Gevo – Butamax back and forth Ongoing Infringment Lawsuits

It looks like a never-ending infringement lawsuit between Gevo Inc. and Butamax Advanced Biofuels LLC on IP rights of bio-isobutanol, a well-known biofuel.

On September 13, 2011, Gevo Inc. was granted two patents by USPTO that involved technologies enabling low-cost, high-yield production of bio-based isobutanol. Gevo’s patent 8,017,375 (‘375), “Yeast Organism Producing Isobutanol at a High Yield” focuses on the modification of yeast to produce isobutanol instead of ethanol. Patent 8,017,376 (‘376), “Methods of Increasing Dihydroxy Acid Dehydratase Activity to Improve Production of Fuels, Chemicals, and Amino Acids” covers enzymatic steps on isobutanol production from yeast.

Office action response of Gevo’s 375 patent

The Examiner had rejected claims 131-149 of Gevo’s application over US 7,851,188 (of Donaldson/Butamax) citing that it disclosed the genes encoding the enzymes for isobutanol synthesis. On 28 April 2011, Gevo made a response to the rejection by the Examiner stating Butamax had NOT disclosed pdc disruption. Further, for PDC disruption, the Examiner cited van Maris (2004), and thus gave a 103 rejection. Gevo overcame this by adding the requirement: an .alpha.-ketoisovalerate decarboxylase from Lactococcus lactis to catalyze the conversion of .alpha.-ketoisovalerate to isobutyraldehyde.

Claim 1 of issued US 8,017,375 states:

A recombinant yeast microorganism for producing isobutanol, the recombinant yeast microorganism comprising an isobutanol producing metabolic pathway, wherein said isobutanol producing metabolic pathway comprises the following substrate to product conversions: (i) pyruvate to acetolactate; (ii) acetolactate to 2,3-dihydroxyisovalerate; (iii) 2,3-dihydroxyisovalerate to .alpha.-ketoisovalerate; (iv) .alpha.-ketoisovalerate to isobutyraldehyde; and (v) isobutyraldehyde to isobutanol; wherein said recombinant yeast microorganism expresses: (a) an acetolactate synthase to catalyze the conversion of pyruvate to acetolactate; (b) a ketol-acid reductoisomerase to catalyze the conversion of acetolactate to 2,3-dihydroxyisovalerate; (c) a dihydroxy acid dehydratase to catalyze the conversion of 2,3-dihydroxyisovalerate to .alpha.-ketoisovalerate; (d) an .alpha.-ketoisovalerate decarboxylase from Lactococcus lactis to catalyze the conversion of .alpha.-ketoisovalerate to isobutyraldehyde; and (e) an alcohol dehydrogenase to catalyze the conversion of isobutyraldehyde to isobutanol; wherein the recombinant yeast microorganism has been engineered to disrupt, mutate, or delete one or more endogenous pyruvate decarboxylase (PDC) genes, wherein said recombinant yeast microorganism has reduced endogenous PDC activity as compared to the corresponding yeast microorganism that has not been engineered to have reduce endogenous PDC activity, and wherein said recombinant yeast microorganism produces: (A) isobutanol at a yield which is at least 10% of the theoretical yield of isobutanol from glucose; and/or (B) ethanol at a yield which is 1.8% or less of the theoretical yield of ethanol from glucose.

The first claim of the Butamax ‘188 patent states:

A recombinant microbial host cell comprising heterologous DNA molecules encoding polypeptides that catalyze substrate to product conversions for each step below: i) pyruvate to acetolactate; ii) acetolactate to 2,3-dihydroxy-isovalerate; iii) 2,3-dihydroxy-isovalerate to .alpha.-ketoisovalerate; and iv) .alpha.-ketoisovalerate to isobutyraldehyde; wherein said microbial host cell produces isobutanol; and wherein a) the polypeptide that catalyzes a substrate to product conversion of pyruvate to acetolactate is acetolactate synthase having the EC number 2.2.1.6; b) the polypeptide that catalyzes a substrate to product conversion of acetolactate to 2,3-dihydroxy-isovalerate is acetohydroxy acid isomeroreductase having the EC number 1.1.1.86; c) the polypeptide that catalyzes a substrate to product conversion of 2,3-dihydroxy-isovalerate to .alpha.-ketoisovalerate is acetohydroxy acid dehydratase having the EC number 4.2.1.9; d) the polypeptide that catalyzes a substrate to product conversion of .alpha.-ketoisovalerate to isobutyraldehyde is branched-chain .alpha.-keto acid decarboxylase having the EC number 4.1.1.72.

