* DDT February 2009 Covers:DDT Cover/Back April 2006.qx 1/30/09 2:43 PM Page 2
`
`February 2009 Vol 9 No 2
`
`www.drugdeliverytech.com
`IN THIS
`ISSUE
`
`INTERVIEW WITH
`PRO-PHARMACEUTICALS’
`CHIEF EXECUTIVE OFFICER
`DAVID PLATT
`
`Diabetes
`Management
`Daniel Ruppar
`
`Prefilled Syringe
`Gas Bubbles
`Shawn Kinney, PhD
`
`Nanoparticles &
`Cancer
`Maulik A. Acharya
`
`Particle Size
`Optimization
`Thomai Panagiotou, PhD
`
`FEATURING
`
`Central Lab
`Strategies
`Cindy H. Dubin
`
`Surverying
`Big Pharma
`Josef Bossart, PhD
`
`30
`
`42
`
`48
`
`53
`
`64
`
`70
`
`The science & business of drug development in specialty pharma, biotechnology, and drug delivery
`
`Madhu
`Hariharan,
`PhD
`Orally Dissolving Film
`Strips: The Final
`Evolution of Orally
`Dissolving Dosage
`Forms
`
`Frank Y. Xie,
`PhD
`Systemic Delivery of
`Therapeutic siRNA:
`Opportunities &
`Challenges
`
`Maria J.
`Gutierrez, MD
`A Spring-Powered
`Device for
`Subcutaneous,
`Intramuscular &
`Intradermal Injections
`Using an Auto-Disable
`Syringe
`
`Regeneron Exhibit 1214.001
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`2-4 DDT Feb 09 front pages :DDT Frntmttr apr06 06.2-4.qx 1/30/09 2:34 PM Page 2
`
`Regeneron Exhibit 1214.002
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`2-4 DDT Feb 09 front pages :DDT Frntmttr apr06 06.2-4.qx 1/30/09 2:34 PM Page 3
`
`Regeneron Exhibit 1214.003
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`2-4 DDT Feb 09 front pages :DDT Frntmttr apr06 06.2-4.qx 1/30/09 2:34 PM Page 4
`
`February 2009 Vol 9 No 2
`PUBLISHER/PRESIDENT
`Ralph Vitaro
`
`EXECUTIVE EDITORIAL DIRECTOR
`Dan Marino, MSc
`dmarino@drugdeliverytech.com
`
`CREATIVE DIRECTOR
`Shalamar Q. Eagel
`
`CONTROLLER
`Debbie Carrillo
`
`CONTRIBUTING EDITORS
`Cindy H. Dubin
`Debra Bingham
`Jason McKinnie
`
`TECHNICAL OPERATIONS
`Mark Newland
`
`EDITORIAL SUPPORT
`Nicholas D. Vitaro
`
`ADMINISTRATIVE SUPPORT
`Kathleen Kenny
`
`Corporate/Editorial Office
`219 Changebridge Road, Montville, NJ 07045
`Tel: (973)299-1200
`Fax: (973) 299-7937
`www.drugdeliverytech.com
`
`Advertising Sales Offices
`
`East & Midwest
`Victoria Geis - Account Executive
`Cheryl S. Stratos - Account Executive
`103 Oronoco Street, Suite 200
`Alexandria, VA 22314
`Tel: (703) 212-7735
`Fax: (703) 548-3733
`E-mail: vgeis@drugdeliverytech.com
`E-mail: cstratos@drugdeliverytech.com
`
`West Coast
`
`Warren De Graff
`Western Regional Manager
`818 5th Avenue, Suite 301
`San Rafael, CA 94901
`Tel: (415) 721-0644
`Fax: (415) 721-0665
`E-mail: wjdegraff@drugdeliverytech.com
`
`International
`Ralph Vitaro
`219 Changebridge Road
`Montville, NJ 07045
`Tel: (973) 299-1200
`Fax: (973) 299-7937
`E-mail: rvitaro@drugdeliverytech.com
`
`Mailing List Rental
`Candy Brecht
`Tel: (703) 706-0383
`Fax: (703) 549-6057
`E-mail: cbrecht@mgilists.com
`
`All editorial submissions are handled with reasonable care, but the publishers assume no responsibility for the safety
`of artwork, photographs, or manuscripts. Every precaution is taken to ensure accuracy, but publishers cannot accept
`responsibility for the accuracy of information supplied herein or for any opinion expressed. Drug Delivery Technology
`(ISSN 1944-818X) is published 10 times in 2009, January, February, March, April, May, June, July/August, September,
`October, and November/December by Drug Delivery Technology LLC, 219 Changebridge Road, Montville NJ 07045.
