Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 54

DECLARATION re #53 Memorandum in Opposition to Motion of Michael R. Gottfried in Support of Amgen Inc.'s Opposition to Defendants' Motion to Dismiss for Lack of Subject Matter Jurisdiction and Failure to State A Claim for Which Releif May be Granted by Amgen Inc.. (Attachments: #1 Exhibit 1#2 Exhibit 2#3 Exhibit 3#4 Exhibit 4#5 Exhibit 5#6 Exhibit 6#7 Exhibit 7#8 Exhibit 8#9 Exhibit 9#10 Exhibit 10#11 Exhibit 11#12 Exhibit 12#13 Exhibit 13#14 Exhibit 14#15 Exhibit 15#16 Exhibit 16#17 Exhibit 17#18 Exhibit 18#19 Exhibit 19#20 Exhibit 20 (part 1 of 2)#21 Exhibit 20 (part 2 of 2))(Gottfried, Michael)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

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EXHIBIT 1

Dockets.Justia.com

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Roche Annual Report 2005 Business Report

We Innovate Healthcare

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Innovative solutions spanning the healthcare spectrum

Our combined capabilities in diagnostics and pharmaceuticals enable us to meet needs across the entire healthcare spectrum. From identifying disease susceptibilities and screening for disease in at-risk populations to prevention, diagnosis, therapy and treatment monitoring, our innovative products are advancing the fight against disease on a wide range of fronts, and making a real difference for patients and health professionals. At Roche our commitment to innovating healthcare is matched by a commitment to corporate social responsibility. Sustainability is one of our company's guiding values. We recognise that economic, social and environmental concerns are intertwined and that progress in each of these sectors requires progress in all three. As a research-intensive company with a long-term strategic focus, Roche strives to deliver sustainable value to all its major stakeholders.

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Predisposition Page 8 'It's so good to know my medication really can help me:

Table of Contents
Business Report 2005 Key figures The year 2005 in brief Letter from the Chairman 2 3 4 10 1o 1o 11
18 18 19 19 25 27 30 30 32 32 33 33 39 40 41

Early detection Page 16 'We couldn't have stood the uncertainty any longer.'

Roche Group Group results Outlook Group strategy Pharmaceuticals Pharmaceuticals Division in brief Results Therapeutic areas Research and development R&D Pipeline Expanding biotech production capacity Access to medicines Diagnostics Diagnostics Division in brief Results Business areas Research and development Key product launches scheduled for 2006 Access to d lag nostics Board of Directors and Corporate Executive Committee, Corporate Governance Board of Directors and Corporate Executive Committee Corporate Governance Responsible and sustainable management Dialogue with our stakeholders Our commitment to employees Our commitment to society

Prevention Page 42 'The medication helps against my osteoporosis, and I only have to take it once a month.'

Diagnosis Page 64 'Suddenly I realised my life was hanging by a thread."

Therapy Pages 70 and 84 'The feeling that I had regained control over my disease gave me a huge psychological lift:

44 48 58 66 72 78

Monitoring Page 100 'I've got my independence back.' Safety, health and environmental protection Assurance Track record 2005/Outlook 2006 The key performance indicators GRI reference list Roche - a Global Market Presence 86
102 104 107 108 112

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Fold-out: R&D Pipeline

Therapeutic proteins building a stronger portfolio
Biopharmaceuticals are promising candidates for innovative therapies in a number of disease areas. However, creating protein-based drugs is a complex process that poses challenges very different to the manufacturing of small molecules. Roche Pharmaceuticals established the Therapeutic Protein Initiative (TPI} to build and expand its expertise in this area. TPI is a global initiative, uniting contributions from many divisional functions, with protein discovery and development activities in Penzberg and protein formulation in Basel as its cornerstones. By acquiring and developing external and internal knowledge and skills. Roche has established novel technologies in cell-line development, automated product isolation and advanced analytical technologies. Since its inception in 200] TPI has helped increase Roche Pharmaceuticals' R&D productivity, with the number of protein-based projects rising from four to now more than 25. Most of these are in the key areas of oncology, inflammatory and autoimmune disorders and transplantation.

