IP Strategies for Green Innovations - An Analysis of European Inventor Awards

To drive sustainability transitions on a global scale for a carbon neutral future, green innovations are needed. In this study, we are keen to understand the role of intellectual property (IP) and particularly, its usage by firms innovating for a sustainable future. Unfortunately, little is known about how IP impacts sustainability transitions. To contribute to a better understanding, we chose to investigate IP usage by award - winning green innovators. We study the winners of the European Inventor Award, a highly prestigious international prize, awarded annually by the European Patent Office since 2006. Among all 210 awardees, we identified 52 winners that we classified as green innovators. Our analysis shows that closed and semi-open IP, particularly non-exclusive licensing, are the preferred IP strategies for green innovations. The IP strategy preferences seem to vary across technology domains. These findings are discussed along with their implications

MUC1-C drives myeloid leukaemogenesis and resistance to treatment by a survivin-mediated mechanism

Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with an unmet need for improved therapies. Responses to standard cytotoxic therapy in AML are often transient because of the emergence of chemotherapy-resistant disease. The MUC1-C oncoprotein governs critical pathways of tumorigenesis, including self-renewal and survival, and is aberrantly expressed in AML blasts and leukaemia stem cells (LSCs). However, a role for MUC1-C in linking leukaemogenesis and resistance to treatment has not been described. In this study, we demonstrate that MUC1-C overexpression is associated with increased leukaemia initiating capacity in an NSG mouse model. In concert with those results, MUC1-C silencing in multiple AML cell lines significantly reduced the establishment of AML in vivo. In addition, targeting MUC1-C with silencing or pharmacologic inhibition with GO-203 led to a decrease in active β-catenin levels and, in-turn, down-regulation of survivin, a critical mediator of leukaemia cell survival. Targeting MUC1-C was also associated with increased sensitivity of AML cells to Cytarabine (Ara-C) treatment by a survivin-dependent mechanism. Notably, low MUC1 and survivin gene expression were associated with better clinical outcomes in patients with AML. These findings emphasize the importance of MUC1-C to myeloid leukaemogenesis and resistance to treatment by driving survivin expression. Our findings also highlight the potential translational relevance of combining GO-203 with Ara-C for the treatment of patients with AML

Exploring the interplay between intellectual property models and sustainability transitions: a multi-level analysis

Research on international technology transfer and partnership agreements provides a comprehensive understanding of country-level impacts of intellectual property (IP) rights on sustainability transitions. However, firm-level studies on how firms use and share their IP to support sustainability practices remains limited. The paper disentangles the relationship between firm-level IP models and sustainability practices drawing from a cross-case analysis of 28 firms offering sustainable innovations across four sectors. Analysis of firms’ year-wise data collected from 854 documents (typically 1996-2021) and 58 in-depth interviews exploring linkage between IP models and sustainability practices of firms engaged in sustainable innovation provide six key findings (1) emphasis on safeguarding registered and unregistered IP assets among firms with sustainable innovations (2) widespread adoption of selectively open inbound IP models coupled with diverse IP sharing mechanisms (3) a preference for collaborative (joint) IP ownership among internally driven firms, contrasting with a tendency for exclusive in-licensing among those reacting to external pressures (4) a divergence in outbound IP models, with internally motivated firms favouring selectively open approaches and externally driven firms favoring closed IP models; (5) the adoption of fully open outbound IP models democratize sustainable innovation diffusion; (6) leveraging broadly open outbound IP models alongside closed or selectively open models balances widespread use with access control and achieves significant social sustainability. A framework is hence developed to guide technology-sharing policies and procedures. Thereby, the paper creates a platform for prescribing sustainable IP incentives for encouraging firms to share IP for wider diffusion of sustainable innovations

The Business Model in Sustainability Transitions: A Conceptualization

Business models direct a firm’s activity to move in coherence with the objectives of the business. Current literature suggests business models can act as vital forces to facilitate sustainability transitions and highlights the urgent research call to understand the role of business model innovations in stimulating sustainability transitions. This paper addresses this research need by investigating how firms create business model innovations for system-level transformation towards sustainability. Through a systematic literature review and deductive content analysis methodology, we identify and categorize different combinations of innovative activities in a firm’s business model. Furthermore, two cases are illustrated to demonstrate the proposed conceptual model. The proposed conceptualization bridges a significant gap in the theme of sustainability and business and presents a defensible and researchable problem for transitions literature. Specifically, we find (1) shared vision and strategic dialogues among firms in different sectors as essential to develop value propositions and leverage business opportunities for sustainability in the long run; (2) companies ensure sustainable value creation and value delivery in the medium term through creation of an interdependent network of the green supply chain and collaboration with stakeholders; (3) in the short term, companies adopt sustainable practices, controlling daily operations, conducting awareness campaigns and experimenting with collaborations to deliver values based on sustainable practices