`Subscription rates: $99.00 for 1 year in the United States, Canada, and Mexico. $153.00 for 1 year outside the United
`States, Canada, and Mexico. All subscriptions are payable in US funds, drawn on US banks. Send payment to: Drug
`Delivery Technology LLC subscription Department, 219 Changebridge Road, Montville NJ 07045. Single copies (prepaid)
`$15.00, US, Canada, and Mexico; $24.00 in all other countries. Add $5.00 per order for shipping and handling.
`Periodicals Postage Paid at Montville, NJ 07045-9998 and additional mailing offices. Postmaster: please send address
`changes to Drug Delivery Technology, 219 Changebridge Road, Montville NJ 07045. All rights reserved under the US
`International and Pan-American Copyright Conventions. All rights reserved. No part of this publication may be
`reproduced or transmitted in any form or by any means, electronic or mechanical, including by photocopy, recording,
`or information storage and retrieval system, without written permission from the publisher. Authorization to photocopy
`items for internal or personal use, or the internal or personal use of specific clients, is granted by Drug Delivery
`Technology LLC for libraries and other users registered with the Copywrite Clearance, 222 Rosewood Drive, Danvers, MA
`01923; phone: (978) 750-8400, fax: (978) 750-4470.
`
`Regeneron Exhibit 1214.004
`Regeneron v. Novartis
`IPR2021-00816
`
`Keep abreast of the marketplace with the
`industry’s only publication entirely devoted
`to drug delivery and development.
`
`Go to www.drugdeliverytech.com
`and click on Subscription Services
`
`Once on the website you can also subscribe
`to our eNewsletter!
`
`For more information contact Ralph Vitaro at 973-299-1200
`or e-mail him at rvitaro@drugdeliverytech.com
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`4
`
`

`

`5-9 DDT February 2009 TOC pages:DDT April 06 TOC 5-9.qx 1/30/09 2:36 PM Page 5
`
`Regeneron Exhibit 1214.005
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`5-9 DDT February 2009 TOC pages:DDT April 06 TOC 5-9.qx 1/30/09 2:36 PM Page 6
`
`24
`
`30
`
`32
`
`Orally Dissolving Film Strips (ODFS):
`The Final Evolution of Orally Dissolving
`Dosage Forms
`Madhu Hariharan, PhD, and B. Arlie Bogue, PhD, focus
`their discussion mainly on films for oral delivery of drug to
`the GI tract as well as address other prospective
`manifestations of this dosage form.
`
`Continued Drug Delivery Opportunities in
`Diabetes Management
`Frost & Sullivan Analyst Daniel Ruppar asks the question of
`whether there is still an opportunity for an inhaled diabetes
`drug.
`
`Systemic Delivery of Therapeutic siRNA:
`Opportunities & Challenges
`Frank Y. Xie, PhD; Qing Zhou, PhD; Ying Liu, MS; Samuel
`Zalipsky, PhD; and Xiaodong Yang, MD, PhD; provides an
`overview of the critical steps in the development of siRNA
`therapeutics, from the selection of siRNA specific for the
`target of interest to the development of novel formulations
`for efficient in vivo systemic delivery of siRNA
`therapeutics.
`
`38
`
`Speeding Drugs With Non-Traditional
`Delivery Mechanisms to Market
`Robert R. Andrews, MS, MBA, and Russell L. Newton, MS,
`provide guidance on how to overcome the most commonly
`encountered issues in developing non-traditionally
`delivered drugs.
`
`42 A Rational Approach to Determining the
`Maximum Allowable Gas Bubble Inside
`a Prefilled Syringe to Minimize Stopper
`Movement & Protect Product Sterility
`Shawn Kinney, PhD; Andrea Wagner, PhD; and Christian W.
`Phillips make the case that reducing or eliminating the
`bubble inside a prefilled syringe is a preferred means for
`ensuring product sterility while enhancing the benefits of a
`prefilled syringe.
