International Stem Cell Corporation Research Articles

Human parthenogenetic neural stem cell grafts promote multiple regenerative processes in a traumatic brain injury model.

International Stem Cell Corporation human parthenogenetic neural stem cells (ISC-hpNSC) have potential therapeutic value for patients suffering from traumatic brain injury (TBI). Here, we demonstrate the behavioral and histological effects of transplanting ISC-hpNSC intracerebrally in an animal model of TBI.Methods: Sprague-Dawley rats underwent a moderate controlled cortical impact TBI surgery. Transplantation occurred at 72 h post-TBI with functional readouts of behavioral and histological deficits conducted during the subsequent 3-month period after TBI. We characterized locomotor, neurological, and cognitive performance at baseline (before TBI), then on days 0, 1, 7, 14, 30, 60, and 90 (locomotor and neurological), and on days 28-30, 58-60, and 88-90 (cognitive) after TBI. Following completion of behavioral testing at 3 months post-TBI, animals were euthanized by transcardial perfusion and brains harvested to histologically characterize the extent of brain damage. Neuronal survival was revealed by Nissl staining, and stem cell engraftment and host tissue repair mechanisms such as the anti-inflammatory response in peri-TBI lesion areas were examined by immunohistochemical analyses.Results: We observed that TBI groups given high and moderate doses of ISC-hpNSC had an improved swing bias on an elevated body swing test for motor function, increased scores on forelimb akinesia and paw grasp neurological tests, and committed significantly fewer errors on a radial arm water maze test for cognition. Furthermore, histological analyses indicated that high and moderate doses of stem cells increased the expression of phenotypic markers related to the neural lineage and myelination and decreased reactive gliosis and inflammation in the brain, increased neuronal survival in the peri-impact area of the cortex, and decreased inflammation in the spleen at 90 days post-TBI.Conclusion: These results provide evidence that high and moderate doses of ISC-hpNSC ameliorate TBI-associated histological alterations and motor, neurological, and cognitive deficits.

Novel Approach to Stem Cell Therapy in Parkinson's Disease.

In this commentary we discuss International Stem Cell Corporation's (ISCO's) approach to developing a pluripotent stem cell based treatment for Parkinson's disease (PD). In 2016, ISCO received approval to conduct the world's first clinical study of a pluripotent stem cell based therapy for PD. The Australian regulatory agency Therapeutic Goods Administration (TGA) and the Melbourne Health's Human Research Ethics Committee (HREC) independently reviewed ISCO's extensive preclinical data and granted approval for the evaluation of a novel human parthenogenetic derived neural stem cell (NSC) line, ISC-hpNSC, in a PD phase 1 clinical trial ( ClinicalTrials.gov NCT02452723). This is a single-center, open label, dose escalating 12-month study with a 5-year follow-up evaluating a number of objective and patient-reported safety and efficacy measures. A total of 6 years of safety and efficacy data will be collected from each patient. Twelve participants are recruited in this study with four participants per single dose cohort of 30, 50, and 70 million ISC-hpNSC. The grafts are placed bilaterally in the caudate nucleus, putamen, and substantia nigra by magnetic resonance imaging-guided stereotactic surgery. Participants are 30-70 years old with idiopathic PD ≤13 years duration and unified PD rating scale motor score (Part III) in the "OFF" state ≤49. This trial is fully funded by ISCO with no economic involvement from the patients. It is worth noting that ISCO underwent an exhaustive review process and successfully answered the very comprehensive, detailed, and specific questions posed by the TGA and HREC. The regulatory/ethic review process is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines or novel therapies.

International Stem Cell Corporation V. Comptroller General of Patents, Designs and Trade Marks (C.J.E.U.)

On December 18, 2014, the Grand Chamber of the Court of Justice of the European Union (CJEU) issued its judgment in International Stem Cell Corporation v. Comptroller General of Patents, Designs and Trade Marks. The Court held that the term “human embryo” does not cover unfertilized human eggs produced by parthenogenesis (parthenotes).

