Details for Patent: 4,530,901
Summary for Patent: 4,530,901
| Title: | Recombinant DNA molecules and their use in producing human interferon-like polypeptides | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Recombinant DNA molecules and hosts transformed with them which produce polypeptides displaying a biological or immunological activity of human interferon, the gene coding for these polypeptides and methods of making and using these molecules, hosts, genes and polypeptides. The recombinant DNA molecules are characterized by structural genes that code for a polypeptide displaying a biological or immulogical activity of human interferon. In appropriate hosts these molecules permit the production and identification of genes and polypeptides displaying a biological or immunological activity of human interferon and their use in antiviral and antitumor or anticancer agents. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Charles Weissmann | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Biogen Inc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US06/118,084 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Patent Claim Types: see list of patent claims | Use; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 4,530,901: Scope, Claims, Expiration, and Recombinant Interferon-Alpha Patent LandscapeUnited States Patent 4,530,901 is a foundational recombinant-DNA patent covering cloned human interferon-alpha DNA, expression constructs, transformed hosts, and biological production methods. The patent issued on July 23, 1985, to Hoffmann-La Roche Inc. Its ordinary pre-URAA patent term expired on July 23, 2002. It no longer creates an enforceable U.S. patent barrier for recombinant interferon-alpha products, generic biologics, biosimilars, manufacturing processes, or follow-on formulations. The claims are broad at the platform level but technically anchored to deposited interferon-alpha DNA clones and their functional equivalents. The principal commercial significance was historical: the patent covered the basic molecular biology route used to produce recombinant human interferon-alpha, including interferon alfa-2a and related alpha-interferon variants. What does U.S. Patent 4,530,901 cover?Patent 4,530,901 covers five related subject-matter groups:
The claims are directed to recombinant production technology rather than to a therapeutic method of treating a patient with interferon-alpha. The patent identifies the following deposited recombinant clones:
Claims 1, 9, and 12 omit the 4c clone from their expressly listed DNA inserts. Claims 5 and 8 include all five deposits. That distinction matters when evaluating literal coverage and prosecution history. How should independent claim 1 be interpreted?Claim 1 is the principal recombinant-DNA claim. It requires a molecule with:
The claim is not limited to one plasmid backbone. Claim 2 confirms that the cloning vehicle may have restriction endonuclease recognition sites, with the interferon DNA inserted at or between those sites. Claim 17 further identifies plasmids and phages as covered vehicles. The claim has three alternative sequence categories: Deposited DNA insertsThe first category is the clearest literal scope. A construct containing one of the listed deposited inserts, operatively linked to a promoter or other expression-control sequence, falls within the claim if the remaining structural limitations are met. Hybridizing sequencesThe second category covers DNA sequences that hybridize to one of the listed inserts and code, on expression, for an interferon-alpha-type polypeptide. This language potentially reaches related interferon-alpha genes with sequence variation. The practical scope depends on the applicable hybridization conditions, the specification, prosecution history, and whether the accused sequence performs the claimed interferon-alpha coding function. Functionally coding sequencesThe third category covers DNA sequences that code for the same type of interferon-alpha polypeptide produced by the listed sequences. This category is broader in functional language than a strict identity claim, but it remains limited by the patent’s disclosure, claim construction, enablement, and written-description requirements. What do claims 5 and 8 add?Claim 5 covers a transformed unicellular host containing the claimed recombinant DNA molecule. It specifically identifies deposited E. coli HB101 strains carrying the relevant plasmids. Claim 8 is materially different because it claims a substantially pure DNA sequence itself. It requires that the sequence code on expression for only a single polypeptide chain. The claim does not expressly require the sequence to be linked to a promoter within the claimed DNA molecule. This creates two distinct enforcement theories:
Modern infringement analysis would examine whether a later sequence falls within the relevant hybridization or functional language and whether the claim remains legally supported by the original disclosure. What do the method claims cover?Claims 9 and 12 cover recombinant production of an interferon-alpha-type polypeptide. The required process generally includes:
Claims 10, 11, 13, and 14 broaden the host and promoter choices. The listed hosts include E. coli, Pseudomonas, Bacillus, yeast, fungi, animal cells, plant cells, and human tissue cells. The listed regulatory systems include lac, trp, phage lambda promoter/operator regions, fd coat-protein control regions, and other prokaryotic or eukaryotic control sequences. The method claims therefore reach beyond E. coli in their literal wording. Their practical enforceability would depend on whether the specification enabled the full range of listed hosts and control systems as construed under the law applicable to the asserted patent term. What is the scope of the hybridization language?The hybridization language is the most important breadth-expanding feature of the claims. A sequence does not necessarily need to be identical to one of the deposited inserts. It may qualify if it:
The claims do not expressly define a percentage identity threshold. As a result, the scope would have depended heavily on the specification’s experimental hybridization conditions and the prosecution record. Potentially relevant sequence classes include:
Codon optimization would not automatically avoid the claims if the resulting sequence still hybridized under the legally relevant conditions or was otherwise covered by the functional language. Conversely, a substantially divergent sequence could fall outside the claims even if it produced a protein with some interferon activity. How strong was the patent estate for recombinant interferon-alpha?The patent was strong historically because it addressed the core technology required to produce interferon-alpha through recombinant DNA. Its protection operated at several levels:
The estate was less effective against products that used:
The patent’s broad language would also have faced modern scrutiny under written-description and enablement standards. The claims cover numerous sequences, hosts, promoters, and expression systems beyond the specific deposited clones. The original disclosure and prosecution history would be central to any validity analysis. When did U.S. Patent 4,530,901 lose exclusivity?The patent expired on July 23, 2002, based on the 17-year term applicable to patents filed before the Uruguay Round Agreements Act changed the U.S. patent term regime.
