Details for Patent: 11,453,655

Which drugs does patent 11,453,655 protect, and when does it expire?

Patent 11,453,655 protects TRIKAFTA (COPACKAGED) and is included in two NDAs.

This patent has fifty-eight patent family members in thirty-seven countries.

Summary for Patent: 11,453,655

Title:	Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
Abstract:	Compounds of Formula (I):pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.
Inventor(s):	Alexander Russell Abela, Timothy Alcacio, Corey Anderson, Paul Timothy Angell, Minson Baek, Jeremy J. Clemens, Thomas Cleveland, Lori Ann Ferris, Peter Diederik Jan Grootenhuis, Raymond Stanley Gross, Anton V. Gulevich, Sara Sabina Hadida Ruah, Clara Kuang-Ju Hsia, Robert M. Hughes, Pramod Virupax Joshi, Ping Kang, Ali Keshavarz-Shokri, Haripada Khatuya, Paul John Krenitsky, Jason McCartney, Mark Thomas Miller, Prasuna Paraselli, Fabrice Jean Denis Pierre, Yi Shi, Muna Shrestha, David Andrew Siesel, Kathy Stavropoulos, Andreas P. Termin, Fredrick F. Van Goor, Johnny Uy, Timothy John Young, Jinglan Zhou
Assignee:	Vertex Pharmaceuticals San Diego LLC , Vertex Pharmaceuticals Inc
Application Number:	US16/994,875
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound;

US Patent 11,453,655: Scope, Claim Breadth, and Landscape for Crystalline Form A

US Patent 11,453,655 claims a specific solid-state material (“Crystalline Form A of Compound 1”) plus a formulation that uses that material. The patent’s enforceable scope is driven by how tightly “Crystalline Form A” is defined: (i) by X-ray powder diffraction (XRPD) peak positions with narrow tolerances, and (ii) by “substantially pure form” and XRPD similarity to a figure.

What is the patent’s core subject matter and how is it defined?

Claim dependency map (what each claim adds)

Claim	Adds/limits relative to claim 1	Practical meaning for scope
1	Baseline definition: “Crystalline Form A of Compound 1”	Locks enforceability to a particular crystal form, not just any polymorph/solid.
2	“substantially pure form”	Narrows coverage to a high purity material; dilutions or mixtures can fall outside.
3	XRPD: at least three peaks from a specified set of 9 candidate 2θ values (each ±0.2)	Broad within the Form A concept: identifies Form A by a minimal peak signature.
4	XRPD: at least three peaks from a reduced set of 6 candidate values	Narrows peak signature options but still allows selection among candidates.
5	XRPD: exactly three specified peaks (6.6, 13.1, 18.2 ±0.2)	Stronger specificity; easier validity and infringement arguments but narrower design-around surface.
6	XRPD: six specified peaks (6.6, 9.6, 13.1, 15.2, 18.2, 18.6 ±0.2)	Most restrictive XRPD profile; higher confidence match to Form A.
7	XRPD “substantially similar to” FIG. 2	Adds a morphology-level evidentiary standard; can capture materials that meet the figure pattern even if peak selection differs slightly.
8	Formulation: at least one crystalline form per claim 1 + pharmaceutically acceptable carrier	Extends into drug product composition (not just API).

What matters in claim construction (XRPD tolerance logic)

The claims use 2θ peak position windows of ±0.2. That is a narrow analytical tolerance, and it typically becomes the central battleground in both validity and infringement:

• Candidate peaks are discretely enumerated, e.g., 6.6 ±0.2 and 18.6 ±0.2.
• Some claims require a subset (3 of 6 or 3 of 9 candidates), and some require a specific set (3 exact peaks or 6 exact peaks).
• Claim 7 imports an “at least similar” standard relative to a figure, which can broaden coverage in practice depending on how “substantially similar” is supported in the specification and how prosecution history treated that language.

How broad are the claims in practice?

