Claim No.1 from Premacure United States Patent Application 20100204101 -
"A composition comprising Insulin Growth Factor I (IGF-I) in combination with Insulin Growth Factor Binding Protein (IGFBP) said combination having a molar ratio of IGF-I to IGFBP being lower than equimolar, in the range from 1:20 to 1:3.33, for the treatment of a patient suffering from complications of preterm birth, very preterm birth and/or extremely preterm birth."
Claim No.1 from Genentech United States Patent 5187151 -
"A method for producing an anabolic state in a mammal comprising co-administering to the mammal by subcutaneous bolus injection effective amounts of IGFBP-3 and IGF-I in a molar ratio of IGFBP-3 to IGF-I of about 0.5:1 to about 3:1 so as to produce a greater anabolic state in the mammal than that achieved using an equivalent dose of IGF-I alone, wherein growth hormone is not also administered to the mammal."
Genentech-patented IGF-1/IGFBP-3 molar ratio - from 1:0.5 to 1:3
Premacure-patented IGF-1/IGFBP-3 molar ratio - from 1:3.33 to 1:20 (i.e. twenty parts to one, not two parts to one)
The Genentech patent expired in 2011, and its European equivalent expired in 2012. But Premacure could only ever have patented a therapy which was outside of the scope of the Genentech patent. Hence the extreme molar ratio of the Premacure patent, which doesn't cover the 1:1 (equimolar) ratio of iPlex.
I assume that a therapy could realistically only fall within the scope of the Premacure patent if the IGF-1 and IGFBP-3 are used as individual proteins, or iPlex is used in combination with additional IGFBP-3.
I've always struggled to see any value in the Premacure patent unless somebody actually manufactures a formulation with a molar ratio of 1:3.33 or wider. As far as I'm aware, the formulation of Premiplex used thus far has been outside of the scope of the Premacure patent. From the (years earlier) Phase I study -
"Individual infusion solutions were prepared at the hospital pharmacy of the Queen Silvia Children's Hospital in the following manner. The study drug was mecasermin rinfabate (IPLEX, Insmed) that is an equimolar preparation of recombinant protein complex of rhIGF-I and rhIGFBP-3. IPLEX (Lots No. DP0506 and DP0609) vials were diluted with 10% glucose solution in two dilution steps to achieve the appropriate doses for each infant."
Assuming the protein complex is manufactured again in the normal (equimolar) ratio under license from Insmed, what rights will Premacure(Shire) have if a third party uses it in the prevention of ROP etc?
I suspect Insmed had been trying to negotiate a deal with Premacure, and that Premacure overplayed its hand. I can only assume that Shire must have obtained some sort of non-competition assurance from Insmed before buying Premacure - perhaps as part of a deal covering the wider development of the protein complex.