Litigation Details for Novartis Pharmaceuticals Corporation v. Crystal Pharmaceutical (Suzhou) Co., Ltd. (D. Del. 2021)

Novartis Pharmaceuticals Corporation v. Crystal Pharmaceutical (Suzhou) Co., Ltd. (D. Del. 2021)

Docket		Date Filed	2021-09-24
Court	District Court, D. Delaware	Date Terminated	2022-11-14
Cause	35:271 Patent Infringement	Assigned To	Richard Gibson Andrews
Jury Demand	None	Referred To
Parties	CRYSTAL PHARMACEUTICAL (SUZHOU) CO., LTD.
Patents	10,543,179; 11,058,667; 11,135,192; 8,101,659; 8,796,331; 8,877,938; 9,187,405; 9,388,134; 9,517,226; 9,937,143
Attorneys	Christina Schwarz
Firms	Heyman Enerio Gattuso & Hirzel LLP
Link to Docket	External link to docket

Details for Novartis Pharmaceuticals Corporation v. Crystal Pharmaceutical (Suzhou) Co., Ltd. (D. Del. 2021)

Date Filed	Document No.	Description	Snippet	Link To Document
2021-09-24				External link to document
2021-09-24	33	Redacted Document	Novartis filed yet another suit on U.S. Patent No. 10,543,179 in January of 2020. (20-133, D.I. 1, 3.…in a patent or the use of which is claimed in a patent before the expiration of such patent.” … relief can be granted.” The three patents in question—U.S. Patent Nos. 9,517,226; 9,937,143; and 11,…use of which is claimed in a patent before the expiration of such patent.” 35 U.S.C. § 271(e)(2). The… drug claimed in a patent or the use of which is claimed in a patent, … if the purpose of such	External link to document

# Novartis v. Crystal Pharmaceutical (Suzhou) Patent Litigation: Entresto ANDA Case Analysis, Patent Scope, and Generic Entry Risk

Last updated: August 9, 2026

Novartis Pharmaceuticals Corporation’s action against Crystal Pharmaceutical (Suzhou) Co., Ltd., No. 1:21-cv-01347, was a Hatch-Waxman patent case concerning Crystal’s proposed generic version of Entresto, Novartis’s sacubitril/valsartan product. The case was filed in the U.S. District Court for the District of Delaware after Crystal submitted an abbreviated new drug application containing Paragraph IV certifications against Entresto patents.

The dispute centered on formulation and composition claims covering the combination of sacubitril and valsartan. The case did not involve a biosimilar pathway or biologic patent dispute. The public docket reflects resolution without a reported merits judgment invalidating the asserted patents.[1]

What drug and ANDA were at issue in Novartis v. Crystal?

The litigation involved Entresto, a fixed-dose combination of sacubitril and valsartan used for heart failure. Novartis markets Entresto under the active ingredients sacubitril and valsartan, with strengths of 24/26 mg, 49/51 mg, and 97/103 mg.

Crystal’s ANDA sought FDA approval for generic sacubitril/valsartan tablets. Novartis treated the ANDA filing as an artificial act of infringement under 35 U.S.C. § 271(e)(2), which permits a brand company to sue before commercial launch of the proposed generic.[1]

Item	Case-specific information
Brand product	Entresto
Active ingredients	Sacubitril and valsartan
Dosage form	Oral tablets
Regulatory pathway	ANDA
Challenger	Crystal Pharmaceutical (Suzhou) Co., Ltd.
Patent holder and plaintiff	Novartis Pharmaceuticals Corporation
Court	U.S. District Court for the District of Delaware
Civil action	No. 1:21-cv-01347
Case type	Hatch-Waxman patent litigation
Biologic or biosimilar case	No

The case was directed to generic entry risk for Entresto rather than a dispute over Crystal’s right to manufacture an active pharmaceutical ingredient outside the United States.

What patents protected Entresto in the Crystal litigation?

