Results of Biopharmaceutical drug
epogen Epogen
(hormone)
Gardasil
(vaccine)
Nutropin
(growth
Hormone)
taceva
Raptiva
(psoriasis)
Enbrel (TNF
blocker AB)
Sequencing
Tobramycin
(aminoglycoside, antibiotic)
Xolair
(antibody)
Neupogen
(colonystimulating factor)
Rituxan
(antibody)
TARCEVA (erlotinib).
Bio-oncology, Genentech
Tarceva is a newly approved second-line therapy and is one of many treatment options for Non-Small Cell Lung Cancer. In November 2004, the U.S. Food and Drug
Administration approved Tarceva for the treatment of patients with locally advanced nonsmall cell lung cancer after failure of at least one prior chemotherapy regimen. Tarceva was approved under the FDA's Pilot Program for Continuous Marketing Applications, a new program designed for investigational products, such as Tarceva, that have been given
Fast Track status and that have demonstrated significant promise in clinical trials as a therapeutic advance over available therapy for a disease or condition.
Tarceva is a small molecule human epidermal growth factor type 1/epidermal growth factor receptor inhibitor which demonstrated, in a Phase 3 clinical trial, an increased survival in advanced non-small cell lung cancer also referred as NSCLC patients. In a
Phase 3 trial, Tarceva has also shown an improvement in overall survival when added to gemcitabine chemotherapy as initial treatment for pancreatic cancer.
In addition to demonstrating a 42 percent improvement in median survival, 31.2 percent of patients receiving Tarceva in the study were alive after one year versus 21.5 percent in the placebo arm. Tarceva also met all secondary endpoints of the trial, including delaying time to symptom deterioration, improving progression-free survival, and increasing tumor response rate.
In November 2005, the FDA approved Tarceva in combination with gemcitabine chemotherapy for the treatment of locally advanced, inoperable or metastatic (has to do with the spread of cancer from one part of the body to another) pancreatic cancer in patients who have not received previous chemotherapy. Tarceva is the first new therapy in nine years approved for pancreatic cancer.

Non-Small Cell Lung Cancer There are more than 1.2 million new cases of lung and bronchial cancer each year worldwide, causing approximately 1.1 million deaths annually. According to the American Cancer Society, lung cancer is the most common cancer-related death in both men and women. An estimated 162,460 deaths, accounting for about 29 percent of all cancer deaths, are expected to occur in the U.S. in 2006. In
Europe, it is estimated that there were approximately 381,500 new cases of lung cancer in
2004 and 936 deaths every day. Lung cancer is reported to be the single largest cause of cancer deaths in the world, responsible for 17.6 percent of all cancer deaths.
References:
Bio-News.com
Genentech.com
Rituxan
In 1997, Rituxan became the first monoclonal antibody approved for the treatment of malignant disease in the United States, when approval was obtained for the treatment of relapsed or refractory low-grade or follicular, CD20+, B-cell non-Hodgkin's lymphoma. Rituxan was discovered by Biogen Idec. It is comarketed by Genentech, Inc. and Biogen Idec in the United States and Roche markets MabThera® in the rest of the world, except Japan, where Rituxan is comarketed with Zenyaku Kogyo Co. Ltd. Rituxan has become the most widely studied and prescribed monoclonal antibody in the world.
Monoclonal antibodies are identical because they were produced by one type of immune cell , all clones of a single parent cell. Montoclonal antibodies used to treat cancer bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell.
NonHodgkin’s lymphoma (NHL) is the most common cancer of the lymphatic system. Since the early 1970’s, incidence rates for non-Hodgkin’s lymphoma have nearly doubled. Over the 25-year period between 1973 and 1998, new cases of NHL seen each year escalated almost 83%, among the highest increases of any cancer. The overall five-year survival rate is only 59%. Of the nearly 500,000 Americans with lymphoma, 332,000 have this form. In 2006, approximately 58,870 new cases of NHL will be diagnosed and 18,840
Americans will die from the disease.
NHL is not a single disease, but rather a group of several closely related cancers that affect the lymphatic system, which is part of the immune system.
NHL is broadly divided into two major groups: B-cell lymphoma (which develops from abnormal B-lymphocytes, which is most common), and T-cell lymphomas
(which develop from abnormal T-lymphocytes). Lymphocytes are a type of white blood cell that helps the body fight infections. B cells develop into plasma cells

that produce antibodies to fight infections, while T-cells attack foreign invaders
(bacteria, viruses, cells, etc.) directly.
Genentech is evaluating Rituxan in Phase III clinical trials for the potential treatment of chronic lymphocytic leukemia (CLL).
Genentech is among the world's leading biotech companies, with multiple products on the market for serious or life-threatening medical conditions and over
40 projects in the pipeline. The company is the leading provider of anti-tumor therapeutics in the United States.
References: Rituxan.com, Genenetech.com, Wikipedia.org http://www.gene.com/gene/pipeline/status/oncology/rituxan/index.jsp?FORM=sC
PN&RS=CHECKED&un=doc&v=1&q=genentech%20clinical%20trials%20rituxan http://www.rituxan.com/rituxan/professional/pi/timeline/index.jsp?FORM=sCPN&
RS=CHECKED&un=doc&v=1&q=rituxan%20cancer http://www.gene.com/gene/about/index.jsp
http://www.gene.com/gene/products/information/immunological/rituxan/index.jsp
By Amgen and Wyeth Pharmaceuticals
(Manufactured by Immunex Corporation that was acquired by Amgen in July 15, 2002)
ENBREL is indicated for reducing signs and symptoms, helping to keep joint damage from getting worse, and improving physical function in patients with moderate to severe active rheumatoid arthritis. ENBREL can be taken in combination with methotrexate or used alone.
ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more DMARDs.

ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone.
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Each of the diseases Enbrel® is approved to treat affects the immune system -- the body’s protection against invasion of infections and toxins. In these diseases, the immune system attacks the body’s own healthy cells, mistaking them for cells that don’t belong. This causes inflammation of the skin or in the lining or connective tissue of the joints.
Tumor necrosis factor (TNF) is one of the chemical messengers that helps regulate the inflammatory process. When the body produces too much TNF, it overwhelms the immune system’s ability to control inflammation of the joints or of psoriasis-affected skin areas. Enbrel is similar to a protein that the body produces naturally, and like this protein, it binds and deactivates some TNF molecules before they can trigger inflammation.
ENBREL is a type of protein called a tumor necrosis factor (TNF) blocker that blocks the action of a substance your body's immune system makes called TNF. People with an immune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, have too much TNF in their bodies. ENBREL can reduce the amount of TNF in the body to normal levels, helping to treat your disease. But, in doing so, ENBREL can also lower the ability of your immune system to fight infections.
Source link: http://www.enbrel.com/index.jsp?f=7
Enbrel (etanercept) approved for the treatment of rheumatoid arthritis.
This article is part of the Arthritis Archives.
Dateline: November 5, 1998
Enbrel Approved
On November 2, 1998, the U.S. Food and Drug Administration announced the approval of the long-awaited, breakthrough drug Enbrel, generic name etanercept, for the treatment of rheumatoid arthritis (RA).
Enbrel (etanercept) is the first in a new class of rheumatoid arthritis drugs referred to as " biologic response modifiers ". Enbrel is a totally new approach to the treatment of rheumatoid arthritis and works by interrupting the inflammatory process of the disease.

Action of Enbrel
The mode of action of Enbrel involves the binding of TNF (tumor necrosis factor).
TNF is one of the cytokines or proteins which play a pivotal role in the reactions which cause the inflammatory process of rheumatoid arthritis. Enbrel competitively inhibits the binding of TNF to
TNF receptor sites. The TNF bound to Enbrel is biologically inactive resulting in reduced inflammatory activity.
Biologic Response Modifier: What is it?
Indication and Dosage
Enbrel is indicated for "the reduction in signs and symptoms of moderately to severely active rheumatoid arthritis in patients who have an inadequate response to one or more diseasemodifying anti-rheumatic drugs ( DMARDs )". Enbrel can be used together with methotrexate in patients not responding to methotrexate alone. The dosage for adults is 25 mg. given two times a week as a subcutaneous injection.
Study Results
More than 1,000 people have participated in clinical trials of Enbrel. In one study of 234 patients with advanced rheumatoid arthritis, 59 percent who took Enbrel for 6 months showed significant improvement compared to 11 percent who were given placebo. About 40 percent of the Enbrel patients saw their symptoms decrease to half. In another study which combined Enbrel with methotrexate, 71 percent of patients taking both drugs experienced improvement compared to 27 percent who took only the methotrexate.
Adverse Effects
Mild to moderate injection site reactions were the most commonly reported adverse effect in
Enbrel trials. Long term effects of Enbrel use or the potential for serious infection, malignancy, or autoimmune disease are not known.
Marketing and Cost
Immunex Corporation and Wyeth-Ayerst Laboratories will market Enbrel in North America while other Wyeth-Ayerst affiliates will market the drug outside North America. The drug is expected on pharmacy shelves within days. A prescription is required to obtain the drug. The cost of Enbrel will be $220 per week ($110 per vial of Enbrel).
Related Resources
Enbrel (etanercept)
Biologic Response Modifiers (TNF Blockers/Biologic DMARDs)
Rheumatoid Arthritis
Sources: Rheumatoid Arthritis Drug Wins OK, AP Online, 11/02/98; Enbrel Receives FDA Approval For Treatment Of Rheumatoid Arthritis,
PRNewswire, 11/02/98; New Rheumatoid Arthritis Drug Approved, UPI, 11/03/98
First published: 11/05/1998
Source link: http://arthritis.about.com/od/enbrel/a/enbrelapproved.htm

Source link: http://www.wyeth.com/content/ShowLabeling.asp?id=101
Pioneering science delivers vital medicines.
Amgen is a global biotechnology company that discovers, develops, manufactures, and markets important human therapeutics based on advances in cellular and molecular biology. For more information on Amgen, please visit our website: http://wwwext.amgen.com
.
Our Mission and Values
Amgen strives to serve patients by transforming the promise of science and biotechnology into therapies that have the power to restore health or even save lives. In everything we do, we aim to fulfill that mission. And every step of the way, we are guided by the values that define us.
Our Mission: To Serve Patients
Our Values:
Be Science-Based
Compete Intensely and Win
Work in Teams
Create Value for Patients, Staff and Stockholders
Trust and Respect Each Other
Ensure Quality
Collaborate, Communicate and Be Accountable
Be Ethical
R&D Vision
Amgen aspires to be the best human therapeutics company. Achieving our goal starts with building the best R&D organization.
At Amgen, we apply four guiding principles to our R&D efforts. The first is to focus on grievous illness. Given the difficulty of successfully developing a new therapy, we focus our efforts on developing therapies to help patients suffering from the greatest unmet medical needs.
Our second guiding principle is to be modality independent -- to fit the tool to the task. Small molecules and biotherapeutics (biologics) each have unique and inherent advantages and disadvantages. Our modality independent approach allows us to leverage the advantageous

