Details for Patent: 4,837,208
Summary for Patent: 4,837,208
| Title: | Treatment of human viral infections | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Treatment of AIDS or humans carrying or infected with the AIDS virus or having antibodies to the AIDS virus is disclosed using the compound 3'-azido-3'-deoxythymidine or a pharmaceutically acceptable basic salt thereof.Also disclosed is the use of the 5'-mono-, di- and triphosphate of 3'-azido-3'-deoxythymidine or a pharmaceutically acceptable basic salt thereof for the same purpose. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Janet L. Rideout, David W. Barry, Sandra N. Lehrman, Martha H. St. Clair, Phillip A. Furman | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | SmithKline Beecham Corp | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US07/110,377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 4,837,208: Scope, Claims, Expiration and Zidovudine Patent LandscapeU.S. Patent No. 4,837,208 covers the therapeutic use of 3'-azido-3'-deoxythymidine, now known as zidovudine or AZT, in humans with antibodies to HTLV-III, the historical designation for HIV-1. The patent claims the free compound and pharmaceutically acceptable salts, including alkali-metal, alkaline-earth and ammonium salts. It does not claim a specific dose, formulation, route of administration, combination regimen, or manufacturing process. The patent issued on June 6, 1989. Under the pre-Uruguay Round patent-term rule, its ordinary term was generally 17 years from issuance, producing an expiration date of June 6, 2006, absent a controlling term adjustment or extension. The claims are no longer enforceable. What drug and therapeutic use does U.S. Patent 4,837,208 protect?The patent protects AZT treatment for an antibody-positive human. The claims use "HTLV III," the name used in the 1980s for the virus now called human immunodeficiency virus type 1, or HIV-1. The protected active ingredient is:
The patent is a method-of-treatment patent. It does not claim AZT as a new chemical compound in the abstract, nor does it claim every possible use of AZT against every disease or virus. The central legal elements are:
The claims are directed to treatment rather than diagnosis, prevention, laboratory use, or manufacturing. What does Claim 1 of U.S. Patent 4,837,208 cover?Claim 1 covers:
Claim 1 is directed to the unmodified AZT molecule. On its face, the claim does not require:
The phrase "effective HTLV III treatment amount" is a functional limitation. It requires an amount used for treatment, but the claim does not state a numerical dose. In infringement analysis, the relevant question would have been whether the administered amount was intended and capable of treating the claimed condition, not whether it matched a single dose in the patent specification. What does Claim 2 of U.S. Patent 4,837,208 cover?Claim 2 covers administration of a pharmaceutically acceptable salt of AZT where the salt is an:
Likely chemical categories include salts associated with sodium, potassium, calcium, magnesium and ammonium, subject to the patent's disclosure and the ordinary meaning of pharmaceutically acceptable salt. Claim 2 is narrower by chemical class than Claim 3. It requires that the salt fall within one of the expressly listed categories. It does not cover the unmodified free-base or neutral AZT molecule unless the accused product is administered in a covered salt form. What does Claim 3 of U.S. Patent 4,837,208 cover?Claim 3 covers administration of any pharmaceutically acceptable salt of AZT, provided the remaining patient and treatment limitations are met. Compared with Claim 2, Claim 3 uses broader salt language. Claim 2 identifies three salt categories. Claim 3 does not repeat those categories and instead refers generally to a pharmaceutically acceptable AZT salt. The claims therefore have the following relationship:
Claim 3 does not necessarily cover the free compound claimed in Claim 1. A neutral AZT molecule is not ordinarily characterized as a salt. How broad is the patient limitation in the AZT patent?The patient must be a human "having antibodies to the HTLV III virus." This language is broader than a limitation requiring a formal AIDS diagnosis. It can encompass an HIV-1-seropositive person who does not yet have clinically diagnosed AIDS, depending on the claim construction and the evidence of treatment intent. The claims do not expressly require:
The historic terminology creates a claim-construction issue. "HTLV-III" was the contemporaneous designation for the virus later standardized as HIV. A modern use of AZT for HIV-1 would therefore fall within the technical subject matter of the claims, although the patent's expired status makes that issue commercially immaterial today. Does U.S. Patent 4,837,208 cover Retrovir or all zidovudine products?No. The patent claims a method of administering AZT or covered salts. It is not a product-by-process claim and does not, by itself, require:
A generic zidovudine product could have implicated the patent during its enforceable term if the product was used for the claimed HIV treatment. The patent did not, however, independently prevent manufacture of AZT for every purpose once no method claim was practiced. What is the expiration date of U.S. Patent 4,837,208?The patent issued June 6, 1989. For a pre-June 8, 1995 patent application, the ordinary term was generally the longer of:
On the issue-date calculation, 17 years from June 6, 1989 was June 6, 2006. U.S. Patent and Trademark Office records should control for any patent-term adjustment, terminal disclaimer or statutory extension. The patent is expired and cannot presently block generic or branded zidovudine use in the United States.[1] Timeline
