Details for Patent: 11,072,577

Which drugs does patent 11,072,577 protect, and when does it expire?

Patent 11,072,577 protects CUVRIOR and is included in one NDA.

This patent has forty-eight patent family members in twenty-seven countries.

Summary for Patent: 11,072,577

Title:	Crystalline form of triethylenetetramine tetrahydrochloride and its pharmaceutical use
Abstract:	The present invention describes a new crystalline form of triethylenetetramine tetrachloride which has improved room temperature stability over known forms and over the dichloride salt. The new crystalline form is characterised by having peaks in an XRPD spectrum at 22.9, 25.4, 25.8, 26.6, 34.6 and 35.3±0.1°2θ and Raman shifts 943, 1173, 1527 and 1612±5 cm−1. The crystalline form of triethylenetetramine tetrachloride is useful in the treatment of Wilson's disease.
Inventor(s):	Timothy James Morley, Ronnie Maxwell Lawrence, Naseem Amin
Assignee:	Gmp-Orphan SA , Orphalan SA
Application Number:	US17/171,358
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,072,577
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 11,072,577: Claims, Exclusivity, Litigation Risk, and Patent Landscape for Trientine Tetrahydrochloride Form B

US Patent 11,072,577 protects methods of treating or preventing Wilson's disease with crystalline triethylenetetramine tetrahydrochloride Form B, commonly referred to as trientine tetrahydrochloride Form B. The patent does not broadly claim trientine tetrahydrochloride, trientine itself, or every treatment method using trientine. Its principal limitation is the use of a defined solid form meeting specified XRPD or Raman spectral characteristics and containing limited amounts of Form A.

The patent is commercially relevant to Cuvrior, the FDA-approved trientine tetrahydrochloride product marketed for Wilson's disease. Its strongest coverage is directed to Form B material used in a pharmaceutical treatment or solid oral dosage product. A generic developer may avoid literal infringement by using a different polymorph, a different salt, or a product that does not contain the claimed Form B. Those alternatives may create regulatory and formulation challenges.

What does US Patent 11,072,577 cover?

The patent covers four related subject-matter groups:

Claim group	Subject matter	Main limitation
Claims 1-3	Treatment or prevention of Wilson's disease	Administration of crystalline trientine tetrahydrochloride Form B
Claims 4-6	Treatment using a pharmaceutical composition	Form B plus a pharmaceutically acceptable carrier or diluent
Claims 7-9	Purity-controlled pharmaceutical composition	Form A limited to no more than 5%, 2%, or 1%
Claim 10	Dosage form	Solid oral dosage composition
Claims 11-12	Dose-limited treatment	Daily Form B dose of 0.1 mg to 10 mg

The patent is therefore a polymorph-and-use patent. It is not a conventional composition-of-matter patent covering the trientine molecule without regard to crystal form.

How should the core Form B claims be construed?

Claim 1 requires all of the following:

1. Treatment or prevention of Wilson's disease.
2. Administration to a subject.
3. An effective amount.
4. Crystalline trientine tetrahydrochloride Form B.
5. Form B identification through either:
   • an XRPD pattern meeting the specified peak limitation; or
   • a Raman spectrum meeting the specified peak limitation.
6. No more than 10 wt% of Form A.
7. XRPD measurement using a wavelength of 1.5418 Å.

The phrase "at least two peaks selected from" means that the claimed XRPD limitation can be satisfied by any two or more peaks from the six listed positions:

• 22.9° 2θ
• 25.4° 2θ
• 25.8° 2θ
• 26.6° 2θ
• 34.6° 2θ
• 35.3° 2θ

The Raman alternative requires any two or more peaks from:

• 943 cm−1
• 1173 cm−1
• 1527 cm−1
• 1612 cm−1

The use of "at least one" before the XRPD and Raman alternatives creates an alternative claiming structure. A product may fall within the identification limitation through the XRPD route, the Raman route, or both, assuming the other limitations are met.

The Form A exclusion is material. Form A is identified by XRPD peaks at 25.2° and 35.7° 2θ. Claim 1 permits up to 10 wt% Form A, while dependent claims narrow the purity requirement.

What do dependent claims 2, 3, and 5 through 9 add?

Claims 2 and 5 narrow the Form B analytical profile by requiring XRPD peaks at:

• 25.4° 2θ
• 34.6° 2θ
• 35.3° 2θ

These claims are narrower than the independent claims but may be easier to prove analytically if the accused product has a well-characterized Form B diffraction pattern.

Claims 3 and 6 require at least 95 wt% Form B. The claims do not simply require the absence of Form A. They establish a positive Form B content threshold, in addition to the Form B XRPD or Raman identification criteria.