aspects of a particular approach that are best suited to interdict a disease. We are not driven to work in a disease area by our drug development capabilities. For us, the question is always:
What’s the best therapeutic approach for a particular disease?
Our third major emphasis is to study disease in patients. All too often our industry has found that experimental models have little predictive value with respect to human disease, which often results in the failure of clinical trials and escalating drug development costs. While it is significantly more complicated to study disease in humans, we believe that this is the only way to successfully develop human therapeutics. Defining the key elements of disease in patient populations drives our R&D investment and the potential therapeutics we pursue. In addition, we are developing clinical trial approaches that allow key decisions earlier in the drug development process, ultimately reducing the overall cost of developing a drug.
Our fourth guiding principle, seamless integration, informs everything we do. We strive to integrate our organization, incorporating the perspectives from sales and marketing, clinical development and basic research into all of our drug development programs. There are important insights that come to basic research and clinical development from understanding the medical marketplace, and vice versa. Aligning our priorities across these functions ensures that we develop potential therapeutics in a manner that will address unmet medical needs and meet the changing demands of the marketplace.
These four guiding principles together are not enough to ensure our success as an organization.
Hard work, intelligence, intuition, and some luck, are also essential. With all of those ingredients, we will achieve our aspiration to become the best human therapeutics company.
Source link: http://wwwext.amgen.com
.
Wyeth is a research-based, global pharmaceutical company responsible for the discovery and development of some of today's most innovative medicines. Our products are sold in more than
140 countries, and our product portfolio includes innovative treatments across a wide range of therapeutic areas. Our worldwide resources include more than 52,000 employees, manufacturing facilities on five continents, and a discovery and development platform encompassing pharmaceuticals, vaccines and biotechnology.
Vision

Our vision is to lead the way to a healthier world. By carrying out this vision at every level of our organization, we will be recognized by our employees, customers and shareholders as the best pharmaceutical company in the world, resulting in value for all.
We will achieve this by being accountable for:

Leading the world in innovation through pharmaceutical, biotech and vaccine

 technologies
Making trust, quality, integrity and excellence hallmarks of the way we do business

Attracting, developing and motivating our people
Continually growing and improving our business

Demonstrating efficiency in how we use resources and make decisions
Source link: http://www.wyeth.com
.
Definition
Rheumatoid arthritis is a chronic (long-term) disease that causes inflammation of the joints and surrounding tissues. It can also affect other organs.
Alternative Names
RA; Arthritis - rheumatoid
Causes, incidence, and risk factors
The cause of rheumatoid arthritis (RA) is unknown. It is considered autoimmune disease.
The body's immune system normally fights off foreign substances, like viruses. But in an autoimmune disease, the immune system confuses healthy tissue for foreign substances. As a result, the body attacks itself.

RA can occur at any age. It usually occurs in people between 25 and 55. Women are affected more often than men.
The course and the severity of the illness can vary considerably. Infection, genes, and hormones may contribute to the disease.
RA usually affects joints on both sides of the body equally. Wrists, fingers, knees, feet, and ankles are the most commonly affected.
Symptoms
The disease usually begins gradually with fatigue, morning stiffness (lasting more than one hour), widespread muscle aches, loss of appetite, and weakness. Eventually, joint pain appears. When the joint is not used for a while, it can become warm, tender, and stiff. When the lining of the joint (synovium) becomes inflamed, it gives off more fluid and the joint becomes swollen. Joint pain is often felt on both sides of the body, and may effect the wrist, knees, elbows, fingers, toes, ankle or neck. Additional symptoms include:





Loss of appetite
Low-grade fever
Limited range of motion
Deformities of hands and feet
Round, painless nodules under the skin (usually a sign of more severe disease)



Inflammation of the lung (pleurisy)
Skin redness or inflammation


Paleness
Swollen glands

Eye burning, itching, and discharge

Numbness or tingling
Anemia may occur due to failure of the bone marrow to produce enough new red cells.
Joint destruction may occur within 1-2 years after the appearance of the disease.
Signs and tests

Joint x-rays

Rheumatoid factor test is positive in about 75% of people with symptoms

Erythrocyte sedimentation rate is elevated

CBC may show low hematocrit ( anemia ) or abnormal platelet counts

C-reactive protein may be a positive indication for patients with no detectable rheumatoid factor

Synovial fluid analysis
Treatment
RA usually requires lifelong treatment, including medications, physical therapy, exercise , education, and possibly surgery. Early, aggressive treatment for RA can delay joint destruction.
MEDICATIONS

Once a diagnosis is confirmed, the current standard of care (in addition to rest, strengthening exercises, and anti-inflammatory drugs) is aggressive therapy with disease-modifying antirheumatic drugs (DMARDs).
Methotrexate (Rheumatrex) is the most commonly used DMARD for rheumatoid arthritis. Others include leflunomide ( Arava ), gold thiomalate ( Myochrysine ), aurothioglucose ( Solganal ), or auranofin ( Ridaura ).
Anti-inflammatory agents used to treat RA include aspirin and non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen ( Motrin , Advil ), fenoprofen , indomethacin , and naproxen
( Naprosyn ). NSAIDS are commonly used to relieve joint pain and inflammation. Although
NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding.
COX-2 inhibitors block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of heart attacks and stroke have prompted the FDA to reevaluate the risks and benefits of the COX-2s. Rofecoxib ( Vioxx ) and valdecoxib ( Bextra ) have been withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. Celecoxib ( Celebrex ) is still available, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible.
Patients should ask their doctor whether the drug is appropriate and safe for them.
Antimalarial medications such as hydroxychloroquine (Plaquenil) and sulfasalazine ( Azulfidine ) are also beneficial, usually in conjunction with methotrexate. It may be weeks or months before a patient sees any benefit from these medications. Because they are associated with toxic side effects, the patient must have frequent blood tests.
Tumor necrosis factor (TNF) inhibitors are a relatively new class of medicatsions used to treat autoimmune disease. They include etanercept ( Enbrel ), infliximab ( Remicade ), and adalimumab
( Humira ). Adalimumab and etanercept are injectable medications. Infliximab is given by IV.
Another relatively new medication is injectible anakinra ( Kineret ), which is a man-made protein that blocks the inflammatory protein interleukin-1. The drug is used to slow the progression of moderate to severe active RA in patients over 18 who have not responded to one or more of the
DMARDs. Kineret can be used with other DMARDs or TNF inhibitors.
Other drugs that suppress the immune system, like azathioprine ( Imuran ) and cyclophosphamide
( Cytoxan ), are sometimes used in people who have failed other therapies. These medications are associated with toxic side effects and usually reserved for severe cases of RA.
Corticosteroids have been used to reduce inflammation in RA for more than 40 years. However, because of potential long-term side effects, corticosteroid use is usually limited to short courses and low doses where possible. Side effects may include bruising, psychosis, cataracts , weight gain, susceptibility to infections, diabetes , high blood pressure , and thinning of the bones

