Journal articles on the topic 'Pharmaceutical biotechnology – Patents'

Background: Alpha-amylases are enzymes capable of degrading polysaccharides, such as starch and glycogen. Found in various organisms, such as fungi and bacteria, these enzymes have great biotechnological potential due to their insertion in several industrial sectors ranging from food to biofuels. Objective: The aim of this study was to analyze patents deposited in intellectual property databases on alpha-amylases in the fields of food, beverages, detergents, animal feeds, biofuels, pharmaceuticals and textiles, with the search period being 5 years. Methods: This study targeted the use of alpha-amylases in various industrial sectors, so searches were carried out on the intellectual property database Espacenet website (European Patent Office - EPO) which contains more than 90 million patents deposited in its database. Results: During the search for patents filed in the last 5 years, 186 were found related to the use of alpha-amylases. These were disturbed as follows: 84 (biofuel), 41 (drinks), 16 (pharmaceuticals), 15 (detergents), 11 (food), 10 (animal feed), 9 (textiles). From the total number of patents found, we selected 6 from each area, except pharmaceutical products, to discuss and provide information on the application of this enzyme. Conclusion: This study demonstrated that the sectors of beverages and animal feed have preferences for thermostable alpha-amylases while sectors such as food, biofuels and textiles only regarded the importance of enzymatic efficiency. The detergent sector presented the greatest use of alpha-amylases which had distinct biochemical characteristics as solvent resistance and thermostability. The pharmaceutical sector was the one that presented less patents related to the application of alpha amylases. In addition, this work showed that China is the country with the highest patent registration for the use of alpha-amylases in the analyzed period.

This study investigated the effect of patent value on the renewal (survival) of patents. The private value of patents can be one of the main pillars sustaining a firm’s value, and the estimation of the value may contribute to the strategic management of firms. The current study aimed to confirm the recent research findings with survival analysis, focusing on the more homogeneous patent data samples. In this study, a dataset is constructed from a cohort of 6646 patents from the 1996 and 1997 application years, using patent data from the European Patent Office (EPO). We found that the family size and non-patent backward citations exhibited profound impacts on patent survival. This result is in line with numerous studies, indicating the positive impact of science linkages in the biotechnology and pharmaceutical fields. It was also found that the effect of the ex-post indicator is not as strong as the ex-ante indicators, like traditional family size and backward citations. In short, the family size matters most for the survival of patents, according to the current research.

In this paper, we discuss the implications of the recent Intellectual Property Right (IPR) enforcement in the European Union (EU) as a potential factor affecting agrifood biotechnology industry stagnation. After presenting a theoretical framework justifying patents, we describe some controversial questions in the European patent protection related to: a) the distinction between discovery and invention and; b) the morality and ordre public exception to the patentability. Although we provide some evidence about the reduction in importance of agrifood activities compared to that of pharmaceutical areas of application, we conclude that differences between EU and other developed countries IPR legislations are not the principal regulatory controversial factor affecting activities in the agrifood biotechnology sector.

There has long been a debate centered around genomic and biomedical data patenting. The opposition expresses concern that the patenting of genomic and biomedical data will hinder the manufacturing and distribution of medical and scientific discoveries to those who need them. On the other hand, supporters of patenting genomic and biomedical data explain that patents are beneficial. For example, genomic and biomedical patents allow pharmaceutical companies and research labs to recoup their massive investments in researching and developing new medical and scientific methodologies and technologies. Patents also incentivize these companies to make discoveries to prevent future pandemics and diseases. In 2020, the COVID-19 pandemic broke out and left the world struggling to create more effective vaccines to combat the virus and its variants. At the center of this battle against the virus, various pharmaceutical companies, such as Pfizer, Moderna, BioNTech, and Arcturus, have been working endlessly to develop possible vaccine candidates for the COVID-19 vaccine. The question of whether these pharmaceutical companies will be allowed the protections afforded by genomic and biomedical patenting to spur more advances in the fields of science and medicine to combat new viruses has come to the forefront once again. With two landmark Supreme Court cases that discuss the patenting of biomedical data and genomic processes, the U.S. Supreme Court has barred the patenting of isolated DNA and naturally occurring processes. However, amid a global pandemic, there are benefits to patenting biomedical data. The U.S. Patent Regime should allow genomic and biomedical data patenting to encourage innovation and incentivize researchers and scientists by taking measures to broaden the scope of patent-protected subject matters and by adopting aspects of foreign patent regimes, such as Japan’s patent regime, to expand the treatment of patent protection and encourage innovation in biotechnology and medicine.

This paper aimed to identify and analyse the evolution of the generic pharmaceutical market in Brazil, specifically olanzapine drugs. For this purpose, it has been demonstrated trends through access free tools. By bibliographical survey in indexed databases as well as official data in Brazil for generic drugs and public policy, it was analyzed and performed a case study . In 2012, global pharmaceutical industry surpassed US$ 950 billion in sales with trend to reach US$ 1,2 trillion by 2016. In Brazil market has grown in its global ranking, jumped from 10th place to 7th place in five years and projection it’ll stay Top five by 2015. Brazil has significant presence in pharmerging markets by increasing US$ 10 billion/year. Generics segment accounts approximately to 20% of the total market. 2003-2011 registered a growth of 42.3%. Patents expiration in the neuroleptics area becomes more promising like a market of olanzapine in the last eight years is around US$ 120 million. After the end of the olanzapine patent (2011) sales increased 270% which demonstrate potential Brazilian market in this new century. Management problems for developing nations and undeveloped such as network management and patents analysis for health care might reveal great opportunities for investors, e.g., creation of the Big Brazilian biotechnology pharmaceutical industry. Keywords: competitive intelligence, pharmaceutical trends, technological and innovation management.

