OHMR Innovator OFFICE FOR HEALTH AND MEDICAL RESEARCH

Mary O’Kane and Jillian Skinner, Minister for Health with recipients of the 2015 Medical Devices Fund.

Medical Devices Fund 2015: successful applicants On 25 November 2015 I was delighted to attend the third NSW Medical Devices Fund (MDF) announcement at Parliament House, in my capacity as Chair of the MDF Expert Panel. This event saw seven new medical devices showcased to a room filled to capacity with NSW industry, researchers and investors.

I wish to thank the Minister for Health, the Hon. Jillian Skinner, for championing this game-changing program. The MDF has demonstrated that it provides tangible outcomes to the NSW health system by encouraging innovation and linking research with industry to improve patient outcomes. As the Fund has evolved, we have seen the importance of early engagement with clinicians in the development process to ensure devices are relevant - not ‘solutions looking for problems’.

The medical devices sector in NSW has shown real strengths in recent years with a number of world leading companies such as Cochlear and ResMed based here in NSW.

Through programs like the MDF, we will discover the next generation of technologies. Already the MDF seems to have given the State real traction in terms of fostering a more robust and diverse medical devices industry here in NSW. Since the Fund commenced in 2013, the projects that have been funded offer NSW a new range of exciting and pioneering devices with the potential to not only transform the delivery of health care but offer life saving benefits to patients.

By supporting innovation through the Medical Devices Fund we can ensure that we realise the benefits of these devices in NSW, nationally and internationally.

Once again the Expert Panel was impressed by the number and the quality of the applications this year. Assessing these high quality applications was not an easy job and I want to thank the wonderful members of the Expert Panel: Neville Mitchell, Dr Bob Frater AO, Michael Still and Dr Greg Keogh.

I also wish to thank the sub-committee, who assisted with the shortlisting and the assessment of the applicants and the MDF Secretariat, led by Dr Antonio Penna.

The MDF Expert Panel are excited to see the projects presented to us in the next round. We also look forward to seeing new products in development but also those previously unsuccessful applicants who have taken on the expert advice, strengthened their business cases and submitted improved applications for consideration.

Above all, I congratulate the recipients of the Medical Devices Fund 2015 whose innovative and inspiring work will have a lasting and meaningful impact on the health system and the wider community.

By Mary O’Kane, Chair of the MDF Expert Panel

February 2016 © NSW Ministry of Health • 1

CONTENTSMedical Devices Fund (MDF) 2015 ......... 1

The commercialisation challenge ..........2

MDF past successes & future opportunities .............................................3

MDF 2015 grant recipients ..................... 4

MTP Connect and commercialisation ... 4

Entrepreneurs Programme: accelerating commercialisation .............5

Medical Devices Commercialisation Training Program ..................................... 6

Update on the Medical Research Commercialisation Fund ......................... 6

NSW Government: supporting commercialisation ....................................7

Current funding opportunities through OHMR ..........................................8

Office for Health and Medical Research

The commercialisation challengeThe history of ideas is replete with the miracles of mankind’s ingenuity and the perseverance required to bring those ideas to usefulness. For example, the ways we have found to generate funding for an idea that is barely formed. We’ve heard many a heroic story of a family re-mortgaging their home to finance a daughter’s research or an angel funding and mentoring an aspiring designer of a device. Yet, what are we dealing with here?

These are actually tales of courage in the face of market failure. It appears that the risk of financing early stage development of ideas is too great for the professional investor. And, if an investor is willing to invest, it needs too great a proportion of the equity to take the risk. Globally, there are only a few institutional investors, those with specialised managed funds, who are willing to provide risk capital at a price which sustains the motivation of those behind an idea, a process or a device.

Then there is geography. As I again found on a recent study tour in the US, professional investors and big pharma still see Australia as being a long way away and without sufficient volume of opportunities to provide a portfolio. It is assumed that those looking for funding, when intellectual property is ready for commercialisation, will come to them. This all boils down to the cost of that capital. Yet there are ways of reducing the cost of capital for development and commercialisation.

One of those ways has been the Medical Devices Fund (MDF). It has already been successful in choosing to support a number of technologies with outstanding potential. It has provided seed funding so that these technologies can be taken to a further stage of proof or development before further financing is sought from the market.