Some Problems Related to the “Human Embryo” in the European Union Law

Abstract The following article is dedicated to the topic of human dignity - the human embryos and the legal framework they are regulated by in the EU: The Charter of Fundamental Rights of European Union and the EU Court practice. For the purpose, the authors look first and foremost at the EU Directive 98/44, regulating the legal protection of biotechnological inventions which aim at balancing the human beings' dignity and integrity with the need to preserve the social function of patents as a vector for the competiveness of the European biotech industry. Two key EU Court cases are analyzed, both of which reflecting the evolution of the Court of Justice on the European Union's Case Law on Stem Cell Patents, namely Case C-34/10 Oliver Brüstle v Greenpeace е. V. and Case C-364/13 International Stem Cell Corporation. The article looks then at the European Citizens’ Initiative “One of us”, which aims at securing Juridical protection of the dignity, the right to life, as well as to the integrity of every human being from conception in those areas of EU competence where such protection has a particular importance.

A “Ray of Hope” for European Stem Cell Patents or “Out of the Smog into the Fog”? An Analysis of Recent European Case Law and How it Compares to the US

In Case C-364/13, International Stem Cell Corporation (ISCO) v. Comptroller General of Patents (18 December 2014), the Court of Justice of the European Union distinguished its earlier ruling in Brustle v. Greenpeace (Brustle) with regard to the patent eligibility of non-fertilised human ova stimulated by parthenogenesis. The Court found that in order to be considered a human embryo – and thus to be unpatentable under the EU Biotechnology Directive – the stimulated ovum must have the “inherent capacity to develop into a human being”. This permits the patenting of innovative pluripotent parthenotes and their applications. Yet the ISCO decision also leaves considerable discretion to national courts. Hence, the full impact of the decision still depends on national implementations. Moreover, ISCO only applies to very specific human embryonic stem cells (hESCs) and lacks further clarification concerning other non-totipotent hESCs, such as stem cells created through somatic cell nuclear transfer. Considering the significance of Brustle and ISCO for regenerative medicine and cellular therapy, the persistent legal uncertainty is unfortunate. Irrespective of these flaws, however, ISCO has opened patentability doors that were previously closed and thereby reinvigorated crucial debates. Thus, this might have the “inherent capacity” of developing into a reasonable doctrine on stem cell patenting. Paradoxically, the patentability of isolated hESCs is now less certain in the US, making a brief comparison inevitable.

Comment on “International Stem Cell”: The EU Court of Justice Revisits the Patentability of Processes for the Production of Human Stem Cells – The Decision in International Stem Cell Corporation

The brocard ius excludendi omnes alios describes the essence of patentability. These four words define a very basic principle: each patent confers to the owner a crystal-clear right to exclude others from the utilisation of the invention. However, as we move from the general ground of patentability to the specific field of human stem cells (hSCs), this crystal starts to reveal blurry edges and opacities. The aim of this paper is to shed light on these opacities. The recent decision of the Court of Justice of the European Union (CJEU) in International Stem Cell Corporation v. Comptroller General of Patents, Designs and Trade Marks will be used as a means to interpret hSCs patentability. The CJEU returned, after its decision in Brustle, on the definition of a human embryo expunging any unfertilised human ovum whose division and further development have been stimulated by parthenogenesis.

The Court of Justice of the European Union Clarifies when Human Embryonic Stem Cells Can Be Patented

On 18 December 2014, in International Stem Cell Corporation v. Comptroller General of Patents, Designs and Trade Marks (C-364/13), the Court of Justice of the European Union (CJEU) delivered an important decision regarding the scope of the exclusion from patentability on morality-related grounds under Article 6(2) of the EU Biotech Directive. The Court made an important distinction between embryonic stem cell technologies based on fertilised human ovum and those based on unfertilised human ovum stimulated by parthenogenesis. The CJEU held, in particular, that a human ovum: (i) who is unfertilized and (ii) whose division and further development has been stimulated by parthenogenesis, is not a human embryo under Article 6(2)(c) of the Biotech Directive, if it in itself has not the inherent capacity of developing into a human being, this matter to be ascertained by the national court in the light of current scientific knowledge. By doing so, the Court clarified its previous ruling in Brustle (October 2011).

Patentability of Parthenogenic Stem Cells: International Stem Cell Corporation v. Comptroller General of Patents.

