A Pill by Any Other Name Would Work As Neat

The title of the post, according to me, is the essence of the decision of the Indian Supreme Court in the Novartis case. I think the Supreme Court has done justice to the object of inclusion of Section 3(d) and has effectively sent out a very balanced positive (yes, not negative) message in the process- India does encourage genuine enterprise and innovation.

The Supreme Court has been pragmatic and careful enough to categorically draw an unequivocal distinction between “ever-greening” and “incremental innovation”, which is evident from the manner in which ever-greening was established in the facts of the case, and the following observation of the Court:

“191. We have held that the subject product, the beta crystalline form of Imatinib Mesylate, does not qualify the test of Section 3(d) of the Act but that is not to say that Section 3(d) bars patent protection for all incremental inventions of chemical and pharmaceutical substances. It will be a grave mistake to read this judgment to mean that section 3(d) was amended with the intent to undo the fundamental change brought in the patent regime by deletion of section 5 from the Parent Act. That is not said in this judgment.”

If there was any doubt about the status of incremental innovation under the Patents Act, 1970 (“Act”), this paragraph removes all such doubts/myths with abundant clarity. Therefore, there need not be any fear-mongering that the decision has shut the doors on incremental pharma innovation.

If anything, this decision has only clarified the position of the law by etching the contours of “efficacy” as envisaged in the Act, thereby reducing uncertainty to a fair extent, which is significant from a commercial standpoint. Lack of clarity in law leads to capricious application, and to the extent the Novartis decision “enhances known clarity” of the law, it is a positive development for all prospective patent applicants.

What is also to be critically noted is that, contrary to what is popularly assumed, the Supreme Court did not even take the blanket position that “enhanced bioavailability” cannot be used to satisfy the requirement of “enhanced efficacy” under Section 3(d). Here’s the relevant extract of the judgment which bears out my point:

“189. Thus, even if Mr. Grover’s submission is not taken into consideration on the question of bioavailability, the position that emerges is that just increased bioavailability alone may not necessarily lead to an enhancement of therapeutic efficacy. Whether or not an increase in bioavailability leads to an enhancement of therapeutic efficacy in any given case must be specifically claimed and established by research data. In this case, there is absolutely nothing on this score apart from the adroit submissions of the counsel. No material has been offered to indicate that the beta crystalline form of Imatinib Mesylate will produce an enhanced or superior efficacy (therapeutic) on molecular basis than what could be achieved with Imatinib free base in vivo animal model.

190. Thus, in whichever way section 3(d) may be viewed, whether as setting up the standards of “patentability” or as an extension of the definition of “invention”, it must be held that on the basis of the materials brought before this Court, the subject product, that is, the beta crystalline form of Imatinib Mesylate, fails the test of section 3(d), too, of the Act.”

It is evident that the finding with respect to absence of enhanced efficacy in the case was on the basis of the record of the case, rather lack of it, to establish enhanced efficacy. Had the patent applicant presented a co-relation between increased bioavailability and enhanced efficacy, which was supported by empirical evidence, nothing stops us from plausibly assuming that the Court would have ruled in its favour.

What is also surprising is that once the arguments before the Supreme Court commenced, surely Novartis would have sensed the mood of the Court, and realized that empirical data to prove the relationship between bio-availability and efficacy was absolutely necessary if its case was to have a decent chance of success. And yet, based on the contents of the judgment, it does not appear that there was any attempt to present any such data or scientific evidence. It is even more surprising considering that lack of data has been the primary flaw in the application right from the stage of opposition before the Patent Office.

Now, let’s look at a few other positives of the decision. The Novartis judgment, despite a few avoidable inconsistencies, is a fairly reasoned one, at least on critical issues such as Section 3(d). Also, contrary to what was expected by a cross-section of foreign investors, the decision does not take an anti-patent or anti-patentee stance. In fact, there is a clear message to protect genuine inventions using patents, and prevent subversion of the patent system, which is after all a re-statement of the stated goals of patent jurisprudence. Here’s the relevant observation of the Court:

“156. However, before leaving Hogan and proceeding further, we would like to say that in this country the law of patent, after the introduction of product patent for all kinds of substances in the patent regime, is in its infancy. We certainly do not wish the law of patent in this country to develop on lines where there may be a vast gap between the coverage and the disclosure under the patent; where the scope of the patent is determined not on the intrinsic worth of the invention but by the artful drafting of its claims by skilful lawyers, and where patents are traded as a commodity not for production and marketing of the patented products but to search for someone who may be sued for infringement of the patent.”

For a fledgling patent regime which is still exploring itself, setting out these first principles is important. One hopes that this sentiment percolates every level of the Indian Patent establishment, right from the Department of Industrial Policy and Promotion to the Indian Patent Office to the Intellectual Property Appellate Board and finally to Indian Courts.

A word of caution here would not be out of place- a few enthusiastic health professionals seem to be reacting to the decision of the Supreme Court with unmeasured glee and jubilance, thereby contributing to a situation where India is pitted against innovator drug companies. I don’t think such a situation is in the best interests of the country. India needs innovator companies which have solutions to the ever-growing list of life-threatening diseases, and equally needs the generic industry which has mastered the art of providing cost-effective access to drugs. Until such time the Indian industry is capable of confidently undertaking high-end drug development, it would help to observe a sense of restraint since the law has anyway proved its effectiveness.