As well, scientists and developers are being supported and educated in commercialisation and coached so that their work may bear fruit quickly.

There are two particularly enlightened elements of the MDF. The funding is a grant – not equity or a loan – meaning that there is no balance sheet impact for the grantee, so when the time comes to raise money from the market, neither the owner of the IP nor the incoming financier has its equity diluted. In addition, the MDF has no carried interest that would dilute the gains to original or new equity in the event of successful commercialisation.

All of this is very significant to our success in:

Encouraging Australian institutional and superannuation investment funds to invest in Australian born technology

Attracting international capital to Australia rather than our people needing to move away to find it

Promoting Australia to the technically ambitious from other countries as the best place to realise their commercialisation dreams and for capital to be competitively priced.

Reducing the cost of capital, reduces the risk to investors and paves the way for Australian investment houses to allocate funds to a sector that is essential to our future. Australia needs to take investment in the development of science very seriously if it is to lift its gaze and honour its potential. The Federal Government’s science and innovation agenda is supporting this vision with new funding, particularly for translation and commercialisation. New South Wales, having put in place world class administrative structures with an intelligent strategy, is in poll position to be successful in a new age of scientific exploration.

By Michael Still MBA Chair South West Sydney LHD

February 2016 © NSW Ministry of Health • 2

Reducing the cost of capital, reduces the risk to investors and paves the way for Australian investment houses to allocate funds to a sector that is essential to our future.

OHMR Innovator – Issue 4 February 2016

February 2016 © NSW Ministry of Health • 3

Medical Devices Fund: past successes and future opportunities The NSW Government established the Medical Devices Fund (MDF) in 2012 to help encourage and support investment in the development and commercialisation of medical devices and related technologies in NSW.

In its inaugural year (2012/13) the Fund committed over $10 million to five projects including devices for chronic pain management; sealing technology for minimally invasive heart valve replacement; diagnostic audiology; skin repair; and portable intravenous infusion.

In the second round (2013/14) of the MDF, over $6 million was committed to four projects including a synthetic ‘load bearing’ bone graft; patient specific planning and simulation solutions for orthopaedic surgeons; an in vitro diagnostic test for detection of viruses and bacteria; and a paediatric implant to treat children born with brittle bones or malformed legs.

MDF grant winners from previous rounds have made notable achievements and milestones since receiving an MDF grant.

Image provided by Saluda, showing electrode placement

For example, since receiving MDF grants from the first round in 2012/13:

Saluda Medical Pty Ltd has completed development for its fully implantable pain relief system and has begun implanting devices

as part of its Australian Chronic Trial. In October 2015 this spinal implant for pain relief described as a ‘breakthrough’ in the Sydney Morning Herald after the device was implanted into a patient at Royal North Shore Hospital.

Image provided by Elastagen, showing elastin synthesis

Elastagen Pty Ltd and its collaborators at the University of Sydney and the Concord Hospital Burns Unit have demonstrated preclinical proof of concept for the use of tropoelastin, a synthetic version of the elastin protein in the regeneration of skin following surgical excision of severe scars and wound repair. Elastagen recently secured $13 million from investors to support the development of the company’s lead products. This includes funding from the Wellcome Trust in the UK to further evaluate the role for tropoelastin in skin regeneration and tissue repair.

HEARworks Pty Ltd has developed the Cortical Automatic Threshold Estimator (CATE), the third software test module developed specifically for use in HEARLab®. CATE will provide the world’s first fully automated frequency-specific objective test of hearing thresholds through detection of evoked electrical signals originating from the brain’s auditory cortex. Pilot testing and clinical assessment with an adult cohort has been completed. HEARworks is currently leading clinical assessment with an infant cohort and is in discussions regarding potential collaborations with a major hearing care provider group to extend use of HEARLab and CATE to developing markets.

Image provided by HEARworks

Due to the overwhelming response seen in the first two rounds of the MDF, and the early successes of the grant winners, in 2015 the NSW Government increased funding to the MDF, taking the fund to $32.8 million over the next four years.

The Office for Health and Medical Research (OHMR) has opened the next round (2016/17) of the MDF with over $7 million available for grant winners. Online self-assessments and preliminary applications are currently open, and close on 12th February 2016.