The European Court of Justice (ECJ) has recently issued a ruling in Case C-364/13 International Stem Cell Corporation v. Comptroller General of Patents Designs and Tademarks (Case) that aims at harmonising the patenting practices regarding interpretation of Article 6.2.c of Directive 98/44/EC (Biotech Patent Directive) in respect of patentability of human parthenogenic stem cells (hpSCs). The Case alters the patenting regime for human embryonic stem cell (hESC) applications, by stating that moral restrictions against hESC-patents are only applicable to such cells derived from embryos that had the potential to develop into a human being. Consequently, hpSC-based inventions may be patentable in Europe. This Case represents a leap forward to striking a balance between protecting human dignity and integrity whilst granting patent incentives for biomedical research.

European Court of Justice. ECJ 2015/2, International Stem Cell Corporation v. Comptroller General of Patents, Designs and Trade Marks, 18 December 2014 (C-364/13).

European Court of Justice. ECJ 2015/2, International Stem Cell Corporation v. Comptroller General of Patents, Designs and Trade Marks, 18 December 2014 (C-364/13).

The Evolution of the CJEU's Case Law on Stem Cell Patents: Context, Outcome and Implications of Case CC364/13 International Stem Cell Corporation.

On 18th December 2014, the CJEU rendered its’ much-anticipated decision in C‑364/13 International Stem Cell Corporation v Comptroller General of Patents (ISCC). Qualifying its’ earlier ruling in Brustle v. Greenpeace (Brustle) with regard to non-fertilised human ova stimulated by parthenogenesis, the Court held that in order to constitute a ‘human embryo’ - and thus to be unpatentable under the EU Biotechnology Directive - the stimulated ovum must have the “inherent capacity to develop into a human being”. This would allow patents on innovative parthenotes which had not been genetically modified to achieve totipotent capabilities. Hence the judgment establishes a crucial limitation of the broad interpretation of “human embryos” in Brustle, where the CJEU held that parthenotes are covered by the term “human embryo” since they are “capable of commencing the process of development of a human being”. The ISCC decision is to be welcomed since it provides an ethically justifiable leeway for patenting and offers reasonable support to the commercial viability of European cell therapy research. Yet, ISCC’s impact still depends on national implementations and only applies to certain hESC cells. Thus, further clarifications would be helpful concerning other non-totipotent hESCs.

INSIDE INDUSTRY

NCCS doctor wins recognition in the prestigious Singapore Youth Awards 2014 Singapore - Republic of Korea collaboration on biomedical technology shows results International Stem Cell Corporation signs agreement with Rohto Pharmaceutical of Japan AstraZeneca and Max Planck Institute enter research agreement to create satellite chemistry unit for cardiovascular and metabolic diseases Reaction Biology receives NIH grant award for epigenetic database New Zealand and Singapore to collaborate on food and nutrition research 5th Biomass Pellets Trade & Power spotlights on Asia's unprecedented biomass industry growth and mega opportunities 'Sustainability' issues take center-stage when 6th Palm Oil Asia Summit returns to Jakarta this August Asia's supremacy in oleochemicals market takes center stage at 2nd Olechemicals Outlook Summit in Jakarta, this August

Industry Watch

CSL to Set up Biotech Facility in Victoria. Merck to Work with Sinopharm to Market HPV Shot and Other Vaccines in China. China PharmaHub Corp. Signs Merger Agreement with World Wide Relics. Lambda Therapeutic Research Acquires North American CRO. Cochlear Commences Operations in India. CordLife Introduces Quality Guarantee Program in India. Opto Circuits Acquires US-based Unetixs Vascular. Stem Cell-Based Treatment Collaboration for Corneal Vision Impairment, International Stem Cell Corporation. Axiogenesis In-Licenses Yamanaka Patent Portfolio from iPS Academia Japan. ArQule, Daiichi Sankyo to Conduct trials for NSCLC Drug. Pfizer, Samsung Medical Center to Study Liver Cancer. Agilent Technologies Signs Agreement with Government of Malaysia to Cooperate in Biotechnology. Bayer Animal Health, Paraco Agree on Access to Lead Molecules. A*STAR & Cytos Biotechnology Collaborate on Influenza Vaccine.