'Recombinant proteins, especially monoclonal antibodies, have demonstrated their value as novel therapeutic agents due to their high target specificity. They already provide safe and effective therapies for many patients,' says Stephan Fischer, Global Head of Biologics Research and Development at Roche. 'Our expertise and competence in all functions involved in protein research, development and manufacturing put the Roche Group in a unique position to keep delivering breakthrough medicines:

the treatment of adjuvant colon cancer, advanced renal cell carcinoma, and pancreatic, prostate and Oncology ovarian cancer. It is also being tested in combinaMajor clinical development programmes are tion with Tarceva in non-small cell lung cancer exploring the benefits of MabThera/Rituxan, Her- (NSCLC). ceptin, Avastin, Tarceva and Xeloda in additional important indications. Roche is evaluating MabThera/Rituxan in chronic
Major development activities

Recent phase III data have shown that Avastin has significant survival benefit in metastatic non-small cell lung cancer and metastatic breast cancer, increasing the drug's potential to become a mainstay of cancer treatment (see Setting new standards in cancer treatment, p. 30). Regulatory filings for these new indications are planned for 2006. In addition, Avastin is being studied in phase III trials in

lymphocytic leukemia (CLL) in two phase III programmes exploring its use as first-line treatment and in the therapy of relapsing CLL. Phase III and IV trials with Herceptin are ongoing in the metastatic and adjuvant settings in breast cancer. Herceptin is also being evaluated in the treatment of gastric cancer. Data from four large clinical trials in patients with early-stage breast

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R& D pipeline: all major development projects successfully brought forward

enzyme mo(/uletOr

hLmlanlee(~ entl-lL-6 receptor monOclonal inhD©Oy humaniae~ ant~-IL-6 receptor monocional 8ntibOOy nurnsnlled antI-CD20 monoclonal anttbooy IMPDH inhibitor IMPDH Inhibitor

inti-CD20 rnonoctonal entJhedy antl-CD20 rnonOclonal antibody antt-CD20 monoclOnal antibody

chronic rjmphocytic leukemia (l~t li~e~)

Ill

EGFR InhlbAor EGFR Inhibitor + ant~-VEGF m onoclonal antibody

an~*CD20 monoc~onal an~booy

OL#.t

At the end of 2005 the Phermaceu~Lcals Division's R&D pipeline comprised 108 projects, i~clUdl[~g 59 new molecular ent=tle~, LNMEs) aria 49 additional indica1=ons. Fourteen NMEs are currently m oha~e 0 2] ~ phase I, 19 ~n phase ~1 and hve m phase III or f~led for regulatory review. In 2005 13 ~rc~ects ~ntered pPase I devetopmm=t ~2 entered r~llase II and ]3 entere~ phase III Blue type s=gndies first ind=cation, black type additional indications, Curr~nt as of 31 December 2005.

Phase 0: Phase h Phase I1: Phase Ill:

Transition from orechnicalto chnical develcpment Initial studies In healthy volunteers and possibly in Efficacy, tolerability and dose-finding studies it1 Large-scale studies in Dat=en[s [or statistical c~[~fif~llatlon o1 safety and

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Partnering for innovation
Partnering is a key element in Roche's strategy to develop innovative, differentiated medicines for patients. Pharma Partnering (PP}, the company's business development and licensing department, analyses over 1,500 external opportunities each year to find cutting-edge science to complement Roche's own R&D. How does Roche find external innovation? 'We focus on emerging, innovative science,' says immunologist and marketing veteran Hari Kumar, one of PP's 'finders'. 'Strategy teams tell us what they need, be it a drug for a condition with no effective treatment or a technology, and we go out and look for it.' Finders are specialists who combine scientific expertise with business acumen. Their job is to identify opportunities that could lead to new treatments, including new uses for existing Roche products. Once a finder identifies an opportunity, a larger PP team assesses it based on three key questions: Is the science viable and differentiated? Will the opportunity complement Roche's overall strategy? What is its commercial potential? Senior management then make a decision based on the answers.