( osteoporosis ). A number of medications can be administered with steroids to minimize osteoporosis.
Consult a health care provider before using any medication, including over-the-counter drugs.
SURGERY
Occasionally, surgery is needed to correct severely affected joints. Surgeries can relieve joint pain, correct deformities, and modestly improve joint function.
The most successful surgeries are those performed on the knees and hips. The first surgical treatment is a sysnovectomy, which is the removal of the joint lining (synovium).
A later alternative is total joint replacement with a joint prosthesis . In extreme cases, total knee or hip replacement can mean the difference between being totally dependent on others and having an independent life at home.
PHYSICAL THERAPY
Range-of-motion exercises and individualized exercise programs prescribed by a physical therapist can delay the loss of joint function.
Joint protection techniques, heat and cold treatments, and splints or orthotic devices to support and align joints may be very helpful.
Sometimes therapists will use special machines to apply deep heat or electrical stimulation to reduce pain and improve joint mobility.
Occupational therapists can construct splints for your hand and wrist, and teach you how to best protect and use your joints when they are affected by arthritis . They also show people how to better cope with day-to-day tasks at work and at home, despite limitations caused by RA.
Frequent rest periods between activities, as well as 8 to 10 hours of sleep per night , are recommended.
PROSORBA COLUMN
The Prosorba column is for the treatment of moderate to severe RA in adults with long-standing disease who have not responded to DMARDs. The device removes inflammatory antibodies from the blood. The procedure takes 2-3 hours, and must be done once a week for 12 weeks.
Studies have reported that RA slows down or stops getting worse in about one third to one half of the people who receive this treatment. Side effects include anemia, fatigue, fever , low blood pressure, and nausea.
Some people have developed an infection from the tube used to remove the blood. Often there is a flare-up of joint pain for several days after the treatment.
Support Groups

For additional information and resources, see arthritis support group .
Expectations (prognosis)
Regular blood or urine tests should be done to determine how well medications are working and if drugs are causing any side effects.
The course of RA differs from person to person. People with rheumatoid factor or subcutaneous nodules seem to have a more severe form of the disease. People who develop RA at younger ages also have a more rapidly progressive course.
Remission is most likely to occur in the first year. The probability decreases over time. By 10 to
15 years from diagnosis, about 20% of people have remission.
More than half (50 - 70%) of patients are able to work full-time.
After 15-20 years, 10% of patients are severely disabled, and unable to do simple daily living tasks such as washing, dressing, and eating.
The average life expectancy for a patient with RA may be shortened by 3 to 7 years. Those with severe forms of RA may die 10-15 years earlier than expected. However, as treatment for rheumatoid arthritis improves, severe disability and life-threatening complications appear to be decreasing.
Complications
Rheumatoid arthritis is not solely a disease of joint destruction. It can involve almost all organs.
A life-threatening joint complication can occur when the cervical spine becomes unstable as a result of RA.
Rheumatoid vasculitis (inflammation of the blood vessels) is a serious , potentially lifethreatening complication of RA. It can lead to skin ulcerations and infections, bleeding stomach ulcers, and nerve problems that cause pain, numbness, or tingling. Vasculitis may also affect the brain, nerves, and heart, which can cause stroke, heart attack, or heart failure.
RA may cause the the outer lining of the heart to swell (pericarditis) and cause heart complications. Inflammation of heart muscle, called myocarditis, can also develop. Both of these conditions can lead to congestive heart failure.
The treatments for RA can also cause serious side effects. If you experience any side effects, immediately tell your health care provider.
Fortunately, better therapies appear to be reducing the occurrence of these severe complications.
Calling your health care provider
Call your health care provider if you think you have symptoms of rheumatoid arthritis.

Prevention
Rheumatoid arthritis has no known prevention. However, it is often possible to prevent further damage of the joints with proper early treatment.
Because RA may cause eye complications, patients should be have regular eye exams.
Reviewer Info: A.D.A.M. editorial. Stanford Peng, M.D., Ph.D., Division of Rheumatology,
Washington University School of Medicine, St. Louis, MO. ; ADAM Health Illustrated
Encyclopedia , 8/19/2005
Source link: http://www.healthline.com/adamcontent/rheumatoid-arthritis/1
The product I chose is Xolair (Omalizumab) which developed under an agreement among Novartis Pharma AG, Genentech, Inc. and Tanox, Inc., and will be co-marketed in the United States by Genentech and Novartis Pharmaceuticals Corporation.. The U.S.
Food and Drug Administration (FDA) approved Xolair in June 2003.
Xolair treats people with moderate to severe persistent asthma.
XOLAIR is a different type of asthma medication called an "IgE blocker." IgE, or immunoglobulin E, is a substance that occurs naturally in the body in small amounts.
When people with allergic asthma breathe in an allergen that occurs year-round—such as dust mites or the dander produced by a cat or dog—their bodies make more IgE. This may cause a series of chemical reactions that can lead to asthma symptoms and attacks.
XOLAIR works by helping to block IgE.
Novartis Pharmaceuticals Corporation, the U.S. affiliate of Swiss-based Novartis AG
(NYSE: NVS), a world leader in health care, with core businesses in pharmaceuticals, consumer health, generics, eye care and animal health. They provide treatment for a broad range of disease.
Genentech focuses primarily on oncology , immunology , and disorders of tissue growth and repair , including angiogenic disorders. Genentech is among the world's leading biotech companies, with multiple products on the market for serious or life-threatening medical conditions and over 40 projects in the pipeline.