In its inaugural year (2012/13) the Fund committed over $10 million to five projects

Office for Health and Medical Research

Medical Devices Fund: 2015 grant recipients

Demonstration of Sound Scouts, by cmee4 Productions

In the 2015/2016 round of the Medical Devices Fund, over $10 million was committed to seven projects with the potential to transform the delivery of health care and deliver life-saving benefits for patients:

PAFtec Australia Pty Ltd for CleanSpace™, the world’s smallest and lightest powered respirators and a game changer for respiratory protection of health care workers at high risk of infectious disease.

AllVascular Holdings Pty Ltd for Arterial & Venous Access System (AVAS), a novel patented vascular access device that enables repeated access to a patient’s vasculature and facilitates more effective and efficient treatments.

University of New South Wales for Thru-Fuze™, a new orthopaedic device for fusion of adjacent spinal vertebrae that facilitates rapid fusion of bone and compared to existing devices is cheaper, easier and less time consuming to implant.

Maverick Biomaterials Pty Ltd for innovative materials used in the manufacture of cardiovascular devices implanted via keyhole surgery techniques that reduce the patient’s time in intensive care and enable device implantation into frail patients.

cmee4 Productions Pty Ltd for Sound Scouts, a mobile game created to check a child’s hearing and detect any undiagnosed hearing issues that would otherwise affect a child’s social and academic development.

Atomo Diagnostics Pty Ltd for Atomo HIV Self-test, that uses an innovative all-in-one self-test technology to replace the complex test with multiple components, and incorporates links to services for people who return reactive (positive) test results.

Kleer-i, a next-generation, biological ‘patch’, which seals eye lacerations without sutures while simultaneously delivering drugs, without the toxic side-effects and high failure rates associated with existing therapies.

Several of the 2015 grant recipients have already reported early successes. For example, Maverick Biomaterials has been awarded a Federal Government Accelerating Commercialisation Funding Grant of $987,500, while Atomo has secured an additional $6 million in funding from the Bill Gates Foundation. On 22 January, cmee4 Productions launched their Sound Scouts app at the Concord Early Childhood Health Centre alongside Minister for Health, the Hon. Jillian Skinner.

For more information on the 2015 MDF grantees and their devices, please see: http://www.health.nsw.gov.au/ohmr/mdf/Pages/2015-mdf-grant-recipients.aspx.

MTP Connect and commercialisationThe Medical Technologies and Pharmaceuticals Growth Centre (MTP Connect) is part of the $225 million Industry Growth Centres Initiative. The 2015 National Innovation and Science Agenda (NISA) identifies healthcare as a sector where innovation and commercialisation will play an important role. Equally, there is recognition that we can do better. Industry Growth Centres have a key role to play in delivering the NISA. To understand the role of MTP Connect it is important to answer a few simple questions:

What is commercialisation?The process of introducing a new product and making it available on the market, along with the movement of research and development from the laboratory into commerce.

Why is commercialisation important?Australia is acknowledged to have world class researchers and research institutes; commercialisation of this work brings benefit to end-users everywhere and creates jobs and knowledge.

When have we done commercialisation well?Many times, but iconic examples are Cochlear, ResMed, CSL and Starpharma.

What role will the Growth Centres have in commercialisation?The Growth Centres are focused on achieving four primary outcomes:

Encouraging collaboration and the commercialisation of new products

Enhancing management and improving workforce skills

Identifying opportunities to reduce regulatory burden

Improving capabilities to engage with international markets and global supply chains.

MTP Connect will work nationally to link and align the many excellent programs being delivered by States, Territories and by the various national agencies and bodies. In this way, these programs all have an important role to play in achieving the commercial- isation objectives of the NISA.

Dr Bronwyn Evans, FIEAust, FTSE, Chief Executive Officer,

Standards Australia

February 2016 © NSW Ministry of Health • 4

OHMR Innovator – Issue 4 February 2016

February 2016 © NSW Ministry of Health • 5

Entrepreneurs’ Programme: accelerating commercialisationThe Entrepreneurs’ Programme is the Australian Government’s flagship initiative for business level competitiveness and productivity. The programme supports the Government’s newly announced National Innovation and Science Agenda (NISA) which includes a number of initiatives designed to boost business capability, enable innovation, and embrace new ideas.

The NISA acknowledges that technology is changing the way business is done around the world, and ensures that Australia doesn’t fall behind.