PP's alliance directors take over once a deal ~s approved. While the contract is being negotiated, they prepare Roche for the project's integration and ensure that communication with partners is open and clear. Throughout the process Roche relies on its core partnering values: flexibility, respect for partners" culture and autonomy, and commitment that both sides will benefit from the collaboration. An organisation-wide partnering culture helps ensure our continued access to a broad range of external innovation and expertise.

cancer (adjuvant setting) have shown that adding Herceptin to chemotherapy significantly reduces the risk of cancer recurrence in this population. US and EU £dings for this indication are planned for the first quarter of 2006.

Extensive late-stage programmes studying Xeloda in adjuvant breast cancer, in combination with chemotherapy in the adjuvant colon cancer setting, and in first- and second-line therapy of metastatic colorectal cancer are continuing. Recent interim analysis of a large collaborative group study of the Tarceva, a human epidermal growth factor receptor drug as first-line treatment for advanced pancreatic (HER1/EGFR) inhibitor, is designed to interfere cancer showed that adding Xeloda to standard with a molecular signal that plays a significant role chemotherapy (gemcitabine) significantly extends in tumour cell growth in numerous types of cancer. patient survival and improves quality of life. It is currently being tested in the first-line and adjuvant NSCLC settings and in combination with A head-to-head phase Ill study comparing BonAvastin in second-line NSCLC. Tarceva is also being dronat and zoledronic acid in the treatment of evaluated in the treatment of glioblastoma multi- metastatic bone pain has commenced, with results forme, one of the most aggressive types of primary expected in 2007. Filings for this indication are planned in the US and Europe. brain tumour.

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Hematology and nephro~ogy (aaemia) Clinical development of CERA, the first continuous erythropoietin receptor activator for the treatment of anemia, is progressing on track. The phase III renal programme for this product includes six trials involving over 2,400 patients with chronic kidney disease (both on dialysis and not on dialysis). The first four phase III trials in dialysis patients were successfully completed at the end of 2005. CERA is the only anti-anemia drug ever studied using long dosing intervals (once every four weeks) in all patients for its initial filing. Roche plans to file marketing applications worldwide for CERA in renal anemia in 2006. Roche does not view the patent infringement litigation initiated by Amgen in the US as an impediment to the development and launch of CERA in the United States.

Development of Actemra (tocilizumab, formerly MRA) in RA is progressing well. Phase III data from Japan were presented at the American College of Rheumatology meeting in November. They show that treatment with Actemra significantly reduces the progression of joint damage and improves RA signs and symptoms. Based on these data, Chugai plans to file a marketing application for Actemra for RA in Japan in the first half of 2006. Patient recruitment for international phase III trials is proceeding as planned. Regulatory filings in the US and EU are expected in 2007. In 2005 Chugai launched Actemra in Japan in its first indication, Castleman's disease, a rare condition that causes severe enlargement of the lymph nodes. CellCept is being developed in collaboration with Aspreva Pharmaceuticals for autoimmune applications, including the treatment of lupus nephritis (kidney complications associated with the autoimmune disease lupus erythematosus) and myasthenia gravis (a chronic autoimmune disease characterised by episodes of muscle weakness). Phase III clinical trials of the drug in both indications are under way. CellCept is the first potential new treatment for either of these debilitating and sometimes fatal conditions in many years. In January 2006 CellCept was designated an orphan drug in the treatment of myasthenia gravis by the FDA.

