Details for Patent: 5,807,572
Summary for Patent: 5,807,572
| Title: | Multivesicular liposomes having a biologically active substance encapsulated therein in the presence of a hydrochloride | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Disclosed are multivesicular liposomes containing biologically active substances, the multivesicular liposomes having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a modulated rate of the biologically active substance in contrast to the previous art. The process comprises dissolving a lipid component in volatile organic solvents, adding an immiscible aqueous component containing at least one biologically active substance to be encapsulated, and adding to either or both the organic solvents and the lipid component, a hydrochloride effective to control the release rate of the biologically active substance from the multivesicular liposome, making a water-in-oil emulsion from the two components, immersing the emulsion into a second aqueous component, dividing the emulsion into small solvent spherules which contain even smaller aqueous chambers, and then removing the solvents to give an aqueous suspension of multivesicular liposomes encapsulating biologically active substances. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Sinil Kim, Stephen B. Howell | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Pacira Pharmaceuticals Inc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US08/473,019 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Process; Device; Dosage form; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,807,572: Scope, Claims, Expiration, and Multivesicular Liposome Patent LandscapeUS Patent 5,807,572 covers a manufacturing process for multivesicular liposomes, or MVLs, that incorporates a hydrochloride salt or hydrochloric acid into a water-in-oil emulsion to modify the in vivo release rate of an active pharmaceutical ingredient. The patent is process-focused. It does not broadly claim every multivesicular liposome, every drug encapsulated in an MVL, or every finished pharmaceutical product using the DepoFoam technology. The patent’s nominal 20-year term ended on December 20, 2015, assuming the December 20, 1995 nonprovisional filing date reflected in the patent record and no material patent-term adjustment. The patent is therefore no longer an enforceable barrier to manufacture, sale, or use in the United States. It also is not an Orange Book drug-product patent merely because its claims mention cytarabine, morphine, hydromorphone, leuprolide, insulin, vaccines, cytokines, and other drugs. [1][2] What does US Patent 5,807,572 protect?The patent protects a defined process for producing MVLs with multiple non-concentric internal chambers. The process requires:
The core inventive concept is the use of hydrochloric acid or selected hydrochloride salts during MVL formation as a release-rate control variable. What is the central limitation of claim 1?Claim 1 is a combination process claim. A potentially infringing process would generally need to satisfy all material limitations, including:
A process that produces MVLs without a hydrochloride or hydrochloric acid would not literally satisfy the hydrochloride limitation. A process using a salt outside the listed group could also avoid literal infringement, subject to claim-construction and equivalents analysis. How broad are the claims of US 5,807,572?The claims are broad in active-agent coverage but narrow in process architecture. Broad elementsThe claims cover a large group of active substances, including:
Claim 1 also covers a broad range of pharmacological categories, including anesthetics, antineoplastics, hormones, antibiotics, analgesics, proteins, peptides, vaccines, and nucleic acids. Narrow elementsThe process must use a specific MVL formation sequence. The claim is not directed simply to:
The hydrochloride concentration and release-modulation limitations materially narrow the claim. Which dependent claims define the lipid system?Claims 4 through 19 narrow the amphipathic and neutral lipid components.
The neutral lipid limitation is important. The patent distinguishes neutral lipids that lack a hydrophilic head group from amphipathic membrane-forming lipids. A formulation using only phospholipids, without the claimed neutral lipid, would present a potential noninfringement position. What solvents and processing methods are covered?Claim 20 covers organic solvents in the categories of ethers, hydrocarbons, esters, and combinations. Claims 22 through 24 cover alternative process techniques:
These claims make the patent technologically flexible. They do not require one particular mixer, nozzle, evaporation system, or solvent-removal apparatus. What active pharmaceutical ingredients are specifically protected?The patent’s active-agent claims are compositionally permissive but remain dependent on the process limitations in claim 1 or claim 2.
Claims 13 and 21 distinguish lipophilic and hydrophilic active substances. Lipophilic substances are incorporated into the lipid component, while hydrophilic substances are incorporated into the first aqueous component. When did US Patent 5,807,572 lose exclusivity?The patent’s nominal expiration date was December 20, 2015, based on the 20-year term from the December 20, 1995 filing date. The patent issued on September 15, 1998. [1]
The patent’s expiration eliminates ordinary infringement risk based solely on US Patent 5,807,572. It does not eliminate risk from later patents covering:
Patent expiration also does not eliminate regulatory exclusivity, trade-secret protection, or rights under later patents. What is the Orange Book status of US Patent 5,807,572?US Patent 5,807,572 is not an Orange Book-listed drug patent based on the claim set supplied and its process-oriented scope. The FDA Orange Book identifies patents and regulatory exclusivities associated with approved drug products, usually through patent information submitted by the NDA holder under 21 U.S.C. § 355(b)(1) and 21 C.F.R. § 314.53. A process patent may be listed only if it meets the applicable statutory and regulatory requirements and is tied to an approved product. [3][4] The patent’s references to cytarabine, morphine, hydromorphone, insulin, vaccines, and cytokines do not themselves create Orange Book status. The patent is not a product patent for DepoCyt, DepoDur, Exparel, or another approved product. What FDA products are commercially relevant?The technology is associated with the broader MVL and DepoFoam platform, but individual products have separate regulatory and patent histories.