Cystic fibrosis (CF) is a life-threatening genetic disease affecting approximately 30,000 people in the United States. CF occurs in approximately one of every 3,200 live Caucasian births (in one of every 3,500 live births of all Americans).
For people with the disease, a defective gene causes the body to produce a faulty protein that leads to abnormally thick, sticky mucus that clogs the lungs and can result in fatal lung infections. The mucus also obstructs the pancreas, causing difficulty for a person to absorb nutrients in food and can block the bile duct in the liver, eventually causing permanent damage in approximately six percent of people with CF
Preventing Cystic Fibrosis
Currently, the only way to prevent cystic fibrosis is to avoid having two carriers conceive a child together.
Inhaled Theraupetics
Chiron currently markets TOBI ® tobramycin solution for inhalation, the leading inhaled antibiotic for the most prevalent type of lung infection caused by Pseudomonas aeruginosa.
TOBI® (Tobramycin Inhalation Solution, USP) is an approved antibiotic that is inhaled directly into the lungs which is widely accepted in the cystic fibrosis community for its value in treating CF patients with Pseudomonas aeruginosa, decreasing their hospitalization rates and increasing their lung function.
Tobramycin sulfate is an aminoglycoside antibiotic used to treat various types of bacterial infections, particularly Gram-negative infections.
Systematic ( IUPAC ) name
4-amino-2-[4,6-diamino-3- [3-amino-6-(aminomethyl) -5-hydroxytetrahydropyran-2-yl]oxy- 2-hydroxy-cyclohexoxy]-6-
(hydroxymethyl) tetrahydropyran-3,5-diol
Chemical data
Formula C
18
H
37
N
5
O
9
Mol. weight
467.515 g/mol
Mechanism of action
Tobramycin works by binding to a site on the bacterial ribosome , causing the genetic code to be misread.
Administration
Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract , so for systemic use it can only be given intravenously or intramuscularly . This formulation for injection is branded Nebcin®. Patients with cystic fibrosis will often take an inhalational form (Tobi®) for suppression of Pseudomonas aeruginosa infections.

Side effects
Like other aminoglycosides, tobramycin can cause deafness or a loss of equilibrioception in genetically susceptible individuals. These individuals have a normally harmless mutation in their DNA that allows the tobramycin to affect their cells. The cells of the ear are particularly sensitive to this.
Tobramycin can also be highly toxic to the kidneys , particularly if multiple doses accumulate over a course of treatment.
For these reasons, when tobramycin is given parenterally , it is usually dosed by body weight .
Various formulae exist for calculating tobramycin dosage. Also serum levels of tobramycin are monitored during treatment.
Improving Drug Delivery
The biggest limitation to fighting respiratory infections is getting sufficient concentrations of the right anti-infectives to the respiratory tract without subjecting the patient to dangerous drug side effects. Since treatment is typically administered orally or intravenously, the entire body is exposed to the antibiotic even when the infection is localized in the lung.
Chiron, in partnership with Nektar is working in development of a better delivery devise for tobramycin. Nektar and Chiron (recently adquired by Norvatis), are undergoing clinical trials for TIP Phase III. The program includes two clinical trials and will evaluate the efficacy and safety of TIP in the treatment of lung infections caused by Pseudomonas aeruginosa in patients living with cystic fibrosis (CF).
About TIP
What is Tobramycin Inhalation Powder?
Tobramycin inhalation powder (TIP) is a dry-powder formulation of the antibiotic tobramycin in combination with a small, hand-held, breath-activated delivery device. TIP has the potential to offer a short administration time, is fully portable and operates without electricity. In addition, TIP does not need refrigeration.
Description
Tobramycin inhalation powder (TIP)
Preclinical Phase 1 Phase 2 Phase 3 Registration
What are the ASPIRE Trials?
The ASPIRE trials are two, Phase 3, multinational, clinical trials that are intended to determine the safety and efficacy of tobramycin inhalation powder (TIP). TIP is an

investigational product that has not been approved by the United States Food and Drug
Administration. TIP is being evaluated for the management of cystic fibrosis (CF) patients with Pseudomonas aeruginosa infection.
The ASPIRE Trials consist of two, independent, Phase 3 pivotal trials:
ASPIRE I:
A randomized, double-blind, multi-center, multinational, placebo-controlled trial to assess the safety and efficacy of TIP in CF patients. During the first 28 days, patients will receive either TIP or placebo, followed by two treatment cycles with TIP.
ASPIRE II:
A randomized, open-label, multi-center, multinational trial to assess the safety of TIP versus
TOBI ® (Tobramycin Inhalation Solution, USP)* in CF patients.
How is Tobramycin Inhalation Powder used?
To administer the dry-powder tobramycin, insert a capsule filled with the dry-powder tobramycin into the body of the delivery device. Attach the mouthpiece and press the button to puncture the capsule. Then inhale the dry-powder tobramycin. The process is repeated four times as four capsules of dry-powder tobramycin are inhaled per dose. As with the
TOBI ® solution treatment cycle, TIP will be inhaled twice a day for 28 days, followed by 28 days off TIP, before starting the next treatment cycle.
References: www.chiron.com
www.novartis.com
www.nektar.com
www.wikpedia.com
www.cff.org
Neupogen
Filgrastim is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. It is marketed by Amgen Inc. as NEUPOGEN, which has been selected as the name for recombinant methionyl human granulocyte colonystimulating factor (r-metHuG-CSF). Neupogen is indicated for reducing the incidence of infection from chemotherapy-induced neutropenia in cancer patients with nonmyeloid malignancies. Neupogen was approved by the FDA in 1991. Neupogen is a genetically engineered protein that stimulates the production of infection-fighting white blood cells

