Business Method Patents Following Alice v. CLS Bank

This panel will discuss Alice v. CLS Bank, 134 S. Ct. 2347 (2014)

Business Method Patents Following Alice v. CLS Bank

This panel will discuss Alice v. CLS Bank, 134 S. Ct. 2347 (2014)

Rand Patents and Exclusion Orders: Submission of 19 Economics and Law Professors to the International Trade Commission

In this comment to ITC Investigation 337-TA-745 (Certain Wireless Communication Devices, Motorola v. Apple) we, as teachers and scholars of economics, antitrust and intellectual property, remedies, administrative, and international intellectual property law, former Department of Justice lawyers and chief economists, a former executive official at the Patent and Trademark Office, a former counsel at the ITC Office of the General Counsel, and a former Member of the President’s Council of Economic Adviser take the position that ITC exclusion orders generally should not be granted under § 1337(d)(1) on the basis of patents subject to obligations to license on “reasonable and non-discriminatory” (RAND) terms. Doing so would undermine the significant pro-competitive and pro-consumer benefits that RAND promises produce and the investments they enable. A possible exception may arise if district court jurisdiction is lacking, the patent is valid and infringed, and the public interest favors issuing an exclusion order. We explain our position in the comment

Mimicking human disease in Escherichia coli: Properties of methylenetetrahydrofolate reductase and a model for the effect of folate in hyperhomocysteinemia.

The enzyme methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the generation of the amino acid methionine. A variant of MTHFR (basepair change C677T corresponding to amino acid substitution Ala222Val) was identified in collaboration with Dr. Rima Rozen which was thought to be a genetic risk factor for cardiovascular disease and neural tube defects. This variant is found in a homozygous form in 10 to 15% of humans and results in elevated homocysteine levels. Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. Noting that the Escherichia coli MTHFR shows significant homology with the human MTHFR, the mutation corresponding to the mutation linked to cardiovascular disease in humans was generated in the E. coli MTHFR. The mutation results in an alanine to valine substitution at residue Ala177 which is homologous to Ala222 in humans. Purification protocols were devised to generate homogeneous wildtype and Ala177Val E. coli MTHFR enzyme. Using the physiological CH\sb2-H\sb4folate-NADH oxidoreductase assay, the Ala177Val protein was found to have catalytic properties similar to wildtype E. coli MTHFR. Size exclusion chromatography, differential scanning calorimetry and fluorimetry techniques were used to determine the oligomeric state, melting temperature and affinity for the flavin cofactor, respectively. These experiments showed that upon dilution the tetrameric enzyme dissociates into a dimer and loses activity and its flavin cofactor. Activity loss, flavin and protein dissociation, and melting temperature were all shown to be increased at low concentrations of the protein. We also demonstrated that supplementation with folate protected the enzyme from activity and FAD loss by shifting the equilibrium between holoenzyme (active) and apoenzyme (inactive). In addition, collaboration with Drs. Brian Guenther and Martha Ludwig, has generated an x-ray structure of E. coli MTHFR which corroborates and complements the enzyme characterization data. Based on our results, we propose that in humans homozygous for the Ala222Val polymorphism, the equilibrium between apoenzyme and holoenzyme is shifted, which results in decreased amounts of active MTHFR enzyme and increased levels of homocysteine, thus increasing the chance of cardiovascular problems.Ph.D.BiochemistryBiological SciencesHealth and Environmental SciencesMolecular biologyPathologyPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131538/2/9909992.pd

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Purification and Properties of NADH-Dependent 5,10-Methylenetetrahydrofolate Reductase (MetF) from \u3ci\u3eEscherichia coli\u3c/i\u3e

A K-12 strain of Escherichia coli that overproduces methylenetetrahydrofolate reductase (MetF) has been constructed, and the enzyme has been purified to apparent homogeneity. A plasmid specifying MetF with six histidine residues added to the C terminus has been used to purify histidine-tagged MetF to homogeneity in a single step by affinity chromatography on nickel-agarose, yielding a preparation with specific activity comparable to that of the unmodified enzyme. The native protein comprises four identical 33-kDa subunits, each of which contains a molecule of noncovalently bound flavin adenine dinucleotide (FAD). No additional cofactors or metals have been detected. The purified enzyme catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, using NADH as the reductant. Kinetic parameters have been determined at 15°C and pH 7.2 in a stopped-flow spectrophotometer; the Km for NADH is 13 mM, the Km for CH2-H4folate is 0.8 mM, and the turnover number under Vmax conditions estimated for the reaction is 1,800 mol of NADH oxidized min-1 (mol of enzyme-bound FAD)-1. NADPH also serves as a reductant, but exhibits a much higher Km. MetF also catalyzes the oxidation of methyltetrahydrofolate to methylenetetrahydrofolate in the presence of menadione, which serves as an electron acceptor. The properties of MetF from E. coli differ from those of the ferredoxin-dependent methylenetetrahydrofolate reductase isolated from the homoacetogen Clostridium formicoaceticum and more closely resemble those of the NADH-dependent enzyme from Peptostreptococcus productus and the NADPH-dependent enzymes from eukaryotes