`
`48
`
`Nanoparticles in Cancer Research: A
`Novel Drug Delivery & Pharmacological
`Approach
`Priyal Patel, Maulik A. Acharya, and Jayvadan Patel, PhD,
`provide a balanced update on exciting pharmacological and
`potentially toxicological developments of nanoparticles in
`cancer research.
`
`Regeneron Exhibit 1214.006
`Regeneron v. Novartis
`IPR2021-00816
`
`Therapeutic
`siRNA
`
`“Compared to the local siRNA
`deliveries that were used in many early
`siRNA clinical trials, systemic siRNA
`delivery faces more challenges and
`hurdles that have slowed down the
`expansion of siRNA therapeutics. With
`increasing efforts dedicated to the
`development of more efficient systemic
`siRNA delivery technologies, it is
`conceivable the key delivery hurdles
`could be overcome and the potential of
`RNAi-based therapeutics may be
`realized in a not too distant future.”
`
`p.32
`
`DrugDeliveryTechnologyFebruary2009Vol9No2
`
`6
`
`

`

`5-9 DDT February 2009 TOC pages:DDT April 06 TOC 5-9.qx 1/30/09 2:36 PM Page 7
`
`Regeneron Exhibit 1214.007
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`5-9 DDT February 2009 TOC pages:DDT April 06 TOC 5-9.qx 2/2/09 2:07 PM Page 8
`
`Central Lab
`Strategies
`
`“The best trial plans will fail if they
`cannot enroll patients. Through feasibility,
`we help clients select the inclusion and
`exclusion criteria, model enrollment,
`incorporate feedback from investigators,
`consultants, epidemiologists, and analyze
`prescription and insurance data. The
`triangulation of this data gives us
`information to improve country selection,
`site identification, and enrollment
`forecasts, as well as identify back-up
`strategies and alternative plans, tailored
`to the client’s needs.”
`
`p.64
`
`53
`
`61
`
`64
`
`70
`
`Achieving Optimal Particle Size
`Distribution in Inhalation Therapy
`Thomai (Mimi) Panagiotou, PhD, addresses many of the
`concerns medical device manufacturers and their
`pharmaceutical partners have when attempting to achieve
`the correct particle size for an inhalation device.
`
`The Untapped Potential of
`Carbohydrates in Drug Discovery &
`Development
`Executive Summary: David Platt, CEO of Pro-Pharmaceuticals,
`says carbohydrate molecules have been shown to play an
`important role in major diseases, including cancer,
`cardiovascular disease, Alzheimer’s disease, inflammatory
`disease, and viral infections.
`
`How Your Central Lab Can Keep
`Clinical Trials Flexible & Cost Effective
`Contributor Cindy H. Dubin poses questions to central lab
`executives about how improved forecasting methods and
`alternative foreign locations could result in better data
`generated during clinical trials.
`
`Drug Delivery Prospects for the Next
`Decade: An Informal Survey of Big
`Pharma
`Josef Bossart, PhD, conducted an informal survey with Big
`Pharma personnel to get their sense of how drug delivery
`fits into their plans now and for the next decade.
`
`DEPARTMENTS
`Market News & Trends . . . . . . . . . . . . . .
`Advanced Delivery Devices . . . . . . . . . .
`A Spring-Powered Device for Subcutaneous,
`Intramuscular & Intradermal Injections
`Using an Auto-Disable Syringe
`
`Technology Showcase . . . . . . . . . . . . . . .
`External Delivery . . . . . . . . . . . . . . . . . .
`But Mom & Dad... You Promised
`
`12
`18
`
`58
`74
`
`Regeneron Exhibit 1214.008
`Regeneron v. Novartis
`IPR2021-00816
`
`DrugDeliveryTechnologyFebruary2009Vol9No2
`
`8DrugDeliveryTechnologyMarch2007Vol7No3
`
`8
`
`

`

`5-9 DDT February 2009 TOC pages:DDT April 06 TOC 5-9.qx 1/30/09 2:36 PM Page 9
`
`Regeneron Exhibit 1214.009
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 1/30/09 2:48 PM Page 10
`
`John A.