Novartis Decision: Disclosure and its Nexus to Section 3(d)

In the Novartis case, the Supreme Court dealt with the law on disclosure and anticipation. This is because in order to apply Section 3(d) to the Glivec application, it was imperative to first prove that the beta crystalline form was a “new form of a known substance”. Therefore, whether there was a “known substance”, if yes, which was the “known substance” were to be answered as part of this enquiry.

Novartis took the position that the Imatinib free base must be treated as the “known substance” with reference to which the issue of enhanced efficacy must be addressed. According to Novartis, Imatinib Mesylate was not a known substance with respect to its application since there was no literature which enabled the manufacture of the mesylate salt. Therefore, the mesylate salt was not a known substance according to Novartis. This was the position adopted by the IPAB as well.

The Court, on the other hand, took the view that the Mesylate salt had been disclosed in the Zimmerman patent. In Paras 108-126, the Court has dealt with the specification of the Zimmerman patent (Column 3, Lines 21-65), and Novartis’s own application for term extension of the Zimmerman patent where it was stated thus:

“(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.”

Clearly, if one were to apply the infringement test to the Zimmerman patent, it becomes apparent that on the basis of the said patent Novartis could have prevented manufacture of the mesylate salt by a third party. And this is precisely what Novartis did with respect to NATCO’s VEENAT product, whose active ingredient was imatinib mesylate. From the decision, it appears that Novartis sent a legal notice to NATCO alleging infringement of its Zimmerman patent by VEENAT. If this be the case, then the mesylate salt is clearly disclosed and claimed in the Zimmerman patent.

Apart from these documents, the Court also placed reliance upon journal publications of 1996 by Novartis’s inventor Jurg Zimmerman wherein the mesylate salt had been disclosed.

To this, Novartis argued that these documents merely “covered”/mentioned the mesylate salt, but had not disclosed it. It was also submitted with respect to the Zimmerman patent that “claim defines through language the various ways the invention could be used, i.e., possible but not actualized products” and that the standard for disclosure was higher than this.

I am not sure how tenable this argument is on facts because a reading of column 3 of the specification of the Zimmerman Patent  makes it difficult to claim that imatinib mesylate was not “disclosed” in the patent. Below are certain paras from Column 3:

“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, for example aliphatic mono- or di-carboxylic acids, such as trifluoroacetic acid, acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, fumaric acid, hydroxymaleic acid, malic acid, tartaric acid, citric acid or oxalic acid, or amino acids such as arginine or lysine, aromatic carboxylic acids, such as benzoic acid, 2-phenoxy-benzoic acid, 2-acetoxybenzoic acid, salicylic acid, 4-aminosalicylic acid, aromatic-aliphatic carboxylic acids, such as mandelic acid or cinnamic acid, heteroaromatic carboxylic acids, such as nicotinic acid or isonicotinic acid, aliphatic sulfonic acids, such as methane-, ethane- or 2-hydroxyethane-sulfonic acid, or aromatic sulfonic acids, for example benzene-, p-toluene- or naphthalene-2-sulfonic acid. When several basic groups are present mono- or poly-acid addition salts may be formed. 

For the purposes of isolation or purification, as well as in the case of compounds that are used further as intermediates, it is also possible to use pharmaceutically unacceptable salts. Only pharmaceutically acceptable, non-toxic salts are used for therapeutic purposes, however, and those salts are therefore preferred.

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.”

The argument/approach advanced by Novartis also seeks to leave out of the discussion, the knowledge of a person skilled in the art to make a pharmaceutically acceptable salt of a new compound. Critically, it appears that according to Novartis, it is possible to claim/cover a product, without disclosing/enabling it, warranting the following reaction from the Supreme Court:

“139. The dichotomy that is sought to be drawn between coverage or claim on the one hand and disclosure or enablement or teaching in a patent on the other hand, seems to strike at the very root of the rationale of the law of patent. Under the scheme of patent, a monopoly is granted to a private individual in exchange of the invention being made public so that, at the end of the patent term, the invention may belong to the people at large who may be benefited by it. To say that the coverage in a patent might go much beyond the disclosure thus seem to negate the fundamental rule underlying the grant of patents.”

Assuming one were to hold Novartis to its own position, does this mean the Zimmerman patent claims pharmaceutically acceptable salts without disclosing the method of making it? In fact, in the Zimmerman patent, from my reading of it, salt claims have been appended to independent claims as “or a pharmaceutically acceptable salt”. So if these salts have only been claimed but not disclosed/enabled, wouldn’t this be violative of Section 112 of the US patents Act?...

In light of the above, it becomes apparent that “Imatinib Mesylate”, not the free base, is the “known substance” with respect to which enhanced efficacy must be established. The other reason why imatinib free base must not be used as the benchmark to judge efficacy is that, if efficacy were to be hypothetically treated as including bioavailability, wouldn’t it be obvious that the salt form would have greater bioavailability than the free base? If yes, wouldn’t this be an obvious contribution lacking in inventive step? I think so. 

Novartis Decision: Interpretation of “Invention”, “Inventive Step” and Interplay with Section 3(d)

The Novartis decision raises several fundamental questions which quite a few of us have been pondering over for quite some time. For instance, the need for and relevance of definition of “new invention” in Section 2(1)(ta) of the Act. If the definition of invention under Section 2(1)(j) already refers to a “new product or process” which is then governed by “Anticipation” in Chapter VI, where is the need for another term called “new invention”? I’d be grateful if readers could point out any section or rule of the Patents Act other than  Section 2(1)(ta) which uses the term “new invention”.