Claims 7, 8, and 9 progressively tighten the Form A limit:

Claim	Maximum Form A content
Claim 7	5 wt%
Claim 8	2 wt%
Claim 9	1 wt%

These purity claims are directed to the practical manufacture and control of the pharmaceutical product. They may be important where Form A is an impurity, conversion product, or competing polymorph generated during crystallization, milling, storage, granulation, or tableting.

What formulations are protected by US 11,072,577?

Claim 4 protects a method using a pharmaceutical composition containing:

• Crystalline Form B trientine tetrahydrochloride;
• The specified XRPD or Raman characteristics;
• No more than 10 wt% Form A; and
• A pharmaceutically acceptable carrier or diluent.

Claim 10 narrows this coverage to a solid oral dosage composition. The claim does not require a tablet specifically. On its face, a solid oral dosage composition could include a tablet, capsule, powder-filled capsule, granule, or another solid oral presentation, provided that the composition satisfies the other limitations.

The patent does not, based on the supplied claims, require a particular excipient, dissolution profile, tablet weight, coating, release mechanism, particle size, or manufacturing process. Those limitations could appear in unquoted claims or in related patents, but they are not present in claims 1 through 12 as provided.

A formulation containing Form B but more than 10 wt% Form A would not literally satisfy claim 4. A formulation containing no Form B would not satisfy the claim either, even if it contains trientine tetrahydrochloride in another crystalline or amorphous state.

What is the practical scope of the XRPD and Raman limitations?

The analytical limitations create both coverage and enforcement issues.

XRPD coverage

The XRPD requirement is tied to peak positions with a ±0.1° 2θ tolerance and a specified Cu Kα-type wavelength of 1.5418 Å. A generic or competing product would need testing under comparable conditions. Differences in instrument configuration, sample preparation, preferred orientation, crystallinity, hydration state, and peak intensity can affect the observed pattern.

A product does not necessarily avoid the patent merely because it has additional peaks. The independent claims require at least two selected peaks, not an exact six-peak pattern. Conversely, the absence of two required peaks under a reproducible test could support a noninfringement position.

Raman coverage

The Raman route is broader in one respect because it requires only two of four listed peaks. It may also create evidentiary questions involving laser wavelength, sample preparation, spectral resolution, calibration, fluorescence, and baseline correction. The claim specifies Raman shift values and tolerance, but the supplied claims do not specify the laser wavelength or instrument model.

Form A contamination

The Form A limitation makes polymorphic control central to infringement analysis. A batch could satisfy Form B identity yet fall outside a narrower claim if Form A exceeds the applicable threshold. The relevant question is generally the wt% of Form A in the claimed crystalline material or pharmaceutical composition, not merely whether Form A is detectable.

When does US Patent 11,072,577 lose exclusivity?

US Patent 11,072,577 was issued on September 7, 2021. Public patent records identify a June 2014 priority date and an expected ordinary patent term extending into 2035. The commonly reported expiration date is June 18, 2035, subject to any applicable patent-term adjustment or terminal disclaimer shown in the official file history. [1]

Event	Date
Earliest reported priority	June 18, 2014
Patent grant	September 7, 2021
Reported expected expiration	June 18, 2035
FDA approval of Cuvrior	May 2022
Patent term remaining after FDA approval	Approximately 13 years at approval

The patent's expiration does not automatically determine the earliest lawful generic launch. FDA regulatory exclusivity, other listed patents, litigation settlements, pediatric exclusivity, and approval timing may affect launch.

What is the FDA and Orange Book status of the patent?

Cuvrior, containing trientine tetrahydrochloride, received FDA approval in May 2022 for the treatment of Wilson's disease in adults and children at least 12 years old who are stable and tolerating penicillamine. [2] The product is marketed by Orphalan.

Patent 11,072,577 has been associated with Cuvrior's patent protection and is relevant to an abbreviated new drug application seeking approval of a product that relies on the Cuvrior labeling. The precise Orange Book listing, use code, and current patent status must be read from the FDA's contemporaneous electronic Orange Book record because listing status can change through delisting, correction, expiration, or regulatory update. [3]

The patent's claim language is particularly suited to a method-of-use or product-specific polymorph listing rather than a broad active-ingredient listing. An ANDA applicant may need to address the patent through a certification under 21 U.S.C. § 355(j), depending on how FDA lists the patent and whether the proposed product relies on the protected indication or formulation.

Which companies are challenging US 11,072,577?