In recent years, the number of drugs of biotechnological origin available for many different diseases has increased exponentially, including different types of cancer, diabetes mellitus, infectious diseases (e.g. AIDS Virus / HIV) as well as cardiovascular, neurological, respiratory, and autoimmune diseases, among others. The pharmaceutical industry has used different technologies to obtain new and promising active ingredients, as exemplified by the fermentation technique, recombinant DNA technique and the hybridoma technique. The expiry of the patents of the first drugs of biotechnological origin and the consequent emergence of biosimilar products, have posed various questions to health authorities worldwide regarding the definition, framework, and requirements for authorization to market such products.

The development of pharmaceutical and biotechnology industries indicates that people around the world use different types of drugs for disease treatment and prevention. In the case of high demand for medicines, great attention to pharmacy industry is paid. Since the drugs are directly linked to human health and life, the state pays special attention to the safety of medicines and the quality of eligibility. Therefore, the companies wishing to become a part of this area are to obtain and then keep the license. The protection of intellectual property allows companies to use substantial investment in new drugs and treatment methods and to conduct research in the future. This is a particular concern for originator companies. Undefended patents also inhibit the creativity of local people as local innovators know that their products can be immediately copied, thus discouraging investment in new investigation.

In appropriate activation of c-MYC proto-oncogene contributes to the development of human cancers. Searches for therapies that target genes and proteins related to neoplastic phenotypes have become frequent. Therefore, inhibiting c-MYC expression has been the target for developing and testing multiple drugs and strategies for the treatment of various human cancers. This study aimed to map scientific and technological productions on the MYC gene at the Scielo, PubMed and Orbit Intelligence platforms between 2000 and 2019. The scientific prospecting revealed 1,259 articles. The most detected categories were: molecular biology, MYC mutations and those addressing the MYC as a drug target or therapeutic strategies. A progressive increase in the number of articles in this last category was found. Technological mapping detected 10,059 patent documents, with 20.2% granted. China and the USA were the largest filers, accounting for more than 40%. Biotechnology was the field with the highest number of patents. Biotechnology and the pharmaceutical sector predominated in the second half of the period investigated, both in scientific and technological prospecting. Our study points to a scientific and technological effort in the development of therapeutic strategies against cancer, in which MYC is among the main targets.

Background: Avocado (Persea Americana, Mill.), belonging to the Lauraceae family, is considered a tropical fruit originating in Central America, with Mexico being the largest producer in the world. The fruit stands out for its economic potential and high nutritional value and its oil has good commercial value, however, its production is still incipient, being mainly used by the pharmaceutical and cosmetic industries. Despite producing a significant amount of oil, the avocado seed is still considered a by-product of fruit processing. Methods: Thus, the objective of this work was to evaluate the technological potential of the oil obtained from the avocado and avocado seed through the research and analysis of patent documents available worldwide, in order to identify the main countries that have the technology researched as well as, the main areas of application. We revised all the patents related to acquisition, application and the use of avocado oil. For this, a search was carried out for the database of the Derwent Innovation Index (DII), which compiles the collection of documents published around the world. Results: A total of 144 patent documents were identified, which were evaluated for the country of origin of thepublisher, the type of thepublisher, inventors, rate of publication over time and areas of application. There has been an increase in the number of patents producded as of 2011, which proves it to be a current and interesting technology. The main countries were the United States and the European Union. Conclusion: The documents identified referred to different processes applied to obtain oil, as well as the application for the development of new food, cosmetic and veterinary products. In this way, although incipient, the researched technology proved to be a promising area of research to be explored by universities and companies in view of the characteristics and potential of the product.

The application of biocatalysis and White Biotechnology tools in chemical areas concerning the production of bulk compounds and other related low-added value products (with high volumes) has been gaining importance in recent years. The expected drivers of biocatalysis for these sectors are energy savings, regioselectivity (leading to cleaner products), the possibility of using thermolabile substrates, as well as the generation of less by-products and manageable wastes. This paper explores some recent industrial granted patents related to biocatalysis and bulk chemicals. Several patents have been identified in fields such as biodiesel and esterification reactions, and sugar or furan chemistry. Overall, innovative strategies involve the identification of novel enzymes, the set-up of improved immobilization methods, as well as novel reactor designs that can offer improved performances and economics. The reported examples indicate that biocatalysis can certainly offer opportunities for these areas as well, far from the typical pharmaceutical and fine chemical applications often reported in the literature.

The right of a person to access medicines is derived from the right to health. At the time of the establishment of fundamental human rights, the issue of lack of access to medical supplies was not considered a violation of human rights. The spread of pandemics has led to the gradual recognition of the right of access to medicines. The TRIPS agreement fundamentally reformatted the discussion on access to medicines. Prior to the TRIPS Agreement, states had considerable independence in the formation and implementation of state policy in the field of intellectual property. TRIPS obliges countries to provide pharmaceutical patents. The growing influence of the international patent system has aroused widespread interest and concern about the impact on access to medicines. The Doha Declaration on the TRIPS Agreement defines the importance of the implementation and interpretation of the Agreement in the most favorable way for the protection of public health by making available to the public existing medicines and creating conditions for the production of new ones. Ukraine is on the way to creating its own legislation in the field of intellectual property. Art. 219 of the Association Agreement between Ukraine and the European Union contains provisions according to which the parties recognize the importance of the Declaration on the TRIPS Agreement in the field of health care. Positive changes in the field of intellectual property include the provisions of the Law of Ukraine «On Amendments to Certain Legislative Acts of Ukraine on the Reform of Patent Legislation» № 816-IX as of 21.07.2020. This law limited the range of objects to be patented. The implementation of these legislative changes is impossible without a proper methodology for the examination of novelty. Reforming the national system of intellectual property protection has created good preconditions for the formation of a civilized pharmaceutical market in Ukraine. Among the areas of legislation in Ukraine, there is an urgent need to form an institution of compulsory licensing. A separate area is the introduction of the pre-grant and post-grant procedures of the opposition. An important area of legislative work is the formation of a favorable domestic policy for innovation and invention in the field of medicine and biotechnology.

This article reports the results of a national survey of patenting activity in UK universities carried out by Kathryn Packer and Andrew Webster as part of a wider project on patenting in the areas of pharmaceuticals and biotechnology. The article seeks to explain the variation in the propensity for universities to patent, and their potential to generate significant income from these patents by reference to a number of factors, including research funding and industrial liaison staffing levels.

