Last Updated: November 9, 2026

Details for Patent: 5,036,102

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Summary for Patent: 5,036,102
Title:Method of treating autoimmune diseases comprising administration of psoralen dosage forms
Abstract:A method of treating leukocyte mediated autoimmune and skin diseases using psoralen reagent composition comprising sterile aqueous solutions suitable for extracorporeal administration to blood from a subject being treated by ultraviolet-A photophoresis.
Inventor(s):Maria O. Bachynsky, Martin H. Infeld, Richard J. Margolis, Dennis A. Perla
Assignee: Therakos Inc
Application Number:US07/582,467
Patent Claim Types:
see list of patent claims
Use; Composition; Formulation;
Patent landscape, scope, and claims:

U.S. Patent 5,036,102: Scope, Claim Analysis, Expiration, and Photopheresis Patent Landscape

U.S. Patent 5,036,102 covers a specific extracorporeal photopheresis method using a sterile acidic psoralen solution, ultraviolet-A irradiation, and reinfusion of treated blood. The patent is directed to treatment protocol and composition parameters, not to a broad monopoly over photopheresis, 8-methoxypsoralen, or ultraviolet-A therapy. Its statutory term expired in 2008, so the claims no longer create an enforceable U.S. patent barrier.

What does U.S. Patent 5,036,102 protect?

U.S. Patent 5,036,102 protects a method with five core limitations:

  1. Blood is withdrawn from a patient.
  2. A psoralen-containing composition is administered extracorporeally.
  3. The blood undergoes ultraviolet-A photopheresis.
  4. The treated blood is reinfused into the same patient.
  5. The composition contains specified ingredients, concentration limits, and pH limits.

The patent is therefore a combination claim. A competing method would need to satisfy every limitation of an asserted claim to present literal infringement risk.

Claim element Requirement
Medical use Therapy of a leukocyte-mediated disease
Treatment setting Extracorporeal administration to blood
Light exposure Ultraviolet-A photopheresis
Active ingredient A psoralen
Psoralen concentration About 0.005 mg/mL to about 1 mg/mL
Other formulation components Ethyl alcohol, propylene glycol, and water
Formulation pH About 2.0 to about 5.5
Post-treatment step Reinfusion of treated blood

The patent does not claim ordinary oral or topical psoralen therapy. It also does not claim ultraviolet-A treatment of skin without blood removal.

What is the legal status and expiration date of U.S. Patent 5,036,102?

U.S. Patent 5,036,102 issued on July 30, 1991. Based on the pre-1995 patent-term rules applicable to the patent, its 17-year term ran from issuance and expired on July 30, 2008, absent a term adjustment, terminal disclaimer, or patent-term extension. The patent is therefore expired and cannot presently support a new infringement action for activities occurring after expiration. [1, 2]

The expiration analysis is important because later commercial products may have practiced the claimed method while the patent was enforceable, but current use of the same protocol does not infringe an expired patent.

Was the patent eligible for pharmaceutical patent-term extension?

The patent’s subject matter is a treatment method involving extracorporeal blood processing. The patent does not appear to have operated as the principal Orange Book-listed product patent for UVADEX. The available regulatory history does not establish a patent-term extension that would move the operative expiration date beyond 2008. The relevant enforceability conclusion is that U.S. Patent 5,036,102 is expired.

How should Claim 1 be interpreted?

Claim 1 is the broadest independent claim. It requires both a treatment method and a particular composition.

Leukocyte-mediated disease

The phrase “leukocyte mediated diseases” provides the therapeutic context but does not, standing alone, define every disease in which leukocytes participate. Claim 2 narrows the scope by identifying eight conditions:

  • Scleroderma
  • Systemic lupus erythematosus
  • Psoriasis
  • Pemphigus
  • Psoriatic arthritis
  • Atopic dermatitis
  • Rheumatoid arthritis
  • Multiple sclerosis

Claim 1 is broader than Claim 2 because it is not limited to those eight named conditions. A method directed to another leukocyte-mediated condition could fall within Claim 1 if the remaining limitations are met.

Extracorporeal administration

The psoralen must be introduced into blood outside the patient’s body. A formulation administered orally, intravenously, topically, or directly into the patient would not meet the express “extracorporeal” limitation.

The claim also requires ultraviolet-A photopheresis and subsequent reinfusion. A blood-processing system that adds psoralen but does not expose the treated blood to UVA would not satisfy Claim 1.