The Entrepreneurs’ Programme offers support to businesses through three elements:

Accelerating Commercialisation, helping entrepreneurs, researchers, and businesses address key challenges in the commercialisation pathway of bringing novel products, processes, and services to the market.

Business Management provides advice and facilitation services to improve business capabilities and networks.

Innovation Connections, helping small and medium businesses to access knowledge, engage with researchers, and foster innovation.

The Accelerating Commercialisation element of the Entrepreneurs’ Programme focuses on Australian start-up companies. This is because these early stage and new technology companies play such an important role in our economy: they break new ground, develop innovative solutions and punch above their weight in creating highly-skilled jobs and export revenue.

The entrepreneurs and small to medium sized companies participating in Accelerating Commercialisation have access to matched grants through a

competitive evaluation process and receive guidance from expert industry Commercialisation Advisers.

These individuals and companies are also able to join the Accelerating Commercialisation Portfolio, which gives them exposure and global visibility to investors and multi-national corporations. Business Development Advisers support the Portfolio members to form strategic relationships with global companies and investors who can assist them to commercialise.

Another valuable resource for Accelerating Commercialisation participants is the Expert Network which is comprised of a select group of successful entrepreneurs, domain experts, professional investors, and corporations, including key representatives of some of the world’s largest corporations.

The Expert Network is a mechanism for successful business builders to share their experience and insight with Australia’s aspiring entrepreneurs. The links between the younger Portfolio companies and the well-established Expert Network companies and individuals are benefitting all parties by facilitating critical connections and funding opportunities.

The support Accelerating Commercialisation provides to our high-potential emerging companies is helping to create the right conditions for growth.

For more information:

Accelerating Commercialisation and the Entrepreneurs’ Programme at www.business.gov.au/ac

National Innovation and Science Agenda at www.innovation.gov.au

By Karen Dado Business Development Adviser Accelerating Commercialisation Entrepreneurs’

Programme

OHMR Update on Initiatives (Reform, REGIS and Metrics)By invitation only to Chief Executives and Research Directors of LHDs, and Executive Directors of MRIs. Tuesday 16 February

Endurance exercise and the heartFriday 5 Feb, 5.30–7.30pm. Caves Lecture Theatre, Hunter Medical Research Institute. For more information and to register please visit https://hmri.org.au/hmri-event/endurance-exercise-and-the-heart-public-seminar/

Pancreatic, ovarian and other rare and neglected cancersWednesday 20 Apr, 10am. Auditorium, Garvan Institute. For more information and to register please visit https://www.giving.garvan.org.au/register-now

To suggest an event for inclusion in a future issue please contact OHMR Innovator at ohmr@doh.health.nsw.gov.au

E V E N T SUpcoming

The Expert Network is a mechanism for successful business builders to share their experience and insight with Australia’s aspiring entrepreneurs.

Office for Health and Medical Research

MDCTP 2015 graduates with Jillian Skinner, Minister for Health

Medical Devices Commercialisation Training Program (MDCTP)The NSW Medical Devices Commercialisation Training Program (MDCTP) bridges the gap between a good idea and a commercial success. The program takes participants through an intensive three month training program to develop their entrepreneurial skills, and prepare them for the realities of business.

Through this program we are developing a pool of talented researchers, technologists and clinicians who are able to translate complicated science and engineering into clear value propositions that solve real world health problems.

Over the two years MDCTP has been running, the program has graduated 32 researchers and clinicians from various specialities. Dr Sheridan Gho and Dr Michael Weaver, from the 2014 cohort, were selected to attend the NSW-QB3 Rosenman Institute Scholar Program in San Francisco. At the Rosenman Institute, Drs Gho and Weaver are working on a device to address lymphedema, a condition of localised fluid retention and painful tissue swelling, and are benefiting from having access to clinician-innovators and medical device commercialisation experts.

The 2015 round was successfully completed by 12 participants, with four members of the graduating class awarded scholarships to further develop their research:

Professor Stephanie Watson, Kleer-i – $50,000 in seed funding for the Kleer-i patch, a sutureless wound sealing device for cataract surgery.

Dr David Yeo, Royal Prince Alfred Hospital – $25,000 in seed funding for Pivot Sphincterotome, a procedure for the management of bile duct pathology.

Dr Dharmica Mistry, BCAL Diagnostics Pty Ltd – $10,000 international engagement scholarship for higher accuracy breast imaging and screening tests.