Background: Membrane filtration process produced good quality of permeate flux due to which it is used in different industries like dairy, pharmaceutical, sugar, starch and sweetener industry, bioseparation, purification of biomedical materials, and downstream polishing etc. The cross-flow mode of operation has also been used to improve the quality of the Rubber Industrial effluent of Tripura, India. </P><P> Method: The Computational Fluid Dynamics (CFD) simulation of the cross-flow membrane is done by using ANSYS Fluent 6.3. The meshing of the geometry of the membrane is done by Gambit 2.4.6 and a grid size of 100674, the number of faces is 151651 and number of nodes being 50978 has been selected for the simulation purpose from the grid independence test. We have revised and included all patents in the manuscripts related to the membrane filtration unit. </P><P> Results: Single phase Pressure-Velocity coupled Simple Algorithm and laminar model is used for the simulation of the developed model and Fluent 6.3 used for the prediction of pressure, pressure drop, flow phenomena, wall shear stress and shear strain rate inside the module is studied for cross flow membrane. </P><P> Conclusion: From the study, it has been found that CFD simulated results hold good agreement with the experimental values.

Background: L-ASNase (L-asparagine aminohydrolase EC 3.5.1.1) is used for the conversion of L-asparagine to L-aspartic acid and ammonia and also it was found as an agent of chemotherapeutic property according to recent patents. It is known as an anti-cancer agent and recently it has received an immense attention. Various microorganisms have the ability to secrete the L-ASNase. It is famous world-wide as anti-tumor medicine for acute lymphoblastic leukemia and lymphosarcoma. L-ASNase helps in deamination of Asparagine and Glutamine. </P><P> Source: L-ASNase mainly found in two bacterial sources; Escherichia coli and Erwinia carotovora. Isolation from plants: Endophytes were also a great source of L-ASNase. It was isolated from four types of plants named as; C. citratus, O. diffusa, M. koengii, and also P. bleo. </P><P> Applications: L-ASNase is used as a potential anti-tumor medicine. It plays a very much essential role for the growth of tumor cells. Tumor cells require a lot of asparagine for their growth. But ASNase converts to aspartate and ammonia from asparagine. So the tumor cell does not proliferate and fails to survive. The L-ASNase is used as the medicine for the major type of cancer like acute lymphocytic leukemia (ALL), brain. It also used as a medicine for central nervous system (CNS) tumors, and also for neuroblastoma. Two types of L-ASNase have been found. </P><P> Conclusion: L-ASNase becomes a powerful anti-tumor medicine and researchers should develop a potent strain of asparaginase which can produce asparaginase in the industrial level. It is also used in the pharmaceutical industry and food industry on a broader scale.

Purpose The application of laser and optical technologies in the industry is wide and extensive; the development and application of laser and optical technologies have become a promising research domain. However, most existing studies have focused on the technical aspects or the application aspects; these studies have not highlighted the technology distribution and application development of laser and optical technologies from the big picture. Additionally, the manner in which the research and development (R&D) results of universities correspond to the needs of enterprises and industry has become a topic of concern for the public. Therefore, this study aims to adopt the academic patents as the basis for analysis and to construct a laser and optical technology network. Design/methodology/approach Therefore, in the current study, the researchers have analyzed relevant academic patent technology networks, using academic patents of laser and optical technologies as a basis of analysis. Findings The study results indicated that the key technologies mainly lie in nanostructures, metal-working, material analysis and semiconductor devices. Additionally, these technologies are mainly applied in industries, such as optics, medical technology, pharmaceuticals, biotechnology and organic fine chemistry; this indicated that a large proportion of academia’s R&D outcomes are applied in these industries. Originality/value In this study, the researchers have constructed a technology network model to explore the technical development direction of laser and optical technologies; the results of the current study could serve as a reference for universities and industry for allocation of R&D resources.