called neutrophils that are depleted by cytotoxic chemotherapy, a condition called neutropenia.
While developing Neupogen, Amgen administered Neupogen to monkeys, dogs, hamsters, rats, and mice as part of a preclinical toxicology program which included single-dose acute, repeated-dose subacute, subchronic, and chronic studies.
NEUPOGEN is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. NEUPOGEN is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of adults with AML. NEUPOGEN is indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae, eg, febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by marrow transplantation. NEUPOGEN is indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
Neupogen is generally used to treat neutropenia (a low number of neutrophils), stimulating the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation. Filgrastim is also used to increase the number of myeloid stem cells before collection by leukapheresis for use in bone marrow transplantation.
Neupogen is a 175 amino acid protein manufactured by recombinant DNA technology.1 Neupogen is produced by Escherichia coli (E coli) bacteria into which has been inserted the human granulocyte colony-stimulating factor gene. Neupogen has a molecular weight of 18,800 daltons. Neupogen is a sterile, clear, colorless, preservativefree liquid for parenteral administration containing Filgrastim at a specific activity of 1.0
± 0.6 x 108 U/mg.
Neupogen works by stimulating the growth of neutrophils, a type of white blood cell. To make sure Neupogen is working, your doctor will ask that you have regular blood tests to count the number of white blood cells you have. It is important that you follow your doctor's instructions about getting these tests.
Amgen is a leading human therapeutics company in the biotechnology industry.
For 25 years, the company has tapped the power of scientific discovery and innovation to dramatically improve people’s lives. Amgen pioneered the development of novel products based on advances in recombinant DNA and molecular biology and launched the biotechnology industry’s first blockbuster medicines.
Works Cited:
1.) Amgen. “Neupogen(Filgrastim).” 20 December 2004.
<http://www.neupogen.com/pi.html#description>
2.)
Wikipedia. “Filgrastim.” 10 July 2006.
< http://en.wikipedia.org/wiki/Filgrastim>

EPOGEN® (Epoetin alfa)
How it works:
EPOGEN® is a recombinant protein that works in a similar way as the body’s natural erythropoietin — a glycoprotein produced by the kidneys that circulates through the bloodstream to bone marrow, where it stimulates red blood cell production. Red blood cells perform the essential function of transporting oxygen throughout the body. When the kidneys fail, production of erythropoietin decreases and the production of red blood cells is hindered, usually resulting in anemia.
Discovery and biological role
The existence of a humoral factor regulating red blood cell production was first postulated in 1906 based on transfusion experiments in rabbits. In 1950 , the still unidentified erythropoietic factor was found to be stimulated in rats breathing a low-oxygen atmosphere, thus establishing the elements of its biological regulation. In the 1960s its source was identified as the kidneys . Human
EPO was first purified from human urine by T. Miyake, C. K. Kung and E. Goldwasser at the
University of Chicago in 1977 . Limited quantitites of the native human protein were used experimentally to treat patients with anemia .
EPO has now been identified as a glycoprotein with a molecular mass of about 30,000 Daltons . It has a 165 amino acid chain with four oligosaccharide side chains and circulates in the blood plasma at a very low concentration (about 5 pmol / L ).
In adult humans, EPO is produced primarily by peritubular cells in the kidneys , where its production is stimulated by low oxygen levels in the blood . Some EPO is also produced by the liver , which is the primary source in the fetus .
EPO acts by binding to a specific erythropoietin receptor (EpoR) on the surface of red cell precursors in the bone marrow , stimulating them to transform into mature red blood cells . As a result the oxygen level in blood reaching the kidney rises and the amount of EPO produced decreases.
Because the kidneys are the primary source of erythropoietin, chronic kidney disease often results in a systemic deficiency of EPO and consequent anemia . Anemia can also occur in cancer patients, sometimes as a direct result of the malignancy but usually as an adverse effect of chemotherapy .
Also, in patients who may require a blood transfusion or undergo surgery where blood loss is expected, EPO is given in advance as a precaution. The bone marrow produces more red blood cells, and if blood is lost during the operation, there is still enough to sustain the patient.
EPO as a therapeutic agent
Therapeutic human erythropoietin was initially isolated and purified from urine in 1977. In 1983 , the gene coding for erythropoietin was identified by a team headed by Fu-Kuen Lin at U.S. biotechnology company Amgen . Researchers at The Genetics Insitute (now part of Wyeth ) independently discovered the gene at approximately the same time. The resulting patent dispute led to Amgen gaining exclusive marketing rights for erythropoietin in the U.S. Recombinant DNA technology was used to express the protein in Chinese hamster ovary cells , which allowed a synthetic form of EPO (rEPO) to be produced in commercial quantities for the first time.

