Patent: 10,028,955

Summary for Patent: 10,028,955

Title:	FGFR inhibitor for use in the treatment of hypophosphatemic disorders
Abstract:	The present invention relates generally to 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimid-4-yl}-1-methyl-urea or a pharmaceutically acceptable salt or solvate thereof or a pharmaceutical composition comprising 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimid-4-yl}-1-methyl-urea or a pharmaceutically acceptable salt or solvate thereof for use in the treatment of X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), tumor-induced osteomalacia, post-renal transplant hypophosphatemia, epidermal nevus syndrome, osteoglophonic dysplasia or McCune-Albright syndrome.
Inventor(s):	Kneissel; Michaela (Basel, CH), Guagnano; Vito (Basel, CH), Graus Porta; Diana (Basel, CH), Wohrle; Simon (Vienna, AT)
Assignee:	Novartis AG (Basel, CH)
Application Number:	15/272,633
Patent Claims:	see list of patent claims

United States Patent 10,028,955: Claim-by-Claim Risk Appraisal and U.S. Landscape View

US Patent 10,028,955 centers on a single compound, 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-yl}-1-methyl-urea (and its salts), used to treat a disease set dominated by FGF-pathway / phosphate disorders. The core infringement questions in the U.S. are (1) whether the asserted claims survive validity challenges such as obviousness and written description, (2) whether the disease list is supported and clearly linked to the mechanism, and (3) whether the dosing and salt-form limitations materially narrow scope enough to carve out competitors.

Because the full specification, prosecution history, and the complete published patent family record are not provided here, the analysis below treats the claim text you supplied as authoritative and focuses on the structural landscape features that drive freedom-to-operate (FTO): how the claims constrain compound identity, salt form, dosing, duration, disease selection, and combination therapy. Where a competitor can plausibly differentiate, the analysis flags the likely design-around levers.

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What do the claims cover, in technical scope?

Claim 1: Disease method + exact compound (or salt)

Claim 1 is the anchor. It recites a method of treating a disease selected from:

• post-renal transplant hypophosphatemia
• epidermal nevus syndrome
• osteoglophonic dysplasia
• McCune-Albright syndrome

with a therapeutically effective amount of the defined compound or a pharmaceutically acceptable salt.

Scope mechanics

• Disease selection is permissive: “selected from the group consisting of …” means the method must match one of the listed indications, but the claim does not require specific patient biomarker thresholds.
• Compound identity is strict: infringement depends on using that exact chemical entity (free base or salt), not a class of FGFR inhibitors broadly.
• Salt language widens claim 1: “pharmaceutically acceptable salt thereof” captures many salt forms beyond monophosphoric acid, unless the specification defines otherwise.

Landscape implication

• If you are evaluating a generic or salt-form variant, claim 1 is often the hardest claim to route around because it already accepts “pharmaceutically acceptable salts.”

Claim 2: Duration and dose + monophosphoric acid salt

Claim 2 narrows Claim 1 with:

• a treatment that lasts at least 8 weeks
• dose is about 1–50 mg of the compound as the monophosphoric acid salt.

Scope mechanics

• Duration limitation can be a practical carve-out for studies or regimens shorter than 8 weeks. For chronic conditions, this is less of a carve-out.
• Dose range introduces a numerical constraint. “About 1–50 mg” typically supports some experimental tolerance.
• Salt form narrows identity versus Claim 1. This is significant for design-around: using a different salt could avoid Claim 2 while still potentially triggering Claim 1 (because Claim 1 still covers “pharmaceutically acceptable salts”).

Claim 3: Dose narrowing to 1–25 mg

Claim 3 further narrows claim 2:

• dose about 1–25 mg (still monophosphoric acid salt) and at least 8 weeks (inherited from Claim 2).

Scope mechanics

• This is a more limited regimen. A competitor picking higher or lower dosing could attempt to avoid this dependent claim. But if they land in the broader Claim 2 range, Claim 2 still applies.