Background: ENA is an oral, selective inhibitor of IDH2 approved for the treatment (Tx) of patients (pts) with relapsed/refractory IDH2 mutated (IDH2m) AML. Here we report the results of a Phase 2 expansion and Phase 1b of the Beat AML Master Trial Phase 2/1b sub-study to assess the efficacy of Tx of newly diagnosed (ND) IDH2m AML pts ≥ 60 years of age with ENA monotherapy (ENAm) and subsequent response-driven addition of AZA Tx. (ClinicalTrials.gov NCT03013998). Methods: The study initiated with a 3-outcome, 2-stage Phase 2 design, which enrolled patients on ENAm for up to 5 cycles. Pts without CR/CRi after 5 cycles of ENAm, or progression/intolerance prior to this time, were transferred to Phase 1b to receive ENA + AZA (Figure 1). Key eligibility included ND IDH2m AML pts with age ≥ 60 years and ECOG performance status 0-2. Pts received ENAm 100 mg/day in continuous 28-day cycles and ENA + AZA (75 mg/m2 days 1-7 every 28 days) for Phase 1b. Response was assessed using 2017 ELN AML criteria. The primary endpoint was CR/CRi rate. The 2-stage design required 24 pts and tested the null hypothesis (H0) that CR/CRi rate equaled 20% vs 50% and then expanded to test a revised H0 of 30% vs 50% in 60 pts (conditional alpha=0.025, power=77%). Expansion also allowed further assessment of safety of this treatment regimen. Results: At data cut off (06/18/2020), 60 pts enrolled, received ENAm, and were evaluable for the primary endpoint. Median age was 75 years and 52% were female (Table 1). Median time on ENAm was 4.7 months (mos). At data cut off, 12 pts were still on ENAm Tx. Most common reasons for discontinuing ENAm were Tx failure (defined as no response to treatment) (23 or 38%), disease progression (loss of response to treatment) (7 or 12%) and adverse events (AEs; 6 or 10%). Five pts (8%) went to transplant. CR/CRi was achieved in 28 pts (47%; adjusted 95% CI 28-59, unadjusted exact 95% CI 34-60) (Table 2). Responses were higher (p=0.04) among the 44 pts with IDH2 R140 (55%) as compared to the 16 with IDH2 R172 mutation (25%) further supporting distinct biology between these subsets. After a median follow up of 14.6 mos, the median overall survival (mOS) was 24.4 mos (95% CI 10.6-not reached). The median duration of response was not reached with 12 mos estimation of 57% (95% CI 34-75). Overall, 20 ENA-related serious adverse events (SAEs) occurred in 15 pts, the most common was differentiation syndrome (12 or 20%) and 1 had ENA-related SAE of tumor lysis syndrome (1.7%). One pt had ENA-related Grade 5 AE (renal failure/death). Most common AEs of any grade (in ≥20%) were nausea, anemia, and low potassium (Table 3). The 7-day/30-day/60-day deaths observed with ENAm were 2%/5%/11%, respectively. Phase 1b: Seventeen pts had inadequate response to ENAm and transferred to Phase 1b to receive ENA + AZA. Median time on Tx (including ENAm) was 6.2 mos and median time on Tx after pts started ENA + AZA was 2.1 mos (Table 2). Most common reasons for discontinuing ENA + AZA included Tx failure (5 or 29%), disease progression (2 or 12%), transplant, death and AEs (each 2 or 12%). CR/CRi was 41% (exact 95% CI 18-67). After a median follow up of 12.7 mos, the mOS from start of ENA + AZA combination Tx was 8.9 mos. Four ENA-related SAEs occurred in 3 pts on ENA + AZA Tx and the most common was differentiation syndrome (2 or 12.5%). One dose-limiting toxicity (Grade 3 nausea) related to both Txs was observed. Most common AEs (≥20%) of any grade were anemia, low albumin and vomiting (Table 3). One death occurred at day 13 of ENA + AZA. Conclusions: In newly diagnosed pts ≥60 years old with IDH2m AML, ENA had a low early death rate, high CR/CRi rate (47%, adjusted 95% CI 28-59), and yielded durable remissions. The most common unique toxicity with ENA was differentiation syndrome that occurred in 20% of patients. In pts who did not achieve CR/CRi with ENAm, a subset of patients achieved CR/CRi with addition of AZA. This combined approach of serial therapy with ENA monotherapy followed by AZA addition in pts with sub-optimal response resulted in a mOS exceeding 2 years for pts enrolled on study. Further focus on improving response among patients with IDH2 R172 mutations, identifying subsets of pts not responding to ENA monotherapy, and integrating new targeted agents into this treatment regimen are warranted. Figure 1 Disclosures Stein: Syndax: Consultancy, Research Funding; Celgene Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Biotheryx: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Borate:Genentech: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Research Funding; AbbVie: Other: Investigator in AbbVie-funded clinical trials; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Baer:Takeda: Other: Institutional research funding; AbbVie: Other: Institutional research funding; Astellas: Other: Institutional research funding; Forma: Other: Institutional research funding; Kite: Other: Institutional research funding; Oscotec: Other: Institutional research funding; Incyte: Other: Institutional research funding. Kovacsovics:Agios: Honoraria; Astella: Honoraria; Pfizer: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Jazz: Honoraria. Schiller:Astellas Pharma: Honoraria, Research Funding; Celator: Research Funding; Constellation: Research Funding; Abbvie: Research Funding; Actinium: Research Funding; Ariad: Research Funding; Stemline: Speakers Bureau; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Deciphera: Research Funding; DeltaFly: Research Funding; Bristol-Myers Squibb: Current equity holder in publicly-traded company, Research Funding; Forma: Research Funding; FujiFilm: Research Funding; Gamida: Research Funding; Genentech-Roche: Research Funding; Geron: Research Funding; Jazz Pharmaceuticals: Research Funding; Karyopharm: Research Funding; Kite Pharma: Research Funding; Mateon: Research Funding; MedImmune: Research Funding; Onconova: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Regimmune: Research Funding; Samus: Research Funding; Sangamo: Research Funding; Tolero: Research Funding; Trovagene: Research Funding; Kaiser Permanente: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Agios: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; AstraZeneca: Consultancy; Incyte: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding; Ono Pharma: Consultancy; Celgene: Research Funding, Speakers Bureau; Sanofi: Speakers Bureau; Gilead: Speakers Bureau. Olin:Astellas: Other: Site PI; Genentech: Other: Site PI; Pfizer: Other: Site PI; Daiichi Sankyo: Other: Site PI; Genentech: Consultancy; Amgen: Consultancy. Foran:Trillium: Research Funding; Xencor: Research Funding; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Boehringer Ingelheim: Research Funding; Actinium: Research Funding; Aprea: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Takeda: Research Funding; Revolution Medicine: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Lin:Trovagene: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Prescient Therapeutics: Research Funding; Abbvie: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding; Incyte: Research Funding; Pfizer: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Jazz: Research Funding; Gilead Sciences: Research Funding; Genetech-Roche: Research Funding; Celyad: Research Funding; Celgene: Research Funding. Patel:DAVA Pharmaceuticals: Honoraria; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy; France Foundation: Honoraria. Foster:Daiichi Sankyo: Consultancy; Bellicum Pharmaceuticals: Research Funding; Macrogenics: Consultancy, Research Funding. Druker:Leukemia & Lymphoma Society: Research Funding; Henry Stewart Talks: Patents & Royalties; Iterion Therapeutics (formerly Beta Cat Pharmaceuticals): Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; GRAIL: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Patient True Talks: Consultancy; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millipore (formerly Upstate Biotechnology): Patents & Royalties; MolecularMD (acquired by ICON): Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; McGraw Hill: Patents & Royalties; Merck & Co: Patents & Royalties; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dana-Farber Cancer Institute: Patents & Royalties; EnLiven: Consultancy, Research Funding; Aptose Therapeutics Inc. (formerly Lorus): Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; Blueprint Medicines: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Aileron Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Oregon Health & Science University: Patents & Royalties. Byrd:Acerta Pharma: Research Funding; Syndax: Research Funding; Vincera: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Novartis: Research Funding; Kartos Therapeutics: Research Funding; Trillium: Research Funding; Leukemia and Lymphoma Society: Other; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding. Levine:Loxo: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Qiagen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Research Funding; Amgen: Honoraria; Astellas: Consultancy; Morphosys: Consultancy; Novartis: Consultancy; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Lilly: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Gilead: Honoraria. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy; Novartis: Speakers Bureau. OffLabel Disclosure: Enasidenib is not approved for the treatment of newly diagnosed AML.