The Supreme Court has attempted to address some of these issues in its decision. For instance, in Paras 25 and 26, the Court asks thus:

“25. Some important provisions of the Patents Act, 1970, as they stand after the amendment of the Act in 2005, and with which we are especially concerned in this case, indeed present a problem of interpretation. Why was section 5, which, in one sense, was the distinctive feature of the patent law in India, taken off the statute book? What does the legislature wish to say through clauses (j) and (ja) of section 2(1), section 3 and several other sections? How is it that some of the provisions of the Act apparently seem to be of no use or purpose, e.g., sections 2(1)(l) and 2(1)(ta)? Why is it that some of the crucial provisions in the Act appear to be wanting in precision and clarity?

26. It is easy to know why section 5 was deleted but to understand the import of the amendments in clauses (j) and (ja) of section 2(1) and the amendments in section 3 it is necessary to find out the concerns of Parliament, based on the history of the patent law in the country, when it made such basic changes in the Patents Act. What were the issues the legislature was trying to address? What was the mischief Parliament wanted to check and what were the objects it intended to achieve through these amendments?”

Though these questions were raised in Page 14 of the decision, the Hon’ble Court goes on to discuss the entire history of the Indian Patent regime and its tryst with TRIPS until Para 86@Page 50....It is only again in Para 87 that the Court returns to the issue of “invention” and “inventive step”.

In an earlier post titled “Inventive Step under the Patents Act: Where is the Confusion”, I had taken the following view to clear a few prevalent misconceptions about the definition:

“Therefore, inventive step does not refer solely to a “non-obvious technical advance”, but in fact refers to a “non-obvious feature” which involves either a technical advance or has economic significance or both.

...

The other important corollary is that the presence of technical advance is not the sole criterion to judge if an invention has an inventive step. Economic significance of a feature which is non-obvious too by itself could help the product or the process satisfy the “inventive step” requirement. Importantly, the criterion of economic significance is equally applicable to products and processes.”

Following is what the Supreme Court has held in Para 90@Page 52 of its decision:

“90. On a combined reading of causes (j), (ac) and (ja) of section 2(1), in order to qualify as “invention”, a product must, therefore, satisfy the following tests:

(i) It must be “new”;

(ii) It must be “capable of being made or used in an industry”

(iii) It must come into being as a result of an invention which has a feature that:

(a) entails technical advance over existing knowledge;

Or

(b)has an economic significance

And

           (c) makes the invention not obvious to a person skilled in the art.”

Clearly, according to the Supreme Court, a feature which has an economic significance, which feature also makes the invention non-obvious qualifies as “inventive step” under the Patents Act. In other words, it is not just technical advance that qualifies as “inventive step”. The “or” in the definition is meant to distinguish between “technical advance” and “economic significance”. That settles the issue for good...

Relationship Between Section 2(1)(j) and Section 3: “Invention” and “Patentability”

The Supreme Court, in Paras 91 and 92, has taken the view that “invention” and “patentability” are two distinct requirements that a patent application has to satisfy for grant of a patent. The Court has noted that “Something may be an “invention” as the term is generally understood and yet it may not qualify as an “invention” for the purposes of the Act. Further, something may even qualify as an “invention” as defined under the Act and yet may be denied patent for other larger considerations as may be stipulated in the Act.”

With specific reference to the nature of proscriptions under Section 3, the Court observed in Para 92 that “section 3, it puts at one place provisions of two different kinds: one that declares that certain things shall not be deemed to be “inventions” [for instance clauses (d) & (e)]; and the other that provides that, though resulting from invention, something may yet not be granted patent for other considerations [for instance clause (b)]”

Again in Para 181, the Court took the following view:

“181. While dealing with the explanation it must also be kept in mind that each of the different forms mentioned in the explanation have some properties inherent to that form, e.g., solubility to a salt and hygroscopicity to a polymorph. These forms, unless they differ significantly in property with regard to efficacy, are expressly excluded from the definition of “invention”.....(continued)”

In other words, if the subject-matter of a patent application fails to overcome the requirement of Section 3(d), it is not an invention within the meaning of the Act under Section 2(1)(j). Therefore, at least with respect to pharmaceutical substance, Section 3(d) must be used as the first filter before the subject-matter is tested on the anvils of Section 2(1)(j). This was exactly the view taken by the IPAB in the Yahoo decision on Section 3(k), which was as follows:

“Finally we come to the ground of non-patentability under S. 3 (k). If the claimed subject matter is not an invention or if the invention is not patentable or if it is excluded by S.3 of the Act, then none of the other objections need to be considered. Only if the claimed subject matter is a patentable invention we need to look at anticipation, obviousness etc.”

It is another matter that the IPAB itself was inconsistent in the application of this logic in the very same Yahoo decision...

