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What is the true import of section 3(d) of the Patents Act, 1970? How does it interplay with clauses (j) and (ja) of section 2(1)? Does the product for which the appellant claims patent qualify as a "new product" which comes by through an invention that has a feature that involves technical advance over the existing knowledge and that makes the invention "not obvious" to a person skilled in the art?

We are clearly of the view that the importance of the amendment made in section 3(d), that is, the addition of the opening words in the substantive provision and the insertion of explanation to the substantive provision, cannot be under-estimated. It is seen above that, in course of the Parliamentary debates, the amendment in  section 3(d) was the only provision cited by the Government to allay the fears of the Opposition members concerning the abuses to which a product patent in medicines may be vulnerable. We have, therefore, no doubt that the amendment/addition made in section 3(d) is meant especially to deal with chemical substances, and more particularly pharmaceutical products. The amended portion of  section 3(d) clearly sets up a second tier of qualifying standards for chemical substances/pharmaceutical products in order to leave the door open for true and genuine inventions but, at the same time, to check any attempt at repetitive patenting or extension of the patent term on spurious grounds.

We have so far seen section 3(d) as representing "patentability", a concept distinct and separate from "invention". But if clause (d) is isolated from the rest of section 3, and the legislative history behind the incorporation of Chapter II in the Patents act, 1970, is disregarded, then it is possible to see section 3(d) as an extension of the definition of "invention" and to link section 3(d) with clauses (j) and (ja) of  section 2(1). In that case, on reading clauses (j) and (ja) of  section 2(1) with section 3(d) it would appear that the Act sets different standards for qualifying as "inventions" things belonging to different classes, and for medicines and drugs and other chemical substances, the Act sets the invention threshold further higher, by virtue of the amendments made in section 3(d) in the year 2005.

Admittedly, the genesis of this patent application lies in one of the derivatives of N-phenyl-2- pyrimidine-amine in free base called Imatinib[30], vide example 21 of the Zimmermann patent. According to the appellant, beginning with Imatinib, the subject product, i.e., Imatinib Mesylate in beta crystalline form, was brought to being by not one but two inventions.

The first invention lies in selecting example 21 out of the 37 examples given in the Zimmermann patent and then choosing methanesulfonic acid to produce the methanesulfonic acid addition salt of the free base Imatinib, called Imatinib Mesylate. It was emphasized by both Mr. Gopal Subramanium and Mr. Andhyarujina, Senior Advocates appearing for the appellant, that the Zimmermann patent did not teach or suggest to a person skilled in the art to select example 21 in preference to other compounds of which examples were given in the Zimmermann patent. Further, even if example 21 was selected, the Zimmermann patent did not teach a person to select one particular salt. The Zimmermann patent did not teach a person how to prepare Mesylate salt of example 21. Hence, the coming into being of Imatinib Mesylate from Imatinib in free base was the result of an invention that involved technical advance as compared to the existing knowledge and brought into existence a new substance.

In the second invention, the appellant arrived at the beta crystal form of methanesulfonic acid addition salt of Imatinib. It was contended on behalf of the appellant that once the salt form of Imatinib was arrived at, the inventors had to further research to be able to ensure that that particular salt form of Imatinib is suitable for administration in a solid oral dosage form. This research further required defining the process parameters that brought into being the beta crystalline form of Imatinib Mesylate. It was argued on behalf of the appellant that there is certainly no mention of polymorphism or crystalline structure in the Zimmermann patent. The relevant crystalline form of the salt that was synthesized needed to be invented. There was no way of predicting that the beta crystalline form of Imatinib Mesylate would possess the characteristics that would make it orally administrable to humans without going through the inventive steps. It was further argued that the Zimmermann patent only described, at most, how to prepare Imatinib free base, and that this free base would have anti-tumour properties with respect to the BCR ABL kinase. Thus, arriving at the beta-crystalline form of Imatinib Mesylate for a viable treatment of Chronic Myeloid Leukemia required further invention - not one but two, starting from Imatinib in free base form, as stated above.

