By: lovingitall0
22 Apr 2004, 09:08 AM EDT
Msg. 148397 of 148400
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MS and glandular fever virus link

BBC, 2004/04/22

Doctors have found more evidence to suggest that children who develop glandular fever may have an increased risk of multiple sclerosis.

Doctors in Canada carried out tests on 120 children, 30 of whom had MS.

They found those with MS were twice as likely to be infected with the virus that causes glandular fever.

Writing in the Journal of the American Medical Association, they said the findings suggested the virus may play a role in the development of MS.

Previous studies have suggested that there may be a link between Epstein-Barr virus and MS.

However, it has been difficult to prove, not least because so many people have had glandular fever.

Common virus

The Epstein-Barr virus is a member of the herpes virus family. About 95% of adults show signs of being infected with it by the time they are 40. Most have been infected by the age of 20.

This latest study is one of the first time doctors have carried out tests on children to see if those with MS are more likely to have had the virus than healthy children.

Dr Brenda Banwell and colleagues at Toronto's Hospital for Sick Children carried out tests on 30 children with MS and 90 healthy children, with an average age of 13.
They found antibodies in the blood of 83% of those with MS, showing they had been exposed to the Epstein-Barr virus. This compared to just 42% of the healthy children.

The doctors said the findings suggested there may be a link between the virus and MS. "The results suggest an association," they wrote.

Multiple sclerosis affects about 2.5m people around the world. The disease attacks the nervous system.

Initially it causes loss of balance, reduced vision and bouts of localised paralysis. Eventually, patients may become totally paralysed and wheelchair-bound.

Scientists believe the condition is caused by a chemical in the body called interferon gamma.

Under normal circumstances this chemical helps to activate the immune system to attack foreign invaders, such as viruses and bacteria.

'Trigger not cause'

In multiple sclerosis patients interferon gamma causes the immune system wrongly to identify body cells are foreign invaders.

As a result, the myelin sheath coating nerves in the brain and spinal cord is destroyed by mistake.

Transmission between nerve cells then slows down and becomes irregular.

Some scientists believe that interferon gamma may see antibodies from the Epstein-Barr virus as a potential attacker, causing it to damage nerve cells.

The MS Society welcomed the study but said further research is needed.

"It is another piece of useful research," said a spokesman.

"It is further indication that viruses may have a role to play in triggering MS.

"However, it is talking about a trigger rather than a cause. The number of children with glandular fever who go on to develop MS is really very small."


By: 4titudinous
22 Apr 2004, 10:06 AM EDT
Msg. 148409 of 148458
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June 5-8th ASCO conference may flesh out the following:

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United States Patent Application 20040033244
Kind Code A1
Hirschman, Shalom Z. February 19, 2004

Treatment of cancers of lymphocytic cells with product R

Abstract

A method of treating a patient suffering from cancers of lymph cells such as acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma comprises parenterally administering to said patient an effective acute lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation.


Inventors: Hirschman, Shalom Z.; (Riverdale, NY)
Correspondence Name and Address:
    COHEN, PONTANI, LIEBERMAN & PAVANE
    551 FIFTH AVENUE
    SUITE 1210
    NEW YORK
    NY
    10176
    US
Assignee Name and Adress: Advanced Viral Research, Corp.

Serial No.: 446895
Series Code: 10
Filed: May 28, 2003

 
U.S. Current Class: 424/400; 514/7
U.S. Class at Publication: 424/400; 514/7
Intern'l Class: A61K 038/16; A61K 009/00


Claims



I claim:

1. A method of treating a patient suffering from acute lymphocytic leukemia, comprising parenterally administering to said patient an effective acute lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation.

2. The method of claim 1, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

3. The method of claim 1, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

4. A method of treating a patient suffering from chronic lymphocytic leukemia, comprising parenterally administering to said patient an effective chronic lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation.

5. The method of claim 4, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

6. The method of claim 4, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

7. A method of treating a patient suffering from Hodgkin's disease, comprising parenterally administering to said patient an effective Hodgkin's disease treatment amount of Product R in a pharmaceutically acceptable formulation.

8. The method of claim 7, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

9. The method of claim 7, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day. The treatment of patients with Hodgkin's disease with Product R.

10. A method of treating a patient suffering from non-Hodgkin's lymphoma, comprising parenterally administering to said patient an effective non-Hodgkin's lymphoma treatment amount of Product R in a pharmaceutically acceptable formulation.