`Bermingham
`President & CEO
`The Lang Companies
`
`Derek G. Hennecke,
`MBA
`President & CEO
`Xcelience
`
`James N. Czaban,
`JD
`Partner, FDA Department
`WilmerHale
`
`Keith Horspool, PhD
`Director, Research
`Formulations
`Pfizer Global Research &
`Development
`
`Uday B. Kompella,
`PhD
`Professor, Department of
`Pharmaceutical Sciences
`University of Colorado
`Denver
`
`Marc Iacobucci,
`MBA
`VP, Marketing & Project
`Management
`DPT Laboratories
`
`Cornell Stamoran
`VP, Strategy & Business
`Process
`Catalent Pharma
`Solutions
`
`Beth A-S. Brown, PhD,
`MS
`Director, Pharmaceutical
`Development
`Upsher-Smith Laboratories
`
`Der-Yang Lee, PhD
`Research Fellow, R&D
`Technology, R&D Labs
`McNeil Consumer Healthcare,
`Johnson & Johnson
`
`Gary W. Cleary, PhD,
`PharmD, MBA
`President & CTO
`Corium International
`
`John Fraher
`President, North America
`Eurand
`
`Ali Rajabi-Siahboomi,
`PhD
`Global Technical Director,
`Modified Release
`Technologies
`Colorcon
`
`James W. McGinity,
`PhD
`Professor of Pharmaceutics
`University of Texas
`at Austin
`
`Michael A. Repka,
`PhD, DDS
`Chair & Associate Professor
`Department of
`Pharmaceutics
`University of Mississippi
`
`Tom Tice, PhD
`Executive Vice President
`and Chief Scientific Officer
`Brookwood
`Pharmaceuticals
`
`Henry Y. Wu, PhD, MS
`Director
`Merck Research
`Laboratories
`
`Regeneron Exhibit 1214.010
`Regeneron v. Novartis
`IPR2021-00816
`
`Dan Marino,
`MSc
`Executive Editorial
`Director
`Drug Delivery
`Technology
`
`Shaukat Ali, PhD,
`MSc
`Technical Service Manager
`BASF Pharma Solutions
`
`Sarath Chandar, MBA
`Vice President, Global
`Marketing & Commercial
`Development
`SPI Pharma
`
`Ms. Debra Bingham
`Partner
`Valeo Partners
`
`Philip Green, PhD
`Director of Business
`Development
`Advanced Drug Delivery
`BD
`
`David Monteith, PhD,
`MBA
`Senior Director, Drug
`Delivery & Life Cycle
`Development
`Schering-Plough
`
`Josef Bossart, PhD
`Managing Director
`Bionumbers LLC
`
`Peter Hoffmann,
`PhD
`Vice President, New
`Technology Development
`Genzyme Corporation
`
`James Vaughan
`Division Vice President
`3M Drug Delivery
`Systems
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`10
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 1/30/09 2:48 PM Page 11
`
`Regeneron Exhibit 1214.011
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 2/3/09 2:15 PM Page 12
`
`PII Enters Strategic Collaboration With NexMed; Launches Drug Delivery
`Solutions Initiative
`PII, (Pharmaceutics International, Inc.) and NexMed, Inc.
`
`recently announced they have signed a Memorandum of
`Understanding (MOU) for a strategic product development
`collaboration utilizing NexMed’s NexACT drug delivery
`platform. Pursuant to the MOU, PII will promote the NexACT
`technology to its clients and may independently identify new
`product development opportunities for this collaboration with
`NexMed. PII will be responsible for the research and
`development of the new pharmaceutical products with technical
`guidance and oversight from NexMed, and will also assume
`responsibility for clinical trial material manufacturing and
`commercial manufacturing of the new products.
`“We are very pleased to enter into this collaboration with PII,”
`said Hem Pandya, NexMed’s COO. “The strategic goal of this
`agreement is to broaden the promotion of the NexACT
`technology platform and permit us access to PII’s research and
`development and commercial manufacturing infrastructure. We
`will also be able to continue with our current product
`development efforts at significantly reduced monthly overhead
`expenses.”
`“The collaboration between the companies will offer PII’s
`customers opportunities for product development without having
`to move their compounds elsewhere,” added Steve King, PII’s
`Senior Vice President. “This technology fits well with PII’s Drug
`Delivery Solutions initiative.”
