Details for Patent: 10,695,350

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Which drugs does patent 10,695,350 protect, and when does it expire?

Patent 10,695,350 protects IMBRUVICA and is included in three NDAs.

Protection for IMBRUVICA has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has forty-five patent family members in fourteen countries.

Summary for Patent: 10,695,350

Title:	Methods of treating and preventing graft versus host disease
Abstract:	Described herein are methods for treating and preventing graft versus host disease using ACK inhibitors. The methods include administering to an individual in need thereof an ACK inhibitor such as ibrutinib for treating and preventing graft versus host disease.
Inventor(s):	John C. Byrd, Jason A. Dubovsky, Natarajan Muthusamy, Amy J. Johnson, David Miklos
Assignee:	Pharmacyclics LLC
Application Number:	US16/582,945
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,695,350
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 10,695,350: Scope, Claims, Expiration and Ibrutinib GVHD Patent Landscape

US Patent 10,695,350 protects a narrow method of using ibrutinib, marketed as Imbruvica, at 420 mg once daily in adults with chronic graft-versus-host disease refractory to systemic therapy. The patent does not claim ibrutinib itself, a formulation, a manufacturing process, or every use of ibrutinib in GVHD.

Its commercial value depends on whether the patent remains enforceable against an ANDA applicant or other competitor that markets ibrutinib for refractory chronic GVHD. The strongest practical limitation is the required 420 mg once-daily regimen. The most vulnerable limitations are the outcome-based requirements of "complete resolution" and "preventing recurrence" of hematological malignancy.

What does US Patent 10,695,350 protect?

The patent protects treatment methods meeting several cumulative conditions:

Requirement	Independent claim 1	Independent claim 3
Patient	Adult	Adult
Disease	Chronic GVHD	Chronic GVHD
Prior treatment status	Refractory to systemic therapy	Refractory to systemic therapy
Active malignancy requirement	None	Hematological malignancy
Drug	Ibrutinib	Ibrutinib
Dose	420 mg	420 mg
Administration	Oral, once daily	Oral, once daily
Claimed result	Complete resolution of GVHD symptoms	Complete resolution of GVHD symptoms and prevention of malignancy recurrence
Discontinuation limitation	Yes, when therapy is no longer required	No express discontinuation limitation

The patent is therefore a use patent directed to a specific treatment regimen and clinical outcome. It does not create a monopoly over the ibrutinib molecule or over all ibrutinib treatment of chronic GVHD.

How broad are claims 1 and 3?

Claim 1: refractory chronic GVHD treatment

Claim 1 requires:

1. An adult patient.
2. Chronic GVHD.
3. Chronic GVHD refractory to systemic therapy.
4. Oral administration of 420 mg ibrutinib once per day.
5. Complete resolution of symptoms.
6. Discontinuation when the patient no longer requires therapy.

The claim reaches patients who have failed or not adequately responded to prior systemic treatment. It does not specify the prior systemic agent, the organ affected, the duration of treatment, the transplantation history, or the underlying hematological malignancy.

The discontinuation language narrows the claim. A treatment course that continues indefinitely, without a clinical determination that the patient no longer requires therapy, may not satisfy the express discontinuation limitation. The claim does not state how "no longer requires therapy" must be determined.

Claim 3: treatment plus prevention of malignancy recurrence

Claim 3 adds two important limitations:

• The patient must have a hematological malignancy.
• Ibrutinib must both resolve cGVHD symptoms and prevent recurrence of that malignancy.

This claim is materially narrower than claim 1 because it requires a second therapeutic outcome. It is also more exposed to validity and enforcement disputes because "preventing recurrence" can involve a long follow-up period and difficult causation questions.

A patient who experiences improvement in GVHD but later relapses from the underlying malignancy may fall outside claim 3, even if the ibrutinib treatment otherwise satisfies every dosing and disease limitation.

What do dependent claims 2 and 4-8 add?

