MAPPING TECHNOLOGICAL TRENDS: AN ANALYSIS FROM THE

TECHNOLOGICAL EFFORT IN THE PHARMACEUTICAL INDUSTRY.

Fernanda G. Basso

Geciane S. Porto

Introduction and Background ■ Capacity to identify technological trends:

– Key competitor; – Potential partner; – Reduce risk and costs;

■ Technology-intensive sectors: – Pharmaceutical industries;

■ Use patents data: – 80% of the technical information;

■ Social Network Analysis (SNA): – Create relation between the information;

■ TECHNOLOGY ROUTES. – Combined the process of a radical change followed the incremental

innovations.

Objetives

■ Identify how the technological trajectories resulting from the R&D&I effort of the 20 largest pharmaceutical industries for the development of patents protected inventions are configured;

– Verify the areas of technological development in the technological routes of the pharmaceutical sector;

– Identify which organizations are present on the main technological routes and what role they exert on these routes.

Introduction and Background

■ Some studies show us the relevance of these kind of methodology

– (Pereira et al, 2019); (Pereira, Picanco-Castro, Covas & Porto, 2018); (Mina, Ramlogan, Tampubolon, & Metcalfe, 2007); (Coccia, 2015); (Kim & Lee, 2017); (Dunlap, Marion & Friar, 2014); (Cantner & Rake, 2014);

■ In majority are focus in specific technology or in a multi-case areas;

■ Don’t discuss the performance of companies;

– Aggregate information of clinical trial and studies.

Companies 2017 Sales

(US$ billion)

Spending on R&D&I

2017 (%)

Country of

Origin

Number of patents

deposited 1997-2018

Pfizer 49.417 16.8% USA 9,092

Novartis 42.706 18.7% Switzerland 8,271

Roche 39.693 22% Switzerland 10,068

Merck & Co 35.151 21.4% USA 6,900

Sanofi 33.767 18.1% France 6,892

Johnson & Johnson 33.464 24.3% USA 15,246

Gilead Sciences 29.953 13.7% USA 750

GlaxoSmithKline 27.961 17.4% UK 7,351

AbbVie 25.683 17.4% USA 1,429

Amgen 21.892 16% USA 1,640

Astrazeneca 20.97 5.63 UK 3,328

Allergan 18.6 2.85 USA 3,021

Teva 18.46 2.11 Israel 1,336

Bristol-Myers Squibb 18.16 4.41 USA 4,425

Eli Lilly 17.17 4.93 USA 2,910

Bayer 16.89 3.08 Germany 5,864

Novo Nordisk 16.61 2.16 Denmark 2,410

Boehringer Ingelheim 13.32 3.18 Germany 4,040

Takeda 12.77 2.92 Japan 6,035

Shire 11.11 2.76 USA 542

Method

■ Companies chosen;

– Top 20 in sales in 2017;

– The sales represent ≅ 50% of the sector;

■ Period: 1997-2018;

■ SNA metrics:

– Modularity;

– Betweenness Centrality;

■ Technique: SPLC (Search Path Link Count).

Method

Phases Features T-Base Not have the technological focus of the route;

They are more generic; Present some method; Patents from other areas can be identified; There are few patents with backward citation.

T-Link They are more specific; More cumulative and gradual technological development; The period from the first patent to the emerging patent is approximately 10 years.

T-Emergent

Robust technologies; Technology considered mature enough; Product Development (Clinical Studies); It has in general 5 years of deposit.

(Achilladelis & Antonais, 2001); (Malerba & Orsenigo, 2015)

Data in clusters

■ INPADOCS (alive) with citation: 62,267.

■ Nº nodes: 386,872;

■ Nº edges: 1,125,459

■ The cluster that we choose represent 50% os the data (considering nodes and more than 50% of edges).

Route Purple ■ Composed by 63 nodes;

■ Deals with treatments aimed at the immune system, focusing on the modification of antibodies and antigens;

■ Has 16 cooperation patents;

■ Genentech (Roche’s group) has 13 patents.

■ T-BASE: High heterogeneity in assignees, including chemical corps (DU PONT); Just 5 cooperation, but include hospitals, RI, US government and univ.;

■ T-LINK: Domain by Genentech and Novartis/Univ Pennsylvania partner;

■ T-EMERGENT: Kite Pharma (1) and Novartis/Univ Pennsylvania are the assignees (3), Novartis (1).

Route Purple

■ T-BASE: Begins in 1983 and treat tumor necrosis factor. There are drugs for other diseases, such as hemophilic, Antithrombin III; Influenza prevention and treatment.

■ T-LINK: Treatments for proteins that malfunction are related to cancer and autoimmune diseases;

■ T-EMERGENT: 4 patents in 2017 and 1 in 2018, focus in hematologic cancer and melanoma. This one are in clinical trial.

T-Base Some patents don’t have technological focus; They are more generic; Present some method; Patents from other areas can be identified; There aren’t patents with backward citation.

T-Link They are more specific; More cumulative and gradual development; Extension period of 10 years.

T-Emergent

Robust technologies; Mature Technology (without clinical studies); Product Development (Clinical Studies); 5 years of deposit.

Route Green

■ Composed by 25 nodes;

■ Treatments for vascular diseases and related diseases such as diabetes and heart problems;

■ T-BASE: Beecham (GSK group) 4 patent and LeBun (French laboratory) has 1.

■ T-LINK: Shering Corp (1), Merck (1), Novo Nordisk (1) and Boehringer Ingelheim (13);

■ T-EMERGENT: Astrazeneca (1), Novo Nordisk (1) Boehringer Ingelheim (3).

■ Only cooperation between subsidiary.

■ Only companies.

