917 is close to APIXABAN. However, as noted above, prior art documents show teachings away from removal of hydrogen. Besides there are fundamental differences in Example 99 and APIXABAN.” (paras 7, 41)
9. Section 3(d). To the contention that “the suit patent IN-381 does not demonstrate an enhanced efficacy as required under Section 3(d) of the Patents Act” (para 43), the Court held: “This Court has already noted that no drug came out of IN-917 and the first marketable drug came pursuant to the suit patent IN-381 which itself is sufficient to show enhanced efficacy.” (paras 43, 45)
10. Procedure. Ramrameshwari Devi. “In the present case, the defendants have been heard extensively before granting ad interim injunction.” “The decision of the Supreme Court thus does not apply to the facts of this case as no material has been shown at the moment to show that false, fabricated or manipulated proceeding are instituted by the plaintiffs against the defendants.” (para 46)
11. The triple test. “Consequently, the defendant admitting tendering and intending to sell the plaintiff’s drugs APIXABAN thereby amounting to infringing the plaintiff’s suit patent, the plaintiff has made out a prima facie case, as the suit patent on the basis of the prior art documents relied upon is not amenable to revocation for being obvious.” Relying on Merck Sharp and Dohme v Glenmark (2015): “In case no interim injunction is granted, the plaintiffs would suffer an irreparable loss as held by the Division Bench of this Court” ... “The balance of convenience also lies in favour of the plaintiffs and against the defendants as the defendants have not commercially sold APIXABAN in the open market as yet but has only filed tenders for the same.” (para 47)
12. Procedure. Disposition. “Consequently, an ad-interim injunction is granted in favour of the plaintiffs and against the defendants in terms of prayer ‘A’ of Para 17 of the application.” (para 47) “Reply affidavit to the application be filed within three weeks. Rejoinder affidavit in two weeks thereafter.” “List the application before Court on 31st March, 2020.” (paras 47–49)

Subsequent treatment

• Followed — In Bristol-Myers Squibb Ireland Unlimited Company v Micro Labs Limited (16 August 2021) the Delhi High Court listed this order among the earlier interim orders passed on the same patent (paras 5, 27) and granted an ex parte ad interim injunction against another generic apixaban (para 36).