The subject product admittedly emerges from the Zimmermann patent. Hence, in order to test the correctness of the claim made on behalf of the appellant, that the subject product is brought into being through inventive research, we need to examine in some detail the Zimmermann patent and certain developments that took place on that basis

An application for grant of patent for the Zimmermann invention (Pyrimidine Derivatives and Processes for the Preparation thereof) was filed in the United States of America on April 2, 1993, by Ciba Geigy[31] (US Patent Application No. 08/042,322). This application was abandoned and another continuation-in-part application was then filed on April 28, 1994 (US Patent Application No. 5,521,184). The Zimmermann invention[32] related to N-phenyl-2-pyrimidine-amine derivatives (called, "formula I" in the patent application), and the compounds thereof, the process for their preparation, and to their therapeutic uses. In the patent application, it was expressly stated that the compounds of formula I included their respective salts:

"Salt-forming groups in a compound of formula I are groups or radicals having basic or acidic properties. Compounds having at least one basic group or at least one basic radical, for example a free amino group, a pyrazinyl radical or a pyridyl radical, may form acid addition salts, for example with inorganic acids, such as hydrochloric acid, sulfuric acid or a phosphoric acid, or with suitable organic carboxylic or sulfonic acids…" Further:

"Owing to the close relationship between the novel compounds in free form and in the form of their salts, including those salts that can be used as intermediates, for example in the purification of the novel compounds or for the identification thereof, hereinbefore and hereinafter any reference to the free compounds should be understood as including the corresponding salts, where appropriate and expedient." (emphasis added)

In the claim at the end of the application under serial no. 23, it was stated as follows:

"The compound according to claim 1 of the formula I, said compound being N-{5-[4-(4-Methyl-piperazino-methyl)-benzoylamido]-2-methyl- phenyl}-4-(3-pyridyl)-2-pyrimidine-amine or a pharmaceutically acceptable salt thereof." (emphasis added)

The US Patent No. 5,521,184 (the Zimmermann patent) was granted on May 28, 1996.

Later, the appellant made the application for patent for beta crystalline form of Imatinib Mesylate (the subject of the present appeals) in the US on January 18, 2000. The US patent for beta crystalline form of Imatinib Mesylate was granted to the appellant about five and a half years later on May 17, 2005 following the order of the US Appellate Court dated November 23, 2003. It is, however, interesting to note that Gleevec, the drug was launched much earlier in the market, on the basis of the Zimmermann patent itself.

116. On April 9, 1998, the appellant filed the Investigational New Drug Application (IND # 55,666) for Gleevec and on February 27, 2001, the original New Drug Application (NDA # 21-335) before the Food and Drug Administration (FDA), USA, for Imatinib Mesylate, formerly STI571, CGP57148B (capsules) for the treatment of patients with Chronic Myeloid Leukemia. The application contained results of extensive preclinical, technical and clinical research, and it stated as under:

"The clinical studies discussed in this NDA include one multiple dose tolerability/dose-finding study (phase I) and three large open, uncontrolled efficacy and safety studies (phase II), as an accelerated development to allow early registration in CML patients. A total of 1234 patients with CML and other Ph+ leukemias have been enrolled in these trials. The results of the Glivec studies are discussed in the perspective of the current state of knowledge in the treatment of CML as described with a comprehensive review of the literature for each target population (Appendix 4-6 of the Integrated Summary of Efficacy)."

117. In the patent information furnished in connection with the NDA as required under (US Code) 21 C.F.R. § 314.53, the active ingredient of the drug was stated as Imatinib Mesylate. The Drug Substance[33] (active ingredient), Drug Product[34] (composition/formulation) and method of use were declared to be covered by US Patent No. 5,521,184 (i.e. the Zimmermann patent). It was further declared that the United States Patent No. 5,521,184 covered the composition, formulation, and/or method of use of Imatinib Mesylate (STI571).

118. In the chemistry review(s) of the NDA # 21-335 (drug approval for capsules) made on March 27, 2001, there was again a reference to US Patent # 5,521,184 (expiration date - 5/28/2013).

119. The FDA approval for the drug Gleevec (Imatinib Mesylate) 50 mg and 100 mg capsules was granted vide Letter dated May 10, 2001.[35] Following this, the drug was commercially launched in the market long before the grant of patent for beta crystalline form of Imatinib Mesylate.

