Glatiramer acetate( copolymer-1) application fails to qualify the section 3(d) of the Indian Patent Act

Application at issue- “A co-polymer fraction-1”, application number 93/DEL/2003, assigned to Yeda Research/ Teva.
Opponent Natco submitted that the copolymer-1 with the exact amino acid composition & mole ratio (alanine/glutamic acid/lysine /tyrosine as 6:2:5:1) as claimed in the present invention is already described and published in 1971 vide European Journal. Immunol, 1971,1;242-248.The same product has been patented as US 3849550 (Nov 19,1974) with the title “Therapeutic copolymer “ having the same composition mentioned above.
The only contribution in the current invention apparently is the manipulation of the molecular weight of the copolymer-1. In 93/DEL/2003 application applicants had demonstrated that low molw weight polymer (7.3 & 8.4 kDa) were less toxic as compared to prior art high molecular weight (22kDa) polymers.
Natco cited a reference clinical trial data reported in “New England Journal of Medicine” of 1987 which reported that copolymer-1 with molecular weight between 14 kDa to 23kDa was found to be non-toxic during short term and long term administration in mice, rabbit and dogs. Teva in their reply stated that the New England Journal of Medicine 1987, did not provide any satisfactory or sound argument with respect to the serious discrepancy pointed out and that they only tried to conclude that the data referring to 60% death of mice showed that the material would have toxicity in humans although it may not cause death. Controller however was not persuaded with this argument of Teva’s.
Natco also relied upon a second document EP-383620 which discloses that the product of molecular weight in the range of 5-50 kDa synthesized by polymerizing alanine, glutamic acid, lysine and tyrosine or tryptophan . This prior art teaches that copolymer-1 comprises random amino acid sequences mixture, which is non-uniform with respect to amino acid and having average molecular weight 23 kDa. Natco argued that combining the teaching of these two citations a person skilled in the art would obviously be motivated to further reduce the molecular weight of the copolymer-1 to reduce further toxicity. The prior art mentioned that the best results have been found for copolymer of 23 kDa or lower range preferably 14 to 23 kDa. Therefore it would be obvious for a person skilled in the art to further decrease the molecular weight copolymer-1, than known in the art with reduced toxicity.

Controller stated the following

“Copolymer-1 of the prior art as well as of the present invention is a potential therapeutic agent for multiple sclerosis & known for long. The applicant in the present invention has modified/ isolated the prior art copolymer-1 by known method like chromatography, acid/enzymatic hydrolysis etc. to obtain a lower average molecular weight copolymer-1 species particularly in the range of 2-20 kDa with no more than 5% species having molecular weight above 40 kDa.
The selection of lower average molecular weight copolymer-1 was motivated from three prior arts cited by Natco” emphasis added

Controller also stated that Applicant’s experimental report is not reliable, further experimental evidence should have been forwarded at least during prosecution, particularly on the face of it being contradictory to the report of annexure 7 as well as the inferences shown in Annexure 3 and prior art EP/0383620 specification of copolymer-1.

Finally it was concluded that the present invention is definitely a selection from the prior art, & is a subject of section 3(d) being a product, made up of component species. Every selection will lack in inventiveness if it is not accompanied by surprising efficacious effect. The specification of the present invention does not provide any such effect. The toxicity analysis appears to be inadequate and applicant ought to have forwarded more evidences of its experiments. Therefore under section 3(d) of the Indian Patent Act which takes cognizance of such modification under this section , is not satisfied or in other word the requirement of this section not fulfilled. The application fails to qualify the section 3(d) of the Indian Patent Act and is obvious and does not contain an inventive step.