Similarly, in the Novartis decision, having stated clearly in Para 181 that forms of a chemical substance which do not exhibit significantly different efficacy characteristics are “expressly excluded from the definition of invention”, the Supreme Court again blurs this position by stating as follows in Para 192 (read with Para 104):

“192. Section 2(1)(j) defines “invention” to mean, “a new product or …”, but the new product in chemicals and especially pharmaceuticals may not necessarily mean something altogether new or completely unfamiliar or strange or not existing before. It may mean something “different from a recent previous” or “one regarded as better than what went before” or “in addition to another or others of the same kind”. However, in case of chemicals and especially pharmaceuticals if the product for which patent protection is claimed is a new form of a known substance with known efficacy, then the subject product must pass, in addition to clauses (j) and (ja) of section 2(1), the test of enhanced efficacy as provided in section 3(d) read with its explanation”

The above-underscored line gives room for some to say that only after the claimed subject-matter is tested under Section 2(1)(j) and (ja), it must be additionally scrutinized under Section 3(d). In the absence of the above statement, it would have been possible to test the invention first for satisfaction of Section 3(d), and if it failed to overcome the provision, there would be no further need to examine it under Section 2(1)(ja). This would have been better since a Section 3(d) analysis, by its very nature, entails a check for novelty as well.

It remains to be seen how the Patent Office and the IPAB interpret and apply the decision of the Supreme Court in this regard to pharma and chemical applications henceforth. 

Novartis Decision: Is Beta Crystalline Form of Imatinib Mesylate the same as Glivec?

In my last two posts, I have blogged on the Novartis decision of the Supreme Court. Most of us have been using Glivec and Beta Crystalline form of Imatinib Mesylate interchangeably. Here’s Para 193 of the Supreme Court’s finding on the issue:

“193. Coming back to the case of the appellant, there is yet another angle to the matter. It is seen above that in the US the drug Gleevec came to the market in 2001. It is beyond doubt that what was marketed then was Imatinib Mesylate and not the subject product, Imatinib Mesylate in beta crystal form. It is also seen above that even while the appellant’s application for grant of patent lay in the “mailbox” awaiting amendments in the law of patent in India, the appellant was granted Exclusive Marketing Rights on November 10, 2003, following which Gleevec was marketed in India as well.

On its package, the drug was described as “Imatinib Mesylate Tablets 100 mg” and it was further stated that “each film coated tablet contains: 100 mg Imatinib (as Mesylate)”. On the package there is no reference at all to Imatinib Mesylate in beta crystalline form. What appears, therefore, is that what was sold as Gleevec was Imatinib Mesylate and not the subject product, the beta crystalline form of Imatinib Mesylate.

194. If that be so, then the case of the appellant appears in rather poor light and the claim for patent for beta crystalline form of Imatinib Mesylate would only appear as an attempt to obtain patent for Imatinib Mesylate, which would otherwise not be permissible in this country.”

Now let’s examine the basis for this finding. The Supreme Court seems to have proceeded under the assumption that Novartis was obliged under law to mention the ‘beta-crystalline (BC)” form on its package, failing which, according to the Court, it was fair to assume that Imatinib Mesylate was being sold under the EMR granted for the BC form.

Before assuming thus and arriving at an adverse finding, it would have helped to undertake the following: 

1.  Branding of drugs is governed by Section 9 of the Drugs and Cosmetics Act, 1940 read with the manner of labeling prescribed under Rules 96 and 97 of the Drugs and Cosmetics Rules, 1945. Assuming that the Court deemed it relevant to address the issue of branding in a proceeding for grant of a patent, there appears to be no such discussion on the relevant provisions of the law. Unless these Drug Rules and their interpretation by Courts mandate mentioning the polymorphic form of the drug as part of the packaging, the patent applicant need not mention “beta crystalline form” as part of its package. 

2.  It would have also helped to understand the labelling practices prescribed by Indian Pharmacopoeia or the official pharmacopoeias in order to form an informed opinion on the facts of the case. 

3.  Tests could have been undertaken to check if what was being sold under the name of Glivec was Imatinib Mesylate or its BC form.

There is no discussion in the decision on the above aspects of the issue, and the Hon’ble Court seems to have proceeded on the basis of the packaging. Also, the packaging relied upon by the Hon'ble Court does not seem to state that its contents are the subject-matter of the impugned patent application.

I request better-informed readers to share with us their inputs to understand the issue better. 

A Brief Primer on the Novartis Case

Yesterday, I had blogged on the pronouncement of the decision of the Supreme Court on the Novartis case. In the next few posts, I will discuss various significant aspects of the decision in detail. Before I do so, I thought it fit to provide a brief factual summary of the case to set the context.

Facts leading to the Supreme Court Decision

Title of the Patent:  Application number 1602/MAS/1998- “Crystal Modification of a N-Phenyl-2-Pyrimidineamine derivative, processes for its manufacture and its use”- Beta Crystalline Form of Imatinib Mesylate (“BCIM”)

July 18, 1997: Swiss basic application filed

July 17, 1998: Indian Application filed claiming priority from the Swiss application

November 10, 2003: Exclusive Marketing Rights (EMR) granted

January 25, 2006: Patent office refuses to grant patent after 5 pre-grant oppositions are filed by Cancer Patients Aid Association, Natco Pharma Limited, Cipla Limited, Ranbaxy Laboratories Limited, and Hetero Drugs Limited. 