Nheumatoid arthritis and autoimmune diseases Rheumatoid arthritis (RA) is an autoimmune disorder characterised by joint inflammation that, even when treated, can result in progressive joint destruction and, ultimately, loss of function. Its exact cause is unknown, and as yet there is no cure. Within two years of developing RA, up to 70% of patients have X-ray evidence of joint destruction, and within ten years 80% are unable to work or perform everyday tasks. RA is one of the most common autoimmune disorders and is now thought to affect over 21 million people worldwide. Current treatments include disease-modifying antirheumatic drugs (DMARDs) Diabetes Roche has now completed the two-year animal carand biologic therapy such as the anti-TNF drugs. cinogenicity programme for the insulin sensitiser In 2005 Roche significantly advanced the devel- R483, required by the FDA for all members of this opment of two medicines with the potential to sub- class of agents. A final decision on the commencestantially improve the treatment of RA. ment of phase tit clinical testing of the compound in type 2 diabetes will be taken once the FDA and MabThera/Rituxan is the first selectively targeted other agencies have completed their reviews of the B cell therapy to be studied in this disease. The US carcinogenicity data. and EU filings in August and September for the product's first rheumatoid arthritis indication rep- Two other compounds being developed for the resent a significant milestone. The filings, based on treatment of type 2 diabetes moved into phase II data from the pivotal REFLEX trial, cover the use of clinical testing in 2005, a glucokinase activator and MabThera/Rituxan in patients who have failed to a dipeptidyl peptidase (DPP-IV) inhibitor. respond adequately to current biologic therapies, the subgroup of RA patients considered to be the most difficult to treat. Positive outcomes have also been seen in a phase IIb clinical trial (DANCER) with patients who had previously failed treatment with one or more DMARDs.

Bushless Report 2005

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Setting new standards in cancer treatment At the 41st meeting of the American Society of Clinical Oncology ([ASCO), in Orlando, Florida, in May Roche and its partners presented data from an ~nprecedented eight major phase ]]! trials t~at had Suc£essfully met their Primary endpoints. Benefit Product Cgenericname) Indication (clinical trial) 49o/0 improvement in overall survival Metastatic H ER2-negative breast cancer, Avastin (bevacizumab) 1st line treatment (E2100) Metastatic non-small cell lung cancer, 1st line treatment ([E4599) Metastatic colorectal cancer, 2nd line treatment (E3200D Herceptin ([trastuzumab) H ER2-positive breast cancer, adjuvant treatment ([NSABP B-3] and NCCTG N9831, joint analysis) H ER2-positive breast cancer, adjuvant treatment (HERA) Relapsed indolent NHL, maintenance treatment (GS LG) Pancreatic cancer, 1st line treatment (PA3) 300/o improvement in overall survival 240/0 reduction in risk of death 52o/o reduction in risk of disease recurrence 46% reduction in risk of disease recurrence 100% improvement in response duration at 3 years 23o/0 improvement in overall survival

MabThera/Rituxan (rituximab) Tarceva (erlotinib)

Expanding biotech production capacity
In 2005 the Roche Group continued to reconfigure its manufacturing capacities to meet the requirements of a changing product portfolio and increase the efficiency of its global manufacturing operations. In particular, a shift from chemically derived active pharmaceutical ingredients towards biologics and a corresponding trend towards sterile liquid dosage forms are driving current activities in this area. Technical development activities also reflect the impact of the Pharmaceuticals Division's dynamic R&D portfolio (including development of in-licensed products by Roche). Ongoing projects to further reduce supply chain complexity and optimise inventory levels remain on track. Four major new facilities were dedicated last year: new biotech production facilities for epoetin and CERA in Penzberg (Germany); a state-of-the-art packaging and storage facility for injectable drugs in Mannheim (Germany); and a plant for highpotency pharmaceutical products in Shanghai. The new Penzberg and Mannheim facilities have been operational since the middle of 2005. The Shanghai facility, the first of its kind in China, is scheduled to come on stream this year; it will produce CellCept and Xeloda for the Chinese market.

The Oceanside (California) facility acquired by Genentech from Biogen Idec last June is currently being converted to produce Avastin; manufacturing of bulk drug substance is expected to commence in 2006, with FDA licensure expected in the first half of 2007. In 2005 Genentech received FDA ticensure for a new Avastin manufacturing facility in Porrifio, Spain. Work on the new Basel (Switzerland) and Penzberg production facilities for therapeutic antibodies, both scheduled for technical completion in 2007, is moving ahead as planned.