Route Green ■ T-BASE: Begins in 1970 with a aminoteophylline chemical

compound used to diuretic, spasmolytic, vasodilating, anti-inflammatory and analgesic boncodilator activities. The others 4 are xanthine compounds used to treat allergic disorders, neuronal degeneration and vascular diseases

■ T-LINK: The first patent used nowadays to erectile dysfunction. Focus on new breakthroughs for diabetes and other metabolic disorder treatment.

■ T-EMERGENT: The 2015 patent had the drug approved in 2019 for type 2 diabetes (Astrazeneca). Novo Nordiks patent is a diabetes treatment using degludecin. Boehringer Ingelheim patent are focus in empaglidlozin (drug in market) and linagliptin and metformin.

T-Base They are more generic; There aren’t patents with backward citation.

T-Link They are more specific; More cumulative and gradual development; Extension period of 10 years.

T-Emergent

Robust technologies; Mature Technology (without clinical studies); Product Development (Clinical Studies); 5 years of deposit.

Route Blue ■ Composed by 18 nodes;

■ Treatments for cancer and immune and autoimmune diseases;

■ T-BASE: Develop by Smithkline Beecham (GSK group) and Takeda.

■ T-LINK: Takeda develop all the patents.

■ T-EMERGENT: MSD Oss and Acerta Pharma (Astrazeneca group);

■ The acquisition of Acerta happens a few month before the acalabrutinib drug was released for commercialization.

■ NO cooperation

■ Only Companies.

Route Blue ■ T-BASE: Begins in 1997 with cloning to

treat cardiovascular effects and REM sleep. Method involving antibodys. The other 4 identify a drug to Kisspeptide protein, useful for screening potential anticancer agents

■ T-LINK: From 2004 to 2009 metastine was used to Kisspeptide malfunction adding treats to pancreatic and prostate cancer; fetal hypoplasia, sugar dysbolism, infertility, endometriosis, Alzheimer's disease, choriocarcinoma, and autism.

■ T-EMERGENT: the 2012 patent present new solution a kisspeptide-pentasaccharide conjugate useful in the treatment of female infertility, metastatic cancer, endometriosis and hot flashes in breast cancer. No clinical studies. The other one is a treatment of Bruton's tyrosine kinase (BTK), known as Acalabrutinib.

T-Base Some patents don’t have technological focus; They are more generic; Present some method; There is a patent with backward citation.

T-Link They are more specific; More cumulative and gradual development; Extension period of 10 years.

T-Emergent

Robust technologies; Mature Technology (without clinical studies); Product Development (Clinical Studies); 5 years of deposit.

Route Red ■ Composed by 26 nodes;

■ Technologies directed to immunological treatments of infect contagious diseases;

■ T-BASE: 2 RI from Cuba, Pasteur(1) and a cooperation between univ and a corp.

■ T-LINK: Novartis Group domain: Chiron (4), Novartis (9) and Novartis/IRM (1);

■ T-EMERGENT: 2 cooperation: GSK/US government; Novartis/Intellia.

■ The cooperation was important to the Novartis’s acquisition, but nowadays, part of the patent portfolio of the company is part of GSK.

■ 4 cooperation.

■ Diversity actors.

Route Red ■ T-BASE: Neisseria antigen to treats meningitis,

gonorrhea and influenza.

■ T-LINK: Using genetics knowledge the patents: eliminate a membrane of the bacterium causing meningitis and potentiated immunological drugs.

■ T-EMERGENT: Immune response against diseases caused by flavivirus; Treating to Human Papillomavirus and Rhinovirus. Immunogenic to treatment for Zika virus.

T-Base They are more generic; Present some method; There is a patents with backward citation.

T-Link They are more specific; More cumulative and gradual development; Extension period of 10 years.

T-Emergent

Robust technologies; Mature Technology (without clinical studies); Product Development (Clinical Studies); 5 years of deposit.

Conclusions

■ The emerging technologies are:

– Modified antibodies that help the immune system to treat cancer; Viral infections; Vascular and related diseases such as diabetes and heart problems; and Immune and autoimmune diseases.

■ Considered trends in the healthcare industry and others are on the public health discussion agendas;

■ The TR shows the movement of traditional pharmaceutical corporations, which are expanding their product portfolio, to biopharmaceuticals.

Conclusions

■ Companies opted for the strategy of seeking competencies from the merger and acquisition, with companies that have expertise in a certain development.

■ Patents of TR are mostly proprietary technology developed exclusively by the head office or in partnership only with its subsidiaries.

■ There are exceptions involve some RI, universities and US government.

■ There has also been a decrease in cooperation over the years. This may indicate that the initial subsidy of technologies, require more cooperation, because they are disruptive bets.

Conclusions

■ The results of the technological route analysis contribute to identify the most promising trends and reduce uncertainties in the choices of P&D projects, decide the technology licensing strategies, opt for mergers and acquisitions, as well as stimulate cooperation.

■ The use of INPADOC may be a limitation, due to the risk of not grouping some deposit, and some data citation have been lost.

■ Another limitation: patent authorities that do not provide citation data.

■ As an unfolding of the study, it is expected to encourage discussions in greater depth on the technological trends identified, suggesting a research agenda in the pharmaceutical sector.

Me. Fernanda Basso - fernanda.basso@usp.br - https://www.linkedin.com/in/fernanda-basso-4b63ab3a/ - https://www.researchgate.net/profile/Fernanda_Gisele_Basso

Thank You!!

This paper was supported by the following grants: 1. Grant nº2017/25364-6 from the São Paulo Research Foundation (FAPESP); 2. The Coordination for the Improvement of Higher Education Personnel (CAPES).