Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. 'For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: 'There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as 'novelty', 'inventive step', and 'utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the 'Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

A multi-criteria analysis approach for ranking and selection of microorganisms for the production of oils for biodiesel production

Oleaginous microorganisms have potential to be used to produce oils as alternative feedstock for biodiesel production. Microalgae (Chlorella protothecoides and Chlorella zofingiensis), yeasts (Cryptococcus albidus and Rhodotorula mucilaginosa), and fungi (Aspergillus oryzae and Mucor plumbeus) were investigated for their ability to produce oil from glucose, xylose and glycerol. Multi-criteria analysis (MCA) using analytic hierarchy process (AHP) and preference ranking organization method for the enrichment of evaluations (PROMETHEE) with graphical analysis for interactive aid (GAIA), was used to rank and select the preferred microorganisms for oil production for biodiesel application. This was based on a number of criteria viz., oil concentration, content, production rate and yield, substrate consumption rate, fatty acids composition, biomass harvesting and nutrient costs. PROMETHEE selected A. oryzae, M. plumbeus and R. mucilaginosa as the most prospective species for oil production. However, further analysis by GAIA Webs identified A. oryzae and M. plumbeus as the best performing microorganisms.

The ASAS criteria for axial spondyloarthritis: Strengths, weaknesses, and proposals for a way forward

Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

Manufacturing and use of human placenta-derived mesenchymal stromal cells for phase I clinical trials: Establishment and evaluation of a protocol

Background/Aim. Mesenchymal stromal cells (MSCs) have been utilised in many clinical trials as an experimental treatment in numerous clinical settings. Bone marrow remains the traditional source tissue for MSCs but is relatively hard to access in large volumes. Alternatively, MSCs may be derived from other tissues including the placenta and adipose tissue. In an initial study no obvious differences in parameters such as cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability, were detected when we compared human marrow derived- MSCs to human placenta-derived MSCs. The aim of this study was to establish and evaluate a protocol and related processes for preparation placenta-derived MSCs for early phase clinical trials. Methods. A full-term placenta was taken after delivery of the baby as a source of MSCs. Isolation, seeding, incubation, cryopreservation of human placentaderived MSCs and used production release criteria were in accordance with the complex regulatory requirements applicable to Code of Good Manufacturing Practice manufacturing of ex vivo expanded cells. Results. We established and evaluated instructions for MSCs preparation protocol and gave an overview of the three clinical areas application. In the first trial, MSCs were co-transplanted iv to patient receiving an allogeneic cord blood transplant as therapy for treatmentrefractory acute myeloid leukemia. In the second trial, MSCs were administered iv in the treatment of idiopathic pulmonary fibrosis and without serious adverse effects. In the third trial, MSCs were injected directly into the site of tendon damage using ultrasound guidance in the treatment of chronic refractory tendinopathy. Conclusion. Clinical trials using both allogeneic and autologous cells demonstrated MSCs to be safe. A described protocol for human placenta-derived MSCs is appropriate for use in a clinical setting, relatively inexpensive and can be relatively easily adjusted to a different set of regulatory requirements, as applicable to early phase clinical trials.

Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.

Criteria for working-correlation-structure selection in GEE: Assessment via simulation

Efficiency of analysis using generalized estimation equations is enhanced when intracluster correlation structure is accurately modeled. We compare two existing criteria (a quasi-likelihood information criterion, and the Rotnitzky-Jewell criterion) to identify the true correlation structure via simulations with Gaussian or binomial response, covariates varying at cluster or observation level, and exchangeable or AR(l) intracluster correlation structure. Rotnitzky and Jewell's approach performs better when the true intracluster correlation structure is exchangeable, while the quasi-likelihood criteria performs better for an AR(l) structure.

Bi-criteria single machine scheduling problem with a learning effect: Aneja-Nair method to obtain the set of optimal sequences

In this paper, we consider the bi-criteria single machine scheduling problem of n jobs with a learning effect. The two objectives considered are the total completion time (TC) and total absolute differences in completion times (TADC). The objective is to find a sequence that performs well with respect to both the objectives: the total completion time and the total absolute differences in completion times. In an earlier study, a method of solving bi-criteria transportation problem is presented. In this paper, we use the methodology of solvin bi-criteria transportation problem, to our bi-criteria single machine scheduling problem with a learning effect, and obtain the set of optimal sequences,. Numerical examples are presented for illustrating the applicability and ease of understanding.

