Constraining sub-grid physics with high-redshift spatially-resolved metallicity distributions

Aims. We examine the role of energy feedback in shaping the distribution of metals within cosmological hydrodynamical simulations of L* disc galaxies. While negative abundance gradients today provide a boundary condition for galaxy evolution models, in support of inside-out disc growth, empirical evidence as to whether abundance gradients steepen or flatten with time remains highly contradictory. Methods. We made use of a suite of L* discs, realised with and without "enhanced" feedback. All the simulations were produced using the smoothed particle hydrodynamics code Gasoline, and their in situ gas-phase metallicity gradients traced from redshift z similar to 2 to the present-day. Present-day age-metallicity relations and metallicity distribution functions were derived for each system. Results. The "enhanced" feedback models, which have been shown to be in agreement with a broad range of empirical scaling relations, distribute energy and re-cycled ISM material over large scales and predict the existence of relatively "flat" and temporally invariant abundance gradients. Enhanced feedback schemes reduce significantly the scatter in the local stellar age-metallicity relation and, especially, the [O/Fe]-[Fe/H] relation. The local [O/Fe] distribution functions for our L* discs show clear bimodality, with peaks at [O/Fe] = -0.05 and +0.05 (for stars with [Fe/H] > -1), consistent with our earlier work on dwarf discs. Conclusions. Our results with "enhanced" feedback are inconsistent with our earlier generation of simulations realised with "conservative" feedback. We conclude that spatially-resolved metallicity distributions, particularly at high-redshift, offer a unique and under-utilised constraint on the uncertain nature of stellar feedback processes

Simulating a White Dwarf-dominated Galactic Halo

Observational evidence has suggested the possibility of a Galactic halo which is dominated by white dwarfs (WDs). While debate continues concerning the interpretation of this evidence, it is clear that an initial mass function (IMF) biased heavily toward WD precursors (1 < m/Msol < 8), at least in the early Universe, would be necessary in generating such a halo. Within the framework of homogeneous, closed-box models of Galaxy formation, such biased IMFs lead to an unavoidable overproduction of carbon and nitrogen relative to oxygen (as measured against the abundance patterns in the oldest stars of the Milky Way). Using a three-dimensional Tree N-body smoothed particle hydrodynamics code, we study the dynamics and chemical evolution of a galaxy with different IMFs. Both invariant and metallicity-dependent IMFs are considered. Our variable IMF model invokes a WD-precursor-dominated IMF for metallicities less than 5% solar (primarily the Galactic halo), and the canonical Salpeter IMF otherwise (primarily the disk). Halo WD density distributions and C,N/O abundance patterns are presented. While Galactic haloes comprised of ~5% (by mass) of WDs are not supported by our simulations, mass fractions of ~1-2% cannot be ruled out. This conclusion is consistent with the present-day observational constraints.Comment: accepted for publication in MNRA

Arthritic Flexibilities: Analysis of WTO Action Regarding Paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health

This paper explores the tortured history of developing countries’ pursuit of access to affordable generic medicines that they are unable to produce efficiently on their own. Having lost rights to treat medicines as essential commodities and as generalized exceptions to patent protections in the WTO TRIPS Agreement, developing countries and public health activists temporarily reasserted the primacy of health over profits in the Doha Declaration on the TRIPS Agreement and Public Health in November of 2001. However, since most developing countries lack meaningful pharmaceutical capacity to manufacture medicines efficiently on their own, they needed flexibility to import medicines from countries with robust generic industries, especially since important exporting countries like India will soon loss their right to routinely reverse-engineer and manufacture pharmaceutical products for export. Thus, Paragraph 6 of the Doha Declaration mandated that member states negotiate an efficient mechanism for producing medicines for export/import, a mandate that was honored in the breach by delayed adoption and by an overly restrictive and procedurally burdensome set of requirements imposed by the August 30, 2003, Paragraph 6 Implementation Agreement. This paper outlines the many mechanisms that developing countries have to secure generic medicines produced, under compulsory licenses and otherwise, and explores in detail the arthritic flexibilities of the August 30 Agreement. In addition to analyzing largely theoretical sourcing options, the paper recommends pragmatic legislative reform in developing countries aimed at maximizing intellectual property flexibilities under the TRIPS Agreement, the Doha Declaration, and the Paragraph 6 Implementation Agreement. More controversially, the paper recommends that developing countries implement a more vigorous competition policy slanted towards the granting of compulsory licenses and the regulation of voluntary licenses. The paper contextualizes a developing country’s decision of whether to invest in and perhaps subsidize domestic production with the “lowest-cost” procurement requirements of the Global Fund to Fight AIDS, TB, and Malaria and with a brief analysis of economies-of-scale in pharmaceutical manufacture. Finally, the paper urges developing countries to resist efforts to expand drug companies’ intellectual property rights in bilateral and regional trade agreements and instead argues that countries should continue to pursue a short-term strategy of exporting life-saving medicines pursuant to the Article 30 limited exception rule in the TRIPS Agreement and a long-term strategy of rolling back patent protects and data exclusivity rules for pharmaceutical products. Too many lives are at stake, most obviously people living with HIV/AIDS, to let the U.S., the E.U., and Japan, and the pharmaceutical industries that they represent, succeed in extending pharmaceutical hegemony

Kenya’s Intellectual Property Bill, 2020, and Its Shortcomings in Adopting all Lawful TRIPS Public Health Flexibilities