11. The method of claim 10, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

12. The method of claim 10, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

13. A method of shrinking enlarged lymph nodes in patients with Hodgkin's disease or Non-Hodgkin's lymphoma, comprising parenterally administering to said patient an effective amount of Product R for shrinking lymph node in a pharmaceutically acceptable formulation.

14. The method of claim 13, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

15. The method of claim 13, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

16. A method of shrinking enlarged spleen in patients with Hodgkin's disease or Non-Hodgkin's lymphoma, comprising parenterally administering to said patient an effective amount of Product R for shrinking spleen in a pharmaceutically acceptable formulation.

17. The method of claim 16, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

18. The method of claim 16, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

19. A method of treating body wasting, lose of appetite and fatigue in patients suffering from acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma, comprising parenterally administering to said patient an effective acute lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation.

20. The method of claim 19, wherein said Product R is administered in a range from about 2.5 microliters to about 40 microliters per kilogram of body weight per day in a pharmaceutically acceptable formulation.

21. The method of claim 19, wherein said Product R is administered in an amount of 2 ml per day for about 2-4 weeks and subsequently 1 ml per day.

22. A method of treating a patient suffering from cancers of lymphocytic cells which comprises acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma, comprising parenterally administering to said patient an effective cancers of lymphocytic cells treatment amount of Product R in a pharmaceutically acceptable formulation.
Description



RELATED APPLICATION

[0001] This application claims priority from the provisional application Serial No. 60/383,639, filed May 28, 2002. The contents of provisional application Serial No. 60/383,639 are incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] Present invention relates to a method of treating patients suffering from cancers of lymphocytic cells such as acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma with Product R, a peptide-nucleic acid preparation by administering Product R to the patients.

[0004] 2. Related Art

[0005] Cancers of lymphocytic cells including acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma are common forms of cancer. The American Cancer Society estimates that 60,900 cases of lymphoma will occur in the U.S. in the year 2002, comprising 7,000 cases of Hodgkin's disease and 53,900 cases of non-Hodgkin's lymphoma. These cancers are estimated to cause a total of 25,800 deaths in the U.S. in the year 2002. It is estimated that 30,800 new cases of leukemia will occur in the U.S. in the year 2002 and that 21,700 patients will die with leukemia in 2002.

[0006] Although there have been significant strides in the treatment of these cancers in the past two decades, many patients still succumb to these diseases. Even in childhood lymphocytic leukemia where the results have been improving in terms of prolonging the life of the patient, and in achieving 5 year cures, approximately 15% of children still succumb to the disease with present chemotherapeutic agents.

[0007] Therefore, it is evident that new and effective agents to treat these cancers are sorely needed. Product R is a peptide-nucleic acid preparation that has broad effects on immune functions. Product R can stimulate pro-inflammatory responses when necessary such as in patients with viral infections or cancers. When an aberrant immune response already exists as in patients with autoimmune disorders such as rheumatoid arthritis, Product R will turn off the aberrant immune response thereby relieving the symptoms of the disease.

[0008] In the laboratory, Product R stimulates the synthesis of a variety of chemokines and cytokines. These include interleukin 1, interleukin 6, interleukin 8, MCP-1, interferon gamma and tumor necrosis factor alpha. In macrophages that are maximally activated in cell culture Product R will turn off the synthesis of proinflammatory cytokines and chemokines.

[0009] Product R has been used for treating many viral infections or diseases related to immune system disorders. Some of the uses of Product R are disclosed in the U.S. Pat. Nos. 6,268,349, 6,355,226, 5,902,786, 5,807,839 and U.S. patent application Ser. Nos. 09/189,172, 08/838,134, 08/839,651, 09/316,374, 08/964,250, 09/705,618, 09/706,305, 09/257,739 and 09/948,221, which are incorporated by reference in their entirety.

[0010] However, Product R has never been tested or suggested to be used in patients who suffer from non-solid tumors such as Lymphocytic Leukemias, Hodgkin's Disease and Non-Hodgkin's Lymphoma. Thus, an object of the present invention is to provide a method for treating patients having non-solid tumors such as Lymphocytic Leukemias, Hodgkin's Disease and Non-Hodgkin's Lymphoma by administering Product R to such patients.

SUMMARY OF THE INVENTION

[0011] An object of the present invention is to provide a method of treating a patient suffering from cancers of lymphocytic cells such as acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma, which comprises parenterally administering to said patient an effective acute lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation.