Exact solutions of linear reaction-diffusion on a uniformly growing domain: criteria for successful colonization

Many processes during embryonic development involve transport and reaction of molecules, or transport and proliferation of cells, within growing tissues. Mathematical models of such processes usually take the form of a reaction-diffusion partial differential equation (PDE) on a growing domain. Previous analyses of such models have mainly involved solving the PDEs numerically. Here, we present a framework for calculating the exact solution of a linear reaction-diffusion PDE on a growing domain. We derive an exact solution for a general class of one-dimensional linear reaction—diffusion process on 0

A mixed-methods research approach to the review of competency standards for orthotist/prosthetists in Australia

Aim: The requirement for an allied health workforce is expanding as the global burden of disease increases internationally. To safely meet the demand for an expanded workforce of orthotist/prosthetists in Australia, competency based standards, which are up-to-date and evidence-based, are required. The aims of this study were to determine the minimum level for entry into the orthotic/prosthetic profession; to develop entry level competency standards for the profession; and to validate the developed entry-level competency standards within the profession nationally, using an evidence-based approach. Methods: A mixed-methods research design was applied, using a three-step sequential exploratory design, where step 1 involved collecting and analyzing qualitative data from two focus groups; step 2 involved exploratory instrument development and testing, developing the draft competency standards; and step 3 involved quantitative data collection and analysis – a Delphi survey. In stage 1 (steps 1 and 2), the two focus groups – an expert and a recent graduate group of Australian orthotist/prosthetists – were led by an experienced facilitator, to identify gaps in the current competency standards and then to outline a key purpose, and work roles and tasks for the profession. The resulting domains and activities of the first draft of the competency standards were synthesized using thematic analysis. In stage 2 (step 3), the draft-competency standards were circulated to a purposive sample of the membership of the Australian Orthotic Prosthetic Association, using three rounds of Delphi survey. A project reference group of orthotist/prosthetists reviewed the results of both stages. Results: In stage 1, the expert (n = 10) and the new graduate (n = 8) groups separately identified work roles and tasks, which formed the initial draft of the competency standards. Further drafts were refined and performance criteria added by the project reference group, resulting in the final draft-competency standards. In stage 2, the final draft-competency standards were circulated to 56 members (n = 44 final round) of the Association, who agreed on the key purpose, 6 domains, 18 activities, and 68 performance criteria of the final competency standards. Conclusion: This study outlines a rigorous and evidence-based mixed-methods approach for developing and endorsing professional competency standards, which is representative of the views of the profession of orthotist/prosthetists.

Oscillation criteria for differential equations of second order

In this article, we give sufficient condition in the form of integral inequalities to establish the oscillatory nature of non linear homogeneous differential equations of the form where r, q, p, f and g are given data. We do this by separating the two cases f is monotonous and non monotonous.

Stability criteria for single pulse solutions of cw passive mode-locked lasers

The stability of the steady-state solutions of mode-locking of cw lasers by a fast saturable absorber is imvestigated. It is shown that the solutions are stable if the condition (Ps/Pa) = (2/3) (P0Pa) is satisfied, where (Ps/Pa) is the steady-state la ser power, (P0/Pa) is the power at mode-locking threshold, and Pa is the saturated power of the absorber.

Soil nitrogen—crop response calibration relationships and criteria for winter cereal crops grown in Australia