120. In the package insert of Gleevecâ„¢ (Imatinib Mesylate capsules) the description of the drug was stated as follows:

"GLEEVEC™ capsules contain imatinib mesylate equivalent to 100 mg of imatinib free base. Imatinib mesylate is designed chemically as 4-[(4- Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl]amino]-phenyl]benzamide methanesulfonate…"

121. After the grant of drug approval for Gleevec, on July 3, 2001, the appellant made a Patent Term Extension Application for the Zimmermann patent (US Patent No. 5,521,184) under 35 USC § 156(g)(1)(B), for extending the term of the patent for the time taken in the regulatory review for Gleevec. This application leaves no room for doubt that Imatinib Mesylate, marketed under the name Gleevec, was submitted for drug approval as covered by the Zimmermann patent. In column 4 of the application, it was stated that the sole active ingredient in Gleevec is Imatinib Mesylate. Further, it was stated that Imatinib, or any salt thereof, including Imatinib Mesylate, had not previously been approved for commercial marketing under the Federal Food, Drug and Cosmetic Act prior to the approval of NDA # 21-

235. In column 9 of the application, it was stated as under:

"(9) Statement Showing How the Claims of the Patent for Which Extension is Sought Cover the Approved Product:

The operative claims in question are Claims 1-5, 10-13, and 21-23. Each of claims 1-5, 10-13 and 23 claim a compound or compounds which include the approved product, imatinib mesylate. Claim 21 claims a composition containing a compound or compounds which include the approved product, imatinib mesylate. Claim 22 claims a method of treating tumors in warm-blooded animals with a compound or compounds which include the approved product, imatinib mesylate."

122. The application was accepted and the term of the patent, which was due to expire on May 28, 2013, was extended for the period of 586 days.

123. It is noted above that the appellant had made an application no. 09/463,097 in the USA for grant of patent for beta crystalline form of Imatinib Mesylate. The application was rejected by the examiner and, against the examiner's decision, the appellant preferred an appeal (that is, appeal no. 2003-0919) before the Board of Patent Appeals and Interferences. The Board of Patent Appeals, by its judgment and order dated November 23, 2003, allowed the appellant's appeal and reversed the examiner's decision, rejecting claims 1 through 8, 10, and 13 through 16. Dealing with the examiner's rejection of appellant's claim 14 under 35 USC § 112, the Board of Patent Appeals referred to claims 21 and 22 of the Zimmermann patent. With reference to those claims in the Zimmermann patent, the Board of Patent Appeals observed and held as under:

"Under the provisions 35 U.S.C. § 282, a patent shall be presumed valid; and each claim of a patent shall be presumed valid independently of the validity of other claims.

Accordingly, claims 21 and 22 of the U.S. Patent No.5,521,184 (the Zimmermann patent), shall be presumed valid. We may presume, therefore, that claims 21 and 22 are based on an enabling disclosure; and that the specification of the Zimmermann patent teaches any person skilled in the art how to use a compound of formula I, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition for treating tumours or in a method of treating warm-blooded animals suffering from a tumoral disease. In claim 23, Zimmermann recites imatinib, a specific compound within the scope of formula I, or a pharmaceutically acceptable salt thereof. In light of 35 U.S.C. § 282, therefore, we may presume that the specification of the Zimmermann patent teaches any person skilled in the art how to use imatinib, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition for treating tumours or in a method of treating warm-blooded animals suffering from a tumoral disease. On these facts, we disagree that the examiner has set forth adequate reasons or evidence to doubt the objective truth of statements in applicants' specification that an effective amount of the ß-crystal form of imatinib mesylate may be administered to a patient as the manipulative step in a method for treating tumour disease in a patient.

The rejection under 35 U.S.C. § 112, first paragraph, is reversed." (emphasis added)

124. From the above passage from the judgment, it is evident that, according to the Board of Patent Appeals, the Zimmermann patent teaches any person skilled in the art how to use Imatinib, a compound of formula I, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition for treating tumours or in a method of treating warm-blooded animals suffering from a tumoral disease. However, the Board of Patent Appeals held that the teaching in the Zimmermann patent did not go beyond Imatinib Mesylate and did not extend to beta crystalline form of Imatinib Mesylate, which represented a manipulative step[36] in a method of treating tumor disease in a patient.