Claim 4: Monophosphoric acid salt + combination with another FGFR inhibitor or phosphate/PTH/OPN/Vit D

Claim 4 adds:

• compound is monophosphoric acid salt
• combination therapy includes “another FGFR inhibitor, phosphate, calcium, osteopontin (OPN), parathyroid hormone or its analogue (PTH), vitamin D or vitamin D analogue.”

Scope mechanics

• This claim is built as an open-ended combination list: the method “is used in combination with another FGFR inhibitor, phosphate, calcium…” gives multiple pathways to satisfy the limitation.
• The “another FGFR inhibitor” option is especially important for landscape mapping, because it covers co-administration with a broad set of known FGFR ligands or kinase inhibitors used in FGFR-driven indications. The claim does not limit which FGFR inhibitor.

Landscape implication

• If a competitor’s clinical program uses the compound plus any established phosphate metabolism agent or PTH analog, Claim 4 can be implicated even without FGFR co-therapy.

Claim 5: Salt form confirmation (monophosphoric acid salt)

Claim 5 narrows Claim 1 by specifying:

• compound is monophosphoric acid salt.

Claim 6: Free base confirmation

Claim 6 narrows Claim 1 by specifying:

• compound is free base.

Scope mechanics across claims

• Claim 5 and Claim 6 show the drafting intent to cover both salt and free-base preparations, while Claim 4 and Claim 2 anchor key regimen restrictions to the monophosphoric acid salt.

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Where are the legal and technical pressure points?

1) Disease list breadth vs mechanistic linkage

Claim 1’s disease group spans:

• hypophosphatemia (post-renal transplant),
• epidermal nevus syndrome,
• osteoglophonic dysplasia,
• McCune-Albright syndrome.

From a patentability and enforceability perspective, the key issue is whether the specification ties the claimed compound’s activity to all listed diseases with a level of support that satisfies enablement and written description for each indication. If the compound is broadly FGFR-pathway acting, the diseases may be argued to share signaling biology, but examiners and later courts typically look for indication-specific support when claims are method-of-treatment across multiple rare disorders.

Practical FTO impact

• Competitors often seek to narrow by using only unlisted conditions, or by focusing on patient subsets. Claim 1’s “selected from the group consisting of” makes the indication set a binary gate: if a competitor’s label is outside the list, claim coverage can be avoided even if the mechanism is identical.

2) Overbreadth via “therapeutically effective amount”

Claim 1 uses a functional dose phrase without a numeric range. That is enforceable but can be vulnerable in validity challenges:

• “therapeutically effective amount” can be attacked as indefinite if the specification does not define operable ranges or guidance.
• Obviousness can also be argued if known FGFR inhibition already suggested dosing regimes for these disorders.

The dependent claims 2 and 3 cure part of that by adding numeric ranges and a duration floor.

3) Salt-form strategy (monophosphoric acid vs other pharmaceutically acceptable salts)

The claims create a layered enforcement structure:

• Claim 1 covers “pharmaceutically acceptable salt” broadly.
• Claim 2/3/4/5 lock additional limitations to monophosphoric acid salt.
• Claim 6 covers the free base.

Design-around patterns

• If a competitor can use a salt that is not “pharmaceutically acceptable,” they could aim to avoid Claim 1. That is uncommon commercially because most salts used in drugs are “pharmaceutically acceptable.”
• More realistic is to avoid dependent claims by avoiding monophosphoric acid specifically while staying within Claim 1’s general salt coverage.
• Salt selection also affects patent claim construction: courts often treat salt identification as a definitional element. Avoidance must change the salt form materially, not just in trace impurities.

4) “At least 8 weeks” and regimen carve-outs

Claim 2 requires therapy lasting at least 8 weeks. Competitors can try to structure:

• induction regimens shorter than 8 weeks, then switch to alternative therapies,
• or discontinuation after clinical endpoints earlier than 8 weeks.

For chronic phosphate and FGFR-pathway conditions, this is harder to sustain in practice. But for trial protocols or compassionate use, it can matter.

5) Combination therapy breadth in Claim 4

Claim 4 is broad because it enumerates multiple agents and does not require a particular ratio or sequencing with the co-therapy. It is enough that the method “is used in combination with” one of the listed categories.