Dr Robert Gorkin, University of Wollongong – $10,000 international engagement scholarship for new condoms utilising an advanced hydrogel material with anti-STI agents.

All graduates have gained valuable skills that will help turn their ideas into health improvements. The skills that the graduates have gained during the program will have a lasting influence on their own research and practice, which will in turn help to grow the medical device sector.

Update on the Medical Research Commercialisation FundA key issue in translating research from bench to bedside is finding risk tolerant investment funding for promising but unproven research. The Medical Research Commercialisation Fund (MRCF) was established in 2007, as a national body that supports early stage development and commercialisation opportunities for biomedical technologies from medical research institutes and allied research hospitals.

The aim of the funding is to support commercialisation through spinout companies, as well as supporting licensing transactions and proof of concept projects. The MRCF benefits from the membership of leading medical research institutes from across Australia. Each Member Institute is represented on the Investment Review Committee and contributes to the peer review of investment proposals.

To date, the MRCF has committed a little over $49 million to projects across Australia including $16.8 million to NSW projects. This funding has been actively leveraged, leading to a total cash investment of $304 million into Member Institute projects.

The MRCF has now completed investments in 25 start-up companies, with 14 of these now progressed from proof-of-concept studies through to human clinical and for several, international regulatory approval and market launch.

February 2016 © NSW Ministry of Health • 6

OHMR Innovator – Issue 4 February 2016

February 2016 © NSW Ministry of Health • 7

For example, in the last 12 months, MRCF has provided $2m investment funding to the Garvan Institute for a formulation technology that improves the stability, delivery attributes, and manufacturing yields of biologic drugs (antibodies).

The NSW Government has provided $2.1 million in operational support to the MRCF over 7 years.

This investment represents an immediate return of eight times the support provided by the NSW Government. In 2015 the New South Wales Government provided continued grant support to MRCF of $0.3m.

Dr Chris Nave, Principal Executive Medical Research Commercialisation Fund

NSW Government: supporting commercialisationBeyond the programs administered by OHMR, the NSW Government offers a range of support to organisations to commercialise their ideas. For example, the NSW Department of Premier & Cabinet assists organisations with international growth opportunities through its International Trade & Investment team, and the NSW Department of Industry leads a range of initiatives aimed at supporting NSW-based organisations to grow and create new jobs.

NSW Department of Premier & CabinetBoosting exports – for NSW

businesses that are exporting or have potential to export, our experienced export advisors provide practical information on doing business in international markets including entry strategies, international insights or more tailored services. For further information contact: export@industry.nsw.gov.au

Attracting investment – onshore and offshore teams undertake research, connect with relevant industry players and develop strategies to assist with investment into NSW. For a list of overseas representatives please go to http://www.industry.nsw.gov.au/contact-us/international-network

NSW Department of IndustryThe Medtech Knowledge Hub – is

a collaborative network between academia, industry and government to improve the business environment by working together on common issues. Coordinated by the Medical Technology Association of Australia (MTAA), the Hub focuses on accelerating the translation of NSW’s research investments into commercial products by addressing local challenges that prevent commercialisation opportunities and raising the global standing of the local industry (www.knowledgehubs.com.au).

Innovate NSW – connects technology developers and businesses in key sectors of the economy to develop globally competitive business to business solutions. Solutions should use enabling technologies such as mobile, cloud, analytics, sensors, advanced materials or biosciences. There are three funding streams: TechVouchers, Minimum Viable Product and Collaborative Solutions (www.industry.nsw.gov.au/innovatensw).

Research Attraction and Acceleration Programme (RAAP) – The NSW Government, through the Office of the NSW Chief

Scientist and Engineer, pledged $18 million to support innovation and investment in the State’s research and development capacity. $10 million has been allocated to programmes to encourage and support high-quality, high-impact research, and increase innovation in the state’s R&D system. Funding includes support for highly prestigious, high-impact ARC Centres of Excellence Programme and competitively-allocated research infrastructure for our state’s universities (www.chiefscientist.nsw.gov.au/investing-in-science).