125. Further, NATCO Pharma Ltd., one of the Objectors to the grant of patent to the appellant in this country, had marketed a drug called VEENAT 100 (capsules) in the UK. A legal notice on behalf of the appellant was given to NATCO Pharma Ltd. on February 13, 2004. The notice stated that the appellant was the proprietor of European patent EP-A- 0 564 409 (the Zimmermann patent) and that this patent claimed, among other things, the compound Imatinib and acid addition salts of that compound such as the Mesylate salt. In the notice it was pointed out that NATCO Pharma Ltd. was selling, in the UK market, VEENAT 100 capsules, the active pharmaceutical ingredient of which was Imatinib Mesylate as claimed in the Zimmermann patent. The importation, sale and offer to sell VEENAT 100 capsules in the UK market infringed the Zimmermann patent and NATCO Pharma Ltd. was therefore warned to immediately cease the importation, sale and promotion of VEENAT 100 capsules and other pharmaceutically substances containing "Imatinib". The matter was finally settled out of court, we are told, at considerable expense to NATCO Pharma Ltd. which of course had to stop marketing its drug VEENAT 100 capsules in the UK.

126. From the above discussion it would be clear that the drug Gleevec directly emanates from the Zimmermann patent and comes to the market for commercial sale. Since the grant of the Zimmermann patent, the appellant has maintained that Gleevec (that is, Imatinib Mesylate) is part of the Zimmermann patent. It obtained drug approval for Gleevec on that basis. It claimed extension of the term of the Zimmermann patent for the period of regulatory review for Gleevec, and it successfully stopped NATCO Pharma Ltd. from marketing its drug in the UK on the basis of the Zimmermann patent. Not only the appellant but the US Board of Patent Appeals, in its judgment granting patent for beta crystalline form of Imatinib Mesylate, proceeded on the basis that though the beta crystal form might not have been covered by the Zimmermann patent, the Zimmermann patent had the teaching for the making of Imatinib Mesylate from Imatinib, and for its use in a pharmacological compositions for treating tumours or in a method of treating warm-blooded animals suffering from a tumoral disease. This finding was recorded by the US Board of Patent Appeals, in the case of the appellant itself, on the very same issue that is now under consideration. The appellant is, therefore, fully bound by the finding and cannot be heard to take any contrary plea.

127. We have looked, so far, at the Zimmermann patent and the developments that have taken place on its basis. We now propose to take a look at certain publications. A journal called Cancer Research, in its issue of January 1996, published an article under the title "Inhibition of the Abl Protein-Tyrosine Kinase in Vitro and in Vivo by a 2-Phenylaminopyrimidine Derivative". This article was authored by several people, including Jürg Zimmermann. In this article there is a detailed discussion about the anti- tumoral properties of Imatinib and its methanesulfonate salt, i.e., Imatinib Mesylate. In the abstract at the beginning of the article, it is stated as under:

"ABSTRACT Oncogenic activation of Abl proteins due to structural modifications can occur as a result of viral transduction or chromosomal translocation. The tyrosine protein kinase activity of oncogenic Abl proteins is known to be essential for their transforming activity. Therefore, we have attempted to identify selective inhibitors of the Abl tyrosine protein kinase. Herein we describe an inhibitor (CGP 57148[37]) of the Abl and platelet-derived growth factor (PDGF) receptor protein-tyrosine kinases from the 2-phenylaminopyrimidine class, which is highly active in vitro and in vivo. Submicromolar concentrations of the compound inhibited both v-Abl and PDGF receptor autophosphorylation and PDGF-induced c-fos mRNA expression selectively in intact cells. … Furthermore, anchorage-independent growth of v-abl- and v-sis-transformed BALB/c 3T3 cells was inhibited potently by CGP 57148. When tested in vivo, CGP 57148 showed antitumor activity at tolerated doses against tumorigenic v-abl- and v-sis- transformed BALB/c 3T3 cells. In contrast, CGP 57148 had no antitumor activity when tested using src-transformed BALB/c 3T3 cells. These findings suggest that CGP 57148 may have therapeutic potential for the treatment of diseases that involve abnormal cellular proliferation induced by Abl protein-tyrosine kinase deregulation or PDGF receptor activation." (emphasis added)

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