Claim	Added limitation	Practical effect
2	Full donor chimerism before discontinuation	Narrows claim 1 to transplant-related patients meeting a specified chimerism condition
4	Full donor chimerism	Narrows claim 3
5	Hematological malignancy is refractory CLL	Targets a specific high-risk patient subgroup
6	Prior allogeneic hematopoietic cell transplant	Requires transplant history
7	Oral cGVHD of the oropharyngeal region	Narrows the disease site
8	Prior anticancer agent is rituximab	Creates a highly specific treatment-history limitation

Claim 8 is the narrowest disclosed species. It requires the combination of refractory CLL, prior allogeneic hematopoietic cell transplantation, oral oropharyngeal cGVHD, and prior rituximab exposure.

The dependent claims may be harder to practice broadly but can provide fallback positions if broader claims are invalidated. A competitor could avoid a dependent claim by using a patient without the specified transplant history, disease location, prior rituximab exposure, or full donor chimerism, while still potentially implicating claim 1 or claim 3.

What patent family and ownership are associated with US 10,695,350?

US Patent 10,695,350 is associated with the Pharmacyclics and Janssen ibrutinib development program. Pharmacyclics developed ibrutinib with Janssen Biotech under a collaboration arrangement, and AbbVie later acquired Pharmacyclics. Janssen is part of Johnson & Johnson.

The patent claims are directed to the chronic-GVHD clinical use of ibrutinib rather than to the base compound. They should be analyzed separately from the foundational ibrutinib composition patents and from patents covering solid formulations, crystalline forms, combination therapy, and other indications.

The nominal patent term is expected to run into 2036 based on the family’s 2016 international filing date, subject to patent-term adjustment, terminal-disclaimer issues, maintenance fees, and any later legal events. The exact enforceable expiration date should be determined from the USPTO patent record and the patent’s term-adjustment calculation.

When does ibrutinib lose exclusivity for chronic GVHD?

Ibrutinib has several separate exclusivity layers:

Exclusivity layer	Relevance
Active pharmaceutical ingredient patents	Protect ibrutinib itself and may expire earlier or later than the GVHD patent family
Formulation and solid-form patents	Can restrict particular product presentations or manufacturing routes
Method-of-use patents	Include US 10,695,350 and other indication-specific claims
FDA orphan-drug exclusivity	The cGVHD indication received orphan-drug treatment and accelerated approval
New chemical entity exclusivity	Applied to the original ibrutinib approval, not necessarily to the later cGVHD indication
Pediatric exclusivity	May extend certain listed patents if granted and applicable
Regulatory exclusivity for the indication	Separate from patent term and potentially affected by withdrawal of the indication

The FDA granted accelerated approval for Imbruvica in adult patients with chronic GVHD after failure of one or more lines of systemic therapy in August 2017. The cGVHD indication was later voluntarily withdrawn in the United States after the confirmatory trial did not establish the required benefit-risk profile. The withdrawal affects the regulatory indication, but it does not automatically invalidate US Patent 10,695,350.

A patent can remain enforceable even when the corresponding FDA indication is withdrawn. The commercial effect is different: a generic applicant may have a stronger argument for a label carve-out if the patented use is no longer included in the reference product’s approved labeling.

What is the Orange Book status of US Patent 10,695,350?

The key Orange Book issue is whether US 10,695,350 is listed against the relevant Imbruvica product and whether FDA assigns it a chronic-GVHD method-of-use code.

For a listed method-of-use patent, an ANDA applicant generally must address the patent through one of four certifications:

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will wait until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A fifth practical route is a section viii statement that the applicant is carving out the patented method from its labeling. That route is particularly important for a method patent because a generic may seek approval for non-patented ibrutinib uses while omitting chronic GVHD language.

Listing alone does not establish validity or infringement. It creates an ANDA notification and litigation framework. The use code and the exact proposed generic label determine whether the applicant must make a Paragraph IV certification or can use a skinny-label strategy.

How strong is the patent estate for ibrutinib chronic GVHD?

The estate is stronger as a narrow clinical-use barrier than as a broad product monopoly.

Strengths

• The dose is exact: 420 mg once daily.
• The disease population is clinically identifiable.
• The claim targets patients refractory to systemic therapy.
• The claimed use corresponds to the cGVHD treatment population evaluated in clinical development.
• Dependent claims provide several narrower fallback positions.
• The patent can potentially cover a generic label that expressly includes refractory cGVHD.