The patent was issued before the modern 20-year-from-filing system applied to later-filed U.S. applications. That distinction is important when comparing Patent No. 4,837,208 with later pharmaceutical patents. What was the FDA status of zidovudine?The FDA approved zidovudine under the Retrovir brand in 1987. The initial approval addressed treatment of HIV infection and was based on the drug's antiviral activity and clinical evidence available at the time.[2] Zidovudine was later approved in generic versions. Generic approvals rely on the abbreviated new drug application pathway and must demonstrate pharmaceutical equivalence and bioequivalence to the reference product, subject to the FDA's applicable requirements.[3] Because U.S. Patent 4,837,208 has expired, it has no current blocking effect on an abbreviated new drug application for zidovudine. Any current regulatory barriers would arise from issues such as product quality, bioequivalence, labeling, manufacturing compliance or other listed intellectual-property rights, not from this patent. What was the Orange Book status of U.S. Patent 4,837,208?The Orange Book's relevant function is to identify patents submitted by an NDA holder for an approved drug product and to establish patent-certification obligations for generic applicants.[4] Patent No. 4,837,208 is no longer an active Orange Book barrier because it has expired. During its life, a patent covering the use of AZT for HIV treatment could have been relevant to a generic applicant's Paragraph IV or Section VIII certification, depending on the listing, approved labeling and the precise use claimed. The patent should not be confused with any separate AZT composition, formulation or process patent. Orange Book analysis must be performed patent by patent and product by product. Were there Paragraph IV challenges to AZT patents?Generic applicants could have challenged enforceable AZT patents through Paragraph IV certifications by asserting that the listed patents were invalid, unenforceable or not infringed. A Paragraph IV certification is a regulatory assertion under the Hatch-Waxman framework, not a judicial determination that a patent is invalid.[5] The principal legal issues for an AZT method patent would have included:
No current Paragraph IV risk remains for Patent No. 4,837,208 because the patent has expired. Historical Paragraph IV activity involving other AZT patents should not automatically be attributed to this patent. Which other patent rights were relevant to zidovudine?The AZT patent estate included more than one possible category of rights:
Patent No. 4,837,208 is principally a method-of-use patent. Its three claims do not expressly cover a formulation architecture, manufacturing process or combination therapy. What formulations are protected by Patent 4,837,208?No formulation is expressly claimed. A tablet, capsule, oral solution or injectable product could fall within the claims only through the act of administering AZT or a covered salt to a qualifying human. The patent does not require:
A separate formulation patent would require independent analysis. The existence of a formulation patent would not expand the scope of the claims in Patent No. 4,837,208. Does the patent create biosimilar risk?No. Zidovudine is a chemically synthesized small molecule, not a biologic. Biosimilar approval under the Public Health Service Act is therefore not the relevant pathway. Generic zidovudine is regulated through the small-molecule abbreviated new drug application system.[3] The relevant competitive products are generic equivalents and authorized or branded versions, not biosimilars. What manufacturing and licensing issues affected AZT?The claims do not cover a manufacturing method. A manufacturer could therefore face a separate patent risk from a process patent even if it avoided practicing the treatment method claimed in Patent No. 4,837,208. AZT commercialization also involved licensing and institutional research rights. Early HIV research was conducted across government, academic and commercial institutions. Patent ownership, licensing and enforcement must be determined from the assignment and license records for each patent. The existence of a government or academic inventorship connection does not, by itself, establish that every AZT-related patent was government-owned or that every commercial product was licensed under this specific patent. How strong was the patent estate?Patent No. 4,837,208 had commercially meaningful scope during its term because it targeted the principal therapeutic use of AZT in HIV-seropositive humans. Its breadth was limited by four factors:
The estate was stronger when the drug was used for the claimed HIV population and weaker for non-HIV uses, laboratory applications, manufacturing activities and products whose labeling did not support the claimed treatment. The patent's current strength is zero as an enforcement asset because it expired in 2006. What generic launch risks existed, and what risks remain?During the patent term, a generic launch could have faced:
Today, Patent No. 4,837,208 presents no generic launch risk. Current risks would need to be assessed against any unexpired patent covering a specific formulation, combination, manufacturing route or later therapeutic use. How does Patent 4,837,208 compare with a composition patent?
A composition patent generally creates broader commercial leverage because it can reach manufacture, sale and use of the compound without proving the claimed patient condition. Patent No. 4,837,208 was narrower but directly aligned with the initial clinical use of AZT. Key Takeaways
FAQsCan Patent 4,837,208 cover treatment of asymptomatic HIV infection?Yes. The claims require antibodies to HTLV-III, not a formal AIDS diagnosis. The language can therefore reach treatment of an HIV-seropositive person before AIDS develops. Does the patent cover AZT in combination with other antiretroviral drugs?Potentially, if AZT is administered to the claimed patient in an effective treatment amount. The claims do not exclude combination therapy, but they also do not expressly claim a combination regimen. Does Patent 4,837,208 cover AZT tablets?Only indirectly through administration of the claimed active ingredient. The patent does not claim a tablet formulation, excipient system or dosage-form architecture. Could a generic manufacturer have avoided the patent by using a different AZT salt?Not necessarily. Claim 3 uses broad pharmaceutically acceptable salt language. A different salt could still have fallen within Claim 3 if it satisfied the claim limitations. Is an HIV diagnostic test covered by the patent?No. The claims require treatment by administering AZT or a covered salt. They do not claim detecting antibodies, diagnosing HIV or monitoring a patient's condition. References
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Drugs Protected by US Patent 4,837,208
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| >Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >Approval Date | >TE | >Type | >RLD | >RS | >Patent No. | >Patent Expiration | >Product | >Substance | >Delist Req. | >Patented / Exclusive Use | >Submissiondate |
International Family Members for US Patent 4,837,208
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| African Regional IP Organization (ARIPO) | 11 | ⤷ Start Trial | |||
| African Regional IP Organization (ARIPO) | 8600027 | ⤷ Start Trial | |||
| African Regional IP Organization (ARIPO) | 8600044 | ⤷ Start Trial | |||
| African Regional IP Organization (ARIPO) | 90 | ⤷ Start Trial | |||
| Austria | 113603 | ⤷ Start Trial | |||
| Austria | 135011 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