The primary grounds for rejection of the Application by the Patent Office were:

1.       BCIM lacked novelty. 

2.       BCIM fell within the ambit of Section 3(d).

On Section 3(d), the Patent Office observed thus:

“9. The Opponent (Cipla) said that the application claims only a polymorphic form of the known substance, imatinib mesylate. There is no enhancement of known efficacy as required under Section 3(d) of the Patents Act. Moreover the present specification states that all the inhibitory and pharmacological effects are also found with the free base, or other salts thereof.

10. Countering the arguments of the Opponent, the Applicant (Novartis) said that the crystal form of imatinib mesylate is an invention and not a more discovery. They further said that, a discovery graduating into a patentable invention solely on the basis of efficiency defies logic and, therefore, Section 3(d) may be unable to stand legal scrutiny. The Applicant submitted that this aspect of Section 3(d) is against the tenets of our patents act and well established principles of jurisprudence and therefore, the said Section cannot be used against the subject application.

11. I do not agree with the contention of the Applicant that this application claims a new substance. It is only a new form of a known substance. As regards efficacy, the specification itself states that where're crystals are used the imatinib free base or other salts can be used. Even the affidavit submitted by the Applicant states that "the proviso to the Section 3(d) is unique to India and there is no analogous provision in the law of any other country of the world".

As per the affidavit the technical expert has conducted studies to compare the relative bioavailability of the free base with that of crystal form of imatinib mesylate and has said that the difference in bioavailability is only 30 per cent and also the difference in bioavailability may be due to the difference in their solubility in water. The present patent specification does not bring out any improvement in the efficacy of the crystal form over the known substances rather it states the base can be used equally in the treatment of diseases or in the preparation of pharmacological agents wherever the crystal is used.

Even the affidavit submitted on behalf of the Applicant does not prove any significant enhancement of known efficacy. It is found that this patent application claims only a new form of a known substance without having any significant improvement in efficacy. Hence, I conclude that the subject matter of this application is not patentable under Section 3(d) of the Patents Act, 1970 as amended by the Patents (Amendment) Act, 2005.”

Against the rejection of the Patent Office, Novartis filed a batch of 5 Writ Petitions before the Madras High Court. All the 5 petitions were converted to appeals and were transferred in 2007 to the then newly-constituted Intellectual Property Appellate Board (IPAB).

By an order dated June 26, 2009, the IPAB upheld the rejection of Novartis’s application by the Patent Office essentially relying on Section 3(d). Here is a link to the decision of the IPAB.  In contrast to the Patent Office, the IPAB held that BCIM was novel, but rejected it citing Section 3(d).

Apart from the above appeals, Novartis had also filed 2 other Writ Petitions before the Madras High Court challenging the constitutionality of Section 3(d). Novartis alleged that Section 3(d) of the Patents Act was violative of Article 14 of the Constitution of India and was also violative of TRIPS. Both the writ petitions challenging the constitutionality of Section 3(d) were dismissed by the Madras High Court in 2007. Here is a link to the decision of the Madras High Court. There was no further challenge to the decision of the Madras High Court on the constitutionality of Section 3(d).

Novartis then proceeded to file Special Leave Petitions (SLPs) against the decision of the IPAB in its 5 appeals.

Decision of the Supreme Court 

It was on these 5 SLPs that the Supreme Court delivered its decision yesterday, 2013, holding the following: 

A.      That BCIM is not a “new product” and therefore it did not deserve the grant of a patent.  

B.     That BCIM is not an “invention” under the Act since it was squarely covered by the prohibition under Section 3(d) of the Act.

More on the decision in the next few posts. 

Link to the Novartis Judgment of the Supreme Court

First things first, I profusely thank a well-wisher of the blog who has been kind enough to share with me the link to the Novartis decision of the Supreme Court. This person has been truly a pillar of strength for his unstinting support to the blog.

For the benefit of our readers, here is the link to 112-page decision of the Supreme Court in the Special Leave Petition filed by Novartis challenging (1) the rejection of its patent application by the IPAB and (2) the decision of the Madras High Court in the Novartis’s writ petition challenging the vires of Section 3(d) of the Patents Act, 1970.

Before we put up a detailed analysis of the decision, here are the relevant excerpts from the judgment, including observations on Section 3(d):

99. In regard to section 3(d) both Mr. Andhyarujina and Mr. Subramanium, learned counsel appearing for the appellant, strenuously argued that section 3(d) is not meant to be an exception to clauses (j) and (ja) of section 2(1) of the Act. Both the learned counsel insisted that section 3(d) has no application to the case of the subject product. The subject product, having satisfied the tests of invention as provided in clauses (j) and (ja) of section 2(1), cannot be denied patent for allegedly failing to satisfy the tests under section 3(d). Mr. Andhyarujina submitted that section 3(d) is a provision put in ex abundanti cautela non nocet to remove all doubts.

100. Mr. Subramanium submitted that section 3(d) is ex majore cautela. The learned counsel submitted that the primary purpose of section 3(d), as is evidenced from the legislative history, is to prevent “evergreening” and yet to encourage incremental inventions. “Evergreening” is a term used to label practices that have developed in certain jurisdictions wherein a trifling change is made to an existing product, and claimed as a new invention. The coverage/protection afforded by the alleged new invention is then used to extend the patentee’s exclusive rights over the product, preventing competition. Mr.Subramanium submitted that, by definition, a trifling change, or in the words of the section “a mere discovery of a new form of a known substance”, can never ordinarily meet the threshold of novelty and inventive step under clauses (j) and (ja) of section 2(1). An invention cannot be characterized by the word “mere”. The word “invention” is distinct from the word “discovery”. He, therefore, submitted that section 3(d) operates only as ex majore cautela, ensuring that mere discoveries can never, by an effort at interpretation of clauses (j) and (ja) of section 2(1), be considered inventions.