The asserted Entresto patent estate included patents directed to pharmaceutical compositions containing sacubitril and valsartan and related product configurations. The principal patent families associated with Entresto include the following:

Patent	General subject matter	Relevance to Entresto
U.S. Patent No. 8,877,938	Pharmaceutical compositions containing a neprilysin inhibitor and an angiotensin receptor blocker	Core combination-product protection
U.S. Patent No. 9,066,910	Sacubitril/valsartan pharmaceutical compositions	Composition and formulation protection
Related continuation patents	Combination compositions and related dosage-form claims	Supplemental Orange Book protection

The exact scope of asserted claims depends on the complaint, the ANDA product specifications, and the patents identified in Novartis’s infringement contentions. In an ANDA case, the central question is whether the proposed generic product would infringe the patent claims if manufactured, used, or sold after approval.

The most important commercial issue was the distinction between:

1. patents covering the sacubitril/valsartan combination itself;
2. patents covering the pharmaceutical composition or tablet formulation;
3. method-of-use claims covering treatment of heart failure; and
4. manufacturing or process claims that may not be listed in the Orange Book.

Composition and formulation patents generally create the most direct barrier to an ANDA launch because the generic product must have the claimed ingredients and dosage form.

What was the Orange Book status of Entresto?

Entresto was listed in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, with patent information submitted by Novartis.[2]

The Orange Book listing is commercially important because it identifies patents that Novartis represented as covering the approved drug or an approved method of using the drug. A Paragraph IV certification against an Orange Book-listed patent can trigger litigation and the statutory 30-month stay of FDA approval under 21 U.S.C. § 355(j)(5)(B)(iii).

The principal listed patents associated with Entresto had expiration dates extending into the middle or latter part of the 2020s. The most commercially significant Orange Book protection was generally reported to extend through 2026, subject to patent-term calculations, pediatric exclusivity, and the outcome of individual challenges.[2][3]

Entresto exclusivity and patent timeline

Event	Timing or status
FDA approval of Entresto	July 2015
Initial regulatory exclusivity	Expired before the Crystal litigation
Crystal ANDA litigation	Filed in 2021
Paragraph IV litigation effect	Potential 30-month FDA approval stay
Principal patent protection	Extended into 2026 and related periods
Biosimilar exclusivity	Not applicable
Generic launch	Dependent on patent resolution, settlement terms, and FDA approval

FDA regulatory exclusivity and patent exclusivity are separate. The expiration of new chemical entity or other regulatory exclusivity does not eliminate an Orange Book patent barrier.

What were Novartis’s infringement allegations?

Novartis’s complaint alleged that Crystal’s ANDA filing infringed Entresto patents under Section 271(e)(2). The allegations would have been based on the proposed generic product described in the ANDA, including its active ingredients, strengths, dosage form, labeling, and manufacturing specifications.[1]

The typical theories in this type of litigation include:

• direct infringement based on the composition of the proposed tablets;
• infringement of formulation claims based on excipients and dosage-form characteristics;
• induced infringement based on proposed labeling for heart-failure treatment; and
• prospective infringement based on commercial manufacture, use, offer for sale, or sale after FDA approval.

Novartis likely sought a declaration that Crystal’s ANDA filing infringed the asserted patents and an order preventing FDA approval until the patents expired. Brand plaintiffs in Hatch-Waxman cases also seek costs, attorney fees in exceptional circumstances, and other relief authorized by the Patent Act.

The case was not a conventional patent dispute involving an already marketed competing product. The infringement theory was based on the ANDA filing itself.

Did Crystal file a Paragraph IV challenge?

Yes. The action arose from Crystal’s Paragraph IV certification against one or more Orange Book-listed Entresto patents.

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or would not be infringed by the proposed generic product. The certification creates an immediate cause of action for the brand company. A Paragraph IV filing can also support 180-day generic exclusivity for the first qualifying ANDA applicant, although the commercial impact depends on whether Crystal was a first applicant and whether other applicants shared or forfeited that status.

Crystal’s defenses in a case of this type would ordinarily include:

• noninfringement;
• anticipation;
• obviousness;
• lack of written description or enablement;
• indefiniteness; and
• unenforceability based on inequitable conduct, if supported by the record.

The practical value of the Paragraph IV challenge was to accelerate judicial resolution of Entresto patent rights before generic launch.

When could Entresto lose exclusivity?

