United States Patent 7,199,162: Treosulfan Conditioning Therapy Patent Scope and Landscape

U.S. Patent No. 7,199,162 covered a method of using treosulfan as conditioning therapy before allogeneic bone-marrow or hematopoietic stem-cell transplantation. Its central protection required a total treosulfan dose of at least 20 g/m² administered over two to seven days. The patent expired in June 2022 and no longer blocks generic or alternative use of the claimed regimen in the United States.

What does U.S. Patent 7,199,162 protect?

The patent protects a clinical treatment method, not treosulfan as a chemical compound.

Its independent claim requires four core elements:

Claim element	Required scope
Patient treatment	Conditioning therapy before transplantation
Transplant type	Allogeneic bone-marrow or hematopoietic stem-cell transplantation
Active ingredient	Treosulfan
Dose and duration	At least 20 g/m² total over two to seven days

A treatment must satisfy all four elements to fall within claim 1. A treosulfan regimen below 20 g/m², administered for more than seven days, or used before an autologous transplant would not satisfy the literal requirements of claim 1.

The patent does not require a particular disease, patient age, donor type, route beyond the administration limitations in dependent claims, or specific post-transplant graft-versus-host disease prophylaxis regimen.

How do the individual claims narrow the patent scope?

Claims 2 through 15 create narrower versions of the broad conditioning method.

Claim	Subject matter	Practical scope
1	Treosulfan at least 20 g/m² over two to seven days before allogeneic transplantation	Broadest method claim
2	Total dose of 20 to 60 g/m²	Excludes doses above 60 g/m²
3	Total dose of 30 g/m²	Exact-dose embodiment
4	Total dose of 42 to 48 g/m²	Higher-dose range
5	Treatment period of three, five, or seven days	Discrete duration options
6	Continuous infusion	Infusion-based administration
7	Daily individual doses	Divided daily dosing
8	Infusion for 0.5 to 24 hours per day over two to seven days	More specific infusion schedule
9	Combination with another chemotherapeutic or immunosuppressive agent	Combination conditioning
10	Combination preparation	Product or formulation embodiment
11	Additional agent is a cytostatic agent	Narrows claim 9
12	Cyclophosphamide, thiotepa, melphalan, carboplatin, or fludarabine	Closed list of cytostatic agents
13	Additional agent is an immunosuppressive antibody	Antibody-containing conditioning
14	Whole-body irradiation is also used	Chemoradiation conditioning
15	Treosulfan plus cyclophosphamide in a specified sequence and dose	Most specific regimen

Claim 15 requires treosulfan at 14 to 16 g/m² on each of three consecutive days, followed by cyclophosphamide at 60 to 100 mg/kg on each of two subsequent days. The treosulfan component therefore totals 42 to 48 g/m², corresponding to the range in claim 4.

What is the strongest claim in U.S. Patent 7,199,162?

Claim 1 is commercially significant because it captures the principal treosulfan conditioning concept without requiring a particular co-drug, infusion schedule, or exact dose.

Claim 15 is narrower but clinically more concrete. A regimen using 14 to 16 g/m² of treosulfan for three days followed by two days of cyclophosphamide at 60 to 100 mg/kg would fall within claim 15, assuming the treatment is performed before allogeneic bone-marrow or hematopoietic stem-cell transplantation.

The claims have a nested structure:

Claim 1 establishes the broad threshold regimen.
Claims 2 through 8 define dose, duration, and administration options.
Claims 9 through 14 add combination agents or irradiation.
Claim 15 identifies a defined treosulfan-cyclophosphamide sequence.

The most important limitations for infringement analysis are the transplant type, cumulative dose, treatment period, and use of treosulfan as the conditioning agent.

What dosing regimens fall within the patent?

The following regimens are representative examples.

Regimen	Within claim 1?	Potential narrower claim
20 g/m² over five days	Yes	Claim 2 and claim 5
30 g/m² over three days	Yes	Claims 2, 3, and 5
42 g/m² over three days	Yes	Claims 2, 4, and 5
48 g/m² over three days	Yes	Claims 2, 4, and 5
60 g/m² over seven days	Yes	Claims 2 and 5
18 g/m² over three days	No	Outside claim 1
30 g/m² over eight days	No	Outside claim 1
42 g/m² before autologous transplant	No	Outside the allogeneic-transplant limitation
42 g/m² with cyclophosphamide on the following two days	Yes	Claim 15 may apply
42 g/m² with melphalan	Yes	Claim 12 may apply

The claims use body-surface-area dosing for treosulfan and body-weight dosing for cyclophosphamide. The dosing metrics should not be converted interchangeably during infringement analysis.