Weaknesses

• The claims require outcome-based limitations rather than only administration steps.
• "Complete resolution of symptoms" may create disputes over clinical measurement and claim construction.
• "Preventing recurrence" is difficult to prove prospectively and may be challenged as indefinite or unsupported.
• "No longer requires therapy" does not provide a precise stopping rule.
• The 420 mg dose is closely associated with the approved adult Imbruvica regimen, making a design-around based only on dose commercially unattractive but legally possible.
• The cGVHD indication’s withdrawal reduces the likelihood that a future generic label will directly reproduce the patented indication.

The patent does not block a competitor from developing another BTK inhibitor, another cGVHD therapy, or an ibrutinib regimen outside the claimed patient population or dose.

What formulation patents protect ibrutinib?

US 10,695,350 does not claim a formulation. It requires oral administration but does not specify:

• Tablet composition.
• Capsule composition.
• Particle size.
• Crystalline form.
• Salt or polymorph.
• Coating.
• Dissolution profile.
• Excipient system.
• Manufacturing process.

Separate ibrutinib patents may protect commercial tablets, solid-state forms, formulation technology, and manufacturing methods. Those patents must be mapped independently because a generic could avoid the GVHD method patent while still infringing a formulation or solid-form patent.

Conversely, a generic could design around a formulation patent but still face a method-of-use claim if its labeling induces use for refractory cGVHD.

What generic entry risks exist?

Full-label generic launch

A full-label generic that includes refractory chronic GVHD would face the clearest risk under claims 1 and 3. The applicant could receive a Paragraph IV notice letter, and the patent owner could bring an infringement action under the Hatch-Waxman framework.

Skinny-label launch

A generic could seek approval for other ibrutinib indications while omitting chronic GVHD. This reduces direct method-of-use exposure, although promotional activity, prescribing instructions, product literature, and other conduct could create induced-infringement arguments.

Dose redesign

Changing the dose from 420 mg once daily may avoid literal infringement of the express dosage limitation. The commercial and regulatory value of a different dose would depend on clinical data and labeling, and the patent owner could still assert equivalents depending on the facts.

Patient-population redesign

A competitor could target newly diagnosed or non-refractory cGVHD, pediatric patients, non-oral administration, or a different disease setting. These approaches would reduce exposure to the claims but may not reproduce the commercial market addressed by the patent.

Which companies challenge the ibrutinib franchise?

The main competitive pressure comes from therapies approved or developed for chronic GVHD rather than from direct copies of the patented regimen.

Product	Company	cGVHD position
Imbruvica, ibrutinib	Pharmacyclics/AbbVie and Janssen	Accelerated approval after prior systemic therapy; cGVHD indication later withdrawn
Jakafi, ruxolitinib	Incyte	Approved for acute or chronic GVHD after failure of one or more lines of systemic therapy
Rezurock, belumosudil	Kadmon/Sanofi	Approved for chronic GVHD after at least two prior lines of systemic therapy
Niktimvo, axatilimab	Syndax and Incyte	Approved for chronic GVHD after multiple prior lines of systemic therapy

Ruxolitinib and belumosudil compete directly for patients who would historically have been considered for ibrutinib. Their presence reduces the practical value of a method patent tied to an indication that is no longer actively marketed in the same regulatory form.

What patent litigation affects US 10,695,350?

The primary litigation risk is an ANDA action involving a generic ibrutinib applicant. The relevant disputes would likely concern:

1. Whether the patent is properly listed.
2. Whether the generic’s proposed label includes the patented cGVHD use.
3. Whether "complete resolution" is a required infringement limitation.
4. Whether the patent adequately supports the claimed prevention of malignancy recurrence.
5. Whether the claims are definite and enabled.
6. Whether the patent term remains active.
7. Whether a settlement permits an agreed generic entry date.

A settlement could authorize entry before the nominal patent expiration date, subject to antitrust review and the terms of the agreement. There is no basis to treat the patent’s issuance alone as evidence of a guaranteed exclusion period.

What is the commercial exposure?

The patent’s direct revenue exposure is narrower than the total Imbruvica franchise.

The relevant market is limited to adult patients with refractory chronic GVHD, particularly patients who have failed systemic therapy. The market contracted after competing therapies entered and after the US cGVHD indication was withdrawn. The patent therefore has greater value as a litigation and label-control asset than as a stand-alone platform for future revenue growth.