`NexMed, Inc. is leveraging its proprietary NexACT drug
`delivery technology to develop innovative topical pharmaceutical
`products that address unmet medical needs. NexMed's novel,
`onychomycosis treatment, licensed to Novartis, is currently in
`pivotal Phase III trials in the US and Europe. In September 2007,
`NexMed filed a New Drug Application with the FDA for its
`alprostadil treatment for erectile dysfunction. NexMed's pipeline
`also includes a Phase II treatment for female sexual arousal
`disorder and an early stage treatment for psoriasis.
`PII also announced the formal launch of a new business
`initiative, PII Drug Delivery Solutions. In response to demand
`from its clients for product development tools that meet the
`challenges of problematic new chemical entities (NCEs) and of
`product life cycle management (LCM), PII has put together a
`strategy and dedicated resources focused on drug delivery. This
`new initiative, named PII Drug Delivery Solutions, builds on the
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`12
`
`PII’s proven track-record in formulation development and
`pharmaceutical manufacturing to help its clients bring new
`products to market with optimized clinical profiles and higher
`commercial value. Since its inception, PII has built considerable
`expertise in drug delivery, including conventional controlled-
`release formulation approaches, a portfolio of PII-developed
`technologies, and programs involving third-party platforms. Its
`alliance with Penwest Pharmaceuticals for TIMERx technology
`being an example.
`The strategy for PII Drug Delivery Solutions is to provide
`dedicated business development, centers of technical excellence,
`proactive partnering, and integrated support from PII core
`resources. PII believes its exciting portfolio of in-house and
`partnered drug delivery technologies can be put to work to assist
`clients with their product development needs, be they early stage
`drug candidate optimization through to the revitalization of a
`marketed compound.
`“Our dedicated business development team lead by Robin
`Mitchell and Susan Wiggins has extensive experience in drug
`delivery and contract services,” said Mr. King. “We aim to
`proactively bring creative problem-solving solutions and product
`concepts to our clients. PII already has a very powerful portfolio
`of technology platforms at our disposal and intends to build on
`this during 2009. PII has quietly developed some impressive
`technologies of its own (nanoparticle formulations and
`MedCrystalForms’ mixed phase co-crystals for enhanced drug
`bioavailability for example).”
`“Through our partnerships with companies like Penwest, we
`can tackle a broad range of controlled-release challenges too,”
`added Robin Mitchell, Senior Director Drug Delivery Solutions.
`“Susan Wiggins and I are very excited about the role we can play
`to strengthen our clients’ business success in today’s very
`competitive markets.”
`A privately held company, Pharmaceutics International, Inc. is
`a leading multinational contract formulation development,
`Clinical Trial Materials (CTM), and commercial manufacturing
`company with corporate headquarters in Hunt Valley, Maryland.
`Founded in 1994, PII can manufacture a wide range of dosage
`forms covering solid, semi-solid, and aseptic filling. This service
`is complemented by full analytical and regulatory support.
`
`Regeneron Exhibit 1214.012
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 2/3/09 2:15 PM Page 13
`
`Regeneron Exhibit 1214.013
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 1/30/09 2:48 PM Page 14
`
`MicroDose & Nexus6 Announce Collaboration to
`Evaluate Application of Remote Patient
`Compliance Monitoring Technology With
`MicroDose’s Electronic DPI
`MicroDose Technologies, Inc. and Nexus6 recently announced they have entered into a
`
`collaboration to investigate the application of Nexus6’s SmartinhalerLive technology
`with MicroDose’s next-generation electronic dry powder inhaler (DPI). Under the terms of
`the agreement, MicroDose will fund the development of prototypes based upon
`MicroDose’s inhaler platform and incorporating Nexus6’s SmartinhalerLive technology.
`MicroDose will receive an option for an exclusive license to the SmartinhalerLive platform
`for certain fields of use.
`The aim of the investigation is to demonstrate the ability to wirelessly upload dosing
`and compliance information from the inhaler to a web-based server for data management
`and reporting. The SmartinhalerLive technology, providing global roaming wireless, is a
`natural extension of MicroDose’s electronic inhaler features and will facilitate better
`communication between the physician, patient, and pharmaceutical company to improve all
`aspects of care.