[0012] Another object of the present invention is to provide a method of shrinking enlarged lymph nodes in patients with Hodgkin's disease or Non-Hodgkin's lymphoma, which comprises parenterally administering to said patient an effective amount of Product R for shrinking lymph node in a pharmaceutically acceptable formulation.

[0013] A further object of the present invention is to provide a method of shrinking enlarged spleen in patients with Hodgkin's disease or Non-Hodgkin's lymphoma, which comprises parenterally administering to said patient an effective amount of Product R for shrinking lymph node in a pharmaceutically acceptable formulation.

[0014] Still, a further object of the present invention is to provide a method of treating body wasting, lose of appetite and fatigue in patients suffering from acute lymphocytic leukemia, chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma, which comprises parenterally administering to said patient an effective acute lymphocytic leukemia treatment amount of Product R in a pharmaceutically acceptable formulation

DETAILED DESCRIPTION AND PREFERRED EMBODIMENT OF THE INVENTION

[0015] Product R is a product developed and manufactured by Advanced Viral Research Corp. (Yonkers, N.Y.). The manufacturing process, composition, and chemical, physical and some biological properties of Product R are described in U.S. Pat. Nos. 6,303,153 and 6,528,098, the content of which is incorporated by reference in its entirety.

[0016] Product R has been found to be effective in the treatment of cancers emanating from lymphocytic cells including patients with acute lymphocytic leukemia, Hodgkin's lymphoma and non-Hodgkin's lymphoma.

[0017] According to the present invention, Product R is preferably administered to the patient parenterally, while other administration routes such as nasal spray or ingestion may also be employed. A suitable effective dose of Product R will be in the range of from about 5 microliters to about 40 microliters per kilogram of body weight per day, preferably in the range of about 10 microliters to about 25 microliters per kilogram of body weight per day. Most preferably Product R is administered in an amount of about 30 microliters per kilogram of body weight per day for about one week, followed by about 15 microliters per kilogram of body weight per day in a sterile injectable formulation. The desired dose may be administered as two, three or more sub-doses at appropriate intervals, generally equally spread in time, throughout the day. Preferably, the full daily dose is administered in one administration.

[0018] Alternatively, Product R may be administered to the patients according to the conventional dosages or any dosages that are apparent to a person of ordinary skill in the art.

[0019] Product R may be administered by any suitable injection route including, but not limited to intravenously, intraperitoneally, subcutaneously, intramuscularly, and intradermally, etc. The presently preferred route of administration is intramuscularly. It will be appreciated that the preferred route may vary with, for example, the condition and age of the recipient.

[0020] Product R may be used in therapy in conjunction with other medicaments including corticosteroid, gamma globulin, glucose, or vitamins, antiviral agents such as interferon or interleukin, etc.

[0021] The present invention is further provide a method for treating patients suffering from non-solid tumors such as Lymphocytic Leukemias, Hodgkin's Disease and Non/Hodgkin's Lymphoma by administering the active components or active portion(s) of Product R to such patients. The active components or portions of Product R are described in the above mentioned U.S. Pat. Nos. 6,303,153 and 6,528,098.

[0022] While it is possible for Product R to be administered as part of a pharmaceutical formulation, it is preferable to present it alone, although it may be administered at about the same time as one or more other pharmaceuticals are independently administered. If Product R is administered as part of a pharmaceutical formulation, the formulations of the present invention comprise at least one administered ingredient, i.e. Product R, as above defined, together with one or more acceptable carriers thereof and optionally other therapeutic ingredients. The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0023] The formulations may conveniently be presented in unit-dose or multi-dose containers, e.g. sealed ampules and vials.

[0024] Preferred unit dosage formulations are those containing a daily dose or unit, daily sub-dose, or an appropriate fraction of the administered ingredient.

[0025] In patients with cancer of lymphocytic cells such as acute lymphocytic leukemima, Hodgkin's lymphoma and non-Hodgkin's lymphoma, patients have been treated initially with 2 ml of Product R administered subcutaneously in equally divided doses in the morning and the evening for 2-4 weeks and then with 1 ml of Product R per day. There were no toxic reactions observed with Product R therapy. The treatment with Product R usually resulted in the shrinkage of enlarged lymph nodes in patients with Hodgkin's disease or Non-Hodgkin's lymphoma with Product R, and the shrinkage of an enlarged spleen in such patients.

[0026] The following examples only serves to further illustrate, but not to limit the scope of the present invention.

