AZT scientists joins GSK patent challenge

- AIDS Drug's recognized co-inventor, Dr. Hiroaki Mitsuya, joins AIDS Healthcare Foundation president Michael Weinstein to Denounce Glaxo patent piracy: Former NIH scientist discovered AZT's use against HIV/AIDS

- Dr. Jerome P. Horwitz, researcher who first discovered AZT in the 1960's as a possible cancer-fighting drug offers letter supporting AIDS Group's effort to invalidate patent on AZT, other HIV drugs

London -- The researcher who first demonstrated that the drug AZT (Retrovir(R) or zidovudine) suppresses the AIDS virus today announced his support for a US lawsuit invalidating the drug's patent. Hiroaki Mitsuya, M.D., Ph.D., a research scientist formerly at the US' National Institutes of Health and recognized in Canada as the drug's co-discoverer, backed AIDS Healthcare Foundation (AHF) lawsuit challenging London-based GlaxoSmithKline (GSK) claims to ownership of the drug. "This company did not invent AZT. I and others at NIH discovered its use against HIV," said Mitsuya. "As someone who has a legitimate claim to this drug, I demand it be made available to patients worldwide. With 8500 deaths a day to this dreaded disease, we have no time to waste."

AHF's lawsuit in the U.S. seeks to invalidate GSK's U.S. patent on AZT and other subsequent HIV drugs that include AZT as a component. The lawsuit was filed against GlaxoSmithKline and related companies earlier this year in the United States Federal Court for Central District of California (Western Division, Case No. 02-5223 TJH Ex) by AIDS Healthcare Foundation (AHF), the largest AIDS organization in the U.S.

"We thank Dr. Mitsuya for speaking out on behalf of people in need of effective, affordable AIDS medications around the world," said Michael Weinstein, AHF president. "His role in identifying AZT as the first medication to contain HIV is, and shall continue to be written in the history of heroes in the fight against AIDS -- so much so, that the country of Canada recognizes his contribution as the co-discoverer of the AZT/HIV connection in the Canadian patent."

In addition, a letter written by Jerome Horwitz, Ph.D., the Michigan Cancer Foundation scientist who discovered AZT in the early 1960's as a possible cancer-fighting drug, in which he outlines his support for the "legal assault to invalidate the existing patent for AZT" was read at the conference. (NOTE: Full text of Dr. Horwitz's letter appears immediately following text of this release).

AHF's lawsuit was filed after the discovery that Burroughs Wellcome (now GlaxoSmithKline) lied to the United States Department of Commerce Patent and Trademark Office in 1986 in order to secure the patent on AZT, a key component in both of GSK's current best-selling AIDS medications. Burroughs neither invented AZT (which was first created in 1964 as a possible cancer drug), nor showed AZT's efficacy against the human immunodeficiency virus (HIV), yet claimed to the Patent Office that "we have now discovered that ... (AZT) is useful for the treatment of AIDS ..." when it filed for and secured the patent.

"AHF's counsel has found fraudulent statements on the patent application for the very first AIDS drug, AZT," said AHF's Weinstein. "We believe that Glaxo's subsequent patents on these newer AIDS drugs should be invalidated as well as one of their primary components -- AZT -- was illegally patented by the pharmaceutical giant. It is our hope that this amended lawsuit will break Glaxo's monopolistic hold on key AIDS drugs worldwide." AHF's amended complaint also adds GSK's two best-selling AIDS drugs, Combivir and Trizivir -- a primary component of which is AZT -- to the suit.

AIDS Healthcare Foundation -- represented by the law firm of Manatt Phelps & Phillips -- challenged the pharmaceutical giant's right to exclude competition in the markets for its anti-viral prescription drugs AZT, Ziagen and 3TC and to price these drugs well above competitive rates. GlaxoSmithKline (GSK) controls 40% of the lucrative U.S. AIDS drug market. Glaxo's current worldwide market for its AIDS medications is estimated to be approximately $5 billion dollars annually. Combivir and Trizivir, Glaxo's best selling AIDS drugs today, are reformulations of existing AIDS drugs that offer patients the convenience of two-in-one and three-in-one pill dosing.

The initial patent application for AZT and its medical use against HIV was rejected by United States Department of Commerce Patent and Trademark Office Primary Examiner Ethel G. Love on January 9, 1986. On July 14, 1986, an attorney for Burroughs (GSK) paid $390 dollar fee -- roughly the cost today of one patient's one year supply of life-saving generic versions of Glaxo's $10,000 AIDS medications -- to respond to the rejection and amend and secure a patent on AZT. In response, the pharmaceutical company's attorney Donald Brown stated: "With all due respect to the Examiner's allegations of obviousness, it is quite apparent that the NIH and others skilled in the art have been searching for a drug that will work, all apparently with little success to date."

In fact, the NIH had been sent samples of AZT ("Compound S" as it was called) by Burroughs for testing. NIH scientist Dr. Hiroaki Mitsuya performed tests using the assay system he had invented in mid-February, 1985 that demonstrated for the first time that AZT or "Compound S" was active against the HIV virus. Burroughs officials were informed of the results by telephone on February 20, 1985 -- a full seventeen months before Burroughs filed its response claiming that the "NIH and others ... have been searching ... with little success to date."

"They lied to the patent office in the 1980's about discovering AZT's ability to treat AIDS, and in doing so secured exclusive rights to manufacture it," said AHF's Weinstein. "AZT was created with federal assistance in the 1960's, and the National Institutes of Health showed it for HIV use in the 1980's, but Glaxo secured patents on the substance in the '80's and locked competitors out. They then priced AZT at thirty-two times the cost of manufacture, a practice repeated with every new AIDS drug since then."