`The combined system would have benefits in both the clinical trials setting and with in-
`market products. By improving compliance through reminder features and through real-
`time tracking of compliance, patient safety, and clinical trial data management are
`improved. Improved control and monitoring of compliance can significantly reduce the
`number of patients enrolled per Phase II or Phase III clinical studies. In marketed products,
`the system represents a move to more personalized care, giving a better understanding of
`drug usage and patient response to therapy, and improved compliance and adherence.
`“The combination of Nexus6 Technology and MicroDose’s dry powder inhaler will
`ensure a continuous flow of real time clinical information, which will benefit physicians,
`patients, and pharmaceutical companies," said Mr. Michael J. Martin, VP of Business
`Development and Licensing of MicroDose.
`“This partnership between Nexus6 and MicroDose will enable the drug delivery
`marketplace to access leading edge data collection and transmission capabilities, thereby
`increasing pharmaceutical adherence, improving patient well-being, and reducing overall
`health care costs,” added David Evans, CEO of Nexus6.
`The MicroDose DPI is among a number of key proprietary drug delivery platforms
`developed by MicroDose. By employing piezo electronics, the MicroDose DPI has the
`potential to deliver enhanced performance versus other inhalers, for efficient and
`reproducible delivery independent of patient coordination, inhalation rate, and posture.
`Microdose believes that the flexibility of the inhaler makes it a true platform technology,
`able to support a broad pipeline of products across the spectrum of patient populations and
`therapeutic categories.
`MicroDose Technologies, Inc., based in Monmouth Junction, New Jersey, is a leading
`privately held drug delivery and specialty pharmaceuticals company, developing advanced
`pulmonary, fixed-dose-combination oral dosage, and other technologies and products for
`the pharmaceutical and biotechnology industries.
`MicroDose’s partnered programs include multi-product development and licensing
`agreements with Merck and Co. and Novartis, the development of an inhaled insulin
`product through MicroDose’s QDose joint venture, and an inhaler for the systemic delivery
`of a nerve agent antidote for the US Department of Defense, in collaboration with the
`University of Pittsburgh. MicroDose is also conducting internal development programs for
`products employing its inhaler technology, and for combination oral dosage products
`employing its PolyCap technology in the areas of diabetes, hypertension, and
`hyperlipidemia.
`Nexus6 Limited is a privately held New Zealand-based developer and manufacturer of
`solutions to increase patient adherence to respiratory medications, leading to improved
`disease management and reduced healthcare costs. Nexus6 SmartinhalerLive devices
`monitor and report patients’ medication usage to their healthcare partners and are used in
`pharmaceutical clinical trials and respiratory disease management applications for chronic
`obstructive pulmonary disease, asthma, and cystic fibrosis. SmartinhalerLive uses wireless
`communications technology to provide real time data collection and reporting from drug
`delivery devices.
`
`Regeneron Exhibit 1214.014
`Regeneron v. Novartis
`IPR2021-00816
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`14
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 2/2/09 2:28 PM Page 15
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`15
`
`that specifically and potently inhibit the function of either of these classes of RNA.
`The Locked Nucleic Acid-based technology developed by Santaris Pharma creates synthetic chemical
`versions (LNAs) of the normal nucleic acid building blocks of RNAs. These LNAs improve the drug-like
`qualities of resulting therapeutics, called oligonucleotides, by increasing resistance to metabolism, increasing
`half-life, and improving tissue uptake. The LNA-based therapeutics also demonstrate improved binding
`affinity to their target RNA, which increases potency many-fold over other nucleotide therapeutics.
`Santaris Pharma is a privately held biopharmaceutical company with exclusive pharmaceutical rights to the
`LNA Drug Platform used to develop new classes of RNA medicines targeting mRNAs and miRNAs
`associated with disease. Santaris Pharma's drug discovery engine provides fast and efficient generation of lead
`LNA drug candidates. The company's own research and development activities focus on microRNAs,
`infectious diseases, and metabolic disorders. Santaris Pharma has repeatedly validated the LNA Drug Platform
`through partnerships with major pharmaceutical companies. Santaris Pharma was founded in 2003, is based in
`Denmark, and the company and its partners currently have three compounds in clinical development and two
`more in late preclinical development. Since 2006, the company has raised more than 60 million Euros through
`private financing and corporate partnerships.