No specific Paragraph IV challenger or final court judgment can be established from the claim text alone. A Paragraph IV certification would be expected to focus on one or more of the following positions:

• The proposed product does not contain Form B.
• The proposed product contains a different crystalline form.
• The proposed product contains Form B but does not meet two required XRPD or Raman peaks.
• Form A exceeds the claimed threshold, placing the product outside the claim.
• The patent is invalid for anticipation or obviousness.
• The method-of-treatment claims are not infringed because the proposed labeling omits the protected use.
• The asserted claim is indefinite or lacks adequate written description or enablement for the analytical and purity limitations.

A generic applicant could also pursue a section viii statement if it seeks approval only for an indication or use outside the patented method. That strategy would be difficult if the approved product has only the Wilson's disease indication and the patent claims the principal approved use.

What patent litigation affects trientine tetrahydrochloride?

The principal litigation risk is likely to arise from an ANDA filing directed to a trientine tetrahydrochloride product that uses the same Form B polymorph. The commercial product's reliance on Form B would make a polymorph-based Paragraph IV challenge more exposed than a product designed around another salt or polymorphic form.

Potential litigation issues include:

Issue	Relevance
Infringement	Whether the generic's material meets the XRPD or Raman criteria
Purity	Whether Form A is present above or below the 10%, 5%, 2%, or 1% thresholds
Claim construction	Meaning of "crystalline form," "at least two peaks," and wt%
Validity	Obviousness and anticipation of Form B and its use
Enablement	Whether the patent enables the full analytical scope
Regulatory use	Whether the ANDA label induces the patented Wilson's disease use
Sampling	Whether testing one batch proves commercial product infringement
Remedies	Potential 30-month stay, injunction, or delayed launch

An ANDA containing a Paragraph IV certification may trigger patent litigation under the Hatch-Waxman framework. If the NDA holder or patent owner brings suit within the statutory period, FDA approval may be stayed for up to 30 months, subject to statutory exceptions and court developments. [4]

How strong is the patent estate for Cuvrior?

Patent 11,072,577 has meaningful but bounded strength.

Strengths

• It covers the specific Form B associated with the commercial product.
• It uses two independent analytical identification routes.
• It includes treatment claims, composition-based method claims, purity claims, dosage-form claims, and dose claims.
• It captures Form B material containing limited Form A contamination.
• It may be difficult for a conventional generic to copy the commercial crystal form without performing a detailed noninfringement analysis.

Weaknesses

• It does not broadly cover all trientine salts or all trientine crystal forms.
• The independent claims require a specific Wilson's disease treatment.
• The XRPD and Raman limitations provide identifiable design-around targets.
• The claim construction may be vulnerable if the specification does not adequately support the full range of peak combinations and impurity thresholds.
• The 0.1 mg-to-10 mg daily dosage limitation in claims 11 and 12 is narrower than ordinary clinical trientine dosing and may have limited practical value if the approved product is administered at substantially higher doses.
• A competitor may attempt to use a non-Form B material or develop a different salt or solid-state form.

What generic entry risks exist?

The most credible entry scenarios are:

Form B copy with Paragraph IV litigation

A generic duplicates the commercial Form B and challenges validity or infringement. This offers the simplest development path but presents the highest direct patent risk.

Different polymorph

A generic develops Form A or another polymorph. This may avoid literal infringement, but the applicant must establish reliable solid-state identity and control interconversion during manufacturing and storage.

Different salt

A company could pursue trientine in another salt form. This may avoid the claims but could require a separate regulatory development program, new pharmaceutical characterization, and potentially clinical bridging.

Label carve-out

A generic may attempt to remove the patented use from its labeling. That route depends on the scope of the approved labeling, the Orange Book use code, and whether the remaining label would still encourage the patented treatment.

Amorphous or noncrystalline material

An amorphous trientine tetrahydrochloride product could avoid a crystalline Form B claim. Manufacturing, stability, hygroscopicity, dissolution, and dose uniformity may make this route difficult.

Does biosimilar risk apply to trientine tetrahydrochloride?

No. Trientine tetrahydrochloride is a small-molecule drug, not a biologic. The relevant competitive pathway is an ANDA for a generic drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Public Health Service Act. [4]

The competitive risk therefore depends on pharmaceutical equivalence, bioequivalence, patent certifications, formulation design, and the availability of a suitable noninfringing solid form. Biosimilar interchangeability, biologic reference-product exclusivity, and biosimilar patent dance procedures do not apply.

What licensing deals affect the patent landscape?

The patent record and FDA product information distinguish patent ownership from commercialization. Orphalan markets Cuvrior, while the underlying intellectual property associated with trientine tetrahydrochloride Form B has been linked to the product's development and commercialization history. A patent assignment, license, or commercial agreement does not expand the scope of the issued claims.