In a statement from California, Robert D. Becker, a partner at Manatt specializing in patent law, said GSK's predecessor Burroughs Wellcome "made matters worse by asserting the invalid patents against two generic manufacturers in the early '90's to block cheaper generic versions of AZT. Although Burroughs successfully blocked the drugs, the validity of the patents was never decided."

AHF -- a non-profit that provides medical services to over 12,000 with HIV/AIDS in the U.S. and Africa -- is suing for damages created by such artificially high prices. "It's patent piracy that has cost untold numbers their lives and is denying treatment to millions today," said Weinstein, "all in the name of corporate greed. How many more lives could we have saved if Glaxo had not gouged the government and AHF for almost 15 years now?"

AHF's lawsuit also describes a pattern of such abuse by GSK in marketing AIDS drugs. AHF charges that Glaxo's abacavir (Ziagen) and 3TC (lamivudine) are manufactured and sold pursuant to exclusive licenses from the University of Minnesota and Emory University. Despite the fact that the drugs were developed with U.S. tax dollars, GSK is doing all that it can to gouge the public and price the drugs out of reach.

AHF claims damages as a major purchaser of these medications for its uninsured patients. "Enron's fraud cost jobs and savings," said Weinstein. "GSK's fraud has cost AIDS patients their lives, and has cost the federal and state governments billions of dollars in ill-gotten gain."

AHF in the past has criticized GSK for spending too little on assisting people with AIDS in the developing world, which by Glaxo's own account is about $55 million over the last decade. "That's three-tenths of one-percent of Glaxo's AIDS drug sales," said Weinstein.

In calling for pricing based on cost, Weinstein contrasts the annual price of triple-combination anti-retroviral care charged by GSK, generics manufacturer Cipla, and the Thai government: "Glaxo charges the U.S. government $10,600 annually, Cipla's price is $440, and the Thai's charge $336. Since Glaxo didn't invent AZT, Ziagen or 3TC, what could possibly justify the difference?" In developing nations, Glaxo's so-called preferential prices are also up to double that charged by Bristol Myers Squibb, Merck and Pfizer," said Weinstein.

Manatt attorneys Ronald S. Katz, John F. Libby, Robert D. Becker, and Noel S. Cohen represent AHF in this action.

FULL TEXT OF LETTER FROM DR. JEROME HORWITZ BELOW:

26 November 2002

Michael Weinstein,
President,
AIDS Healthcare Foundation

Mr. Weinstein:

I should like to submit for your consideration the following points, which I deem to be sufficiently cogent from both historical as well as scientific perspectives, to warrant inclusion in a letter of support for the initiation of your lawsuit against GlaxoSmithKline to invalidate the extant patent for AZT.

(1) Our publication, describing the synthesis of AZT (3'azido-3'deoxy- thymidine, [(trade mark name Retrovir), generic name, Zidovidine], appeared in the Journal of Organic Chemistry, vol. 29, pp. 2075-2078, 1964. It was clearly stated therein that, "This work was supported, in part, by Research Grants CA-02903 and CY-5943 from the National Cancer Institute (United States) Public Health Service, and in part by an institution grant from the United Foundation of Greater Detroit, allocated through the Michigan Cancer Foundation." The publication was actually preceded by an oral presentation of the work before the Division of Medicinal Chemistry, 144th National Meeting, American Chemical Society, Los Angeles, CA. April 1963. The indicated support of this endeavor, as well as the work cited below, would suggest that the preparation of AZT, i.e., a composition of matter claim, was the property of the common domain.

A rationale for the preparation of AZT and as well the synthesis of this class of 2',3'-dideoxynucleosides, was provided in a subsequent publication "Nucleosides. XI. 2',3'-dideoxynucleosides," in which we stated that 3'- dideoxynucleosides, i.e., 2',3'-dideoxynucleosides, which included AZT, D4T (stavudine, Zerit) and DDC (2',3'-dideoxynucleosides, zalcitibine, Hivid) were of interest to our laboratory as possible chain terminators of DNA biosynthesis. This served as rationale for the synthesis of all 2',3'- dideoxynucleosides.

All of these agents failed as anti-cancer agents. However, approximately 10-years later, Dr. W. Ostertag of the Max Planck Institute for Experimental Medicine in Germany, [Proc, Nat, Acad. Sci. USA, Vol71 (number 12) pp. 4980- 4985, 1974] showed that inhibition of Lymphatic Leukemia Helper Virus (LLV-F) replication by AZT occurs via phosphorylation of the latter to the corresponding triphosphate, which cannot be incorporated into the growing strand of DNA. Dr. Ostertag concluded (in accord with our rationale for the synthesis of the 2'.3'-dideoxynucleosides) that AZT-triphosphate is likely to interfere with (DNA)-elongation. Indeed, he suggested that "AZT might favorably replace BrdUrd (known anti-viral agent) for medical treatment of diseases caused by DNA viruses."

This seminal discovery, coupled both with the rationale for our synthetic work and that of the all important demonstration by Dr. Mitsuya and co-workers of the high activity of AZT against the human immunodeficiency virus (HIV) in human cells, should, in my view, comprise the bulwark of a legal assault to invalidate the existing patent for AZT.

Sincerely,

     Jerome P. Horowitz, Ph.D. 
     Professor 
     Department of Internal Medicine 
     Division of Hematology and Oncology 
     Wayne State University 
     Karmanos Cancer Institute 

SOURCE AIDS Healthcare Foundation