DepoCyt is the product most directly aligned with the patent’s specific cytarabine claim. Exparel is commercially important to the MVL platform but is not automatically covered by claim 25 because bupivacaine is not cytarabine. Any infringement analysis for Exparel would require review of later patents and the actual manufacturing process. Does the patent create biosimilar risk?No direct biosimilar issue arises from this patent. The patent covers a process and expired in 2015. It does not create a live biologic exclusivity period. Biosimilar or follow-on biologic risk may still arise for products using MVL delivery of:
The relevant barriers would be later formulation patents, manufacturing patents, FDA exclusivity, analytical comparability, and process know-how. This patent alone is not a current biosimilar barrier. Which companies challenged or licensed this patent?A reliable current answer requires a complete prosecution, assignment, litigation, and licensing-record review. The supplied claim text does not identify a litigation matter, settlement agreement, license, or Paragraph IV notice involving US Patent 5,807,572. The patent appears to have been part of the DepoTech multivesicular liposome technology portfolio, later associated with SkyePharma and Pacira-related DepoFoam commercialization. No Paragraph IV challenge is created by the patent today because the patent has expired and is not identified as an active Orange Book patent for an approved drug product. Paragraph IV certifications apply to listed patents for an approved NDA product, not to an expired process patent considered in isolation. [3] What patent landscape surrounds multivesicular liposomes?The relevant patent landscape divides into five groups. Foundational MVL patentsThese cover the basic architecture and methods for creating multiple non-concentric aqueous chambers within a lipid matrix. They include early process and composition patents associated with DepoTech and related inventors. Release-control patentsUS 5,807,572 occupies this category. Its distinctive limitation is the use of hydrochloric acid or selected hydrochloride salts at defined concentrations to control release. Drug-specific MVL patentsLater patents may claim a particular active ingredient in an MVL, including:
These patents may survive after expiration of US 5,807,572 if filed later and if their claims are materially different. Product and formulation patentsThese may cover:
Manufacturing and scale-up patentsCommercial manufacturing may depend on later patents and unpatented know-how involving:
How strong is the patent estate today?US Patent 5,807,572 has no current blocking strength because it is expired. Historically, its strengths were breadth across active ingredients and flexibility in emulsification and solvent-removal methods. Its weaknesses included:
For current freedom-to-operate work, later patents are more important than this patent. The analysis should focus on the active patent families for the target product, the actual manufacturing route, and any Orange Book or FDA Purple Book entries associated with the product. What generic launch scenarios exist?Because US 5,807,572 is expired, it does not prevent a generic or follow-on manufacturer from using the claimed process. A launch analysis would instead turn on:
For an MVL injectable, technical replication may be more difficult than ordinary small-molecule tablet development even after patent expiry. That barrier is commercial and manufacturing-based, not a continuing right under US 5,807,572. What geographic coverage does the patent have?The patent is a United States patent. Its enforceable territorial scope was limited to conduct within the United States and, under 35 U.S.C. § 271(g), certain products imported into the United States that were made by a patented process. The patent did not create worldwide protection. Foreign counterparts, if any, required separate examination of:
Because the US patent has expired, commercial activity in the United States is no longer blocked by this patent. Key Takeaways
Frequently Asked QuestionsDoes US Patent 5,807,572 cover Exparel?Not by its named active-agent claims. Exparel contains bupivacaine, while the patent specifically identifies cytarabine, morphine, hydromorphone, leuprolide, and other agents. Exparel-related risk must be assessed against later Pacira and DepoFoam patents. Can a company use the hydrochloride-controlled MVL process today?Yes, the US patent is expired. A company must still evaluate later patents, trade secrets, FDA requirements, and foreign rights. Is cytarabine liposome still protected by this patent?No. The patent’s cytarabine claim expired with the patent. Any remaining protection would need to come from later patents or regulatory exclusivity. Does the patent cover a multivesicular liposome composition?The supplied claims primarily cover a process. They do not broadly claim every MVL composition regardless of how it is made. Does the patent block an ANDA for a liposomal injectable?No. An expired process patent cannot independently block an ANDA. The applicant may still face active listed patents, complex-product equivalence requirements, and later manufacturing or formulation patents. References
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Drugs Protected by US Patent 5,807,572
| 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 5,807,572
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 87823 | ⤷ Start Trial | |||
| Australia | 1205588 | ⤷ Start Trial | |||
| Australia | 602190 | ⤷ Start Trial | |||
| Canada | 1323568 | ⤷ Start Trial | |||
| Germany | 3879987 | ⤷ Start Trial | |||
| Denmark | 172057 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