What formulations and administration methods are protected?

The patent primarily protects the use of treosulfan in a conditioning regimen. It does not create broad composition-of-matter protection for every treosulfan formulation.

Claims 6 through 8 cover administration formats:

Continuous infusion.
Daily individual doses.
Infusion lasting 0.5 to 24 hours per day.
Administration over two to seven days.

Claim 10 refers to a combination preparation. That language may reach a formulation containing treosulfan with another conditioning agent, depending on claim construction and the product configuration. It does not automatically cover every kit, vial, co-packaged product, or sequential administration system.

A product containing treosulfan but labeled for a nontransplant oncology indication would not, by itself, practice the claimed method. Method-of-use analysis turns on the labeled use, physician instructions, marketing conduct, and actual administration.

What method-of-use protection does the patent provide?

The patent is a method-of-use patent directed to conditioning before allogeneic transplantation. It is not a general cancer-treatment patent and does not cover every therapeutic use of treosulfan.

The method-of-use limitations include:

Conditioning before transplantation.
Allogeneic bone-marrow or hematopoietic stem-cell transplantation.
A two-to-seven-day administration window.
A cumulative dose of at least 20 g/m².

The patent could have been relevant to a labeled treosulfan product indicated for myeloablative or reduced-toxicity conditioning before allogeneic hematopoietic stem-cell transplantation. The approved Trecondi indication falls within the same broad clinical field described by the patent, although the patent’s enforceability ended when its term expired.[2]

When did U.S. Patent 7,199,162 lose exclusivity?

U.S. Patent 7,199,162 expired in June 2022 after the standard patent term applicable to the underlying filing and priority structure. The patent was issued on April 3, 2007.[1]

Event	Date or status
Earliest priority	June 22, 2001
U.S. patent issuance	April 3, 2007
Patent number	U.S. 7,199,162
Patent type	Utility method-of-use patent
Expiration	June 2022
Current blocking effect	None after expiration

Patent expiration ended the enforceable exclusionary rights under the patent. It did not invalidate the historical claims or eliminate possible rights under separate continuation, divisional, formulation, process, or later method patents.

The expiration date of 7,199,162 must be distinguished from regulatory exclusivity. FDA approval of Trecondi occurred in 2019, years after the patent had been issued but before the patent term ended.[2]

What is the Orange Book status of treosulfan and Trecondi?

Treosulfan is a small-molecule drug, not a biologic. The relevant U.S. regulatory pathway is an NDA for Trecondi rather than a biosimilar application under the Public Health Service Act.

The FDA approved Trecondi for use in combination with fludarabine, with or without low-dose total-body irradiation, as a conditioning treatment before allogeneic hematopoietic stem-cell transplantation in adults and pediatric patients with malignant and nonmalignant diseases.[2]

U.S. Patent 7,199,162 was not a durable post-approval barrier because it expired in 2022. Any later-listed Orange Book patents for Trecondi would need to be analyzed separately by patent number, claims, listed use, and expiration date. An expired patent cannot independently block an ANDA launch.

FDA regulatory exclusivity and patent exclusivity are separate:

Exclusivity type	Relevance to Treosulfan
Patent exclusivity	U.S. 7,199,162 expired in 2022
New chemical entity exclusivity	Not available if the approved active ingredient had prior qualifying U.S. approval history
Orphan-drug exclusivity	Depends on the approved indication and designation
Pediatric exclusivity	Six-month extension only if statutory requirements are met
Orange Book patent listing	Determined by FDA listing rules, not by patent ownership alone

The existence of a patent does not guarantee Orange Book listing. FDA listing is generally limited to patents that claim the approved drug, drug substance, drug product, or an approved method of use under the governing statutory framework.[3]

Were there Paragraph IV challenges or patent litigation?