EXAMPLE 1

[0027] In a 71 year old white male with acute lymphocytic leukemia who failed intensive courses of conventional chemotherapy, Product R was effective in keeping this patient alive for 18 months. Chemotherapy was discontinued soon after commencing Product R therapy. Indeed, after commencing Product R therapy the patient's bone marrow which had contained 30% blast cells lost these blast cells. In addition, blast cells disappeared from the peripheral blood. During this two year period the patient put on weight, had a normal appetite, claimed that he felt well, and was able to live a normal quality of life. The patient died soon after a fall in his home.

EXAMPLE 2

[0028] Product R also proved effective in the treatment of a patient with stage 4B Hodgkin's disease. This patient had failed a stem cell transplant with recurrence of the Hodgkin's disease. The bone marrow was infiltrated with Hodgkin's tumor cells and there were large inguinal and para-aortic lymph nodes. Moreover, the spleen was markedly enlarged filling most of the abdomen and causing the patient pain. She was chronically fatigued and weak and was not able to work. After treatment with Product R she reported a return to normal activity and energy with increased appetite and strength after one week of therapy. She was able to return to work after a year's absence. Moreover, the peripheral lymph nodes disappeared and there was marked shrinkage of the spleen to a more normal size. This patient died due to a blood borne infection secondary to a infected an infected mediport catheter.

EXAMPLE 3

[0029] Method for Preparing Product R

[0030] Suspend about 35.0 g of casein, about 17.1 g of beef peptone, about 22.0 g of nucleic acid (RNA), about 3.25 g bovine serum albumin in about 2.5 liters of water for injection USP at about 3 to 7.degree. C. in a suitable container and gently stir until all the ingredients have been properly wet. Carefully add while stirring about 16.5 g of sodium hydroxide (reagent grade ACS) and continue stirring until sodium hydroxide completely dissolved. Autoclave at about 9 lbs pressure and 200-230.degree. F. for a period of time until RNA is completely digested, for example, about 4 hours. At the end of the period, the autoclave is stopped and the reaction flask and contents are permitted to slowly cool to ambient temperature. Then cool for at least six hours at about 3-8.degree. C. The resulting solution is filtered through 2 micron and 0.45 micron filters using inert gas such as nitrogen or argon at low pressure (1-6 psi). In a similar manner the solution is filtered again through 0.2 micron pyrogen retention filters. The resulting filtrate is sampled and assayed for total nitrogen. A calculation is then performed to determine the quantity of cooled water for injection to be added to the filtrate to yield a diluted filtrate with a nitrogen content between about 165-210 mg/100 ml, the final volume is approximately 5 liters. The pH is then adjusted with either concentrated HCl (reagent grade ACS) or 1.0 normal NaOH to about 7.3-7.6 range. The diluted solution is then filtered again through 0.2 micron filters with inert gas at low pressure. The final filtrate is then filled and sealed into 2 ml glass ampules while in an inert gas atmosphere. The ampules are collected and autoclaved for final sterilization at 240.degree. F. and 20 to 30 pounds pressure for about 30 minutes. Following the sterilization cycle, the ampules with Product R are cooled and washed.

[0031] All quantities are subject to plus or minus 2.5% variation for pH, volume, and analytical adjustments.

* * * * *
By: aven2002
22 Apr 2004, 12:43 PM EDT
Msg. 148432 of 148460
Jump to msg. #  
Hi All,Well this just came out:.....Aven1
22-Apr-2004

Other Events, Financial Statements & Exhibits and Regulation FD Disc


ITEM 5. OTHER EVENTS
Alan Gallantar resigned as the Chief Financial Officer and Treasurer of Advanced Viral Research Corp. (the "Company"), effective April 19, 2004. On April 19, 2004, the Company appointed Martin Bookman as acting Chief Financial Officer and Treasurer. A copy of the press release regarding these events is attached as Exhibit 99.1 to this report and is incorporated herein by reference.


ITEM 7. FINANCIAL STATEMENTS AND EXHIBITS
(c) Exhibits.



Exhibit No. Description
----------- ---------------------------------------------------------------------
99.1 Press Release of Advanced Viral Research Corp. dated April 20, 2004,
reporting the resignation of its Chief Financial Officer and the
appointment of an acting chief financial officer.


ITEM 9. REGULATION FD DISCLOSURE
The press release issued by the Company and attached hereto as Exhibit 99.1 is incorporated by reference into this Item 9. The press release is not being filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not to be incorporated by reference into any filing of the Company.