Recombinant EPO was launched as a pharmaceutical product by Amgen for treatment of anemia resulting from chronic renal failure in 1989 under the brand name Epogen. In 1991 it was also approved for treating anemia resulting from cancer chemotherapy. Johnson & Johnson (J&J), an
American pharmaceutical company, markets EPO under license from Amgen for cancer chemotherapy under the brand name Procrit. Amgen’s patents have so far prevented other companies from entering the U.S. market. Even though the patents are all based on work done in the early 1980s, the last of them will not expire until 2015, thirty-two years after the date of the original application.
EPO is generally injected subcutaneously (under the skin) by the patient, although it may also be given intravenously . Several injections weekly are required for the original forms, but the longacting forms may require injections only once every two weeks. EPO cannot be used by patients with leukemia and should be used cautiously by patients with uncontrolled high blood pressure .
An extremely rare but severe adverse effect of EPO is acquired pure red cell aplasia (PRCA), an auto-immune condition in which the bone marrow loses its ability to produce red blood cells, leaving the patient dependent on blood transfusions . Certain lots of the J&J Eprex product were associated with a higher incidence of this problem. Studies at J&J showed that the PRCA was caused by interaction of EPO protein with a rubber compound in the pre-filled syringe used to distribute the product. Substitution of a teflon-coated syringe plunger eliminated the problem.
EPOGEN® is contraindicated in patients with uncontrolled hypertension.
Related Links: www.epogen.com
Anemia
Anemia is a condition that occurs when the blood does not contain enough red blood cells.
Red blood cells carry oxygen from the lungs to the body’s tissues. In a healthy person, the body sends signals to the bone marrow to create more red blood cells whenever the body needs more oxygen. A hormone called erythropoietin, produced in the kidney, is the signal that stimulates the bone marrow to produce red blood cells. When the body does not produce enough erythropoietin, fewer red blood cells are produced, and therefore less oxygen is delivered to the body.
Certain diseases--such as cancer and chronic kidney disease--are related to anemia. Cancer patients undergoing chemotherapy often suffer from anemia because chemotherapy attacks not only cancerous cells, but other cells in the body as well, including red blood cells. In kidney disease patients, kidney function is reduced. Erythropoetin, the body’s signal that tells bone marrow to make more red blood cells, comes from the kidneys, so in these patients, fewer red blood cells are produced.
Some common symptoms of anemia include: fatigue, weakness, rapid heart beat, shortness of breath, dizziness or fainting, feeling cold, sadness or depression, and shortness of breath.
Anemia can strain the heart as it overworks to deliver oxygen throughout the body. It also can make certain cancer therapies less effective and can interrupt chemotherapy treatment. If left untreated, anemia can result in the need for red blood cell transfusions.
About Amgen
Amgen is a leading human therapeutics company in the biotechnology industry. For 25 years, the company has tapped the power of scientific discovery and innovation to dramatically improve people’s lives.
Amgen pioneered the development of novel products based on advances in recombinant DNA and molecular biology and launched the biotechnology industry’s first blockbuster medicines.
Today, as a Fortune 500 company serving millions of patients, Amgen continues to be an entrepreneurial, science-driven enterprise dedicated to helping people fight serious illness.

The drug Nutropin, discovered by Genentech, is used to treat Growth hormone deficiency. Growth hormone difiency, known as GHD, is a pituitary disorder that results not only in short stature but also in other physical ailments. GHD occurs in the body when the growth hormone secreted by the pituitary gland doesn’t function properly.
Disruption of growth hormone affects many of the body’s natural processes. Growth hormone plays a key role in body growth and development, affecting muscle protein and fat breakdown. Approved by the FDA in March 1994, Nutropin is a human growth hormone that is produced by recombinant DNA technology. Recombinant DNA is DNA from different sources that is bought together by molecular biology and not traditional breeding methods. Nutropin works by replacing the growth hormone that is disrupted in the pituitary gland. It also is found effective in treating turner syndrome (a chromosomal disorder that is characterized by short stature and ovarian dysfunction) and chronic renal insufficiency (loss of kidneys ability to secrete wastes). In December of 1996 Nutropin was FDA approved to treat turner syndrome. In June of 2005 Nutropin was FDA approved to treat idiopathic short stature to help adults get into their normal height range.
Nutropin works by jumpstarting tissue growth, lipid metabolism, mineral metabolism, and connective tissue metabolism which are areas affected by having insufficient growth hormone. But, Genentech is not only responsible for the creation of Nutropin they are responsible for much more they have 18 products approved by the FDA and out on the market from 1976 to 2006. The also won an award in January of 2006, Fortune named them the number one on their list of “100 Best Companies to Work For.” They have over
10,000 employees that are happy to work for the company. Genentech is a great company that is doing great things.
GARDASIL
The first shots of the Australian-developed cervical cancer vaccine, which hit the market this week, have been administered by the inventor, Professor Ian Frazer.
Merck & Co. is a global research-driven pharmaceutical company dedicated to putting patients first. Merck investigational vaccine GARDASIL prevented 100 percent of cervical cancer.
On June 8, the FDA approved GARDASIL to prevent cervical cancer and vaginal and vulvar pre-cancers caused by human papillomavirus (HPV) types 16 and 18 and to prevent low-grade and pre-cancerous lesions and genital warts caused by HPV types 6,
11, 16 and 18. GARDASIL has been approved for use in girls and women aged nine to
26 in Australia and the United States. It’s recommended that patients have three injections over six months.
In clinical trials involving more that 20,000 mostly sexually active women around the world, GARDASIL was 100 percent effective in preventing cervical cancers and 99

percent effective in preventing two types of cervical warts. The effectiveness of the vaccine in the clinical trials makes encouraging reading. Cervical cancer kills about
270,000 women worldwide each.
“These are the first pivotal data to show that vaccination with GARDASIL reduced HPV
16 and 18-reatled cervical pre-cancer and non-invasive cervical cancer,” said Laura
Koutsy, PH.D., principal investigator, HPV research group, University of Washington,
Seattle.
There were no discontinuations due to serious vaccine-related adverse events. Adverse events were higher among those who received GARDASIL compared with placebo recipients. The most common vaccine-related adverse event reported was local discomfort at the injection site.
References:
BrightSurf.com.
Popular Mechanics www. Merck .com
Raptiva (efalizumab)
Raptiva is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation and trafficking of Tcells that lead to the development of psoriasis. Raptiva prevents T-cells from becoming activated and entering the skin. This, in turn, inhibits the process that leads to plaque formation. As Raptiva starts working in the body and plaque formations is slowed, psoriasis symptoms start to clear. The
U. S. Food and Drug Administrative approved Raptiva in October 2003. In clinical studies, Raptiva demonstrated a rapid onset of action, in some patients by four weeks, in the reduction of symptoms associated with psoriasis. Raptiva is administered once-weekly via subcutaneous injection and can be self-administrative by patients at home. Genentech presented final results from a long-term study at the American of Dermatology
Academy
2005 meeting that showed sustained improvements in psoriasis symptoms throughout three years continuous treatment.
Sequencing Strategy Sequencing Plans and Progress Statistics Why Sequence Them?
Information for Collaborators Protocols Genome Portal Site