: With the utilisation of algae, wastewater reuse is becoming a viable option for the energy industry, especially green energy. The growth of these algae in these wastewaters provides an alternative source for bioenergetics, however, the growth of other microorganisms can directly affect the production of bioenergy, requiring the removal and reduction of contaminants in these waters, in addition to being a source of contamination for workers. Therefore, the use of nanoparticles in bioremediation has been an alternative to mitigate the contamination of these wastewaters that have microorganisms capable of reducing the algae growth capacity. The objective of this work was to verify in the United States Patent and Trademarker office database (USPTO) patents that used chitosan nanoparticles as a form of wastewater treatment and to carry out the analysis of patent US20190134086, which addresses the use of zinc oxide nanoparticles associated with chitosan that was developed and used to evaluate their antibacterial activity against resistant microorganisms and biofilm producers present in wastewater. Escherichia coli, Enterococcus faecium, and/or Pseudomonas aeruginosa are the microorganisms involved in the evaluated invention, bacteria present in the gastrointestinal tract, of clinical and environmental importance. The synthesized nanoparticles are arranged as a pharmaceutically acceptable and toxic vehicle against resistant bacteria, thus being described as nanoremediators. Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact that pollution, in general, has on the environment, in addition to the proposed technology serving to maintain the survival and development capacity of the algae that will be able to produce green energy, the nanoparticles with antibacterial potential can help indirectly reduce these pathogenic strains with resistance to several antibiotics in the environment.

A combination of 3D printing techniques and synthetic biology, 3D bioprinting is a promising field. It is expected that 3D bioprinting technologies will have applications across an array of fields, spanning biotechnology, medical surgery and the pharmaceutical industry. Nonetheless, the progress of these technologies could be hindered, unless there is adequate and effective protection for related applications. In this article, the authors examine the patent eligibility of 3D bioprinting technologies. This issue raises concern given that existing patent systems are generally averse to nature-derived inventions and many of them exclude products of nature or discoveries from patentability. This qualitative study analyses the current patent systems in key jurisdictions, particularly, the U.S. and the EU, and their applicability, as well as effectiveness, in the context of 3D bioprinting. The study argues that the main reason for the apathy of existing patent systems towards bio-inventions is that they were designed to deal with mechanical inventions. It suggests an innovation framework that encompasses both mechanical and biological inventions to cater adequately to emerging technologies.

Abstract Background: SNS-062 is a potent, noncovalent (reversible) BTK inhibitor in development for B-cell malignancies and other cancers. SNS-062 has the potential for activity in patients whose cancers are sensitive to BTK inhibition, as well as those that are resistant to ibrutinib through acquisition of a BTK Cys481Ser mutation. In vitro studies have demonstrated that SNS-062 antitumor activity in cells with the mutation is unaffected (Binnerts et al, EORTC 2015, Abstract C186), in contrast to the substantially reduced activity seen with ibrutinib and acalabrutinib. This study was designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SNS-062 in healthy subjects. Methods: This was a phase 1a, first-in-human, randomized, double-blind, placebo-controlled, sequential-group, single-dose study conducted in 3 stages. In stage 1, four sequential cohorts of 8 subjects were randomly assigned to receive ascending SNS-062 dose levels (50, 100, 200, and 300 mg; n=6, 3 male, 3 female) or placebo (n=2, 1 male, 1 female) as a single dose administered orally. The primary endpoint was safety, assessed by adverse events (AEs), laboratory parameters, and cardiac monitoring. Secondary endpoints included PK parameters and PD parameters (inhibition of phosphorylation BTK [pBTK] as determined by ELISA in whole blood lysates). Stages 2 and 3 were designed to evaluate the effects of food and CYP3A4 inhibition, respectively, on the PK of SNS-062. Results: In stage 1 (n=32), the median age was 55 years (range: 22-64) among those who received SNS-062 (n=24) and 42.5 years (range: 29-65) among those who received placebo (n=8). Treatment-emergent AEs (TEAEs) were reported for 8 (33%) subjects who received SNS-062 and for 3 (38%) subjects who received placebo. TEAEs reported for subjects who received SNS-062 included headache (n=5) and nausea, constipation, bronchitis, fatigue, orthostatic hypotension, and supraventricular tachycardia (n=1 each) without obvious evidence of dose dependency. AEs in the placebo group included headache (n=2), nausea (n=2), and diarrhea (n=1). AEs were all reported as Grade 1 except for 1 subject (who received 300 mg SNS-062) who experienced Grade 2 headache and fatigue. No Grade 3 or higher AEs and no serious AEs were reported. SNS-062 was rapidly absorbed (median Tmax: 1 hour [range: 0.5-3.0 hours]). SNS-062 concentrations declined in a multiphasic manner. Exposure increased approximately proportional to dose. Mean PK parameters for each cohort are shown in the Table. SNS-062 demonstrated rapid and near complete inhibition of pBTK at all dose levels. Stages 2 and 3 are in progress and results of the completed study will be reported at the meeting. Conclusions: The observed safety, PK, and PD profiles of SNS-062 in this phase 1a study in healthy subjects support further clinical investigation. This study continues to evaluate the effects of food and CYP3A4 inhibition on SNS-062 PK. Mean SNS-062 exposure at 50 mg, the lowest dose level studied, exceeded those reported for ibrutinib (Imbruvica [package insert]. Sunnyvale, CA: Pharmacyclics, LLC; 2016) and acalabrutinib (Byrd et al, N Engl J Med 2016;374:323:32) when those drugs are administered at recommended dose levels. The extent of SNS-062 exposure and duration of pBTK inhibition are encouraging and support twice-daily dosing in a planned phase 1b/2 study in patients with advanced B-cell malignancies with and without the BTK Cys481-Ser mutation. This study was sponsored by Sunesis Pharmaceuticals. Disclosures Neuman: Puma Biotechnology: Employment; Sunesis Pharmaceuticals: Employment. Ward:Sunesis Pharmaceuticals: Consultancy, Employment. Arnold:Sunesis Pharmaceuticals: Consultancy. Combs:Sunesis Pharmaceuticals: Consultancy. Gruver:Sunesis Pharmaceuticals: Employment. Hill:Sunesis Pharmaceuticals: Employment. Miller:Sunesis Pharmaceuticals: Consultancy. Fox:Amphivena Therapeutics: Consultancy, Equity Ownership, Patents & Royalties: Patent #9212225; Bispecific CD33 and CD3 Binding Proteins; Sunesis Pharmaceuticals: Consultancy, Equity Ownership, Patents & Royalties: Patent Application #20150202189; Methods of Using SNS-595 for Treatment of Cancer Subjects with Reduced BRCA2 Activity.