(Voluntary Disclosure: Position- Long; ST Rating- Strong Buy; LT Rating- Strong Buy)


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By: lovingitall0
22 Apr 2004, 03:22 PM EDT
Msg. 148461 of 148466
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Epstein-Barr virus and lupus

What problem was studied?

Epstein-Barr virus is one of the most common viruses that infect humans, generally resulting in a very mild and brief illness in children. When EBV affects adolescents or young adults, it can result in infectious mononucleosis, a condition that results in fever, sore throat, swollen lymph glands and severe fatigue. Although symptoms usually stop within a few months, EBV remains dormant or latent in the body for the rest of the infected person's life and can become reactivated. EBV infection is more common in people with systemic lupus erythematosus (SLE or lupus) but it is not clear whether this is a cause or effect of a faulty immune system in these individuals. In addition, people with lupus often take drugs that suppress the immune system, making them more susceptible to infections and cancer. To help prevent these complications, research is needed to better understand how the immune system in people with lupus defends against foreign invaders.

Arthritis Foundation-funded researchers involved in the study: Insoo Kang, MD, supported by an Arthritis Investigator Award; Timothy Quan, MD, supported by an AF/American College of Rheumatology Physician Scientist Development Award; and Joseph E. Craft, MD, supported by a Biomedical Science Grant and a Southern New England Chapter grant, Yale University, New Haven, CT

What was done in the study?

The research team collected blood samples from people with lupus and from healthy individuals to look at signs of EBV infection (called "viral loads"). They also examined how the immune system in both groups handled EBV infection by studying subsets of immune cells, called "T cells," which normally play a key role in defending the body against viral infections.

What were the study results?

The researchers found that the patients with lupus had a 40-fold increase in signs of EBV infection compared to the healthy subjects. The people with lupus had a higher frequency of one type of T cell (CD4) but a lower frequency of another type of T cell (CD8). The team concluded that people with lupus have a defect in their ability to control latent EBV infection that probably results from altered T cell responses to the virus.

What's the relevance to people with lupus?

This study is important because it begins to provide insights about how people with an abnormal immune system, such as in lupus, respond to infection. Adds Dr. Kang, "This is clinically important research since patients with autoimmune diseases like lupus are frequently treated with strong immunosuppressive drugs that may suppress immune responses against infection. In this study, we have shown that patients with SLE have defective control of latent EBV infection. However, the clinical significance of such a defect is still elusive and should be determined with future studies."

Source: Journal of Immunology, January 2004 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14707107&dopt=Abstract


By: lovingitall0
22 Apr 2004, 07:46 PM EDT
Msg. 148481 of 148485
Jump to msg. #  
Flying High with Biotechs

March 31, 2004
FUND Q&A From S&P

Franklin Biotechnology Discovery Fund's Evan McCulloch says new drugs, such as Avastin and Cialis, should keep the sector humming

Biotech stocks have soared over the past 18 months, buoyed by a flurry of drug approvals and improving fundamentals. The $659.4 million Franklin Biotechnology Discovery Fund/A (FBDIX ), managed by Evan McCulloch, surged 58.3% for the one-year period through February, while health-care funds gained an average of 43.1%.

McCulloch primarily invests in biotechnology and discovery-research companies, including small-cap outfits. Within biotech, the manager prefers therapeutic companies over platform-technology companies.

Relative to its peers, Franklin Biotechnology Discovery features greater volatility as measured by its three-year standard deviation and beta. On the flip-side, it boasts significantly lower turnover and an expense ratio slightly below the average equity sector fund.

CHART POSITIONS. Despite the current euphoria surrounding biotech, the sector is very volatile -- any scent of bad news from the Food & Drug Administration can send stock prices reeling. Moreover, the process of bringing a drug to market is long and cumbersome. Valuations often ride purely on capricious investor sentiment.

For the three-year period through February, McCulloch's fund dropped 6.1% annualized, vs. an average 1.5% loss by health-care funds. However, over the five years through last month, the fund beat its peers, 16% vs. 9.6%. Illustrating biotech's volatility, this fund declined 20.5% and 42.5%, respectively, in 2001 and 2002, before roaring back with a 43.6% gain in 2003.

Palash R. Ghosh of S&P's Fund Advisor spoke recently with McCulloch about the fund's strategy. Edited excerpts from their conversation follow:

Q: Describe your investment process.

A: We use a bottom-up investment methodology focusing on fundamental analysis and research. We invest in companies with favorable competitive profiles, large market opportunities, and strong intellectual property. Generally speaking, we like companies with excellent management, strong financial characteristics, and attractive valuations.