Hgfr And Fgr2: Their Roles 1 In Progression And Metastasis Of Esophageal Cancer

Esophageal cancer (EC) is the sixth leading cause of malignancy-related death in the world. The disease is characterized by two types of histologies: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC), which are the most common in the Western world. While alcohol has proven to lead to ESCC, it has not been associated with EAC. Progressive dysphagia (first with solids, followed by liquids) and rapid involuntary weight loss are the two most common symptoms, which make most patients seek medical attention. Most patients have a long period of symptoms before they seek care. At diagnosis, ~50% of the patients already have metastasis. The treatment of gastroesophageal cancers continues to pose significant clinical challenges for various defined reasons. The majority of patients fail intensive and toxic multimodality therapy for locoregional disease, and systemic chemotherapy for metastatic carcinoma gives short-term benefits only. Our understanding of the molecular pathology of gastroesophageal cancers has considerably increased during the recent years, leading to the development of novel targeted therapeutic agents that have proven to be promising in improving the patients’ survival with minimal adverse events. Receptor tyrosine kinases (RTKs) play pivotal role(s) in the formation, maintenance, growth, and differentiation of the malignant cells encompassing both histological types of EC. Malignancies treated with chemotherapy/radiation therapy face the challenge of developing resistance and increasing the aggressive nature of cancerous cells leading to undesirable recurrence. In peer-reviewed literature, an array of RTKs have been described in ESCC, and more recently, they are being assessed for their therapeutic utility. Notably, structures of hepatocyte growth factor receptor (HGFR) and fibroblast growth factors receptor 2 (FGR2) are two of the many prominent RTKs studies thus far. In this chapter, we thoroughly discuss the clinical characteristics of the disease and structure-functional aspects of various RTKs with focus on HGFR and FGR2 as it relates to the translational and clinical outcomes of EC

The Business Model in Sustainability Transitions:A Conceptualization

Business models direct a firm’s activity to move in coherence with the objectives of the business. Current literature suggests business models can act as vital forces to facilitate sustain-ability transitions and highlights the urgent research call to understand the role of business model innovations in stimulating sustainability transitions. This paper addresses this research need by investigating how firms create business model innovations for system-level transformation towards sustainability. Through a systematic literature review and deductive content analysis methodology, we identify and categorize different combinations of innovative activities in a firm’s business model. Furthermore, two cases are illustrated to demonstrate the proposed conceptual model. The proposed conceptualization bridges a significant gap in the theme of sustainability and business and presents a defensible and researchable problem for transitions literature. Specifically, we find (1) shared vision and strategic dialogues among firms in different sectors as essential to develop value propositions and leverage business opportunities for sustainability in the long run; (2) companies ensure sustainable value creation and value delivery in the medium term through creation of an interdependent network of the green supply chain and collaboration with stakeholders; (3) in the short term, companies adopt sustainable practices, controlling daily operations, conducting awareness campaigns and experimenting with collaborations to deliver values based on sustainable practices

Functional Consequences And Clinical Significance Of Tyrosine Kinase Inhibitors In Advanced Colorectal Cancer