More than 1200 wheat and 120 barley experiments conducted in Australia to examine yield responses to applied nitrogen (N) fertiliser are contained in a national database of field crops nutrient research (BFDC National Database). The yield responses are accompanied by various pre-plant soil test data to quantify plant-available N and other indicators of soil fertility status or mineralisable N. A web application (BFDC Interrogator), developed to access the database, enables construction of calibrations between relative crop yield ((Y0/Ymax) × 100) and N soil test value. In this paper we report the critical soil test values for 90% RY (CV90) and the associated critical ranges (CR90, defined as the 70% confidence interval around that CV90) derived from analysis of various subsets of these winter cereal experiments. Experimental programs were conducted throughout Australia’s main grain-production regions in different eras, starting from the 1960s in Queensland through to Victoria during 2000s. Improved management practices adopted during the period were reflected in increasing potential yields with research era, increasing from an average Ymax of 2.2 t/ha in Queensland in the 1960s and 1970s, to 3.4 t/ha in South Australia (SA) in the 1980s, to 4.3 t/ha in New South Wales (NSW) in the 1990s, and 4.2 t/ha in Victoria in the 2000s. Various sampling depths (0.1–1.2 m) and methods of quantifying available N (nitrate-N or mineral-N) from pre-planting soil samples were used and provided useful guides to the need for supplementary N. The most regionally consistent relationships were established using nitrate-N (kg/ha) in the top 0.6 m of the soil profile, with regional and seasonal variation in CV90 largely accounted for through impacts on experimental Ymax. The CV90 for nitrate-N within the top 0.6 m of the soil profile for wheat crops increased from 36 to 110 kg nitrate-N/ha as Ymax increased over the range 1 to >5 t/ha. Apparent variation in CV90 with seasonal moisture availability was entirely consistent with impacts on experimental Ymax. Further analyses of wheat trials with available grain protein (~45% of all experiments) established that grain yield and not grain N content was the major driver of crop N demand and CV90. Subsets of data explored the impact of crop management practices such as crop rotation or fallow length on both pre-planting profile mineral-N and CV90. Analyses showed that while management practices influenced profile mineral-N at planting and the likelihood and size of yield response to applied N fertiliser, they had no significant impact on CV90. A level of risk is involved with the use of pre-plant testing to determine the need for supplementary N application in all Australian dryland systems. In southern and western regions, where crop performance is based almost entirely on in-crop rainfall, this risk is offset by the management opportunity to split N applications during crop growth in response to changing crop yield potential. In northern cropping systems, where stored soil moisture at sowing is indicative of minimum yield potential, erratic winter rainfall increases uncertainty about actual yield potential as well as reducing the opportunity for effective in-season applications.

Soil phosphorus–crop response calibration relationships and criteria for winter cereal crops grown in Australia

Soil testing is the most widely used tool to predict the need for fertiliser phosphorus (P) application to crops. This study examined factors affecting critical soil P concentrations and confidence intervals for wheat and barley grown in Australian soils by interrogating validated data from 1777 wheat and 150 barley field treatment series now held in the BFDC National Database. To narrow confidence intervals associated with estimated critical P concentrations, filters for yield, crop stress, or low pH were applied. Once treatment series with low yield (<1 t/ha), severe crop stress, or pHCaCl2 <4.3 were screened out, critical concentrations were relatively insensitive to wheat yield (>1 t/ha). There was a clear increase in critical P concentration from early trials when full tillage was common compared with those conducted in 1995–2011, which corresponds to a period of rapid shift towards adoption of minimum tillage. For wheat, critical Colwell-P concentrations associated with 90 or 95% of maximum yield varied among Australian Soil Classification (ASC) Orders and Sub-orders: Calcarosol, Chromosol, Kandosol, Sodosol, Tenosol and Vertosol. Soil type, based on ASC Orders and Sub-orders, produced critical Colwell-P concentrations at 90% of maximum relative yield from 15 mg/kg (Grey Vertosol) to 47 mg/kg (Supracalcic Calcarosols), with other soils having values in the range 19–27 mg/kg. Distinctive differences in critical P concentrations were evident among Sub-orders of Calcarosols, Chromosols, Sodosols, Tenosols, and Vertosols, possibly due to differences in soil properties related to P sorption. However, insufficient data were available to develop a relationship between P buffering index (PBI) and critical P concentration. In general, there was no evidence that critical concentrations for barley would be different from those for wheat on the same soils. Significant knowledge gaps to fill to improve the relevance and reliability of soil P testing for winter cereals were: lack of data for oats; the paucity of treatment series reflecting current cropping practices, especially minimum tillage; and inadequate metadata on soil texture, pH, growing season rainfall, gravel content, and PBI. The critical concentrations determined illustrate the importance of recent experimental data and of soil type, but also provide examples of interrogation pathways into the BFDC National Database to extract locally relevant critical P concentrations for guiding P fertiliser decision-making in wheat and barley.