Within the biotech universe, we tend to favor therapeutic companies over platform-technology firms. Among the therapeutics, we are focused on the later-stage companies, those with products on the market and/or in the later stages of clinical trials. We occasionally invest in companies where the lead compound is in Phase II trials, but valuations must be very attractive.

Q: What factors drove biotech's strong performance in 2003?

A: It was essentially accelerated FDA drug approvals and the sector's rebound from depressed levels. Biotech bottomed in July, 2002, as a string of unfortunate events weighed on valuations. Then, news turned very positive in 2003, with many drug approvals and successful clinical trials -- the most important being positive Phase III results for Avastin, Genentech's (DNA ) drug for colorectal cancer. This rejuvenated hopes for oncology drugs in development and lifted the entire sector.

Q: What are your top holdings?

A: As of Feb. 29: Amgen (AMGN ), 7.5%; Gilead Sciences (GILD ), 7.5%; Genentech (DNA ), 5.7%; Biogen Idec (BIIB ), 5.6%; Genzyme (GENZ ), 4.6%; MGI Pharma (MOGN ), 2.9%; MedImmune (MEDI ), 2.9%; Chiron (CHIR ), 2.8%; Alkermes (ALKS ), 2.7%; and NPS Pharmaceuticals (NPSP ), 2.6%. These top 10 stocks represented 44.8% of the fund's total assets, with a total of 62 holdings.

Q: What are some newly approved drugs that you think will become blockbusters with at least $1 billion in annual sales?

A: We think Avastin will likely reach the $1 billion figure. It benefits large patient populations and is very expensive.

Other drugs that could reach blockbuster status include Cialis, a treatment for erectile dysfunction jointly developed by ICOS (ICOS ) and Eli Lilly (LLY ), and Risperdal Consta, a treatment for schizophrenia created by Alkermes and Johnson & Johnson (JNJ ). However, these two drugs resulted from partnerships with large pharmas, so the innovator companies will only receive a portion of the profits.

Lastly, two drugs, FluMist, an influenza vaccine developed by MedImmune and Wyeth (WYE ), and Velcade, a multiple myeloma drug made by Millennium Pharmaceuticals (MLNM ), could reach $1 billion in sales if additional trials come out positive.

Q: What's your view of ImClone Systems' (IMCL ) cancer drug, Erbitux?

A: Erbitux is an important development for colorectal cancer patients because it's approved for third-line treatment, a setting where the prognosis for patients is very poor. While we don't expect Erbitux to become a blockbuster, it will still be a significant drug and will probably treat other tumor types.

Q: What's your view of the planned merger of Genzyme and ILEX Oncology (ILXO )?

A: We had mixed emotions on this deal. While it's important to Genzyme, because it expands the company's offerings in oncology -- one of the most promising therapeutic areas for drug development -- we also believe ILEX Oncology is worth more than the $1 billion Genzyme is paying. We own both stocks. Overall, M&A activity is robust in the biotech sector, and we expect more takeovers in 2004.

Q: Do you expect more M&A activity between big drug companies and smaller biotechs in 2004?

A: Yes, because big pharma pipelines remain weak, and biotechs have higher R&D productivity. There were several such deals in 2003, the largest being Johnson & Johnson's (JNJ ) acquisition of Scios.

Q: Tell me about the biggest biotech company, Amgen.

A: 2003 was a fantastic year for Amgen, as its sales grew rapidly and benefited from several new drug launches. Its stock rose about 25.7% during the year. We expect 2004 to be another solid year for the company. Although it's more difficult to grow a larger company than a smaller one, large-cap firms like Amgen benefit from diversified revenues, which decrease the overall risk. There's a trade-off between slower growth and the risks to that growth.

Amgen will need to bolster its new product pipeline to maintain current growth trends. We hope their initiatives meet those demands, but with over $5 billion of cash, Amgen can also acquire smaller companies to fill their pipeline.

Q: Do you believe the biotech sector is overpriced now?

A: We believe there are as many overvalued biotech stocks as undervalued ones. However, a stock like Genentech, which rose 175% in 2003 and now trades at 60 times forward p-e, is selling at a premium.

Q: What's your outlook for the biotech sector in 2004?

A: We're very optimistic about the sector for 2004 and beyond. Valuations are fair, and the macro perspective is benign. There's little on the slate in terms of legislation, and the FDA has been cooperative. Individual companies are making tremendous progress, and the recent flurry of IPOs offers fresh investment options.