This paper aims at exploring intellectual property in relation to patent in medicine in India. Knowledge economy is the engine upon which development and creativity depends that has been instrumental in differentiating countries as developed or underdeveloped. India, being a member of World Trade Organization (WTO) has recognized the importance attached with IP thus investing hugely in intellectual advancement thereby reaping the advantages of second world population. Focusing on three key sectors namely, pharmaceutical, biotechnology, and IT sectors, scholars recognized the contributions these sectors offer to the growth domestic products and economic development of the countries. For instance, in India, many companies are continuously contributing to its economic development and growth at exponential rate. Many issues are discussed with regards to intellectual property.

This section is devoted to giving readers an inside view of the crossing point between intellectual property (IP) law and risk regulation. In addition to updating readers on the latest developments in IP law and policies in technological fields (including chemicals, pharmaceuticals, biotechnology, agriculture and foodstuffs), the section aims at verifying whether such laws and policies really stimulate scientific and technical progress and are capable of minimising the risks posed by on-going industrial developments to individuals’ health and safety, inter alia.

In the pharmaceutical industry, value is being destroyed through longer product development times. Given that patent lives are (normally) fixed at 20 years, the double hit of increasing time to market is evident - higher R & D costs and less time at market before generic competitors are able to be released into the marketplace. The Policy implications are massive: A huge and permanent shift away from internal R & D towards partnerships, licensing deals and acquisitions of more innovative biotechnology companies. In this study, we build a system dynamics model of the product development pipeline for a single company operating in the pharmaceutical market. The study shows that in the presence of loss of value due to longer lead times, it is more advantageous to: (a) work faster to reduce the backlog of projects; (b) increase the number of projects started whenever it is possible reduce complexity in the pipeline; and also (c) the optimal decision on resource allocation is independent of the loss of value due to longer lead times.

In the modern era world has experienced tremendous boost in the field of science and technology, realising its impact on the economic growth and people’s standard of living. India has also maintained its pace in the field of Science and technology. We are among the world’s top 10 nations in the number of scientific publications and patents. The government has made considerable investmentand encouraged public-private partnership to achieve self reliance in different sectors such as space, nuclear power, defence, agriculture, and healthcare. Although, India’s footprint in the life sciences is relatively small, it has taken giant strides to catch up with the rising economic wave to reckon itself as an international player in the life sciences. It has a strong presence in the field biotechnology, particularly related to agriculture, pharmaceuticals, health care, diagnostics, etc. A testimony to this is the accessibility of cutting edge technologies in the market.

The multifaceted nature of the content of biotechnology has turned a science that studies the possibilities of using living orga -nisms, their systems or their vital products to solve technological problems, as well as the possibility of creating living organisms with the necessary properties by genetic engineering, into one of the areas of industry of important macroeconomic importance. In all leadingcountries of the world, national and international programs on biotechnology, funded by public and private capital, are developed andare operating, in addition, the results of scientific research in the field of biotechnology. Implement long-term projects with a highdegree of risk upon receipt of various commercial products, the development results of which must be reliably protected from competitors,possibly while ensuring the granting of exclusive rights to new products and technologies by patenting. Thus, the protection of theright to biotechnology makes the patent an instrument for transferring technology and protecting new markets in the global economy,where the use of such an instrument is most effective in industries with a high cost of research and development, but low productioncost of the final product, typical for biotechnological, microbiological and pharmaceutical industry.The article is devoted, in essence, to the legal identification of a biomedical product, its content, as an object of intellectual pro -perty. It is indicated, using the example of strains and biosimilars, on the unique individual variability of properties and the content ofbiotechnologies, which is prone to constant mutation, as objects of intellectual property, which can directly affect the protection andprotection of biopatents. Risks of the use of post-patent non-comparable biotherapeutic drugs, which are not identical to the originalbiotechnological drugs in three directions: quality, safety, efficacy, are presented in detail, as an example of the necessary legislativecontrol. Attention is drawn to the need for legal classification and the lack of clarity in the definitions of intellectual property objectsfor biotechnology in international and domestic regulatory legal acts, which negatively affect the formation of the legal status ofbiotechnologies, and are mirrored on the use of legal tools for patenting.The article presents an examination of the current classical legislation in the plane of a legal innovation model, taking intoaccount the signs of legislative default and the absence of judicial practice, with a proposal for a reset of the domestic legislative systemin the field of intellectual property on biotechnology, which is strategically very important for the state. The problems of the nationallegal system in the field of intellectual property on biotechnology are outlined, taking into account the emergence of fundamentally newobjects of intellectual property generated by transplantation, cloning and robotization, regarding the determination of the legal status ofthese objects. It is investigated that high-quality provision of protection and protection of intellectual property objects consists in thedevelopment of a relevant legislative procedure on a highly specialized competent basis, taking into account the constant dynamic andinnovative intellectual exclusivity.