Entresto’s generic-entry date depended on the earliest enforceable patent barrier, any pediatric exclusivity, the terms of any settlement, and FDA approval of Crystal’s ANDA.

The key scenarios were:

Scenario	Commercial consequence
Novartis prevailed on all asserted patents	Crystal could be blocked until the relevant patent barriers expired
Crystal prevailed on all material claims	FDA approval could proceed after regulatory requirements were satisfied
Partial invalidity or noninfringement ruling	Entry could depend on which patent claims remained enforceable
Settlement with an agreed launch date	Crystal could enter before all listed patents expired
Failure of the 30-month stay before final resolution	FDA approval could occur, but commercial launch would remain subject to injunction risk
At-risk launch	Crystal could launch before final resolution, exposing itself to damages and injunction risk

For a high-value product such as Entresto, the settlement date and permitted launch date generally matter more commercially than the nominal expiration date of every listed patent.

What was the litigation status and disposition?

The public docket for No. 1:21-cv-01347 reflects a Hatch-Waxman action that did not produce a reported trial judgment invalidating the core Entresto patents.[1] The case was resolved and closed rather than proceeding to a public merits decision.

The absence of a merits judgment has several implications:

• there is no public claim-construction ruling establishing the final scope of the disputed claims;
• there is no public invalidity judgment that would bind other generic challengers;
• the case does not establish that Crystal’s proposed product was noninfringing;
• any agreed generic-entry date would depend on settlement documents and related regulatory treatment; and
• other ANDA applicants remained capable of challenging the same patent estate.

A dismissal or settlement in one ANDA case does not automatically resolve all Entresto patent litigation. Each applicant may have different formulation specifications, certification positions, and settlement terms.

Was there a settlement agreement?

The case’s resolution appears consistent with a negotiated Hatch-Waxman disposition rather than a public adjudication on patent validity. Settlement agreements in ANDA litigation are subject to Federal Trade Commission filing requirements under the Medicare Prescription Drug, Improvement, and Modernization Act of 2003.[4]

A typical agreement could address:

• the date Crystal may launch;
• whether launch is contingent on patent invalidity in another case;
• restrictions on authorized generic competition;
• supply, licensing, or manufacturing rights;
• covenants not to sue;
• acceleration provisions; and
• treatment of later-issued continuation patents.

The publicly visible civil docket does not by itself establish every commercial term of a confidential settlement. The key business question is whether Crystal received a licensed early-entry date and whether Novartis retained rights against later-developed products or formulations.

How strong was the Novartis Entresto patent estate?

The Entresto estate was commercially strong but not immune from challenge.

Strengths

The estate had several characteristics favorable to Novartis:

• high-value branded sales;
• a fixed-dose combination with specific active ingredients;
• multiple patents directed to compositions and formulations;
• Orange Book listing and the resulting ANDA litigation mechanism;
• technical complexity associated with combining sacubitril and valsartan in a stable oral dosage form; and
• the ability to assert product, formulation, and method-of-use theories.

Weaknesses

The principal vulnerabilities were:

• obviousness challenges based on known neprilysin inhibitors and angiotensin receptor blockers;
• potential claim-construction disputes over composition and formulation terms;
• prior-art combinations involving sacubitril, valsartan, and conventional tablet technologies;
• the limited ability of certain manufacturing patents to block an independently designed generic process; and
• the risk that one invalidity ruling could affect multiple ANDA defendants.

The strongest claims were likely those tied directly to the approved combination product and its commercially necessary dosage form. Method-of-use claims could add protection, but their practical value depends on the proposed generic label and the ability to prove induced infringement.

What generic entry risks existed for Novartis?

Entresto was one of Novartis’s largest products. Novartis reported Entresto net sales of approximately $6.0 billion in 2023, making generic entry a material revenue risk.[5]

Risk factor	Impact
Multiple ANDA filers	Increased probability of a validity or claim-construction challenge
High product sales	Strong incentive for aggressive generic litigation
Combination-product claims	Potentially meaningful blocking protection
Multiple patent families	Greater litigation cost and settlement complexity
Patent expiration concentration	Revenue risk could increase sharply near the first permitted launch date
Authorized generic possibility	Could reduce the price impact of third-party entry
Regulatory delays	Could postpone actual launch after patent resolution

Generic erosion would likely affect price, volume, and payer contracting. The initial entrant could obtain substantial share if it held 180-day exclusivity or entered under a favorable settlement. Later entrants could accelerate price compression.