For transaction diligence, the key questions are:

• Whether the patent has been assigned after grant.
• Whether Orphalan holds an exclusive license covering the United States.
• Whether the license includes patent prosecution and enforcement rights.
• Whether royalties or milestone obligations continue after a generic launch.
• Whether related Form B, manufacturing, formulation, or process patents exist outside US 11,072,577.
• Whether any settlement licenses have been granted to potential ANDA applicants.

Those rights must be confirmed in the USPTO assignment database and executed transaction documents. Patent 11,072,577 itself does not disclose the complete commercial licensing arrangement. [1]

How does this patent compare with a broad active-ingredient patent?

Patent type	Coverage	Design-around potential	Relevance to Cuvrior
Active-ingredient patent	Trientine or broad salt class	Low	Broadest protection, but generally earlier-expiring
Salt patent	Trientine tetrahydrochloride	Moderate	Covers salt, potentially independent of crystal form
Polymorph patent	Form B crystal structure	High to moderate	Directly relevant to the commercial solid form
Formulation patent	Tablet, capsule, excipient, release profile	Moderate	Depends on product-specific formulation
Method-of-use patent	Wilson's disease treatment	Moderate	Can support Orange Book and Hatch-Waxman enforcement
Manufacturing patent	Crystallization or purification process	Moderate	May create supply-chain barriers without directly blocking use

US 11,072,577 combines polymorph limitations with method-of-treatment and composition limitations. Its commercial value is therefore greater than a purely analytical characterization patent but narrower than a broad composition-of-matter patent.

Key Takeaways

• US 11,072,577 protects treatment of Wilson's disease using crystalline trientine tetrahydrochloride Form B.
• The patent requires Form B identification through specified XRPD or Raman peaks.
• Claim 1 permits no more than 10 wt% Form A; claims 7 through 9 reduce that threshold to 5%, 2%, and 1%.
• Claims 4 and 10 extend coverage to pharmaceutical compositions and solid oral dosage forms.
• Claims 11 and 12 recite a daily dose of 0.1 mg to 10 mg, a narrow limitation with potentially limited commercial relevance.
• The commonly reported patent expiration date is June 18, 2035, subject to official patent-term calculations.
• The principal generic strategy is to challenge the patent while copying Form B or to develop a different polymorph, salt, or noncrystalline form.
• Biosimilar law does not apply because trientine tetrahydrochloride is a small molecule.
• The patent is strongest against a generic that uses the same Form B and weakest against a product that reliably avoids Form B.
• Patent-specific litigation, settlement, assignment, and licensing conclusions require review of the current USPTO, FDA, and court records.

FAQs About US Patent 11,072,577

Is US 11,072,577 a composition-of-matter patent?

No. The supplied claims are method claims covering administration of a defined crystalline Form B and pharmaceutical compositions containing that form.

Can a generic use trientine tetrahydrochloride without infringing?

Potentially. A generic using a different polymorph, amorphous material, different salt, or a formulation outside the claimed limitations may avoid literal infringement. It would still need to address any other applicable patents and FDA requirements.

What is the critical analytical test for Form B infringement?

The critical tests are XRPD and Raman spectroscopy. The product must be evaluated for the specified peak combinations, tolerances, measurement conditions, and Form A content.

Does Form A itself fall within the patent?

No. Form A is identified as an impurity or excluded competing form. The claims permit limited Form A contamination but do not claim Form A as the protected active crystalline form.

Is Cuvrior protected by more than US 11,072,577?

Potentially. Commercial products can have multiple patents covering polymorphs, formulations, manufacturing methods, dosing, or methods of use. The complete patent position must be determined from the current FDA Orange Book, USPTO records, and related patent families.

References

1. United States Patent and Trademark Office. (2021). US Patent No. 11,072,577, crystalline form of triethylenetetramine tetrahydrochloride and uses thereof.
2. U.S. Food and Drug Administration. (2022). Cuvrior: Prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2023). Small business and industry assistance: Abbreviated new drug application process and patent certifications.

Drugs Protected by US Patent 11,072,577

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Orphalan	CUVRIOR	trientine tetrahydrochloride	TABLET;ORAL	215760-001	Apr 28, 2022		RX	Yes	Yes						A METHOD FOR THE TREATMENT OF ADULT PATIENTS WITH STABLE WILSON’S DISEASE WHO ARE DE-COPPERED AND TOLERANT TO PENICILLAMINE

Foreign Priority and PCT Information for Patent: 11,072,577

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	18290048	May 4, 2018

International Family Members for US Patent 11,072,577

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	115080
Australia	2019263969
Australia	2024227767
Brazil	112020018451
Canada	3096423
China	111479798
China	114394904