Composition limitations

The formulation must include:

  • A psoralen;
  • Ethyl alcohol;
  • Propylene glycol; and
  • Water.

The concentration range is approximately 0.005 mg/mL to 1 mg/mL. The pH must be approximately 2.0 to 5.5.

The use of “about” creates ordinary claim-construction flexibility around the numerical limits. It does not eliminate the requirement that the formulation remain within the claimed concentration and acidity range.

A formulation using a different solvent system, omitting propylene glycol, or having a pH materially above 5.5 would present a stronger non-infringement position, subject to the patent’s specification and any applicable equivalents analysis.

What does Claim 2 add?

Claim 2 limits the method to a defined list of diseases. It is narrower than Claim 1 and would require proof that the treatment was directed to one of the listed conditions.

The claim uses “selected from the group consisting of,” which ordinarily indicates a closed list. Conditions outside the eight listed diseases would not satisfy Claim 2, although they could remain relevant to Claim 1.

The medical scope is much broader than the later FDA-approved indication for UVADEX. The FDA approval was for extracorporeal photopheresis as a palliative treatment for the skin manifestations of cutaneous T-cell lymphoma in patients who had not responded to other forms of treatment. The patent’s disease list does not determine FDA approval, and FDA approval does not determine the full scope of the patent claims. [3]

What does Claim 3 add?

Claim 3 limits the psoralen to 8-MOP, commonly called 8-methoxypsoralen or methoxsalen.

The dependency structure means Claim 3 includes all limitations of Claim 1, plus the requirement that the psoralen be 8-MOP. It does not claim every 8-MOP use. The formulation, extracorporeal administration, UVA exposure, and reinfusion requirements remain mandatory.

This distinction limits the claim’s reach against:

  • Oral methoxsalen therapy;
  • Topical methoxsalen therapy;
  • UVA therapy without extracorporeal blood processing;
  • Blood processing using a psoralen other than 8-MOP; and
  • Extracorporeal methods using a composition that lacks the claimed formulation components.

What does Claim 4 add?

Claim 4 requires that 8-MOP be administered immediately after blood withdrawal and before separation into leukocyte-rich and leukocyte-poor fractions.

This is a process-sequence limitation. It narrows Claim 3 by requiring:

  1. Withdrawal of blood;
  2. Addition of 8-MOP;
  3. Separation into leukocyte-rich and leukocyte-poor fractions; and
  4. UVA photopheresis and reinfusion under the remaining claim limitations.

A system that separates blood before adding 8-MOP may avoid the literal scope of Claim 4, although it could still implicate Claim 3 or Claim 1.

The phrase “just after it is withdrawn” raises a timing issue. The claim does not state a precise number of seconds or minutes. A court would likely examine the specification, technical practice, and prosecution history to determine how close the addition must be to blood withdrawal.

How many patents cover extracorporeal photopheresis?

The historical photopheresis estate consisted of several patent categories rather than one patent:

Patent category Representative subject matter Relevance to U.S. 5,036,102
Foundational treatment patents Psoralen-treated blood exposed to UVA and reinfused Established the basic photopheresis concept
Method patents Treatment of leukocyte-mediated or immune disorders Overlaps with the therapeutic method claimed in 5,036,102
Formulation patents Sterile methoxsalen solutions using alcohol, glycols, water, and controlled pH Potentially relevant to UVADEX-type products
Apparatus patents Blood separation, irradiation, collection, and reinfusion systems Cover equipment rather than the full drug-treatment method
Product and use patents Specific indications, dosing, treatment schedules, or system-drug combinations May have created later commercial barriers

The foundational patents associated with extracorporeal photochemotherapy include U.S. Patent 4,321,919 and related photopheresis patents. Those patents addressed the basic use of psoralen and UVA in extracorporeal blood treatment. U.S. Patent 5,036,102 is narrower in its express formulation, pH, and treatment limitations. [4]

The practical landscape must therefore be analyzed by patent family and expiration date. An expired method patent does not imply that every device, formulation, manufacturing process, or later treatment protocol was unpatented at the same time.

What formulation does U.S. Patent 5,036,102 protect?

The claimed formulation is an acidic hydroalcoholic solution containing psoralen, ethanol, propylene glycol, and water.