Breadth by claim type

1. Material (claims 1-7)

   • Coverage is confined to one crystalline form: “Crystalline Form A of Compound 1.”
   • The XRPD-based dependent claims provide multiple “routes” into infringement: meeting at least three peak conditions (claims 3-4), meeting an exact three-peak set (claim 5), meeting a six-peak set (claim 6), or showing XRPD similarity to FIG. 2 (claim 7).
   • This creates a claim set with overlapping infringement footprints. A defendant is less likely to escape on the basis that their XRPD does not match one specific subset, because other dependent claims allow other subsets.

2. Formulation (claim 8)

   • If a product contains any crystalline form within claim 1, the formulation claim can be asserted even if excipients and dosing differ.
   • The formulation claim does not broaden beyond “at least one crystalline form according to claim 1,” so the formulation is only protected insofar as the API is protected.

Practical “design-around” pressure points

The easiest theoretical escape is to supply a material that fails the claimed XRPD signature. However, claim 7 complicates that:

• Routes that fail claim 6 may still satisfy claim 5 or claim 3 if enough peaks land in windows.
• A material can sometimes produce peak shifts due to instrument calibration, sample prep, hydration, micronization, or preferred orientation. The ±0.2 windows are tight, but real-world XRPD variability can still be litigated.
• Claim 7 (“substantially similar to FIG. 2”) reduces the value of a purely “peak subset” approach because it can be argued as matching the overall pattern.

What does the XRPD claim language cover exactly (peak-by-peak)?

Candidate peak set referenced in claim 3

Claim 3 allows “at least three two-theta values” chosen from this list (each ±0.2):

• 6.6
• 7.6
• 9.6
• 12.4
• 13.1
• 15.2
• 16.4
• 18.2
• 18.6

Reduced candidate peak set referenced in claim 4

Claim 4 allows “at least three two-theta values” chosen from:

• 6.6
• 9.6
• 13.1
• 15.2
• 18.2
• 18.6

Exact peak sets referenced in claims 5 and 6

• Claim 5 (exact three peaks): 6.6, 13.1, 18.2 (each ±0.2)
• Claim 6 (exact six peaks): 6.6, 9.6, 13.1, 15.2, 18.2, 18.6 (each ±0.2)

“FIG. 2” reference in claim 7

Claim 7 requires XRPD that is “substantially similar” to the diffractogram in FIG. 2. This is an evidentiary standard that depends on the actual figure in the patent specification and how the form is described.

How enforceable is Claim 2 (“substantially pure”) and Claim 8 (formulation)?

Claim 2: “substantially pure form”

Claim 2 tightens the material coverage beyond the XRPD signature alone. In infringement disputes, “substantially pure” can become a question of:

• whether impurities or other polymorphs are present,
• whether they materially affect the crystalline identity,
• what purity threshold was supported by examples.

The claim is still likely to be enforced against commercial solids that are dominated by Form A, but it gives an argument for narrower scope where multiple forms persist.

Claim 8: formulation coverage

Claim 8 is straightforward:

• “A pharmaceutical formulation comprising at least one crystalline form according to claim 1 and a pharmaceutically acceptable carrier.”

Key points:

• It covers drug products where the API is Form A.
• It does not require any specific dosage form type (tablet, capsule, suspension), only that it is a “pharmaceutical formulation.”
• It does not specify a dose amount, so the claim is not limited by concentration thresholds.

How does this shape the patent landscape for crystalline forms of Compound 1?

Landscape logic (what you should expect around this patent)

Without the underlying application details (patentee, filing dates, specification, Compound 1 identity, and related family members), the landscape analysis cannot enumerate specific citing/controlling patents. The claims provided indicate a typical crystalline-form strategy:

• Primary coverage: the polymorph itself via XRPD peak signatures (claims 1-7).
• Downstream coverage: drug product formulation using that polymorph (claim 8).

This pattern is commonly used to:

• protect drug substance solid-state differentiation,
• extend patent life after initial compound claims (composition-of-matter or salt/crystal earlier in the family),
• create multiple dependent claims that are robust to measurement variation.

Expected competitor behavior

Given the tight XRPD tolerances, a generic or follow-on developer would usually:

• test whether their isolated solid matches the claimed Form A signature,
• consider producing an alternative polymorph, hydrate, or amorphous form,
• adjust manufacturing so that any “Form A-like” material is eliminated or reduced to below “substantially pure” thresholds.