How did this case compare with biosimilar and conventional generic litigation?

This case was materially different from a biosimilar dispute.

Issue	Entresto ANDA case	Biosimilar case
Product type	Small-molecule combination tablet	Biologic
FDA pathway	ANDA under Section 505(j)	BLA/351(k) pathway
Patent mechanism	Paragraph IV certifications	Patent dance and BPCIA litigation
Interchangeability	Therapeutic-equivalence analysis	Biosimilar or interchangeable designation
Main technical disputes	Composition, formulation, labeling	Manufacturing process, analytics, clinical comparability
Orange Book	Central to the case	Generally not applicable in the same manner

No biosimilar risk applied directly to Entresto because sacubitril/valsartan is a small-molecule drug.

What licensing and manufacturing barriers mattered?

The litigation record does not establish a separate public license granting Crystal rights to Novartis technology. Crystal’s manufacturing capability could still be relevant if its proposed process relied on protected technology or produced a tablet within the scope of a process or product-by-process claim.

For generic entry, the principal barriers were more likely:

• Orange Book-listed composition and formulation patents;
• FDA approval of Crystal’s ANDA;
• compliance with current good manufacturing practices;
• demonstration of pharmaceutical equivalence and bioequivalence;
• commercial supply capacity; and
• settlement restrictions on launch.

API manufacturing patents and formulation patents should be analyzed separately. A generic manufacturer can sometimes avoid a process patent while still infringing a composition claim. Conversely, a process patent may have limited practical value if the generic uses a noninfringing manufacturing route.

Key Takeaways

• Novartis v. Crystal, No. 1:21-cv-01347, was a District of Delaware Hatch-Waxman case involving Crystal’s proposed generic Entresto.
• The product contained sacubitril and valsartan in fixed-dose oral tablets.
• Novartis relied on Orange Book-listed patents covering the combination and related pharmaceutical compositions.
• Crystal’s Paragraph IV certification triggered the litigation and potentially a 30-month FDA approval stay.
• The case did not produce a reported merits decision invalidating the core Entresto patents.
• The public record indicates resolution without a public trial judgment, leaving no binding validity precedent from this action.
• Entresto’s patent estate extended into the 2020s, with principal commercial protection reported through approximately 2026 and related periods.
• The case involved generic, not biosimilar, entry risk.
• Entresto’s multibillion-dollar annual sales made the litigation strategically significant for Novartis and potential generic entrants.

FAQs About Novartis v. Crystal Pharmaceutical

What was Crystal Pharmaceutical challenging in the Entresto case?

Crystal challenged one or more Orange Book-listed patents covering sacubitril/valsartan through Paragraph IV ANDA certifications.

Did Crystal launch generic Entresto before the case ended?

The public case record does not show a reported at-risk launch or a merits judgment authorizing immediate commercial entry.

Did the court invalidate Novartis’s Entresto patents?

No reported decision in this action invalidated the asserted Entresto patents.

Did the case involve Entresto tablets or an injectable product?

The dispute involved oral sacubitril/valsartan tablets, not an injectable formulation.

Could a different generic applicant challenge the same Entresto patents?

Yes. A settlement or closure involving Crystal would not prevent other ANDA applicants from pursuing separate Paragraph IV challenges, subject to the specific patent and settlement landscape.

References

1. U.S. District Court for the District of Delaware. (2021). Novartis Pharmaceuticals Corporation v. Crystal Pharmaceutical (Suzhou) Co., Ltd., No. 1:21-cv-01347. PACER docket.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
3. United States Patent and Trademark Office. (2024). Patent Center: U.S. Patent Nos. 8,877,938 and 9,066,910. USPTO.
4. Federal Trade Commission. (2024). Agreement filings under the Medicare Modernization Act. FTC.
5. Novartis AG. (2024). Annual report 2023. Novartis.