The expiration removes infringement liability for activities that would have been covered solely by this patent. It does not eliminate later patents directed to pegylation, formulations, sustained-release systems, purification, manufacturing controls, or particular commercial products. What is the Orange Book status of Patent 4,530,901?Patent 4,530,901 is not a currently enforceable Orange Book barrier. The patent concerns recombinant DNA technology and interferon-alpha production. It is not a modern product patent listing that controls current generic or biosimilar entry. The Orange Book primarily addresses approved drug products and patent information submitted for those products. Biologics approved under the Public Health Service Act are generally evaluated through the biologics licensing and Purple Book framework rather than through the conventional small-molecule Orange Book process.[2] The relevant regulatory products historically included:
Patent 4,530,901 is not a current listed patent blocking these products or their follow-on regulatory pathways. Which companies were commercially exposed to this patent?The principal commercial exposure was historically associated with Roche’s Roferon-A and other recombinant interferon-alpha products developed by Roche and competing manufacturers.
The patent would have had greater relevance to non-pegylated recombinant interferon-alpha manufacturing than to later pegylated products. Pegylation does not itself eliminate the need to analyze the underlying recombinant protein production, but expired foundational claims no longer create a current U.S. blocking right. What formulation patents and method-of-use patents matter after expiration?Patent 4,530,901 does not claim:
Later patent estates could have addressed those subjects. The main post-foundational patent categories were: Pegylated interferon patentsPegylation patents covered covalent attachment of polyethylene glycol to interferon, linker chemistry, positional isomers, conjugate mixtures, purification, and pharmacokinetic improvements. Formulation patentsFormulation claims could cover pH, buffers, surfactants, stabilizers, protein concentration, container systems, and freeze-thaw stability. Method-of-use patentsLater patents could cover interferon use in hepatitis C, oncology, immune disorders, or specific combination regimens. Those claims were separate from the expired recombinant-DNA platform claims. Manufacturing patentsManufacturing protection could cover fermentation conditions, refolding, purification, viral clearance, aggregate control, and analytical release specifications. A freedom-to-operate review for a current interferon-alpha product therefore must examine later patents separately. Patent 4,530,901 alone presents no current U.S. risk. Are there current Paragraph IV challenges to Patent 4,530,901?No current Paragraph IV challenge has practical significance because the patent expired in 2002. Paragraph IV certifications apply to listed patents associated with an abbreviated new drug application. An expired foundational biotechnology patent does not provide a live basis for delaying approval. Historical litigation involving interferon products may have involved later patents, product-specific patents, formulation claims, or manufacturing rights rather than a currently enforceable claim under Patent 4,530,901. For biologic follow-on products, the relevant pathway is generally the Section 351(k) biosimilar process. The patent dance and related litigation would focus on unexpired patents held by the reference-product sponsor or other patent owners, not on this expired patent.[3] What biosimilar and generic entry risks exist?The direct entry risk from Patent 4,530,901 is zero because the patent is expired. The remaining risks are commercial and regulatory rather than based on this patent:
Interferon-alpha products are biologics, so a conventional small-molecule generic pathway may not provide a complete substitute for a biosimilar or product-specific application. The regulatory route depends on the reference product, approval history, dosage form, and applicable FDA classification. How does Patent 4,530,901 compare with later interferon patent estates?
Geographic coverage and international equivalentsU.S. Patent 4,530,901 provides only U.S. patent rights. International protection would have depended on separately filed national or regional patents, including potential European, Japanese, Canadian, and other counterparts. The U.S. expiration date does not establish the expiration date of foreign counterparts. Pre-TRIPS patent terms varied by jurisdiction, and some foreign family members may have expired earlier or later depending on filing dates, grant dates, maintenance fees, supplementary protection mechanisms, and national prosecution history. A multinational launch therefore requires a country-by-country review of:
Key Takeaways
FAQsWhat interferon products were most closely associated with Patent 4,530,901?Roferon-A, containing interferon alfa-2a, was the product most closely associated with Roche’s recombinant interferon-alpha technology. Intron A, containing interferon alfa-2b, was a major competing recombinant product. Does codon optimization avoid Patent 4,530,901?Not automatically. A codon-optimized sequence could still have fallen within the patent’s hybridization or functional coding categories during the patent term. That issue is no longer enforceable in the United States because the patent expired. Did Patent 4,530,901 claim peginterferon alfa?It did not expressly claim pegylated interferon as a chemical conjugate, formulation, or treatment product. Later pegylation and formulation patents required separate analysis. Can a company use the DSM 1699-1703 materials today?The patent does not itself impose a current U.S. patent restriction because it expired. Access, distribution, biosafety, material-transfer, and institutional rules may still govern the physical deposits. Does expiration of Patent 4,530,901 eliminate all interferon-alpha patent risk?No. It eliminates risk from this patent. Unexpired patents covering pegylation, formulations, purification, manufacturing processes, delivery systems, or therapeutic uses could still affect a commercial program. References
More… ↓ |
Drugs Protected by US Patent 4,530,901
| 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 |
Foreign Priority and PCT Information for Patent: 4,530,901
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| 80.300079.3 | Jan 8, 1980 | |
International Family Members for US Patent 4,530,901
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 9005 | ⤷ Start Trial | |||
| Australia | 553400 | ⤷ Start Trial | |||
| Australia | 6605781 | ⤷ Start Trial | |||
| Bosnia and Herzegovina | 96096 | ⤷ Start Trial | |||
| Canada | 1341567 | ⤷ Start Trial | |||
| Cyprus | 1346 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