Access to medicines
While the primary role of the Roche Pharmaceuticals Division is to discover, develop and commercialise innovative medicines, the adoption of policies that extend access to critically needed products to people affected by poverty throughout the world is an integral part of healthcare's mission. Therefore, in addition to supporting local initiatives to expand healthcare access, Roche has implemented patent and pricing policies and joined major :international efforts aimed at addressing this problem.

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Roche does not file new patents for its medicines in the 50 Least Developed Countries (as defined by the UN), nor does it enforce patents it already holds in these countries. In response to the devastating HIV/AIDS pandemic, the company has extended this policy to sub-Saharan Africa, the poorest and hardest-hit region.

steps taken include implementing a tiered pricing system with significant reductions for pandemic use and licensing agreements with local companies for production of the drug for pandemic use in India and China. In addition to taking unprecedented steps to ramp up Tamiflu production capacity (see Meeting world demand for Tamiflu, p. 23), Roche is working with the US National Institute of The prices Roche charges for its products in low Allergy and Infectious Diseases and international and lower-middle income countries are below the virology experts to expand the information base corresponding prices in Switzerland at launch. regarding the optimal use of Tamiflu against the Roche supplies the HIV medicines Invirase and H5N1 avian influenza strain. Viracept at no profit to Least Developed Countries and sub-Saharan Africa. As a result, reduced prices Access to medicines is an issue that affects more for these products apply to 93% of all people living than the developing world - it can pose significant challenges in industrialised countries, as well. In the with HIV/AIDS worldwide. United States, for example, Roche is committed to In addition, Roche is a member of the Accelerating making sure that every patient who needs a Roche Access Initiative, which is helping increasing num- drug has access to it, whether that patient is a senior bers of HIV/AIDS patients in developing countries citizen being treated for cancer, or a member of a to receive treatment. The company also supports working family facing an organ transplant. The two other HIV treatment access programmes, the Roche Patient Assistance Program, established in CARE programme in four African countries and the 1960s, was the first in the industry to provide the Cambodian Treatment Access Programme. In prescription drugs free of charge to qualifying addition to providing funding, medicines and diag- patients who need them but lack prescription nostics through these programmes, Roche has also coverage and the means to pay for them. contributed to providing training in HIV/AIDS care and treatment to hundreds of healthcare pro- Roche is also a founding member of the Partnerfessionals from more than 14 African countries and ship for Prescription Assistance, a programme Cambodia. (See also Ensuring access to healthcare sponsored by the Pharmaceutical Research and Manufacturers of America, which represents the worldwide, p. 79, and visit www.roche-hiv.com.) country's leading pharmaceutical research and In its most recent move to extend access to vital biotechnology companies. The programme offers a HIV/AIDS treatments in the world's neediest areas, single point of access to over 475 public and private Roche announced in January 2006 that, as part of patient assistance programmes. its new Technology Transfer Initiative, the company will provide local manufacturers within sub- Similarly, Genentech provides its marketed prodSaharan Africa and Least Developed Countries with ucts free of charge to eligible uninsured patients the technical expertise required to produce generic treated in the United States through the Genentech HIV medicines. This assistance will be offered free Access to Care Foundation and the Genentech Endowment for Cystic Fibrosis. Genentech is also a and with no conditions attached. member of the Partnership for Prescription AssisThe threat of an avian flu pandemic represents tance. To further support patient access to therapies another critical global health challenge, and Roche for various diseases, in 2005 Genentech donated is closely involved in ensuring that vital medicines approximately 21 million dollars to independent, are available where they are most needed. Follow- third party, public charities that offer copayment ing warnings by the WHO that the next global assistance to eligible patients. influenza pandemic is imminent, Roche has been doing all it can to ensure worldwide availability of its influenza drug Tamiflu for pandemic use. The
Business Report 2005