Enforcement footprint

This patent is not only about material chemistry. Because claim 8 exists, it can support:

• leverage in product approval and settlement discussions tied to XRPD identity,
• litigation against API suppliers and/or formulation manufacturers depending on who imports and sells the Form A-containing product.

What is the claim scope in relation to alternatives (salts, hydrates, amorphous, and co-crystals)?

What the claims do not explicitly cover (based on claim text)

• The claims explicitly cover “Crystalline Form A of Compound 1.”
• They do not mention salts, hydrates, solvates, amorphous forms, or co-crystals in the provided claim text.
• If “Compound 1” could exist in multiple solid-state variants, infringement likely still depends on whether the accused product’s XRPD matches “Crystalline Form A” and is sufficiently pure.

Likely boundary conditions

• If Form A is a hydrate/solvate, drying or solvent exchange can shift XRPD and reduce match probability.
• If the accused material is the anhydrate (or another polymorph), it may miss one or more required peaks, especially in the “exact set” claims.
• If XRPD peaks overlap due to polymorph similarity, claim 7’s “substantially similar to FIG. 2” can capture materials that are not identical in peak subset selection but are pattern-matched in the overall diffractogram.

Can these dependent claims create multiple “infringement entry points”?

Yes. The dependent claims are structured to create redundancy:

• If an accused XRPD profile includes at least three peaks among the claim 3 candidate set, claim 3 can be met.
• If it includes at least three peaks among the claim 4 reduced set, claim 4 can be met.
• If it includes the specific 3-peak signature, claim 5 can be met.
• If it includes the 6-peak signature, claim 6 can be met.
• If it matches the figure pattern, claim 7 can be met even if a subset argument fails.

This structure makes the defense harder because it reduces the chance that a single missing peak defeats all dependent forms.

---

Key Takeaways

• US 11,453,655 is primarily a crystalline-form patent focused on Crystalline Form A of Compound 1, defined by XRPD peak positions with ±0.2 2θ windows.
• Claims 3-6 create multiple infringement paths based on different combinations and counts of XRPD peaks; claim 7 adds a pattern-based “substantially similar to FIG. 2” standard.
• Claim 2 narrows to “substantially pure” Form A, creating a potential non-infringement lever against mixed-solid products.
• Claim 8 extends protection to formulations that contain the claimed Form A API.
• Competitors’ core risk-control is solid-state control: ensuring their commercial solid does not meet the claimed Form A XRPD signature or purity threshold.

---

FAQs

1. What is the main infringement test for US 11,453,655?
   XRPD identity: whether the accused solid is “Crystalline Form A of Compound 1” and matches the claimed peak windows and/or is “substantially similar” to FIG. 2.

2. Which dependent claims are the most restrictive?
   Claim 6 (six exact peaks) is the most restrictive on the face of the claim language, followed by claim 5 (three exact peaks).

3. Does claim 7 broaden coverage beyond the enumerated peaks?
   Yes. It uses a “substantially similar to FIG. 2” standard that can capture materials whose peak subsets vary but whose overall diffractogram aligns.

4. How does “substantially pure form” affect coverage?
   It adds a purity constraint beyond XRPD peak presence, which can matter if the API is a mixture of solid forms or contains significant amounts of other polymorphs.

5. Is the patent limited to API-only products?
   No. Claim 8 covers pharmaceutical formulations containing the claimed crystalline form plus a pharmaceutically acceptable carrier.

---

References

[1] United States Patent 11,453,655. Claims provided in prompt (Crystalline Form A of Compound 1; XRPD peak-defined dependent claims; formulation claim).

Drugs Protected by US Patent 11,453,655

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-001	Apr 26, 2023		RX	Yes	No			Y	Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-002	Apr 26, 2023		RX	Yes	Yes			Y	Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-002	Jun 8, 2021		RX	Yes	No			Y	Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-001	Oct 21, 2019		RX	Yes	Yes			Y	Y

International Family Members for US Patent 11,453,655

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	110346
Australia	2017371200
Australia	2021211993
Australia	2023203944
Brazil	112019011626
Canada	3046086