Abstract Background The introduction of multiple novel agents and regimens for NDMM and relapsed/refractory MM (RRMM) has improved outcomes while increasing the complexity of treatment selection and disease management. The real-world effectiveness of many novel-agent-based regimens remains to be elucidated. INSIGHT MM (NCT02761187) is the largest global, prospective, observational MM study to date. It aims to understand global NDMM/RRMM disease and pt characteristics, treatment patterns, and clinical outcomes, as well as regional variations. Here we report data for 1056 NDMM pts enrolled from July 1, 2016 to April 27, 2018. Methods INSIGHT MM is enrolling ~4200 adult pts with NDMM/RRMM (1-3 prior therapies) from 15 countries; 9 in Europe (EU), 3 in Latin America (LA), the United States (US), and 2 in Asia. Pts will be followed prospectively for ≥5 yrs. Data are collected from hospital/clinic records at baseline (MM-specific disease characteristics, prior therapies) and every 3 mos (disease management, effectiveness, safety). Results At data cut-off, 1056 NDMM pts had been enrolled from 14 countries, including 495 (47%) from EU, 361 (34%) from the US, 112 (11%) from LA, and 88 (8%) from Taiwan. Median age at enrollment was 64 (range 32-89) yrs and 139 (13%) pts were aged >75 yrs (14%/12%/11%/13% in EU/US/Taiwan/LA); 57% of pts were male (60%/58%/61%/39% in EU/US/Taiwan/LA); 72%, 13%, and 8% were White/Caucasian, Asian, and Black/African American, respectively. Overall, 62% of pts were treated at academic centers and 38% in community settings. Based on accrual at data cut-off, regional differences were observed, with more pts treated at academic centers in EU/Taiwan (88%/91%) vs the US/LA (30%/25%). 87% of pts were treated outside of clinical trials (88%/82%/95%/98% in EU/US/Taiwan/LA). Bone pain (32%, including 33%/28%/40%/37% in EU/US/Taiwan/LA), weakness/fatigue (anemia; 11%, including 12%/10%/6%/18% in EU/US/Taiwan/LA), and kidney problems (5%, including 3%/3%/17%/2% in EU/US/Taiwan/LA) were the most common reasons for pts seeking care; 32% (36%/32%/22%/24% in EU/US/Taiwan/LA) were asymptomatic at diagnosis. At diagnosis, 27%/26%/31% of pts had physician-reported ISS Stage I/II/III MM, and 88% had ECOG PS 0-1; 8% of pts had hypercalcemia, 34% creatinine clearance <60 ml/min, 56% anemia, and 30% >3 bone lesions. The most common reasons for initiating therapy were the presence of CRAB criteria, e.g. bone involvement (54%) and anemia (37%). At start of treatment, fixed-duration therapy, treat-to-best-response, and treat-to-progression approaches were planned for 38%, 29%, and 31% of pts, respectively. The most frequently administered regimens are shown in the Table; 20%/66% of pts received a doublet/triplet. V-based regimens were the most frequently used. Regional differences in regimen selection are emerging: among IMiDs, T is most commonly prescribed in EU, Taiwan, and LA; R is more common in the US. After a median follow-up of 9.3 mos, 72 (7%) pts had discontinued the study, most often due to death (57%), consent withdrawal (14%), or change of treatment provider (11%). At data cut-off, data for 236 (22%) pts who received 1st-line ASCT were available (median age 60 yrs; 12%/63%/25% of pts aged <50/50-65/>65 yrs). Of these, 64% received ASCT at academic centers; 42% of pts each in EU and the US received ASCT vs 11% in Taiwan and 4% in LA. The most frequently administered regimens in ASCT-eligible (n=429) vs ASCT-ineligible (n=571) pts were VC±d (21% vs 21%), VR±d (19% vs 17%) and VT±d (17% vs 10%). At data cut-off, 115 NDMM pts had progressed to 2nd-line therapy; 99 pts received a PI with 1st-line therapy, of whom 33 (33%) then received a PI-based regimen in 2nd line; 61 pts received an IMiD with 1st-line therapy, of whom 35 (57%) then received an IMiD-based regimen in 2nd line. Among 1st/2nd-line pts, 2%/12% received monoclonal antibody therapy. Conclusions PIs and IMiDs remain the global backbones of MM therapy, with V-based regimens most commonly used in NDMM pts, regardless of intended transplant status. These data from INSIGHT MM are beginning to elucidate regional differences in disease presentation and treatment selection, including higher numbers of pts receiving ASCT in the US/EU vs Taiwan/LA, which are likely reflective of differences in healthcare systems and access to MM treatments in the participating countries. Future studies will evaluate the impact of these regional variations on outcomes. Table. Table. Disclosures Usmani: Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Hungria:Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Leleu:Karyopharm: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Davies:Abbvie: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; TRM Oncology: Honoraria; ASH: Honoraria; MMRF: Honoraria. Costello:Poseida Therapeutics, Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Rifkin:Takeda: Consultancy; EMD Serono: Consultancy; McKesson: Equity Ownership; Celgene: Consultancy; Amgen: Consultancy; Sandoz: Consultancy; Boehringer Ingelheim: Consultancy. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding. Chari:Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; The Binding Site: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Puig:Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Boccadoro:Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Berdeja:Teva: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Bluebird: Research Funding; Genentech: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Zonder:Takeda: Honoraria; Coelum: Honoraria; BMS: Research Funding; Celgene: Consultancy, Honoraria; Alnylam: Honoraria; Janssen: Honoraria; Pharmacyclics: Other: DSMC. Abonour:Prothena: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Hajek:Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Spencer:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Omel:Takeda Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Demers:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Ren:Takeda Pharmaceuticals International Co.: Employment. Skacel:Department of Hematology, Charles University General Hospital, Prague, Czech Republic: Other: Affiliation; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Terpos:Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding.