The largest commercial risk would arise if a generic obtained approval with chronic GVHD language and captured treatment in the refractory population. A skinny-label generic would create a smaller direct threat, although off-label prescribing could still reduce branded sales.

Key Takeaways

• US Patent 10,695,350 is a narrow ibrutinib method-of-use patent.
• The core regimen is oral ibrutinib at 420 mg once daily in adults with systemic-therapy-refractory chronic GVHD.
• Claims 3-8 add malignancy recurrence prevention, full donor chimerism, refractory CLL, allogeneic transplant, oral oropharyngeal cGVHD, and prior rituximab.
• The patent does not claim ibrutinib, a tablet, a capsule, a formulation, or a manufacturing process.
• The nominal term is expected to extend into 2036, subject to the USPTO’s final term calculation and other legal events.
• The cGVHD indication’s withdrawal does not itself terminate the patent.
• A generic could pursue a skinny-label strategy if the patented chronic-GVHD use is omitted.
• The most contestable claim elements are complete symptom resolution, prevention of malignancy recurrence, and discontinuation when therapy is no longer required.
• Ruxolitinib, belumosudil, and axatilimab materially weaken the patent’s commercial position by providing alternative cGVHD treatments.

FAQs

Can a generic ibrutinib product launch without infringing US 10,695,350?

Yes. A generic may reduce risk through a section viii carve-out that omits the patented refractory-cGVHD use, provided its labeling and conduct do not induce use for that indication.

Does US 10,695,350 cover ibrutinib doses below 420 mg?

The claims expressly require 420 mg once daily. A materially different dose would create a substantial non-infringement argument, although other patents or equivalent-infringement theories could remain relevant.

Does the patent cover pediatric chronic GVHD?

The issued claims require an adult patient. Pediatric treatment is outside the literal scope of the stated claims.

Does full donor chimerism apply to every claim?

No. Full donor chimerism is required only by claims 2 and 4. It is not a limitation of independent claim 1 or independent claim 3.

Does withdrawal of the Imbruvica cGVHD indication invalidate the patent?

No. Regulatory withdrawal and patent validity are separate legal issues. Withdrawal may affect commercial use, Orange Book strategy, and generic labeling, but it does not automatically cancel the patent.

References

1. AbbVie Inc. (2023). IMBRUVICA (ibrutinib) prescribing information. U.S. Food and Drug Administration.

2. U.S. Food and Drug Administration. (2017). FDA approves ibrutinib for chronic graft-versus-host disease. FDA.

3. U.S. Food and Drug Administration. (2023). Withdrawal of approval of the chronic graft-versus-host disease indication for IMBRUVICA. FDA.

4. U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,695,350: Methods of treating chronic graft-versus-host disease. United States Patent and Trademark Office.

5. Miklos, D., Cutler, C. S., Arora, M., Waller, E. K., Jagasia, M., Pusic, I., Flowers, M. E. D., Weisdorf, D., & others. (2017). Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood, 130(21), 2243-2250.

6. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Drugs Protected by US Patent 10,695,350

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pharmacyclics Llc	IMBRUVICA	ibrutinib	SUSPENSION;ORAL	217003-001	Aug 24, 2022		RX	Yes	Yes	10,695,350					TREATMENT OF ADULT PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) AFTER FAILURE OF ONE OR MORE LINES OF SYSTEMIC THERAPY
Pharmacyclics Llc	IMBRUVICA	ibrutinib	CAPSULE;ORAL	205552-002	Dec 20, 2017		RX	Yes	No	10,695,350*PED				Y
Pharmacyclics Llc	IMBRUVICA	ibrutinib	CAPSULE;ORAL	205552-001	Nov 13, 2013	AB	RX	Yes	Yes	10,695,350*PED				Y
Pharmacyclics Llc	IMBRUVICA	ibrutinib	TABLET;ORAL	210563-001	Feb 16, 2018		RX	Yes	No	10,695,350*PED				Y

International Family Members for US Patent 10,695,350

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	098208
Argentina	131751
Australia	2014339815
Australia	2020204270