From a validity viewpoint, broad combination claims can be challenged for lack of specific support if the specification does not describe those exact combinations. From an enforcement viewpoint, combination dosing is a common clinical standard for phosphate disorders, which increases real-world infringement risk.

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How does the claim set shape infringement risk by competitor type?

If you are developing a close chemical variant (same core compound, different formulation)

• Same compound, any pharmaceutically acceptable salt: Claim 1 remains the dominant risk. Dependent claims 2/3/4/5 become additional hurdles only if you also use the monophosphoric acid salt and satisfy duration/dose/combination elements.
• Same compound, free base: Claim 6 is relevant; Claim 1 still covers it via “therapeutically effective amount” and “pharmaceutically acceptable salt thereof” (though free base is explicitly covered in Claim 6).

If you are developing a different salt of the same compound

• Monophosphoric acid avoided: you may avoid Claims 2/3/4/5, but Claim 1 can still capture other pharmaceutically acceptable salts.
• Free base used: Claim 6 can apply, depending on dose and disease indication; Claim 1 still applies to free base if it qualifies as the defined compound (Claim 1 includes the compound itself; Claim 6 adds explicit free-base limitation).

If you are targeting the same diseases with a different FGFR inhibitor

• These claims are compound-specific. A method-of-treatment using another FGFR inhibitor does not fall inside Claim 1 unless the co-therapy includes this exact compound as the therapeutic agent meeting the “with a therapeutically effective amount of [defined compound]” limitation.
• Combination-only exposure can still implicate Claim 4 if the method is “used in combination with” phosphate or other agents, but the therapeutic agent at the core still has to be the defined compound.

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Patent landscape: what is likely to exist around this asset?

1) Expect a typical U.S. structure: compound claims first, then use claims

In practice, a patent with claims framed as “method of treating” with an exact compound name often sits in a family where:

• earlier filings claim composition/compound structure,
• later continuations pursue narrower use claims and dosage regimens,
• salt and formulation variants can be pursued in separate continuations.

The presence of dependent claims that separately cover:

• monophosphoric acid salt (Claims 2, 3, 4, 5),
• free base (Claim 6), suggests the family may include additional claims on solid forms, salts, and/or composition formulations.

2) Indication clustering: phosphate disorders and McCune-Albright spectrum

McCune-Albright syndrome (MAS) and related phosphate disorders are common targets for FGFR-pathway agents and phosphate pathway modulation. Post-renal transplant hypophosphatemia is also linked to FGF23 dysregulation. Epidermal nevus syndrome and osteoglophonic dysplasia are rare disorders that can share underlying MAPK/FGF signaling features depending on the genetic drivers.

This disease clustering tends to generate:

• multiple method-of-treatment patents across the same families,
• competitor filings around dosing and co-therapies,
• and potential litigation focusing on claim construction of “therapeutically effective amount” and the disease scope.

3) Combination standardization risk

Claim 4 includes phosphate, calcium, OPN, PTH/PTH analogs, and vitamin D/vitamin D analogs. Those agents commonly co-administer in phosphate disorders. That means infringement arguments can anchor on clinical practice rather than novel protocol design, increasing the chance that real-world treatment aligns with Claim 4.

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Key enforceability questions likely driving validity and claim scope

Written description and enablement (support for each disease and regimen)

• Claim 1 is broad across four diseases.
• Claim 2 and 3 require dosing and duration, which typically demands specific example data or guidance in the specification.

Indefiniteness (how “therapeutically effective amount” and dose ranges are anchored)

• Claim 1 depends on functional language.
• Claims 2/3 give ranges, reducing indefiniteness risk for those dependent claims.

Obviousness (prior art around FGFR inhibitors plus phosphate disease context)

• If known FGFR inhibitors already had evidence of benefit in phosphate disorders or related syndromes, an obviousness attack can argue routine optimization.
• The narrowing to a specific chemical compound may preserve novelty if the compound is not disclosed in the prior art.
• But the dependent claims’ regimen specificity (dose range, 8-week duration) can still be attacked as optimization absent strong evidence of unexpected results.