`
`Regeneron Exhibit 1214.015
`Regeneron v. Novartis
`IPR2021-00816
`
`Wyeth
`Pharmaceuticals &
`Santaris Pharma A/S
`Announce Strategic
`Alliance to Develop
`RNA-Based Medicines
`
`Wyeth Pharmaceuticals, a division of Wyeth,
`
`and Santaris Pharma recently announced
`they have entered into a worldwide strategic
`alliance to discover, develop, and commercialize
`new medicines based on Santaris Pharma's
`proprietary Locked Nucleic Acid (LNA) drug
`platform, which allows specific targeting and
`regulation of microRNAs (miRNAs) and
`messenger RNAs (mRNAs) as a means to affect
`gene expression mediated by the targeted RNAs.
`Under the terms of the agreement, Santaris
`Pharma will receive an up-front payment of $7
`million in cash, and Wyeth will make a $10-
`million equity investment in Santaris Pharma.
`Santaris Pharma may receive further milestone
`payments of up to $83 million for each of 10
`potential targets. In addition, Santaris Pharma
`would receive royalties on the worldwide sales of
`all products arising from the alliance. The term of
`the research portion of the collaboration is 3
`years. Wyeth has the right to extend the research
`portion up to 2 additional years.
`Wyeth will select the RNA targets against
`which Santaris Pharma will use their proprietary
`LNA drug platform to generate unique drug
`candidates. Wyeth will be responsible for the
`development and commercialization of products
`arising from the alliance.
`"With this alliance, Wyeth explores a fourth
`platform technology targeting RNAs, which
`complements our expertise in small molecules,
`vaccines, and protein-based therapeutics," says
`Mikael Dolsten, President, Wyeth Research.
`"This will increase our ability to develop and
`bring to market innovative, high-value medicines
`that have the potential to address significant
`unmet needs in critical therapeutic areas."
`"We are delighted to welcome Wyeth as a new
`major partner," says Soren Tulstrup, President
`and CEO of Santaris Pharma. "This strategic
`alliance further consolidates Santaris Pharma's
`leading position in the rapidly evolving RNA-
`based therapeutic field. The scope of this
`collaboration demonstrates the utility of Santaris
`Pharma's proprietary LNA Drug Platform for
`developing new therapies targeting RNAs."
`There are two major classes of RNA targets
`for this collaboration: messengerRNAs and
`microRNAs. miRNAs are recognized as
`important elements in regulation of gene
`expression in both normal and diseased cells,
`whereas mRNAs are translated into the proteins
`that determine all aspects of cell identity and
`behavior. Santaris Pharma's proprietary
`technology allows for the discovery of molecules
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 1/30/09 2:48 PM Page 16
`
`Merrion Announces License Agreement With Novo Nordisk to Develop Oral
`Formulation of GLP-1 Receptor Agonist(s)
`Merrion Pharmaceuticals and Novo Nordisk A/S, a world leader
`The agreement also provides Novo Nordisk with the ability to
`develop additional oral formulations of Novo Nordisk GLP-1 receptor
`agonist compounds using Merrion’s proprietary absorption enhancing
`GIPET technology. Merrion will be due additional milestone payments
`for any additional products developed under the agreement.
`“This second partnership with Novo Nordisk builds on the first oral
`insulin analogue agreement signed in November 2008,” said John
`Lynch, Chief Executive Officer of Merrion. “We believe this
`development further demonstrates the potential for long-term
`partnership between our two companies and also enhances our
`capacity to develop our other products and technologies."
`“We are happy to have signed this partnership agreement with
`Merrion to use the GIPET technology in developing potential oral
`formulations of Novo Nordisk’s proprietary GLP-1 receptor agonists.
`This partnership is another step in Novo Nordisk’s research efforts in
`developing new treatments for people with diabetes,” added Peter
`Kurtzhals, Senior Vice President, Novo Nordisk’s Diabetes Research
`Unit.
`
`in diabetes, have entered into a development and license
`agreement to develop and commercialize oral formulations of a Novo
`Nordisk proprietary GLP-1 receptor agonist using Merrion’s
`proprietary GIPET technology. This is the second license agreement
`between the two companies concerning Merrion’s GIPET technology.
`The first agreement for the development of oral insulin analogues was
`signed in November 2008.