101. In regard to the concerns about public health issues and the flexibility of the TRIPS Agreement coupled with the Doha Declaration, allowing the scope to address the issues of public health, Mr. Subramanium submitted that those concerns are addressed in the Act, in provisions relating to compulsory licensing, revocation of patents, and the multiple stages for opposition to the grant of patent.

102. The submission may appear plausible if the scrutiny of the law is confined only to the Act as it stands today after undergoing the amendments in 2005. But examined in the larger perspective of the development of the law of patent over the past 100 years and especially keeping in mind the debates in the Parliament preceding the 2005 amendment, it would appear completely unacceptable. We find no force in this submission that section 3(d) is a provision ex majore cautela. To our mind, the submission completely misses the vital distinction between the concepts of invention and patentability – a distinction that was at the heart of the Patents Act as it was framed in 1970, and which is reinforced by the 2005 amendment in section 3(d).

103. 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.

104. 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.

On the relevance of the Zimmerman patent, following were the observations of the Court:

“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 warmblooded 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.

132. That Imatinib Mesylate is fully part of the Zimmermann patent is also borne out                               from another circumstance. It may be noted that after the Zimmermann patent, the appellant applied for, and in several cases obtained, patent in the US not only for the betaand alpha crystalline forms of Imatinib Mesylate, but also for Imatinib in a number of different forms. The appellant, however, never asked for any patent for Imatinib Mesylate in non-crystalline form, for the simple reason that it had always maintained that Imatinib Mesylate is fully a part of the Zimmermann patent and does not call for any separate patent.

133. We thus find no force in the submission that the development of Imatinib Mesylate from Imatinib is outside the Zimmermann patent and constitutes an invention as understood in the law of patent in India.”

157. In light of the discussions made above, we firmly reject the appellant’s case that Imatinib Mesylate is a new product and the outcome of an invention beyond the Zimmermann patent. We hold and find that Imatinib Mesylate is a known substance from the Zimmermann patent itself. Not only is Imatinib Mesylate known as a substance in the Zimmermann patent, but its pharmacological properties are also known in the Zimmermann patent and in the article published in the Cancer Research journal referred toabove. The consequential finding, therefore, is that Imatinib Mesylate does not qualify the test of “invention” as laid down in section 2(1)(j) and section 2(1)(ja) of the Patents Act,1970.

158. This leaves us with the beta crystal form of Imatinib Mesylate, which, for the sake of argument, may be accepted to be new, in the sense that it is not known from the Zimmermann patent. (Whether or not it involves an “inventive step” is another matter, and there is no need to go into that aspect of the matter now). Now, the beta crystalline form of Imatinib Mesylate being a pharmaceutical substance and moreover a polymorph of Imatinib Mesylate, it directly runs into section 3(d) of the Act with the explanation appended to the provision. Mr. Subramanium, however, contended that section 3(d) has no application in this case. The main ground on which he denied the applicability of section 3(d) to decide the question of grant of patent to the beta crystalline form of the Imatinib Mesylate is earlier held to be untenable. He, however, questioned the applicability of section 3(d) on another ground. Mr. Subramanium submitted that in order to attract section 3(d), the subject product must be a new form of a known substance having known efficacy. The learned counsel laid some stress on the expression “known” that equally qualifies the substance of which the subject product may be another form, and the efficacy of that substance. The learned counsel submitted that a “conceivable” substance is not a “known substance” within the meaning of the provision. He contended that the word “known” here connotes proven and well-established; “known efficacy” implies efficacy established empirically and proven beyond doubt. He further contended that neither Imatinib nor Imatinib Mesylate had any known efficacy and that, therefore, there was no question of showing that the beta crystalline form of Imatinib Mesylate had any enhanced efficacy over Imatinib or Imatinib Mesylate.

160. On facts also we are unable to accept that Imatinib Mesylate or even Imatinib was not a known substance with known efficacy. It is seen above that Imatinib Mesylate was a known substance from the Zimmermann patent. In the NDA submitted by the appellant before the US FDA, it was clearly stated that the drug had undergone extensive preclinical, technical and clinical research. The clinical studies included one multiple dose tolerability/dose-finding study (Phase I) and three large open, uncontrolled efficacy and safety studies (Phase II); and a total of 1,234 patients with CML and other Ph+ leukemias were enrolled in the studies. The efficacy of Imatinib was equally known, as is evident from the Zimmermann patent itself, besides the two articles referred to above.

161. The subject product, that is, beta crystalline form of Imatinib Mesylate, is thus clearly a new form of a known substance, i.e., Imatinib Mesylate, of which the efficacy was well known. It, therefore, fully attracts section 3(d) and must be shown to satisfy the substantive provision and the explanation appended to it.