Colorectal cancer (CRC) is an important public health issue as the 5-year prognosis is \u3c20% for newly diagnosed metastatic CRC (mCRC). In recent years, screening modalities have led to early detection of the disease, which has shown some promise for improved survival. The advancements in adjunctive treatments and aggressive surgical treatment are also partly responsible for this success, but the deeper understanding of carcinogenesis and targeted molecular therapy has made a stronger impact with the emergence of newer targets in the recent past. Particularly, the development and FDA approval of newer drugs, including capecitabine, irinotecan, oxaliplatin, monoclonal antibodies that block either VEGF (bevacizumab, aflibercept, and ramucirumab) or the EGFR (cetuximab and panitumumab), and most recently, trifluridine/tipiracil and regorafenib (TAS-102), have been remarkable in this area of research. The clinical benefits of these drugs are now generally acceptable/established for mCRC patients, with the median overall survival of \u3e30 months. Currently, limitation in the effectiveness of tyrosine kinase inhibitors (TKIs) is due to (i) combination chemotherapy use that necessitates lowering of the dose density for toxicity profile management, and (ii) these drugs have mainly been developed in molecularly unselected population. The main challenge now is the identification of more reliable and 116 specific predictive biomarkers for selecting the most suitable therapy for mCRC. So far, the only well-established/reliable biomarker for mCRC treatment is RAS mutational status, which predicts negative response to anti-EGFR therapy. Current recommendation for the BRAF mutational status has also been given by the NCCN and the ESMO. Unlike VEGF inhibitor therapy, the resistance mechanisms in the EGFR inhibitor therapy are well understood, as are the drugs blocking the downstream RAS-MAPK pathway. Notably, a number of clinical trials on targeting the RAS signaling pathway have revealed promising efficacy in chemo-refractory mCRC. This chapter discusses the role of TKIs in advanced CRC from both translational and clinical research points of view

Identification and functional characterization of a bacterial homologue of Zeta toxin in Leishmania donovani.

Zeta-toxin is a cognate toxin of epsilon antitoxin of prokaryotic Type II toxin-antitoxin system (TA) and play an important role in cell death. An orthologue of bacterial-zeta-toxin (BzT) was identified in Leishmania donovani with similar structural and functional features. Leishmania zeta-toxin (named Ld_zeta1) harboring similar UNAG and ATP-binding pockets showed UNAG kinase and ATP-binding activity. An active Ld_zeta1 was found to express in infective extracellular promastigotes stage of L. donovani and episomal overexpression of an active Ld_zeta1domain-triggered cell death. This study demonstrates the presence of prokaryotic-like-zeta-toxin in eukaryotic parasite Leishmania and its association with cell death. Conceivably, phosphorylated UNAG or analogues, the biochemical mimics of zeta-toxin function mediating cell death can act as a novel anti-leishmanial chemotherapeutics.pmid: 31074836status: publishe

AML-225: Outcome with Intensive Chemotherapy vs Hypomethylating Agent-Based Induction Strategies in Patients Older Than 70 Years with Newly Diagnosed, Favorable-Risk Acute Myeloid Leukemia

Real-world evidence is lacking regarding the effectiveness of intensive and non-intensive induction strategies in elderly patients with favorable-risk acute myeloid leukemia (AML). To estimate the rates of complete remission (CR), CR+ CR with incomplete count recovery (CRi), and overall survival (OS) in patients receiving intensive chemotherapy (IC) and hypomethylating agent (HMA)-based induction regimens. In this retrospective study, clinical and genomic data were collected by review of records of eligible patients treated at Moffitt Cancer Center. Statistical analyses were performed using SPSS. Elderly (age > 70 years) patients with newly diagnosed, favorable-risk (ELN 2017) AML. CR, CR+ CRi, OS. Out of total 53 patients, 36 (68%) received IC, and 17 (32%) received HMA-based induction regimen. Median age at diagnosis was 74 years (range 70–85). Core binding factor (CBF) abnormalities were detected in 47% patients; 28% had secondary AML. Median blast count was significantly higher in patients receiving IC vs HMA (58% vs 32%, p=0.01). Predominant induction regimen was “7+3” (86%) in the IC group and azacytidine alone (n=11) in HMA cohort. Rate of composite CR (CR+ CRi) was significantly better at 69% (50% CR) in the IC group, compared to 35% (24% CR) with HMA (p=0.01). Six patients on IC and 1 on HMA had early (<30 d) induction-related mortality. Both groups had comparable relapse rates (overall 34%). Median OS was 24.7 months in IC vs 17.5 months in the HMA group, trending toward statistical significance (p=0.058). Overall, 23% patients in the IC group were alive at 5 years, compared to 7% with HMA. In patients with CBF-AML (n=25), median OS was not reached for IC vs 23 months with HMA (p= 0.076); CBF-AML was an independent predictor of survival in the study population. Six patients (3 post-relapse) from the IC group underwent allogeneic stem cell transplant. Elderly favorable-risk AML patients had a significantly better composite CR rate on induction treatment with IC than with HMA, with a trend toward improved OS with IC-based induction. A multicenter study with a larger sample size is ongoing to address this question further