Jobs for NSW – is a private sector-led and NSW Government-backed initiative to create 150,000 new jobs over the next four years in NSW. The Jobs for NSW fund was created to meet the NSW Government’s commitment to provide $190 million over four years to attract and grow businesses. Karen Borg, who was most recently the Asia-Pacific President of medical equipment manufacturer ResMed is the CEO of Jobs for NSW (http://www.industry.nsw.gov.au/invest-in-nsw/why-sydney-and-nsw/jobs-for-nsw).

Office for Health and Medical Research OHMR Innovator – Issue 4 February 2016

February 2016 © NSW Ministry of Health • 8

Current funding opportunities through OHMRMedical Devices Fund (MDF) Applications for funding 2016-2017The Medical Devices Fund (MDF) is competitive technology development and commercialisation program funded by the NSW Government, through the NSW Ministry of Health. In the 2016-2017 funding round, up to $7.8 million will be made available for successful applicants.

The key objective of the MDF is to promote new and innovative medical devices/technologies within NSW that may have a global benefit. Broadly, the MDF aims to:

Provide support to individuals, companies, public and private hospitals, medical research institutes, universities, other public sector research organisations, and the medical devices industry, to take local innovation to market

Increase the uptake of NSW medical devices by the health system where they are cost effective and contribute to improved patient outcomes.

NB: An online self-assessment MUST be completed prior to submitting a preliminary application.

All applications will be assessed against the eligibility and selection criteria set out in the Application Kit and Guidelines. Intending applicants should refer to the following links and documents which are available at: http://www.health.nsw.gov.au/ohmr/mdf/Pages/mdf-applications-for-funding.aspx

All applications must be formally lodged by COB (5:00pm) Friday 12th February 2016

Enquiries may be directed to: Office for Health and Medical ResearchTel. (02) 9391 9228medicaldevicesfund@doh.health.nsw.gov.au

Medical Research Support Program (MRSP) 2016-2020The NSW Government has launched the 2016-2020 round of the Medical Research Support Program (MRSP). MRSP supports state-wide capacity to deliver world class health and medical research by providing infrastructure funding to independent Medical Research Institutes in NSW.

To be eligible for funding from MRSP 2016-2020, applicants must be:

1. A Medical Research Institute located in NSW.

2. Conducting health and medical research as its primary business.

3. An independent and discrete operational entity, able to demonstrate sufficient independence to determine its own research directions and use of funds.

4. A member of at least one of NSW’s nine health and medical research Hubs.

5. Conducting high quality research at a sufficient scale, with an average annual research income from eligible grants of at least $3 million

6. Able to demonstrate that they have sufficient existing capacity to support future growth.

Organisations funded in previous rounds of MRSP may re-apply for funding under this current round. Successful applicants must use this funding to help cover the operational costs associated with delivering world class health and medical research.

The Application Guidelines and Program Details for the MRSP (2016-2020), and related documents are available to download from: http://www.health.nsw.gov.au/ohmr/mrsp

All applications must be formally lodged by COB (5:00pm) on Wednesday 17 February, 2016.

Enquiries may be directed to: Jocelyne AldridgeTel. (02) 9391 9228ohmr@doh.health.nsw.gov.au

Translational Research Grants SchemeThe NSW Ministry of Health launched Translational Research Grants Scheme (TRGS) on 7 January 2016.

Grants are available to staff within NSW Local Health Districts, Ambulance Service of NSW and Specialty Health Networks including medical staff, nursing staff, allied health professionals and population health practitioners.

Funding will be provided for research and evaluation projects that will translate into better patient outcomes, health service delivery, and population health and wellbeing.

Applicants are encouraged to partner with other research organisations such as universities and medical research institutes. The research project must be led by an employee of a host organisation within the health system. The scheme is designed to accelerate the development of research capabilities and evidence translation within the NSW health system.

A total of $9.1 million will be available in this funding round, allocated over a two year period. Grants ranging from $50,000 to $1 million will be provided to successful applicants for projects of one to two years’ duration.

The application process will include three stages: expressions of interest; proposal development; and full applications. The Expression of Interest Form and Guidelines for Applicants are available here: http://www.health.nsw.gov.au/ohmr/Pages/trgs.aspx

Expression of interest close at COB (5.00pm) on 15 February, 2016.

All enquiries should be directed to:TRGS@doh.health.nsw.gov.au

SHPN

 (O

HMR)

1600

32 

ISSN

 220

5-71

02 (P

rint)

 IS

SN 2

205-

7110

(Onl

ine)