Given the importance of access to medicines to human rights and well-being in Kenya, it is appropriate to analyze whether Kenya has currently incorporated the allowed public health flexibilities to the greatest extent possible in its draft Intellectual Property Bill, 2020. This analysis will focus on the patent, utility model, and enforcement measures only as they are the ones directly relevant to access to medicines and other health technologies. The analysis starts with the premise that Kenya wishes to avoid granting unwarranted patents on unworthy inventions, especially with respect to medicines and other health technologies. In particular, the assumption is that Kenya wishes to avoid granting secondary patents or minor variations to known medicines and medical technologies which have the sole effect of extending patent monopolies and preventing local generic production or importation. It is assumed that Kenya wants to have a patent regime that prevents granting patents on new medical uses of medicines and on new formulation and dosages. In a word, the analysis assumes that Kenya wants to avoid evergreening. It assumes instead that Kenya wants to maximize TRIPS-compliant policy space to minimize unneeded patent barriers and further to bypass patents to advance its public health and public interest needs. Finally it assumes that Kenya further desires to expand policy space that would allow growth of domestic and regional pharmaceutical capacity. In crafting these recommendations, the author has relied extensively on EAC and COMESA recommendations that adoption and use of TRIPS-flexibilities be maximized, on academic and think-tank commentary, and on best practices from countries that have adopted and successfully used TRIPS flexibilities. The paper also draws on the positive example of India, which has adopted the vast majority of recommended TRIPS-compliant public health flexibilities. In sum, there are many positives in the proposed Kenyan Intellectual Property Bill, 2020, that have at least partially incorporated desired flexibilities but there are important gaps and omissions as well. On the plus side, the Bill incorporates several important TRIPS public-health flexibilities, including parallel importation and the right to issue government use and compulsory licenses. The Bill also incorporates a research exception and promotes close regulation of anti-competitive provisions in voluntary licenses. Also on the plus side, the Bill has updated the 2001 Act to adopt more rigorous standards of patentability and disclosure, including additional exclusions from patentability for new methods of using and new uses of existing medicines and required disclosures to include the best method for practicing the invention. However, the proposed Bill could still include even higher standards of patentability, more exceptions to exclusive patent rights, and strong pre- and post-grant opposition procedures. It could also make it easier to issue government use and compulsory licenses and broaden even further the grounds for doing. Finally, It should also ensure that utility models do not cover medicines or other medical technologies

MPP COVID-19 Antiviral Medicines Licenses – Licensed Territories, Supply Options for Excluded Territories, and Supply Barriers Arising from Trade-Secret Transfer

This is a paper that analyzes Medicine Patent Pool licenses for three COVID-19 antivirals, including licensed territories, patent landscapes, supply options, regulatory status, and supply barriers arising from licensee acceptance of trade-secret information from the originator licensor. It concludes that at present there is no existing WHO prequalified licensee that can supply nirmatrelvir + ritonavir outside the Pfizer licensed territory, whereas there are potential molnupiravir licensees that can supply outside licensed territories where there is no blocking patent exists or a compulsory license has been issued in the country of import or use. The paper concludes with an assessment that trade-secret offers come with strings attached which prevent licenses from supplying outside of licensed territories

Corporate Power Unbound: Investor-State Arbitration of IP Monopolies on Medicines – Eli Lilly and the TPP

Free trade agreements (FTAs) and bilateral investment treaties (BITs) typically contain investment clauses designed to attract direct foreign investment and protect the interests of foreign investors. In addition to defining foreign investment that are entitled to protection, investment clauses typically allow for investor-state dispute resolution, which allows a foreign investor to launch arbitral proceeding directly against the offending government before a private panel of trade lawyers. This paper focuses first on a pro-investor draft investment chapter in an ongoing regional trade negotiation – the Trans-Pacific Partnership Agreement (TPP) - and second on the first investor-state arbitral claim ever by a patent-holding pharmaceutical company under a U.S. free trade agreement, the Eli Lilly v. Canada case. The analysis of the draft TPP chapter shows that it expands protection for drug companies’ “expectations of profit” beyond those contained in the TPP’s proposed Intellectual Property Chapter and risks opening up many patent-affecting decisions and polices of Member States to pharmaceutical investors’ claims. As an example of that danger, Eli Lilly is currently challenging a well-established patent rule in Canada, the “promise” doctrine, whereby a medicine or any other product’s “utility,” and thus patentability, must be demonstrated or soundly predicted at the time of filing a patent. Eli Lilly, frustrated by the invalidation of its patent on an attention-deficit-disorder drug, makes a number of specific investment chapter claims under NAFTA, including that the Canadian ruling involved a violation of a minimum standard of treatment, indirect expropriation, and discrimination in violation of national treatment norms. A recurrent, indeed dominant feature of Eli Lilly’s investor claim, is that its reasonable expectations of profits may be drawn not just from preexisting Canadian laws and practices, but rather from higher external standards such as utility rules and disclosure norms codified in U.S. and E.U. law. Under the logic of Eli Lilly’s investor-state claim, foreign investors’ expectations have now become unbound. Even the doctrine of legitimate expectations, which is itself a huge stretch of operative minimum standard of treatment principles, is no longer tethered to operative due process (minimum standard of treatment) or to promises of regulatory coherence (indirect expropriation) or to equal treatment compared to domestic firms (national treatment). Instead Eli Lilly hitches its investment expectation to the best deal on IP it has achieved anywhere else. Moreover, it suggests that its expectations tolerate movement on IP policy in only one direction – upward. Any reversal of IP maximalization would dilute the gleam in its eye – unlimited profits on the horizon