162. We now proceed to examine how far the beta crystalline form of Imatinib Mesylate stands up to the test of section 3(d) of the Act. It is noted, in the earlier part of judgment, that the patent application submitted by the appellant contains a clear and unambiguous averment that all the therapeutic qualities of beta crystalline form of Imatinib Mesylate are also possessed by Imatinib in free base. The relevant extract from the patent application is once again reproduced here:

“It goes without saying that all the indicated inhibitory and pharmacological effects are also found with the free base, 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl) pyrimidin-2-ylamino)phenyl] benzamide, or other cells thereof. The present invention relates especially to the β−crystal form of the methanesulfonic acid addition salt of a compound of formula I in the treatment of one of the said diseases or in the preparation of a pharmacological agent for the treatment thereto.” (emphasis added)

163. Now, when all the pharmacological properties of beta crystalline form of Imatinib Mesylate are equally possessed by Imatinib in free base form or its salt, where is the question of the subject product having any enhanced efficacy over the known substance of which it is a new form?

164. It may also be stated here that while going through the Zimmermann patent one cannot but feel that it relates to some very serious, important and valuable researches. The subject patent application, on the other hand, appears to be a loosely assembled, cut-andpaste job, drawing heavily upon the Zimmermann patent. As a matter of fact, Mr. Kuhad,learned Additional Solicitor General, submitted before us a tabular chart showing over a dozen statements and averments made in the subject application that are either lifted from the Zimmermann patent or are very similar to corresponding statements in the Zimmermann patent. The aforesaid chart is appended at the end of the judgment as Appendix II.

170. It is to be noted that the higher solubility of the beta crystalline form of Imatinib Mesylate is being compared not to Imatinib Mesylate but, once again, to Imatinib in free base form. The whole case of the appellant, as made out in the subject application and the affidavits, is that the subject product, the beta crystalline form of Imatinib Mesylate, is derived from Imatinib, and that the substance immediately preceding the beta crystalline form is not Imatinib Mesylate but Imatinib in free base form. This position is sought to be canvassed in the subject application and the affidavits on the premise that the Zimmermann patent ended at Imatinib in free base and did not go beyond to Imatinib Mesylate. Not only is this premise unfounded as shown earlier, but the appellant itself appears to take a somewhat different stand, as before this Court it was contended that the subject product, in terms of invention, is two stages removed from Imatinib in free base, and the substance immediately preceding the subject product is Imatinib Mesylate (non-crystalline).

171. That being the position, the appellant was obliged to show the enhanced efficacy of the beta crystalline form of Imatinib Mesylate over Imatinib Mesylate (non-crystalline). There is, however, no material in the subject application or in the supporting affidavits to make any comparison of efficacy, or even solubility, between the beta crystalline form of Imatinib Mesylate and Imatinib Mesylate (non-crystalline).

On “Efficacy”

179. It may be seen that the word “efficacy” is used both in the text added to the substantive provision as also in the explanation added to the provision.

180. What is “efficacy”? Efficacy means  “the ability to produce a desired or intended result”. Hence, the test of efficacy in the context of section 3(d) would be different, depending upon the result the product under consideration is desired or intended to produce. In other words, the test of efficacy would depend upon the function, utility or the purpose of the product under consideration. Therefore, in the case of a medicine that claims to cure a disease, the test of efficacy can only be “therapeutic efficacy”. The question then arises, what would be the parameter of therapeutic efficacy and what are the advantages and benefits that may be taken into account for determining the enhancement of therapeutic efficacy? With regard to the genesis of section 3(d), and more particularly the circumstances in which section 3(d) was amended to make it even more constrictive than before, we have no doubt that the “therapeutic efficacy” of a medicine must be judged strictly and narrowly. Our inference that the test of enhanced efficacy in case of chemical substances, especially medicine, should receive a narrow and strict interpretation is based not only on external factors but there are sufficient internal evidence that leads to the same view. It may be noted that the text added to section 3(d) by the 2005 amendment lays down the condition of “enhancement of the known efficacy”. Further, the explanation requires the derivative to “differ significantly in properties with regard to efficacy”. What is evident, therefore, is that not all advantageous or beneficial properties are relevant, but only such properties that directly relate to efficacy, which in case of medicine, as seen above, is its therapeutic efficacy

181. While dealing with the explanation it must also be kept in mind that each of the different forms mentioned in the explanation have some properties inherent to that form, e.g., solubility to a salt and hygroscopicity to a polymorph. These forms, unless they differ significantly in property with regard to efficacy, are expressly excluded from the definition of “invention”. Hence, the mere change of form with properties inherent to that form would not qualify as “enhancement of efficacy” of a known substance. In other words, the explanation is meant to indicate what is not to be considered as therapeutic efficacy.

187. In whatever way therapeutic efficacy may be interpreted, this much is absolutely clear: that the physico-chemical properties of beta crystalline form of Imatinib Mesylate, namely (i) more beneficial flow properties, (ii) better thermodynamic stability, and (iii)lower hygroscopicity, may be otherwise beneficial but these properties cannot even be taken into account for the purpose of the test of section 3(d) of the Act, since these properties have nothing to do with therapeutic efficacy.

Breaking News: Supreme Court Rejects Novartis's Patent Application on Glivec

I have just been informed by well-wishers of the blog that the Supreme Court has dismissed Novartis's Special Leave Petition against the rejection of its patent application on Glivec a.k.a Imatinib Mesylate. The patent application has apparently been rejected on grounds of falling foul of Section 3(d), anticipation and obviousness. Apparently, costs too have been imposed on Novartis for challenging the validity of Section 3(d). 