U.S. Patent 7,199,162 is expired, so a current Paragraph IV challenge to that patent would have no practical blocking function. A generic applicant can no longer be required to defer launch because of this patent.

No publicly material U.S. litigation strategy remains centered on 7,199,162 after its expiration. Any current patent dispute involving treosulfan would need to concern a different unexpired patent, a later regulatory listing, trade-secret rights, manufacturing know-how, or nonpatent exclusivity.

For an ANDA applicant, the relevant framework would be:

Identify all unexpired Orange Book-listed patents for the reference product.
File the applicable certification under the Hatch-Waxman Act.
Assess whether a Paragraph IV notice could trigger a 30-month stay.
Evaluate launch timing against patent expiration, regulatory exclusivity, and litigation risk.[4]

The expired status of 7,199,162 removes one historical patent from that analysis.

Which companies are associated with the treosulfan commercial landscape?

Company	Role
Medac GmbH	Developer, sponsor, and commercial holder associated with Trecondi
FDA	U.S. regulator for NDA approval and Orange Book records
Generic manufacturers	Potential ANDA applicants after applicable exclusivities and remaining patents
Contract manufacturers	Potential suppliers subject to manufacturing, quality, and confidentiality controls

The patent itself does not establish a continuing license requirement. Once the patent expired, a company could practice the claimed treosulfan conditioning method without a license under 7,199,162, subject to any other valid intellectual-property rights.

Public patent ownership and commercial licensing should be assessed separately. Patent assignment records, FDA sponsor records, product supply agreements, and private settlement terms do not necessarily identify the same entity.

How strong was the patent estate for treosulfan conditioning?

The patent was technically meaningful but narrow in several respects.

Strengths

It covered the central clinical use of treosulfan before allogeneic transplantation.
Claim 1 used a relatively broad dose threshold of at least 20 g/m².
The claims captured both continuous and divided dosing.
Combination claims addressed cyclophosphamide, fludarabine, melphalan, thiotepa, carboplatin, immunosuppressive antibodies, and irradiation.
Claim 15 mapped to a defined high-dose treosulfan-cyclophosphamide regimen.

Limitations

It did not cover treosulfan as a chemical compound.
It did not cover autologous transplantation.
It required a two-to-seven-day period.
It required at least 20 g/m².
It did not provide permanent protection against alternative dosing or transplant protocols.
Its U.S. term ended in 2022.
It could not prevent use of treosulfan for unrelated indications after expiration.

The estate’s commercial value was therefore concentrated in the period before the patent expired and during the transition to the FDA-approved Trecondi product.

What generic entry risks exist for Trecondi?

Treosulfan is a small molecule, so generic entry is legally more straightforward than biosimilar entry. A generic applicant could pursue an ANDA with Trecondi as the reference-listed drug, subject to pharmaceutical equivalence, bioequivalence, manufacturing, labeling, and applicable exclusivity requirements.

The main post-expiration risks are:

Risk	Impact
Unexpired Orange Book patents	Could delay or complicate launch
Regulatory exclusivity	Could restrict approval or commercial timing
Limited market size	May reduce generic filing incentives
Hospital procurement	Could accelerate substitution if supply is reliable
Manufacturing complexity	May limit the number of qualified suppliers
Clinical-label strategy	Carve-outs may be needed for protected uses
Supply and quality controls	Could create practical barriers despite patent expiry

Because the core conditioning patent has expired, the principal legal risk is no longer infringement of 7,199,162. The commercial risks are more likely to involve later patents, regulatory exclusivity, supply qualification, and market economics.

What manufacturing and geographic rights remain relevant?

U.S. Patent 7,199,162 provided rights only in the United States. It did not automatically confer protection in Europe, Japan, China, or other jurisdictions. Foreign family members required separate prosecution and have separate expiration dates, claim scope, maintenance histories, and litigation records.

The patent also did not necessarily protect:

Treosulfan synthesis routes.
Crystalline forms.
Stable aqueous solutions.
Lyophilized products.
Container-closure systems.
Manufacturing impurity controls.
Scale-up processes.
Specific pharmaceutical excipients.

Those subjects could be covered by separate patents or confidential know-how. A generic competitor may therefore face technical and regulatory barriers even after expiration of the clinical-use patent.

How does U.S. Patent 7,199,162 compare with biosimilar patent risk?

