Wednesday, April 3, 2013

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. 

No comments:

Post a Comment