We will keep our readers posted as and when we get more updates. 

Novartis Supreme Court Update: Arguments on Imatinib Mesylate and Efficacy

In my last update on the Novartis case, I blogged on the submissions made on behalf of Novartis on September 13, 2012. The update of the submissions made on September 12, 2012 is available here by Lawyers’ Collective.

On the 12^th, it appears that the submissions largely revolved around the contents of the patent application and the prior art cited against it. Mr.Gopal Subramanium, counsel for Novartis, seems to have submitted that the Zimmerman patent of 1993 disclosed only the imtainib freebase, whereas the subject-matter of Novartis’s application was beta crystalline form of imatinib mesylate.

Mr. Subramanium further submitted that the Zimmerman patent too was owned by Novartis and pointed out that although the Zimmer man patent disclosed methanesulphonic acid and the imatinib free base, there was no reference to methane sulphonate salt of imatinib.

Further, in light of the fact the Zimmerman patent disclosed a variety of compounds, their salts and acids, any number of combinations were possible, and that a person skilled in the art would not have arrived at the specific compound claimed in Novartis’s application. In short, the Zimmerman patent did not enable the working of beta crystalline form of imatinib mesylate.

It was also submitted that the free base of imatinib could not be administered to patients as it is and that the ingenuity of the invention lay in developing an administrable form, namely the beta crystalline form.

For the rest of the arguments relating to efficacy, I request the readers to read the update provided by Lawyers’ Collective. 

Novartis Supreme Court Update: Purpose and Interpretation of Section 3(d)

In an earlier post, I had blogged  on the update in the Novartis hearings before the Supreme Court.

A well-wisher of the blog has brought to my attention an update of the hearings held on September 13, 2012. It appears that on behalf of the patent applicant, Novartis, Mr.Gopal Subramanium submitted to the Supreme Court that the purpose of Section 3(d) is not to facilitate access to medicines. Its purpose, according to Novartis, is to prevent grant of patents to trivial modifications to existing products.

The submissions appear to have been made in connection with a clarification sought by Justice Aftab Alam. It was further submitted that the Doha Declaration, and consequently the issue of access to medicines has been incorporated in the Indian Act in its compulsory licensing provisions. A good part of the arguments seem to have revolved around the issue of compulsory licensing provisions of the Act.

With respect to Section 3(d), it appears that according to Mr. Subramanium, Section 3(d) applies only to discoveries which do not have an inventive step. Consequently, according to Mr.Subramanium, if something is covered by Section 2(1)(j) and 2(1)(ja), Section 3(d) is not attracted in such an instance. 

It was also submitted that Section 3(d) must be read as an aid to Section 2(1)(ja), and that 3(d) does not limit 2(1)(ja). Therefore, according to Mr. Subramanium, the IPAB had erred in rejecting the patent application of Novartis citing Section 3(d) despite holding that Gleevec was novel and non-obvious.

In my opinion, this is precisely the kind of mess that is created when the IPAB or the Patent Office examine for novelty and non-obviousness instead of first using Section 3 of the Act as a filter. A similar unnecessary analysis was undertaken by the IPAB in the Yahoo order where a patent application of Yahoo was rejected. In my opinion, if Section 3 is used as a filter to weed out what are not inventions under the Act, unnecessary analysis on novelty and non-obviousness can be avoided.

Coming back to the Novartis case, it was submitted on behalf of Novartis that the IPAB erred in applying the test of anticipation under Section 3(d), besides applying it under Section 2(1)(j).

What surprised me are the reported submissions by Mr.Subramanium on the distinction between obviousness and anticipation. It has been reported that the following is what was submitted to the Court by Mr. Subramanium:

“Responding to a clarification sought about the difference between obviousness and anticipation, Mr Subramaniam said that, in the analysis of obviousness, the existing knowledge is complete and enabling and therefore it is obvious to reach the claimed product. He said that, in the analysis of anticipation, full details are not given in the existing knowledge”

Further hearing in the matter was scheduled for September 18, 2012.

Novartis Update: Supreme Court Asks Novartis to Cut Prices

Reportedly, the Supreme Court which has been hearing arguments in the Novartis matter since September 11, 2012, has asked Novartis to reduce the price of Glivec, the drug used to treat Chronic Myeloid Leukemia (CML) which currently costs around INR 1.2 Lakh for a month’s treatment.

The Supreme appears to have asked Novartis’s counsel Mr.Gopal Subramanium if the company would continue its programme for subsidized access to the drug if the patent on crystalline form of imatinib mesylate were to be granted.

This question was asked despite the Supreme Court acknowledging that Novartis had no legal obligation to continue the subsidized access programme. Apparently, the Apex Court urged Novartis to slash prices to earn the goodwill of the people and establish it bonafides.

In response to this suggestion by the Court, Novartis seems to have stated the following in its affidavit:

“In the event of patent being granted to petitioner, Novartis in India, undertakes to continue this programme till July 2018 and subject to there being no further regulatory price control/direction in relation to said (Glivec) product.” 

According to Health India, Novartis submitted to the Court that the number of patients afflicted with CML in India is 41,794, out of which 15,690 have been prescribed the use of Glivec. Out of these 15,690 patients, Glivec was being made available free of cost to 15,155 patients, 370 were being supplied the drug at a subsidized price and only 165 bought the drug at the full price.