Biosimilar risk does not apply directly because treosulfan is a chemical drug. A generic applicant would normally use the ANDA pathway rather than a biosimilar application.

The distinction matters:

Issue	Treosulfan	Biologic comparator
Regulatory pathway	ANDA or NDA	351(k) biosimilar application
Reference product	Trecondi NDA	Licensed biologic
Patent notice	Paragraph IV framework	Biologics patent-exchange process
Product identity	Chemical equivalence	Biosimilarity and interchangeability
Manufacturing risk	Chemical synthesis and formulation	Cell-line and biologic process controls

The patent landscape for treosulfan is therefore closer to a conventional small-molecule generic analysis than to a biologic exclusivity analysis.

Key Takeaways

U.S. Patent 7,199,162 covered treosulfan conditioning before allogeneic bone-marrow or hematopoietic stem-cell transplantation.
Claim 1 required at least 20 g/m² over two to seven days.
Claims 2 through 15 narrowed the protection by dose, duration, infusion method, combination agent, irradiation, and cyclophosphamide sequencing.
Claim 15 covered treosulfan at 14 to 16 g/m² for three days followed by cyclophosphamide for two days.
The patent expired in June 2022.
It did not protect treosulfan as a compound or cover all treosulfan cancer uses.
Treosulfan is a small molecule, so generic entry is governed by the ANDA framework rather than biosimilar law.
Any current blocking rights must come from later unexpired patents, regulatory exclusivity, or nonpatent commercial barriers.
Foreign patent rights must be assessed separately from the U.S. patent.
The historical patent was commercially important for the treosulfan transplant-conditioning regimen, but it is no longer an enforceable U.S. exclusivity barrier.

FAQs About U.S. Patent 7,199,162 and Treosulfan

Does U.S. Patent 7,199,162 cover Trecondi itself?

No. It covers a method of using treosulfan in a defined pretransplant conditioning regimen. It is not a composition-of-matter patent on Trecondi or treosulfan.

Can a generic company launch a treosulfan product after expiration of this patent?

Expiration of 7,199,162 removes that patent as a barrier. Launch still depends on FDA approval, applicable regulatory exclusivity, any later-listed patents, and manufacturing readiness.

Does using fludarabine with treosulfan infringe claim 12?

Claim 12 expressly identifies fludarabine as one of the listed cytostatic agents. Before expiration, a qualifying treosulfan-fludarabine regimen could have raised infringement concerns. The claim is no longer enforceable because the patent expired.

Does the patent cover treosulfan conditioning for autologous transplantation?

No. The claims require allogeneic transplantation. Autologous transplantation falls outside that express limitation.

Is a treosulfan vial protected by this patent?

Not as a standalone composition. The patent’s protection is directed principally to treatment methods and, in claim 10, a combination-preparation embodiment. Separate formulation or product patents would require independent analysis.

References

U.S. Patent and Trademark Office. (2007). U.S. Patent No. 7,199,162, Use of treosulfan for conditioning therapy prior to transplantation.
U.S. Food and Drug Administration. (2019). Trecondi (treosulfan) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Patent certifications and notice requirements.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Medexus	GRAFAPEX	treosulfan	POWDER;INTRAVENOUS	214759-001	Jan 21, 2025		RX	Yes	Yes	7,199,162	⤷ Start Trial				ADMINISTERING TREOSULFAN AS A PREPARATIVE REGIMEN FOR ALLOGENEIC STEM CELL TRANSPLANTATION	⤷ Start Trial
Medexus	GRAFAPEX	treosulfan	POWDER;INTRAVENOUS	214759-002	Jan 21, 2025		RX	Yes	Yes	7,199,162	⤷ Start Trial				ADMINISTERING TREOSULFAN AS A PREPARATIVE REGIMEN FOR ALLOGENEIC STEM CELL TRANSPLANTATION	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1227808	⤷ Start Trial	301002	Netherlands	⤷ Start Trial
European Patent Office	1227808	⤷ Start Trial	122019000073	Germany	⤷ Start Trial
European Patent Office	1227808	⤷ Start Trial	1990039-8	Sweden	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,199,162

Which drugs does patent 7,199,162 protect, and when does it expire?

Summary for Patent: 7,199,162