This page is updated at the beginning of every month.
Organism Proposer Affiliation Status*
Large Eukaryotes
Brachypodium distachyo n
(Poaceae)
Why?
Vogel
Aquilegia formosa
Why?
Hodges
USDA-ARS
UC Santa
Barbara
Pending
Pending
Gossypium (cotton)
Why?
Manihot esculenta
Paterson
Univ. of
Georgia
Pending
(cassava)
Why?
Fauquet
Danforth Plant
Science Ctr.
Pending
Small Eukaryotes
Guillardia theta and
Bigelowiella natans
Why?
Tetranychus urticae (twospotted spider mite)
Why?
Grbic
Mating loci from Volvox
Archibald Dalhousie Univ.
Univ. of
Western Ontario
Pending
Pending
Public
Release**
Mb to be sequenced
2480
3200
500
500
392
790 carteri and
Chlamydomonas reinhardtii
Why?
Fragilariopsis cylindrus
(a diatom)
Why?
Pleurotus ostreatus
(oyster mushroom)
Why?
Thellungiella halophila
Why?
Reef-building corals and dinoflagellate symbionts
Why?
Heterobasidion annosum
Why?
Umen
Mock
Pisabarro
Stenlid
Salk Inst.
Univ. of
Washington
Public Univ. of
Navarre
Schumaker
Univ. of
Arizona
Univ. of
Medina California,
Merced
Swedish Univ. of Agricultural
Pending
Pending
Pending
Pending
Pending
Pending
20
390
280
85
230
1920

Peronosporomycete mtDNAs (26)
Why?
Hudspeth
Northern
Illinois Univ.
Switchgrass
Why?
Riftia pachyptila (deep-
Tobias
Cryphonectria parasitica
(chestnut blight fungus)
Why?
Nuss
USDA-ARS
Univ. of
Maryland
Biotech. Inst.
Pending
Pending
Girguis Harvard Univ. Pending sea tubeworm)
Why?
Three species of
Neurospora
Why?
Univ. of
Taylor California,
Berkeley
Pending
Bacteria and Archaea
Methanomicrococcus blatticola
Why?
Rhizobium
Hackstein
Radboud Univ.
Nijmegen
Pending leguminosarum bv trifolii
(strains WSM1325 and Reeve
WSM2304)
Why?
Murdoch Univ.
Pending
Pending
Methylocella silvestris
BL2, Methylocapsa acidiphila B2, and
Beijerinckia indica subsp.
Dunfield
Sciences
Inst. of
Geological and
Nuclear
Sciences, New
Zealand
Pending indica
Why?
Pedomicrobium manganicum
Why?
Lithifying mat communities of marine stromatolites (6 bacterial strains)
Why?
Mackenzie,
Decho
Univ. of Texas,
Houston
Carolina
Univ. of South
Pending
Pending
Actinobacteria
Why?
Jansson
Swedish Univ. of Agricultural
Sciences
In production
Anaerobic benzenedegrading methanogenic
Edwards
Univ. of
Toronto
Pending consortium
Why?
Haloalkaliphilic sulfurMuyzer Delft Univ. of Pending
60
21
401.5
400
128
400
25.6
128
40
288
58.4
192
28.8

oxidizing bacteria
Why?
Dechlorinating community (KB-1)
Why?
Six freshwater ironoxidizing bacteria
Why?
Edwards
Emerson
Technology
Univ. of
Toronto
Amer. Type
Culture
Collection
Pending
Pending
200
151
Beggiatoa alba
Why?
Near-shore anoxic basin:
Mueller
Saanich Inlet
Why?
Candidatus Amoebophilus
Hallam asiaticus and C.
Cardinium hertigii
Why?
Candidatus
Horn
Morgan State
Univ.
Univ. of British
Columbia
Univ. of Vienna
Pending
Pending
Pending
42
30
235
Endomicrobium trichonymphae , freeliving strain Pei191
Why?
Brune
Max Planck
Institute for
Terrestrial
Microbiology
In production
110
Burkholderia
Why?
Tiedje
Michigan State
Univ.
1 in production,
576 others pending
Thermolithobacter ferrireducens
Why?
Crenothrix polyspora
Wiegel
Univ. of
Georgia
Pending 48 enrichment
Why?
Six Cyanothece strains
Why?
Thauera sp. MZ1T
Why?
Microbial community in
Wagner
Pakrasi
Sayler
Univ. of Vienna
Washington
Univ.
Univ. of
Tennessee
Pending
Pending
Pending
40
32
300 wastewater treatment van der
Meer
Univ. of
Lausanne
Pending 120 plants
Why?
Symbiont from the basal clade of the Frankiaceae
Why?
Benson
Univ. of
Connecticut
Pending 64
*"Pending" indicates that we are waiting for DNA or the DNA is waiting to enter the production process; "in production" includes both library creation and production sequencing; "draft assembly" is the first assembly, made without finishing the genome;

"finishing" is postproduction work not carried out for all organisms; "final assembly" is the process of assembling the finished genome; "annotation" refers to automated finding of genes and assignment of functions; genomes on which we do not plan further work are labeled "done".
**"Reads released" indicates that reads have been sent to the GenBank Trace Archive; release dates indicate the date an assembly was made publicly available.