`Under this new license agreement, Merrion will receive up to $58
`million for the first product developed under the agreement to reach
`the market based on achievement of certain development, regulatory,
`and sales milestones as well as royalties on sales. Novo Nordisk is
`responsible and will pay for the development and commercialization
`of the product candidates. Merrion is responsible for the development
`and manufacture of the initial clinical batches, with the work overseen
`by a joint development committee. Novo Nordisk and Merrion have
`collaborated since 2007 to test the utility of Merrion's GIPET
`technology in preclinical models.
`
`Micromet Enters Agreement for Solid Tumor BiTE Antibody With Bayer
`Schering Pharma
`Micromet, Inc., a biopharmaceutical company developing novel,
`
`proprietary antibodies for the treatment of cancer, inflammation,
`and autoimmune diseases, recently announced the signing of an option,
`collaboration, and license agreement with Bayer Schering Pharma AG,
`Germany, under which Bayer Schering Pharma has the exclusive option to
`obtain a license to one of Micromet's preclinical BiTE antibodies against
`an undisclosed oncology target.
`Under the terms of the agreement, Bayer Schering Pharma will pay
`Micromet a Euro 4.5 million fee (approx. $6 million) to secure a 1-year
`option on a specific BiTE antibody. Bayer Schering Pharma may exercise
`this option prior to January 5, 2010, through the additional payment of an
`option exercise fee. The exercise of the option would trigger a formal
`collaboration between Micromet and Bayer Schering Pharma on the
`development of the BiTE antibody through the completion of Phase I
`clinical trials, at which point Bayer Schering Pharma would assume full
`control of the further development and commercialization of the BiTE
`antibody.
`Micromet would be eligible for an option exercise fee and milestone
`payments of up to Euro 290 million (approx. $390 million) in total and up
`to double-digit royalties based on tiered net sales of the product. In
`addition, Micromet would be reimbursed for its R&D expenses incurred
`in connection with the development of the BiTE antibody in the
`collaboration with Bayer Schering Pharma.
`"We are very pleased with Bayer Schering Pharma's interest in this
`preclinical BiTE antibody program and their financial commitment to
`secure exclusive access for the next 12 months. This deal represents
`further validation of our BiTE antibody technology by a major oncology
`
`February2009Vol9No2
`
`DrugDeliveryTechnology
`
`16
`
`company," said Christian Itin, Micromet's Chief Executive Officer.
`"Oncology is one of our core growth areas, and biologicals are a key
`focus of our strategy. We are excited about Micromet's BiTE antibody
`technology and believe BiTE antibodies represent a novel and promising
`approach to cancer therapy," said Prof. Andreas Busch, Member of the
`Board of Management of Bayer Schering Pharma AG responsible for
`Global Drug Discovery.
`BiTE antibodies are designed to direct the body's cytotoxic, or cell-
`destroying, T cells against tumor cells, and represent a new therapeutic
`approach to cancer therapy. Typically antibodies cannot engage T cells
`because T cells lack the appropriate receptors for binding antibodies.
`Previous attempts have shown the potential of T cells to treat cancer, but
`the therapeutic approaches tested to date have been hampered by cancer
`cells' ability to escape recognition by T cells. The use of BiTE antibodies
`that are specifically designed to engage T cells for attacking cancer cells
`may provide a more effective anti-tumor approach than conventional
`monoclonal antibodies.
`Micromet, Inc. is a biopharmaceutical company with offices in
`Bethesda, MD, and Munich, Germany. The company is focused on
`developing novel, proprietary antibodies for the treatment of cancer,
`inflammation, and autoimmune diseases. The company's novel antibody
`technology is based on its proprietary BiTE antibody platform,
`representing a new class of antibodies that specifically activate T cells
`from the patient's own immune system to eliminate cancer cells or other
`disease related cells. Four of the company's antibodies are currently in
`clinical trials, with the remainder of its product pipeline in preclinical
`development.
`
`Regeneron Exhibit 1214.016
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`10-17 DDT FEb 09 Market News:Layout 1 2/4/09 9:32 AM Page 17
`
`New Interferon Formulations Promise to Eliminate Injections in Multiple Sclerosis
`Treatment
`Nerveda Inc. and Aegis Therapeutics LLC recently announced
`
`preclinical results from their joint collaboration aimed at developing
`non-injectable formulat