The formulation limitations are commercially significant because they resemble the type of sterile methoxsalen product used in extracorporeal photopheresis. The claim does not require a particular trade name, container, vial size, preservative, or commercial device.

The claim also does not require a particular psoralen concentration within the full range beyond the stated lower and upper boundaries. A composition containing 8-MOP at approximately 0.02 mg/mL, 0.02 mg/mL being 20 micrograms/mL, would fall within the numeric range if the other limitations were satisfied.

A formulation patent analysis should distinguish:

  • Composition claims;
  • Method-of-use claims;
  • Manufacturing claims;
  • Sterility and packaging claims; and
  • Device claims.

U.S. Patent 5,036,102 is primarily a method claim with embedded composition limitations. It is not a stand-alone composition claim.

What is the FDA status of the associated photopheresis therapy?

The FDA approved UVADEX, a sterile methoxsalen solution, for use with an approved photopheresis system in the palliative treatment of skin manifestations of cutaneous T-cell lymphoma. The product is administered extracorporeally during photopheresis rather than as a conventional systemic methoxsalen product. [3]

The approved indication is narrower than Claim 1 and differs from the diseases listed in Claim 2. Scleroderma, lupus, psoriasis, rheumatoid arthritis, multiple sclerosis, and the other Claim 2 conditions should not be treated as FDA-approved UVADEX indications solely because they appear in the patent.

The regulatory product is a drug-device combination in practical use. Regulatory rights and patent rights are separate:

  • FDA approval authorizes the labeled use.
  • The patent controls only the claimed legal subject matter during its enforceable term.
  • Device clearance does not create patent protection.
  • Patent expiration does not eliminate FDA manufacturing, labeling, or quality requirements.

What is the Orange Book status of U.S. Patent 5,036,102?

U.S. Patent 5,036,102 is not a current Orange Book barrier for UVADEX because it expired in 2008. Method-of-treatment patents also face listing constraints under FDA Orange Book rules. A patent must meet FDA’s listing criteria for the approved drug product, and a broad disease-treatment claim is not automatically listable merely because it relates to the product. [5]

The commercial implications are:

  • No current Orange Book patent term blocks an ANDA solely through U.S. Patent 5,036,102.
  • A Paragraph IV certification against this patent would have been relevant only before expiration.
  • A current applicant would need to assess any later-listed formulation, method, or drug-device patent separately.

Which companies challenged or litigated this patent?

No material current Paragraph IV or district-court litigation risk remains from U.S. Patent 5,036,102 because the patent expired. Historical litigation involving photopheresis products may have concerned related patents, product access, devices, or licensing rights rather than this specific patent.

The record does not establish a current enforceable settlement obligation tied to this patent. Any historical settlement would not revive the expired patent or extend its statutory exclusion period.

What licensing deals affected the photopheresis market?

The commercial photopheresis market developed around the integration of:

  • The methoxsalen product;
  • Apheresis and blood-separation equipment;
  • UVA irradiation equipment;
  • Treatment protocols; and
  • Hospital and specialty-clinic distribution.

Therakos was the principal commercial developer associated with UVADEX and photopheresis systems. Ownership of the business and product rights changed over time, including later ownership by Mallinckrodt. Those corporate transactions affected commercial control, manufacturing, and distribution, but they did not extend the term of U.S. Patent 5,036,102. [3, 6]

How strong was the patent estate for U.S. 5,036,102?

During its term, the patent had meaningful claim coverage because Claim 1 combined the therapeutic protocol with detailed composition requirements. Its strength was highest against a competitor using the same methoxsalen formulation in the same extracorporeal UVA process.

Its limitations were also clear:

Risk factor Assessment
Broad coverage of all photopheresis Low; the claim requires a defined formulation
Coverage of 8-MOP photopheresis High under Claim 3 if all formulation and process limitations are met
Coverage of alternative solvents Limited
Coverage of oral or topical methoxsalen None
Coverage of pre-separation dosing Specifically addressed by Claim 4
Coverage of post-separation dosing Potentially outside Claim 4, but not necessarily outside Claims 1 or 3
Current enforceability None; patent expired
Current generic-entry barrier None from this patent

What generic launch scenarios existed?

Before expiration, a competitor could have pursued several design-around strategies:

  1. Use a different psoralen.
  2. Use 8-MOP in a formulation without propylene glycol.
  3. Change the solvent system.
  4. Modify the pH outside the claimed range.
  5. Add the psoralen after blood separation.
  6. Develop a different irradiation or reinfusion protocol.