Claim construction (salt form boundaries and “in combination with”)

• Whether a formulation is “monophosphoric acid salt” hinges on chemical identity and characterization.
• “Used in combination with” typically does not require concurrency if the method results in combined administration, but claim interpretation can turn on timing and how “in combination” is treated in this patent family.

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What are the most actionable levers for FTO and design-around?

For an innovator evaluating collision risk

1. Indication discipline: Avoiding the listed indications can eliminate Claim 1 and all dependents.
2. Salt engineering: Avoid monophosphoric acid to target dependent-claim exclusion (Claims 2/3/4/5), while still assessing Claim 1 exposure under other pharmaceutically acceptable salts.
3. Regimen design: If clinically plausible, a treatment strategy not lasting at least 8 weeks can reduce Claim 2/3 exposure.
4. Combination mapping: If this compound is in the regimen, scrutinize whether standard co-therapies for phosphate disorders map onto Claim 4’s listed agents.

For a generic or biosimilar-style entrant (same API)

1. Claim-1 first pass: Determine whether any pharmaceutically acceptable salt or free base includes the defined compound.
2. Then dependent claims: Determine whether the marketed form is monophosphoric acid and whether the dosing and duration fall within Claims 2/3, and whether combination therapy matches Claim 4.

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Claims as a litigation blueprint: how each claim stacks

• Claim 1 is the broadest coverage entry point: disease + therapeutically effective amount of the exact compound (including salts generally).
• Claim 2 adds duration and monophosphoric acid salt and a broad dose band (1-50 mg).
• Claim 3 tightens dose within the Claim 2 band (1-25 mg).
• Claim 4 anchors combination therapy and again requires monophosphoric acid salt.
• Claim 5 and 6 add explicit preparation form limitations (monophosphoric acid vs free base).

In enforcement terms, this structure allows a patentee to plead a wide initial claim (1) and then selectively focus on regimen-formulation specifics (2-4) depending on the defendant’s commercial product and treatment protocols.

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Key Takeaways

• The patent is compound-specific for a single defined urea scaffold used in a method-of-treatment across four named diseases.
• Claim coverage is layered: Claim 1 broadly captures the compound with “pharmaceutically acceptable salts,” while Claims 2/3/4/5 narrow further to monophosphoric acid with dose and duration and potential combination therapy.
• The biggest actionable FTO vectors are salt form, treatment duration (>= 8 weeks), dose window, and whether clinical practice uses co-therapies that match Claim 4’s listed agents.
• Competitors using different FGFR inhibitors are generally insulated unless they also administer the defined compound as the therapeutic agent satisfying Claim 1’s limitation.

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FAQs

1) Does Claim 1 require monophosphoric acid specifically?

No. Claim 1 requires the defined compound or “a pharmaceutically acceptable salt thereof.” Monophosphoric acid is required only in dependent Claims 2, 3, 4, and 5.

2) Can a product avoid Claims 2 and 3 by changing the monophosphoric acid salt form?

Changing away from monophosphoric acid can avoid Claims 2/3 (and Claim 4/5), but Claim 1 can still apply if the product uses another pharmaceutically acceptable salt of the same defined compound.

3) If the therapy lasts 7 weeks, does Claim 2 still apply?

Claim 2 requires “at least 8 weeks,” so a 7-week regimen does not meet that limitation by the claim’s plain language.

4) Does Claim 4 require two drugs that are both FGFR inhibitors?

No. Claim 4 is satisfied if the method uses the defined monophosphoric acid salt in combination with “another FGFR inhibitor” or with phosphate, calcium, OPN, PTH/PTH analog, vitamin D/vitamin D analogue. Only one of the enumerated categories is needed.

5) Would using a different FGFR inhibitor for McCune-Albright avoid infringement?

Yes on the face of these claims, because Claim 1 requires treatment “with … [the defined compound]” (or its salts). Using a different FGFR inhibitor alone does not satisfy that core compound limitation.

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References

[1] United States Patent 10,028,955 (claim text provided in prompt).

Details for Patent 10,028,955

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	NATPARA	parathyroid hormone	For Injection	125511	January 23, 2015	10,028,955	2036-09-22