Abstract Background Ixazomib (ixa), the first oral proteasome inhibitor, is approved in combination with lenalidomide (len)-dexamethasone in >50 countries globally, including the US and EU, for the treatment of relapsed/refractory MM (RRMM) pts who have received ≥1 prior therapy. Outcomes and tolerability in routine clinical practice often differ from data reported in clinical trials for novel-agent-based MM therapies; however, data directly comparing efficacy in clinical trials with effectiveness in routine clinical practice of new MM agents and regimens are currently limited. To evaluate the effectiveness of IRd in RRMM pts in routine clinical practice, we performed a pooled analysis of individual pt-level data for IRd-treated RRMM pts from the ongoing INSIGHT MM (NCT02761187) study and from the Czech RMG. INSIGHT MM is the largest global, prospective, observational MM study conducted to date, which is currently enrolling ~4200 adult pts with newly diagnosed MM or RRMM from Europe (EUR), the US, Asia, and Latin America. The Czech RMG was established by the Czech Myeloma Group in 2007 and comprises clinical data for >6000 MM pts enrolled at 19 Czech and 4 Slovak centers. Methods RRMM pts with 1-3 (INSIGHT MM) or ≥1 (RMG) prior therapies who had been treated with IRd were identified. INSIGHT MM pts required prospectively collected data on IRd therapy; pts who received another regimen or additional treatment within the same line of therapy as IRd were excluded. RMG pts from Czech centers who received IRd were included using the same eligibility criteria as the INSIGHT MM study. Individual pt-level data on demographics, disease characteristics, treatment history, effectiveness, and safety for IRd-treated RRMM pts from INSIGHT MM and the Czech RMG were integrated and analyzed. Best response and PFS were determined as per the assessment of the treating physician or local investigator, utilizing IMWG criteria. Descriptive analyses were performed on the integrated data as well as on data from INSIGHT MM and from the Czech RMG. PFS, TTNT, DOT, and OS were estimated using Kaplan Meier methodology. Results Overall, 163 IRd-treated RRMM pts from 9 countries were included in the analysis (50 INSIGHT MM, 113 Czech RMG); of these, 146 (90%) were from EUR, 16 (10%) from the US, and 1 (1%) from Taiwan. Median age was 67 (range 39-84) yrs, with 23 (14%) pts aged >75 yrs; 86 (53%) pts were male. At initial diagnosis, 38%/36%/26% of pts had ISS Stage I/II/III disease; median time from diagnosis to initiation of IRd treatment was 42.6 mos; 71% of pts had ECOG PS ≥1. Most pts (65%) had IgG MM, and 14% had extramedullary disease. Overall, 50%/30%/20% of pts received IRd as 2nd/3rd/≥4th-line therapy. The most common reasons for starting IRd therapy were relapse/progression (90%), including bone lesions (53%), and anemia (14%). Overall, 61% of pts had received prior stem cell transplant; prior therapies included bortezomib (bor) in 89% of pts, thalidomide (thal) in 42%, len in 21%, carfilzomib (car) in 11%, daratumumab (dara) in 3%, and pomalidomide (pom) in 2%. Median DOT was 14.0 mos; 101 (62%) pts were on treatment at data cut-off. Data on best response to therapy were available for 105 pts; among these, ORR (partial response or better) was 74%, with 31% ≥VGPR (Table); ORR with IRd as 2nd/3rd/≥4th-line therapy was 91%/57%/47%, including 41%/25%/11% ≥VGPR. Median time to first response was 1.1 mos for Czech RMG pts; median time to best response was 3.7 mos for INSIGHT MM pts. Overall, median PFS was 20.9 (95% CI: 13.0-28.7) mos, with a 12-mo rate of 65% (Table). Median PFS with 2nd/3rd/4th/>4th-line therapy was NR/23.2/14.2/5.1 mos. Median TTNT was 26.2 (95% CI: 9.6-42.8) mos, with a 12-mo rate of 73% (Table). Overall, 37 (23%) pts received subsequent therapies including bor (24%), pom (24%), thal (16%), dara (16%), car (14%), or len (8%). Median OS was not reached, with 81% of pts alive at 12 mos (Table). Ixa and len dose reductions were required in 15% and 30% of pts, respectively, with 11% and 21% of pts, respectively, requiring dose reductions due to AEs (Table). Conclusions These findings show that the effectiveness of IRd in routine clinical practice, including an ORR of 74% and a median PFS of 20.9 mos, is comparable to the efficacy of IRd reported in the TOURMALINE-MM1 trial (ORR 78%, median PFS 20.6 mos). IRd is well tolerated in RRMM pts treated in routine clinical practice, with low rates of dose reductions due to AEs for ixa (11%) and len (21%). Table. Table. Disclosures Hajek: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Terpos:Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Chari:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Array Biopharma: Research Funding. Costello:Poseida Therapeutics, Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Puig:Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Leleu:Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Karyopharm: Honoraria. Berdeja:Celgene: Research Funding; Sanofi: Research Funding; Glenmark: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Genentech: Research Funding; Bluebird: Research Funding; Teva: Research Funding; Poseida Therapeutics, Inc.: Research Funding. Davies:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Abbvie: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; ASH: Honoraria; TRM Oncology: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Hungria:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria. Boccadoro:Amgen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Honoraria, Research Funding. Rifkin:McKesson: Equity Ownership; Boehringer Ingelheim: Consultancy; EMD Serono: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Sandoz: Consultancy; Amgen: Consultancy. Zonder:Takeda: Honoraria; Pharmacyclics: Other: DSMC; Alnylam: Honoraria; Coelum: Honoraria; BMS: Research Funding; Janssen: Honoraria; Celgene: Consultancy, Honoraria. Cook:Amgen, Bristol-Myers Squibb, GlycoMimetics, Celgene, Janssen and Takeda and Sanofi: Honoraria; Celgene, Janssen and Takeda: Research Funding. Ren:Takeda Pharmaceuticals International Co.: Employment. Cacioppo:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Skacel:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment; Department of Hematology, Charles University General Hospital, Prague, Czech Republic: Other: Affiliation. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Maisnar:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.