Prior to this case, Butamax in January this year, filed two infringement lawsuits against Gevo, alleging Gevo unlawfully used Butamax technology regarding the 7,851,188 (‘188) patent issued in December 2010 and its related patent-related 7,993,889 (‘889) granted on August 9, 2011. The patent ‘188 covers biocatalysts that Butamax developed to produce isobutanol. The second patent ‘889 covers methods for low-cost production of biobutanol.

Butamax stated that “Butamax and its owners were the first to develop this technology and it is our belief that the protection of intellectual property serves the best interest of the biofuels industry, our customers and the U.S. energy policy.”

However, Gevo highlighted that it did not use the technology claimed in Butamax’s patents, but employed its own distinct technology, GIFT® (Gevo Integrated Fermentation Technology®), which is covered by more than 150 patent applications that enable the efficient production of isobutanol.

Later Gevo filed a lawsuit against Butamax and its parent company DuPont in charge of infringing Gevo’s two newly-issued patents (‘375 and ‘376). The invention described in the two patents involves Gevo’s unique technology to produce isobutanol. Hence the lawsuit is based on Butamax’s own publications describing their use of the technology that Gevo invented first and for which they have received patents.

In regards to this infringement suit, Paul Beckwith, CEO of Butamax stated:

“When Butamax makes isobutanol, we do not use the technology claimed in the Gevo patents. We are so confident about this, that we offered Gevo an opportunity to independently verify that Butamax does not infringe either of these patents. Ignoring both our offer to verify and the facts, Gevo instead filed its lawsuit.”

Butamax further added that it plans to seek legal relief from this frivolous suit and was confident in the eventual result from the court.

The Gevo patents are for a limited technology, which when applied for isobutanol production, are dominated by Butamax’s intellectual property and are invalid, as claimed by company officials.

Moreover, Gevo’s patents are based on Butamax’s technology and cannot be practiced to make isobutanol without infringing Butamax’s rights. Indeed, Gevo’s patents include clear evidence of Gevo’s use of Butamax’s technology and infringement.

Continuing the chain of lawsuits Gevo further filed two petitions in USPTO to re-examine Butamax’s both patents ‘188 and ‘889 statings that the two patents were already known in the scientific community and were already been invented by others before Butamax applied for the patents.

For patent ‘188 of Butamax, Gevo cited references under the light of obviousness under 35 USC 103 of the ‘188 patent. The references include US 2004/0146996 published by Yocum, a Ph.D. thesis “Formation of Amino Acid Derived Cheese Flavour Compounds”, 2004, by Smit, Nakamura’s US 6,013,494 on producing 1,3 propanediol by recombinant microorganisms, a screen capture from the ExPASy Proteomics Server and also a citation from 3rd edition of Lehninger Principles of Biochemistry. None of these were cited the prosecution history of patent ‘188.

Secondly, for patent ‘889, Gevo identified references anticipating claims 1, 3, 11, and 16-19 based on Larroy, Chemico-Biological Interactions (2003), which discloses the pathway from pyruvate to isobutanol. Apart from these, other references include Yocum’s US 20040146996 and Bekkaoui, Current Genetics (1993).

Key take aways:

It is pretty strange for small companies to go against chemical giants like Dupont or its subsidiary companies like Butamax. However, this patent fight seems to signal the growing potential importance of bio-butanol for the biofuel and chemical industries worldwide. In addition, it also gives us a view that if patents are quite strong in their claims and use novel technologies, then any company unlawfully adopting the same technology will be infringing the invention, no matter how big it is.

Minusmita Ray, Patent Associate, IIPRD, [email protected]