A competitor still would have needed to address related patents, FDA requirements, device clearances, manufacturing controls, and any contract or trade-secret restrictions. Since 2008, U.S. Patent 5,036,102 itself has presented no generic launch obstacle.

What geographic coverage did the patent have?

U.S. Patent 5,036,102 provided rights only in the United States. Parallel foreign applications, national-stage filings, or counterpart patents would require separate analysis by jurisdiction. Expiration in the United States did not automatically determine the status of corresponding European, Canadian, Japanese, or other patents.

The relevant commercial markets also differ in regulatory structure. FDA approval, Orange Book listing, and Paragraph IV procedures have no direct legal effect outside the United States.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove the operational barriers to commercial photopheresis. A market entrant would still need to address:

  • Sterile manufacturing of methoxsalen solution;
  • Validated filling and packaging;
  • Solvent compatibility;
  • Photochemical stability;
  • Drug-device compatibility;
  • UVA irradiation performance;
  • Blood-contacting device requirements;
  • Apheresis equipment validation;
  • Clinical evidence for the proposed indication; and
  • FDA approval or clearance for the applicable product configuration.

These are regulatory, technical, and commercial barriers rather than continuing rights under U.S. Patent 5,036,102.

Key Takeaways

  • U.S. Patent 5,036,102 covers extracorporeal UVA photopheresis using a psoralen solution containing ethanol, propylene glycol, water, and controlled pH.
  • Claim 1 is a combination method claim, not a broad claim to all photopheresis.
  • Claim 2 limits the method to eight specified leukocyte-mediated diseases.
  • Claim 3 narrows the psoralen to 8-MOP.
  • Claim 4 requires 8-MOP addition after blood withdrawal and before blood separation.
  • The patent issued July 30, 1991, and expired July 30, 2008.
  • The patent is not a current Orange Book or Paragraph IV barrier.
  • FDA approval for UVADEX is narrower than the patent’s claimed disease scope.
  • Current market barriers are more likely to arise from FDA requirements, device technology, manufacturing controls, related patents, and commercial know-how.

FAQs

Does U.S. Patent 5,036,102 cover UVADEX?

The patent claims a method that may encompass use of a UVADEX-type methoxsalen formulation during extracorporeal photopheresis. It does not claim the UVADEX trade name, and the patent expired in 2008.

Does the patent cover photopheresis for multiple sclerosis?

Claim 2 expressly lists multiple sclerosis, but the patent does not create a current enforceable barrier because it expired. FDA approval for UVADEX should be assessed separately from the historical patent claim.

Can a competitor use methoxsalen in a photopheresis system today?

U.S. Patent 5,036,102 does not prevent current use because it is expired. A competitor must still satisfy FDA, device, manufacturing, and any surviving related patent requirements.

Is Claim 4 broader than Claim 1?

No. Claim 4 is narrower because it includes all limitations of Claim 3 and requires administration of 8-MOP before separation into leukocyte-rich and leukocyte-poor fractions.

Does patent expiration eliminate the need for FDA approval?

No. Patent expiration removes the patent exclusion right. It does not authorize manufacture, marketing, labeling, or clinical use without the required FDA regulatory pathway.

References

  1. United States Patent No. 5,036,102. (1991). Method for treating leukocyte mediated diseases. U.S. Patent and Trademark Office.
  2. United States Code, 35 U.S.C. § 154. Patent term and grant of patents.
  3. U.S. Food and Drug Administration. (n.d.). UVADEX (methoxsalen) sterile solution prescribing information.
  4. United States Patent No. 4,321,919. (1982). Method for inducing immunosuppression. U.S. Patent and Trademark Office.
  5. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations.
  6. Mallinckrodt plc. (2015). Annual report and corporate disclosures regarding Therakos and photopheresis products.

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Drugs Protected by US Patent 5,036,102

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 5,036,102

Country Patent Number Estimated Expiration Supplementary Protection Certificate SPC Country SPC Expiration
Austria 87205 ⤷  Start Trial
Germany 59001061 ⤷  Start Trial
Denmark 0392429 ⤷  Start Trial
European Patent Office 0392429 ⤷  Start Trial
Japan H02290814 ⤷  Start Trial
>Country >Patent Number >Estimated Expiration >Supplementary Protection Certificate >SPC Country >SPC Expiration

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